Dissertations / Theses on the topic 'Speckle tracking echocardiography'

PDA is one of the most common congenital cardiac malformation in the dog. Echocardiography has been the cornerstone in diagnosing and providing hemodynamic information in a wide variety of disease.Recently, speckle tracking echocardiography has been regarded as a useful tool to assess cardiac function. Aim of the study was to compare cardiovascular hemodynamics in dogs with PDA with healthy control dogs and evaluate any change in cardiac contractility before and after PDA closure. A statistically significant difference was found between standard and advanced echocardiographic techniques, with absolute higher values in dogs with PDA as compared to healthy controls. Cardiovascular hemodynamics were markedly different before and after PDA closure. Based on the results, STE should be considered in echocardiographic assessment of dogs with PDA, as they represent an animal model of congenital left ventricular overload not affected.

Left ventricular (LV) ejection fraction (EF) derived from two-dimensional echocardiography has been the cornerstone for LV function assessment for more than half a century. However, EF is only an indirect measure of cardiac output obtained from changes in LV volume, and does not necessarily reflect intrinsic myocardial contractile properties. Furthermore, LVEF measurement has a number of challenges that relate to image quality, LV geometry assumptions, and technical expertise, and has significant issues with intra-observer, inter-observer, and test-retest variability. A more contemporary marker of LV systolic function is speckle tracking echocardiography (STE)-based global longitudinal strain (GLS). Based on deformation of the cardiac muscle, GLS provides a more direct evaluation of myocardial contractile function. GLS is highly sensitive for the detection of overt LV dysfunction, as well as subclinical LV systolic impairment when LVEF is still considered normal. Furthermore, longitudinal strain has great utility in the evaluation of right ventricular (RV) function, as well as atrial function. Two-dimensional GLS, derived from semiautomatic software, has a high temporal and spatial resolution and consequently, improved inter- and intra-observer reproducibility, compared to LVEF. The overall aim of this thesis was to explore the role of STE-derived GLS in a variety of cardiovascular conditions. Firstly, the utility of GLS in patients with ventricular arrhythmias was assessed, including patients with and without structural heart disease. GLS in cardio-oncology, specifically left-sided breast cancer patients undergoing radiation therapy, was also evaluated. RV strain in patients with pulmonary embolism was studied in order to identify its role in the management of these patients. Finally, left atrial function, including left atrial strain, was addressed in a population of elite athletes with and without atrial fibrillation and compared to non-athletes.

The infiltrative cardiomyopathies are a heterogeneous group of disorders classically characterised by increased wall thickness and progressive diastolic dysfunction. While considered relatively rare, they are likely underdiagnosed, and are increasingly recognized as a significant cause of heart failure with preserved ejection fraction, particularly in the case of amyloidosis. Despite varying markedly in their natural histories and treatments available, they are often difficult to distinguish using conventional echocardiographic techniques. For this reason, novel imaging techniques, and multi-modality imaging are playing an increasing role in the diagnosis, prognostication and monitoring of infiltrative cardiomyopathies. This thesis aims to investigate the role of both conventional and novel echocardiographic techniques in the diagnosis and management of amyloidosis and Fabry disease, two of the more common forms of infiltrative cardiomyopathy.

Die technologische Entwicklung im Bereich der Echokardiographie hat in der letzten Dekade neue Methoden zur objektiven Erfassung der regionalen linksventrikulären Wandbewegung ermöglicht. Speckle Tracking erfasst die myokardiale Deformation durch die Positionsänderung einzelner Bildpunkte von einem Bild des analysierten Datensatzes zum nächsten. Diese Methode ist dem Gewebedoppler überlegen, insbesondere wegen ihrer Unabhängigkeit vom Anlotungswinkel. Zwei-dimensionale (2D) Speckle Tracking Analysen wurden für die klinische Praxis validiert. Die drei-dimensionale (3D) Echokardiographie erlaubt inzwischen Speckle Tracking Analysen von 3D Datensätzen, welche jedoch für die klinische Praxis noch nicht ausreichend validiert sind. Bei Patienten mit normaler regionaler linksventrikulärer Wandbewegung (N=37), sowie bei Patienten mit ischämie-bedingten Wandbewegungsstörungen (N=18) wurden 3D und 2D Speckle Tracking Analysen durchgeführt. Die Vergleichbarkeit der beiden Methoden hinschtlich der Quantifizierung von normalen und pathologischen Wandbewegungsmustern wurde anhand dieser Messungen geprüft. Des weiteren wurde der Einfluss der Bildrate und Bildqualität drei-dimensionaler Datensätze auf die Vergleichbarkeit beider Methoden analysiert. Es zeigte sich eine gute Vergleichbarkeit des 2D und 3D Speckle Tracking in der Diagnostik eingeschränkter linksventrikulärer systolischer Funktion, sowie in der Lokalisationsdiagnostik umschriebener Wandbewegungsstörungen. 2D und 3D Speckle Tracking sind jedoch noch nicht als gleichwertige Methoden anzusehen. Die Bildqualität, generell bei beiden Modalitäten - jedoch speziell bei 3D Datensätzen, sowie die Bildrate der 3D Datensätze zeigen signifikante Einflüsse auf die 3D Strain Analysen. Eine korrekte Standardisierung der analysierten Aufnahmen und eine optimale Bildqualität sind wichtige Faktoren, die die Zuverlässigkeit des 2D und 3D Speckle Trackings bestimmen.

Background: Critical care echocardiography has become standard of care in the ICU. New technologies have been developed and have shown potential clinical utility to elucidate myocardial dysfunction not seen with conventional imaging. We sought to determine the feasibility and potential clinical benefit of these techniques in common situations seen in the ICU. Hypothesis: Advanced echo techniques would be feasible in the majority of critically ill patients and have prognostic significance, clinical utility and diagnose cardiac abnormalities, potentially in a more sensitive manner than conventional techniques. Results: (a) Speckle tracking echocardiography (STE) Left ventricle and RV analysis with STE was feasibly in ~80% of patients. More dysfunction was found using STE vs conventional analysis. RV dysfunction assessed by STE held significant prognostic relevance in those with septic shock and highlighted subtle dysfunction induced by mechanical ventilation, both in animal and human studies. (b) 3D transthoracic echocardiography (3D TTE) Despite finding 3D TTE feasible in mechanically ventilated ICU patients (LV 72% and RV 55%), it lacked necessary low variability and high precision vs standard measures. (c) Myocardial contrast perfusion echocardiography (MCPE) Assessing acute coronary artery occlusion in the ICU patient is challenging. Troponin elevation, acute ECG changes, regional wall motion analysis on echo and overall clinical acumen often lack diagnostic capabilities. MCPE was found to be feasible in the critically ill and had better association predicting acute coronary artery occlusion vs clinical acumen alone. Conclusions: STE, 3D TTE and MCPE are feasible in the majority of ICU patients. STE may show dysfunction not recognised by conventional imaging. 3D TTE for volumetric analysis is likely not suitable for clinical use at this stage. MCPE may help guide interventions in acute coronary artery occlusion.

L’analyse de la fonction systolique en échocardiographie représente un challenge majeur depuis une vingtaine d’années dans le but d’améliorer la détection et la quantification des anomalies de la contraction myocardique. L’analyse des déformations myocardiques consiste à étudier le pourcentage d’étirement ou de raccourcissement myocardiques au cours du cycle cardiaque. Après le grand pas en avant dans ce domaine, consécutif à l’avènement du Doppler tissulaire il y a un quinzaine d’années, ces 4 dernières années ont vu naître une nouvelle technique d’analyse bidimensionnelle des déformations, porteuse de grands espoirs car s’affranchissant de la limitation liée à l’angle d’incidence Doppler et basée sur le suivi des marqueurs acoustiques de la paroi myocardique : le « speckle tracking echocardiography » ou « 2D strain ». Cette thèse rapporte tout d’abord une série de travaux orientés sur la validation de ce nouvel outil. Nous avons ensuite appliqué expérimentalement cette technique pour évaluer sa capacité à détecter l’ischémie myocardique lors d’un examen de stress sous dobutamine en comparaison à l’analyse de perfusion myocardique en échographie de contraste. Enfin, nous exposons plusieurs expériences cliniques qui témoignent de quelques applications potentielles de cette technique dans la prise en charge des patients porteurs de cardiopathies diverses : myocardiopathie hypertrophique, fibrillation auriculaire paroxystique et recherche de viabilité sous faibles doses de dobutamine chez les patients porteurs d’une cardiopathie ischémique
For 20 years, analysis of systolic myocardial function by echocardiography is a major challenge to improve the detection and the quantification of myocardial contractility abnormalities. The principle of myocardial deformation analysis consists in evaluating the percentage of myocardial thickening or shortening during the cardiac cycle. After a big step forward with the advent of tissue Doppler imaging for 15 years, the 4 last years have seen the apparition of a new technique of bidimensional analysis, without angle dependency, based on the tracking of the acoustic markers of the myocardial wall, and called « speckle tracking echocardiography » or « 2D strain ». This thesis reports serial studies oriented on the validation of this new tool and on the experimental application of this technique in the detection of myocardial ischemia during pharmacological dobutamine stress echocardiography, in comparison with myocardial perfusion analysis by contrast echocardiography. Finally, we report some clinical experiences using the speckle tracking echocardiography which attest of some clinical potential applications of this technique in the management of the patients with different cardiomyopathies: hypertrophic cardiomyopathy, lone paroxysmal atrial fibrillation, and analysis of myocardial regional deformation during low doses dobutamine infusion to investigate viability in patients with ischemic cardiomyopathy

Haemodialysis patients represent an extreme phenotype of cardiovascular risk with a pattern of disease distinct from that in the general population. Non-traditional risk factors, specific to chronic kidney disease such as hypervolaemia, arterial stiffness and advanced glycation end-product deposition are increasingly recognised. A previously demonstrated non-traditional risk factor associated with worse outcomes is the presence of uraemic cardiomyopathy. This pattern of cardiac morphology and function has previously been defined as the presence of left ventricular abnormalities, including left ventricular hypertrophy, dilatation and left ventricular systolic dysfunction. For the first time the work in this thesis studies an incident haemodialysis population using multi-parametric strain-based imaging. This uses the accuracy of cardiovascular magnetic resonance imaging of resting cardiac and aortic morphology and function augmented with strain by tagging to longitudinal strain changes during haemodialysis by speckle-tracking echocardiography. The general aim of this thesis was to characterise the relationship of left ventricular function to haemodialysis using strain-based imaging. This might allow characterisation of haemodialysis-associated cardiomyopathy which may be distinct from the traditional definition of uraemic cardiomyopathy and may better define those patients who would benefit from modifications to the process of haemodialysis.

Orientador: Aparecido Antonio Camacho
Resumo: O objetivo do presente estudo foi investigar a função miocárdica pela técnica de ecocardiografia bidimensional speckle tracking (2D STE) em pacientes submetidos à procedimentos anestésico prolongado, com a intenção de se detectar possível disfunção sistólica. Inicialmente para se determinar o intervalo normal da função sistólica na espécie, foram utilizados 31 coelhos da raça Nova Zelândia, adultos, hígidos, machos, com peso médio de 4,0 ± 0,53 kg, nos quais foram obtidos os índices sistólicos radiais como, velocidade rotacional e radial, deslocamento rotacional e radial, strain radial e strain rate radial. Posteriormente, para investigação da função sistólica sob diferentes modalidades ventilatórias, 32 coelhos foram distribuídos, aleatoriamente, em quatro grupos de modalidades ventilatórias diferentes constituídos de 8 animais cada, denominados grupo ventilação ciclada à pressão (GP), grupo ventilação ciclada à pressão associada à PEEP (GPP), grupo ventilação mandatória intermitente sincronizada (GM) e grupo ventilação espontânea (GE). Em todos os grupos, os parâmetros foram mensurados 40 minutos após a indução anestésica (M0) e reavaliados a cada vinte minutos, durante duas horas ininterruptas (M1, M2, M3 e M4). Portanto, o resultado demonstrados na presente investigação cientifica revelam que nenhuma modalidade ventilatória estudada proporcionou um quadro de disfunção sistólica a luz da técnica 2D STE quando foram comparados em cada momento de avaliação anestésica.
Abstract: The aim of this thesis was to investigate the cardiac function of patients undergoing prolonged anesthesia with the use of a two-dimensional speckle tracking (2D STE) technique to detect systolic dysfunction in order to maintain safety during anesthetic procedure. The study was carried out in healthy rabbits because this species is widely used as a model of experimentation for both humans and other animal species. Initially, the normal range of left ventricular radial systolic function was measured, for this purpose, 31 healthy male adults New Zealand rabbits were used, with average weight of 4.0 ± 0.53 kg, from a specialized producer; radial systolic indices were obtained, such as rotational and radial speed, rotational and radial displacement, radial strain and strain rate. Subsequently, 32 rabbits were randomly assigned to four groups of different ventilatory modalities consisting of 8 animals each, referred to as pressure-cycling ventilation group (GP), pressure-cycling ventilatory group associated with PEEP (GPP), synchronized intermittent mandatory ventilation group (GM) and spontaneous ventilation group (GE). In all groups, the parameters were measured 40 minutes after anesthetic induction (M0) and reevaluated every twenty minutes, for two uninterrupted hours (M1, M2, M3 and M4). Therefore, the results demonstrated in the present scientific investigation reveal that no studied ventilatory modality provided a picture of systolic dysfunction in light of the 2D STE techni... (Complete abstract click electronic access below)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
A cardiomiopatia arritmogênica do ventrículo direito (CAVD) é uma doença de origem genética, muito prevalente em cães da raça Boxer. Histologicamente ocorre atrofia dos cardiomiócitos do ventrículo direito (VD) e consequente infiltração fibroadiposa, levando ao aparecimento de arritmias ventriculares. Mesmo sendo as alterações miocárdicas microscópicas em sua maioria, estudos recentes têm identificado disfunção contrátil do ventrículo direito, mesmo em estágios iniciais da doença em humanos, tanto por técnicas convencionais de ecocardiografia quanto por técnicas mais avançadas, como no caso do speckle tracking. Por isso, o objetivo deste estudo foi avaliar se há disfunção miocárdica de VD detectável pela ecocardiografia convencional e pela técnica de speckle tracking bidimensional em cães da raça Boxer portadores da CAVD. Para tanto, utilizou-se cães da raça Boxer com idade superior a quatro anos, distribuídos em dois grupos de acordo com o resultado da avaliação Holter (GC: < 50 EVs/24h, n=11 e GD: > 100 EVs/24h, n=11). Os animais foram submetidos a ecocardiografia e avaliou-se diâmetro e comprimento interno do VD em sístole e diástole, encurtamento fracional da área do VD (FAC), excursão sistólica do plano anular da tricúspide (TAPSE), velocidade miocárdica sistólica do ânulo lateral da tricúspide derivada do Doppler tecidual (S’) e deformação (strain) e taxa de deformação (strain rate) longitudinal global da parede livre do VD, derivados da análise por speckle tracking. As variáveis foram comparadas entre os grupos pelo teste t de Student e de Mann-Whitney e a correlação entre variáveis ecocardiográficas convencionais e de speckle tracking e o número e severidade das arritmias pelo teste de correlação de Pearson, com nível de significância de 5%. Os grupos não foram estatisticamente diferentes e não houve correlação entre os dados. Os resultados da pesquisa demonstraram que a ecocardiografia, tanto na avaliação do VD por índices sistólicos convencionais quanto por aqueles derivados da técnica de speckle tracking não foram capazes de detectar disfunção miocárdica do VD em Boxers portadores de CAVD.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease with a high prevalence in Boxer dogs. Histologically, right ventricle (RV) cardiomyocytes’ atrophy occurs, and thus fibrofatty infiltration, triggering ventricular arrhythmias. Although the myocardial changes are mostly microscopic, recent studies in human beings have identified right ventricular systolic dysfunction even in the early stages of ARVC, both by conventional echocardiographic techniques and advanced methods, such as speckle tracking. Therefore, the aim of this study was to investigate if RV myocardial dysfunction is present in Boxers affected by ARVC, evaluated by conventional echocardiography and bidimensional speckle tracking technique. For this purpose, Boxers older than four years were recruited, and based on 24-hour Holter recording were divided in groups: GC:< 50 VPC/24h (n=11), or GD: > 100 VPC/24h (n=11). The following echocardiographic parameters were analyzed: RV internal dimension during systole and diastole; RV fractional area change (FAC); tricuspid annular plane systolic excursion (TAPSE); myocardial systolic velocity of lateral tricuspid annulus (S’), and global longitudinal strain and strain rate. Groups were compared by Student’ t-test or Mann-Whitney test according distribution, and correlation between conventional and speckle tracking echocardiographic variables, as well as number and severity of the ventricular arrhythmias were accomplished by the Pearson test, assuming a level of significance at 5%. Groups were considered similar, and there was no correlation among the evaluated parameters. Our findings suggesting that the echocardiographic evaluation of RV, either by conventional and speckle tracking techniques, were not able to detect systolic myocardial dysfunction in Boxers affected by ARVC.
FAPESP: 16/14800-7

Endurance exercise training stimulates numerous adaptive changes to the structure, morphology and function of the human heart. Recent evidence suggests that a prolonged and strenuous bout of exercise, such as an ultra-endurance marathon or triathlon event, may results in temporary autonomic, biochemical and functional abnormalities which predominantly arise in the right ventricle. The impact of routine day-to-day endurance exercise training on exercise-induced cardiac disturbances is less clear, but likely influenced by hemodynamic, hormonal and metabolic factors that are related to the exercise intensity and duration. This thesis aimed to determine the time-course development (throughout exercise and during recovery) of cardiac perturbations evoked by exercise bouts that are typical of day-to-day endurance training. Indices of cardiac electrical conduction (atrial and ventricular conduction dynamics), autonomic activity (heart rate variability), ventricular mechanical function (left and right ventricular strain), and biomarkers of cardiac injury (serum cTn T & I) were examined in a cohort of recreationally active and trained men. The assessment of ventricular mechanical function during exercise is a key element of this thesis that enabled the exploration of functional cardiac limitations throughout and following endurance exercise. To determine the magnitude and time-course of exercise-induced functional and biochemical cardiac perturbations a laboratory based study was used to manipulate exercise intensity and duration while holding total mechanical work constant.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Allied Health
Griffith Health
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Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease. Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II. Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation. Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

Le remodelage myocardique est une réponse du myocarde à une altération des contraintes pariétales générée par une agression aiguë (ischémie myocardique) ou chronique (surcharge en pression, surcharge en volume, anomalie métabolique). En effet, le cœur est un organe capable de modifier en fonction de ses conditions de travail l’expression de ses fonctions moléculaires et cellulaires pour aboutir à des changements de taille,de morphologie et de fonction. Le remodelage myocardique est un mécanisme adaptatif initialement bénéfique, car en modifiant sa géométrie, le ventricule gauche s’adapte aux modifications de stress pariétal et préserve le volume d’éjection systolique
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Cette thèse porte sur le développement et l’évaluation de techniques d’imagerie en échocardiographie. L’objectif est de proposer des méthodes d’imagerie ultrasonore ultrarapide pour estimer le mouvement cardiaque 2-D et 3-D.Première modalité d’imagerie du cœur, l’échocardiographie conventionnelle permet la mesure des déformations myocardiques à 80 images/s. Cette cadence d’imagerie est insuffisante pour quantifier les mouvements de la totalité du myocarde lors de tests d’efforts, utiles en évaluation clinique, au cours desquels le rythme cardiaque est augmenté. De plus, la résolution temporelle actuelle en échocardiographie 3-D limite ses applications, pourtant essentielles pour une caractérisation complète du cœur.Les contributions présentées ici sont 1) le développement et l’évaluation, pour l’application cardiaque, d’une méthode originale d’estimation de mouvement 2-D par imagerie ultrarapide et marquage des images, 2) l’étude de faisabilité de la mesure globale des déformations cardiaques avec une méthode innovante d’imagerie ultrasonore ultrarapide 2-D et 3) la généralisation de cette approche en 3-D pour l’imagerie des volumes cardiaques à haute résolution temporelle. Cette technique est basée sur l’émission d’ondes divergentes, et l’intégration d’une compensation de mouvement dans le processus de formation des volumes cardiaques.La méthode proposée permet l’estimation des mouvements cardiaques 2-D et l’échocardiographie ultrarapide 3-D. L’évaluation de notre approche pour la quantification des déformations myocardiques locales 2-D et 3-D pourrait permettre de proposer des pistes innovantes pour poursuivre nos études et améliorer le diagnostic en routine clinique
This PhD work focuses on the development and the evaluation of imaging techniques in echocardiography. Our objective is to propose ultrafast ultrasound imaging methods for 2-D and 3-D cardiac motion estimations.Echocardiography is one of the most widespread modality for cardiovascular imaging. Conventional clinical scanners allow measurement of myocardial velocities and deformations at 80 images / s. In some situations, it can be recommended to increase the heart rate during a stress echocardiographic examination. Motion estimation of the whole myocardium at such heart rates is challenging with the conventional imaging systems. In addition, the low temporal resolution of the current conventional 3-D echocardiography limits quantitative applications, which would be needed for a complete characterization of the heart.The three contributions presented here are 1) the development and evaluation of an original method for 2-D cardiac motion estimation, with ultrafast imaging and image tagging, 2) the feasibility study of the global myocardial deformation measurement using an innovative 2-D ultrafast ultrasound imaging method and 3) the generalization of this approach in three dimensions for high frame-rate 3-D echocardiography. This method is based on the transmission of divergent waves and the integration of motion compensation, during the imaging process, to produce high-quality volumetric images of the heart.The proposed method allows 2-D cardiac motion estimation and 3-D echocardiography at high frame-rate. The evaluation of our approach for local 2-D and 3-D myocardial deformation measurements should permit to conduct further study in order to improve medical diagnosis

Background: Acute coronary syndrome is known for its effect on cardiac function and can lead to impaired segmental and even global myocardial function. Evidence exists that myocardial revascularisation whether pharmacological, interventional or surgical results in improvement of systolic and diastolic left ventricular (LV) function, particularly that of the long axis which represents the sub-endocardial function, known as the most sensitive layer to ischaemia. Objective: We sought to gain more insight into the early effect of pharmacological and interventional myocardial revascularisation on various aspects of cardiac function including endocrine, electrical, segmental, twist, right ventricular (RV) and left atrial (LA) function. In particular, we aimed to assess the response of ventricular electromechanical function to thrombolysis and its relationship with peptides levels. We also investigated the behaviour of RV function in the setting of LV inferior myocardial infarction (IMI) during the acute insult and early recovery. In addition, we aimed to assess in detail LA electrical and mechanical function in such patients. Finally, we studied the early effect of surgical revascularisation on the LV mechanics using the recent novel of speckle tracking echocardiography technology to assess rotation, twist and torsion and the strain deformation parameters as a tool of identifying global ventricular function. Methods: We used conventionally Doppler echocardiographic transthoracic techniques including M-mode, 2-Dimentional, myocardial tissue Doppler, and speckle tracking techniques. Commercially available SPSS as a software was used for statistical analysis. Results: 1-The elevated peptide levels at 7 days post-myocardial infarction correlated with the reduced mechanical activity of the adjacent non-infarcted segment thus making natriuretic peptides related to failure of compensatory hyperdynamic activity of the non-infarcted area rather than the injured myocardial segments. 2-RV segmental and global functions were impaired in acute IMI, and recovered in 87% of patients following thrombolysis. In the absence of clear evidence for RV infarction the disturbances in the remaining 13% may represent stunned myocardium with its known delayed recovery. 3-LA electromechanical function was impaired in acute inferior STEMI and improved after thrombolysis. The partial functional recovery suggests either reversible ischaemic pathology or a response to a non-compliant LV segment. The residual LA electromechanical and pump dysfunction suggest intrinsic pathology, likely to be ischaemic in origin. 4-LV function was maintained in a group of patients with multivessel coronary artery disease who underwent coronary artery bypass graft (CABG) surgery. Surgical myocardial revascularisation did not result in any early detectable change in the three functional components of the myocardium, including twist and torsion, as opposite to conventional percutaneous coronary intervention (PCI). Conclusion: The studied different materials in this thesis provide significant knowledge on various aspects of acute ischaemic cardiac pathology and early effect of revascularisation. The use of non-invasive imaging, particularly echocardiography with its different modalities, in studying such patients should offer immediate thorough bed-side assessment and assist in offering optimum management.

Background. Friedreich ataxia (FRDA) is an autosomal recessive degenerative disease characterized by progressive gait and limb ataxia, hypertrophic cardiomyopathy, diabetes and sensory neuropathy. Large GAA repeat expansions in the first intron of the frataxin gene are the most common mutation underlying FRDA. This mutation results in intramitochondrial iron accumulation and oxidative stress increase. FRDA is associated with progressive cardiac hypertrophy; however, subclinical left ventricular (LV) dysfunction may occur in FRDA patients in spite of normal LV ejection fraction (LVEF) and mass. Moreover cardiac sudden death is the most common cause of exitus in these patients. Methods. We enrolled 5 FRDA patients (age: 39.8 ± 19.05 years; 2F and 3M) free of cardiovascular risk factors and 5 sex- and age-matched healthy subjects (age 32.75 ± 6.22 years); they underwent to clinical evaluation, standard echocardiography with Tissue Doppler, 2D and 3D Speckle Tracking. Results. No significant differences were identified in terms of anthropometric characteristics and cardiovascular risk profile between the two groups. All echocardiographic standard parameters, including LV dimensions, LV mass, LVEF and E/E’ ratio resulted in the normal range, in absence of significant differences between patients and healthy subjects. On the other hand, we found a reduction in Global Longitudinal Strain (GLS; 10.93 ± 1.72 % vs 15.92 ± 1.17%, p= 0.003), as already reported in literature. Moreover we compared values of longitudinal strain of LV basal and apical segments between the two groups, thus identifying a significant impairment of apical regions in FRDA patients (10.12 ± 3.48 % vs 18.7 ± 2.57, p =0.02). Conclusions. Our data seem to suggest that the observed reduction in GLS could be due to a segmental impairment of systolic function at apical level. This finding could be explained by the sympathetic denervation reported in other forms of neurodegenerative disorders, such Parkinson’s disease and Multiple sclerosis.

A seminal study by Morganroth et al (1975) demonstrated a differential pattern of cardiac adaptation with prolonged exercise training; of eccentric pattern of left ventricular hypertrophy (LVH) in endurance trained athletes (ET) and concentric LVH in resistance trained athletes (RT). Specific inconsistencies related to the nature of any adaptation to RT; the value of new imaging technologies; the relative importance of scaling of cardiac data for differences in body size; the impact of training on the right ventricle (RV) and the fit of differential pattern of adaptation in athletes with Black ethnicity have driven the rationale for the studies included in this thesis. Study one employed meta-analysis techniques to critically evaluate the evidence base supporting or refuting that MH exists in elite male Caucasian ET & RT. Modern echocardiographic techniques were used to test whether a dichotomous LV and RV structural as well as global and regional functional adaptation was apparent in elite Caucasian ET & RT in studies 2 & 3. The final study (exploratory) was to characterize the athletic heart phenotype in a homogenous population of elite RT of West African origin (WRT) to provide new insight in relation to cardiac adaptation and ECG characteristics in non-Caucasian athlete groups. Allometric scaling approach was deployed to index LV and RV data for individual body variance in body size. The novel findings of this thesis; larger LV data in ET (LVMg: ET 232 (200 to 260), RT 220 (205 to 234), CT 166 (145 to 186)) but no concentric hypertrophy in RT within the meta-analysis, predominance of normal geometry in male athletes (65% of ET and 95% of RT) and the lack of concentric pattern of hypertrophy in RT in a cross-sectional study; no RV adaptation in RT athletes (RVD1mm: ET 45 ± 5 (39 to 57), RT 40 ± 5 (32 to 51) CT 39 ± 4 (31 to 45)); no LV or RV adaptation in WRT athletes; the importance of appropriate scaling of cardiac parameters; provide a useful re-evaluation of concepts and models in the athletic heart literature. The findings have important implications for cardiovascular screening of athletes.

Introdução: A doença falciforme (DF) é a afecção hematológica hereditária de maior prevalência no mundo, sendo que a anemia falciforme (AF) é a forma mais grave com elevada morbidade e mortalidade. Alterações cardíacas são reconhecidamente associadas à AF, como aumento cavitário, hipertensão arterial pulmonar e disfunção diastólica do ventrículo esquerdo. No entanto, ainda não existe consenso quanto à função sistólica ventricular nesses pacientes. O objetivo deste estudo foi o de investigar a função ventricular de pacientes com anemia falciforme utilizando o strain e o twist ventricular obtidos pelo speckle tracking bidimensional, e reconhecer os indivíduos sob maior risco cardiovascular, em que a instituição precoce de tratamento específico poderá beneficiar essa população. Métodos: Foram recrutados 40 pacientes com anemia falciforme (23,5 ± 9,3 anos; 24 homens) e 40 controles saudáveis pareados por sexo e idade, submetidos à entrevista estruturada, ecocardiograma transtorácico, cintilografia pulmonar ventilação perfusão e coleta de amostras de sangue. Todos os indivíduos foram submetidos à avaliação ecocardiográfica convencional padrão e subsequente avaliação offline do strain sistólico biventricular e estudo rotacional do ventrículo esquerdo utilizando speckle-tracking ecocardiográfico. Resultados: Os pacientes com AF apresentaram volume do VE indexado, massa do VE indexado, pressão arterial pulmonar e E/E\' médio superiores aos controles. As medidas de FE do VE, excursão sistólica do plano da tricúspide (TAPSE), Strain Global do VE (longitudinal, circunferencial, radial) e Strain Global do VD (longitudinal) não evidenciaram diferenças entre os grupos. Twist VE se mostrou reduzido em comparação aos controles (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) e Tempo de pico de rotação apical prolongado (366,7 ± 26,1ms vs 344,6 ± 11,7ms , P <0,0001 ). Algumas variáveis se mostraram fortemente relacionadas ao twist VE, como índice de gravidade clínico (Rho= - 0,97, Z value= - 6,05, P < 0,0001), relação E/E\' médio (r = 0,94, F valor= 156.9, p<0,0001), IVDFVE (índice do volume diastólico final do ventrículo esquerdo)(r = 0,81 e p<0,0001) e pressão sistólica arterial pulmonar (r = 0,72 e p<0,0001). Conclusões: Os resultados deste trabalho indicam que o twist ventricular esquerdo derivado do speckle tracking bidimensional encontra-se alterado em pacientes com anemia falciforme e função sistólica ventricular preservada, avaliada pela metodologia convencional, e existe forte correlação entre o twist ventricular esquerdo e o índice clínico de gravidade, relação E/E\', índice do volume diastólico final do ventrículo esquerdo e pressão sistólica arterial pulmonar.
Background: Sickle cell disease (SCD) is the most prevalent hematological condition in the world, with sickle cell anemia (SCA) being its most serious form, displaying a high level of morbidity and mortality. Cardiac changes are known to be associated with SCA, including an increase in cardiac chamber size, pulmonary hypertension and left ventricle diastolic dysfunction. However, there is still no consensus regarding the ventricular systolic function in these patients. The purpose of this study is to investigate the ventricular function of patients with sickle cell anemia utilizing the strain and ventricular twist, obtained by two-dimensional speckle tracking, as well as to identify individuals with higher cardiovascular risk, in which early application of specific treatment could benefit this group of people. Methods: 40 patients were recruited with sickle cell anemia (ages 23.5 ± 9.3 years; 24 males) and 40 healthy control individuals paired by gender and age, submitted to structured interviews, transthoracic echocardiogram, pulmonary scintigraphy and collection of blood samples. All individuals were submitted to a standard echocardiographic evaluation and subsequent off line evaluation of the biventricular systolic strain and rotational study of the left ventricle using echocardiographic speckle-tracking. Results: Patients with SCA presented LV volume indices, LV mass Indices, pulmonary arterial pressure and E/ E\' ratios statistically higher than the control individuals. Measurements of Ejection Fraction (EF) of the left ventricle, tricuspid annular plane systolic excursion (TAPSE), Overall LV Strain (Longitudinal, Circumferential, and Radial) and Overall RV Strain (Longitudinal) did not present differences between the groups. LV twist was significantly lower in relation to the control group (7,4 ± 1,2? vs 10,7 ± 1,8? , P <0,0001 ) and prolonged time to peak apical rotation (366.7 ± 26.1ms vs 344.6 ± 11.7ms , P <0.0001 ). In addition, some variables showed themselves to be strongly related to LV twist such as the clinical severity index ( Rho= - 0.97, Z value= - 6.05, P < 0.0001), E/E\' Ratio (r = 0.94, F value=156.9 e p<0.0001) ), left ventricle end diastolic volume index (LVEDV index) (r = 0,81, p<0,0001) and pulmonary systolic arterial pressure (r = 0.72 e p<0.0001). Conclusions: The results of this study indicate that the left ventricular twist derived from two-dimensional speckle tracking is altered in patients with sickle cell anemia and a preserved ventricular systolic function, evaluated using conventional methodology and that there is a strong correlation between left ventricular twist and the clinical severity index, E/E\' ratio, left ventricle end diastolic volume index and the pulmonary systolic arterial pressure.

A SÃndrome MielodisplÃsica à uma hemopatia clonal de alta prevalÃncia em idosos Anemia à uma caracterÃstica marcante dessa doenÃa Pacientes com dependÃncia de suporte transfusional tem pior prognÃstico Depois das complicaÃÃes relacionadas à prÃpria doenÃa as complicaÃÃes cardiovasculares sÃo a principal causa de morte Novas tÃcnicas ecocardiogrÃficas como o Doppler tecidual e speckle-tracking podem ser Ãteis na anÃlise da funÃÃo cardÃaca nesse grupo Neste estudo foi avaliado um grupo de 34 pacientes e 14 controles saudÃveis emparelhados por sexo e idade sendo submetido à ecocardiograma convencional Doppler tecidual e avaliaÃÃo da deformaÃÃo miocÃrdica (strain) Os pacientes foram subdivididos entre dependentes (13) ou nÃo de suporte transfusional (21) e comparados aos controles Dentre os 13 pacientes do grupo dependentes havia 10 com sobrecarga de ferro (ferritina >1.000 ng/mL) Os pacientes dependentes de suporte transfusional apresentaram maiores volumes diastÃlico e sistÃlico do ventrÃculo esquerdo em relaÃÃo aos controles (p = 0,047 e 0,039) O volume do Ãtrio esquerdo indexado foi maior no grupo de dependentes em relaÃÃo ao grupo controle (p = 0,003) A funÃÃo diastÃlica do ventrÃculo esquerdo (VE) por Doppler convencional e tecidual (razÃo E/A e razÃo E/Eâ) foi normal no grupo de pacientes e nÃo apresentou diferenÃa significante entre os grupos (p = 0,15 e 0,90) Na avaliaÃÃo da funÃÃo sistÃlica do VE por fraÃÃo de ejeÃÃo e por deformaÃÃo miocÃrdica (strain longitudinal global) nÃo houve desvio da normalidade nem diferenÃas entre os grupos (p = 0,71 e 0,097) A espessura do septo interventricular foi maior nos pacientes com ferritina > 1.000 ng/mL (p = 0,012) O nÃvel de hemoglobina mas nÃo o de ferritina apresentou correlaÃÃo com os volumes esquerdos (Ãtrio: r = -0,53 e p = 0,013 / ventrÃculo: r = -0,4 e p = 0,019) Nossa amostra nÃo apresentou disfunÃÃo global nem sistÃlica nem diastÃlica mesmo à anÃlise por novas tÃcnicas de ecocardiograma como Doppler tecidual e deformaÃÃo miocÃrdica (strain) O nÃvel de hemoglobina menor que 8 g/dL foi marcador precoce de pior funÃÃo ventricular nos nossos pacientes com SÃndrome MielodisplÃsica
Myelodysplastic syndrome is a clonal disorder of hematopoietic tissue highly prevalent on elderly Anemia is one of most striking feature of this disorder Patients with transfusional dependence have a poor prognosis Following complications related to the own illness cardiovascular complications are the leading cause of death New echocardiographic techniques such as Tissue Doppler and speckle-tracking may be useful on assessment of the myocardial function in these patients A group with 34 patients and 14 healthy controls matched by sex and age was subjected to conventional echocardiography Tissue Doppler and assessment of myocardial deformation (strain) Patients were divided between those with (13) or without (21) transfusional dependence and compared to controls In the group of transfusional dependence there were 10 subjects with iron overload (serum ferritin levels > 1.000 ng/mL) Those with transfusion dependence had bigger left systolic and diastolic ventricular volumes than controls (p = 0,047 and 0,039) The indexed left atrium volume was larger on those with transfusion dependence compared to controls (p = 0,003) The left ventricular diastolic function assessed by tissue and conventional Doppler (E/A and E/Eâ ratios) was normal in the patient group and has not difference between them (p = 0,15 and 0,9) On the assessment of the systolic left ventricular function by ejection fraction and myocardial deformation (global longitudinal strain) there was no difference between groups or from reference values (p = 0,71 and 0,097) The interventricular septum thickness was larger in the group with serum ferritin > 1.000 ng/mL than patients with ferritin < 1.000 ng/mL (p = 0,012) The hemoglobin level but not ferritin showed linear correlation with the left volumes (atrium: r = -0,53 with p =0,013 / ventricle: r = -0,4 with p = 0,019) Our sample doesnât show diastolic nor systolic global dysfunctions yet with new techniques of tissue Doppler and myocardial deformation (strain). Hemoglobin below 8 g/dL was an early marker of worst ventricular function in our patients with myelodysplastic syndrome

Background:  The right ventricle (RV) is multi-compartmental in orientation with a complex structural geometry. However, assessment of this part of the heart has remained an elusive clinical challenge. As a matter of fact, its importance has been underestimated in the past, especially its role as a determinant of cardiac symptoms, exercise capacity in chronic heart failure and survival in patients with valvular disease of the left heart. Evidence also exists that pulmonary hypertension (PH) affects primarily the right ventricular function. On the other hand, previous literature suggested that severe aortic stenosis (AS) affects left ventricular (LV) structure and function which partially recover after aortic valve replacement (AVR). However, the impact of that on RV global and segmental function remains undetermined.  Objectives: We sought to gain more insight into the RV physiology using 3D technology, Speckle tracking as well as already applicable echocardiographic measures. Our first aim was to assess the normal differential function of the RV inflow tract (IT), apical and outflow tract (OT) compartments, also their interrelations and the response to pulmonary hypertension. We also investigated the extent of RV dysfunction in severe AS and its response to AVR. Lastly, we studied the extent of global and regional right ventricular dysfunction in patients with pulmonary hypertension of different aetiologies and normal LV function. Methods: The studies were performed on three different groups; (1) left sided heart failure with (Group 1) and without (Group 2) secondary pulmonary hypertension, (2) severe aortic stenosis and six months post AVR and (3) pulmonary hypertension of different aetiologies and normal left ventricular function. We used 3D, speckle tracking echocardiography and conventionally available Doppler echocardiographic transthoracic techniques including M-mode, 2D and myocardial tissue Doppler. All patients’ measurements were compared with healthy subjects (controls). Statistics were performed using a commercially available SPSS software. Results: 1-  Our RV 3D tripartite model was validated with 2D measures and eventually showed strong correlations between RV inflow diameter (2D) and end diastolic volume (3D) (r=0.69, p<0.001) and between tricuspid annular systolic excursion (TAPSE) and RV ejection fraction (3D) (r=0.71, p<0.001). In patients (group 1 & 2) we found that the apical ejection fraction (EF) was less than the inflow and outflow (controls:  p<0.01 & p<0.01, Group 1:  p<0.05 & p<0.01 and Group 2: p<0.05 & p<0.01, respectively). Ejection fraction (EF) was reduced in both patient groups (p<0.05 for all compartments). Whilst in controls, the inflow compartment reached the minimum volume 20 ms before the outflow and apex, in Group 2 it was virtually simultaneous. Both patient groups showed prolonged isovolumic contraction (IVC) and relaxation (IVR) times (p<0.05 for all). Also, in controls, the outflow tract was the only compartment where the rate of volume fall correlated with the time to peak RV ejection (r = 0.62, p = 0.03). In Group 1, this relationship was lost and became with the inflow compartment (r = 0.61, p = 0.01). In Group 2, the highest correlation was with the apex (r=0.60, p<0.05), but not with the outflow tract. 2- In patients with severe aortic stenosis, time to peak RV ejection correlated with the basal cavity segment (r = 0.72, p<0.001) but not with the RVOT. The same pattern of disturbance remained after 6 months of AVR (r = 0.71, p<0.001). In contrast to the pre-operative and post-operative patients, time to RV peak ejection correlated with the time to peak outflow tract strain rate (r = 0.7, p<0.001), but not with basal cavity function. Finally in patients, RVOT strain rate (SR) did not change after AVR but basal cavity SR fell  (p=0.04). 3- In patients with pulmonary hypertension of different aetiologies and normal LV function, RV inflow and outflow tracts were dilated (p<0.001 for both). Furthermore, TAPSE (p<0.001), inflow velocities (p<0.001), basal and mid-cavity strain rate (SR) and longitudinal displacement (p<0.001 for all) were all reduced. The time to peak systolic SR at basal, mid-cavity (p<0.001 for both) and RVOT (p=0.007) was short as was that to peak displacement (p<0.001 for all). The time to peak pulmonary ejection correlated with time to peak SR at RVOT (r=0.7, p<0.001) in controls, but with that of the mid cavity in patients (r=0.71, p<0.001). Finally, pulmonary ejection acceleration (PAc) was faster (p=0.001) and RV filling time shorter in patients (p=0.03) with respect to controls. Conclusion: RV has distinct features for the inflow, apical and outflow tract compartments, with different extent of contribution to the overall systolic function. In PH, RV becomes one dyssynchronous compartment which itself may have perpetual effect on overall cardiac dysfunction. In addition, critical aortic stenosis results in RV configuration changes with the inflow tract, rather than outflow tract, determining peak ejection. This pattern of disturbance remains six month after valve replacement, which confirms that once RV physiology is disturbed it does not fully recover. The findings of this study suggest an organised RV remodelling which might explain the known limited exercise capacity in such patients. Furthermore, in patients with PH of different aetiologies and normal LV function, there is a similar pattern of RV disturbance. Therefore, we can conclude that early identification of such changes might help in identifying patients who need more aggressive therapy early on in the disease process.

Introduktion: Vid ekokardiografi används ultraljudsvågor med frekvens över 20 000Hz. Ultraljudssändare med piezoelektriska kristaller används för att generera ljudvågor som skickas ut i kroppen, reflekteras och sedan återvänder till kristallerna för att skapa en ultraljudsbild. Ejektionsfraktionen uttrycker hur stor del av den diastoliska volymen som pumpas ut i kroppen under systole och är en viktig parameter vid bedömning av den globala systoliska funktionen. Den rekommenderade metoden Simpsons biplan jämförs med Philips automatiska funktion a2Dq, som utgår ifrån speckle tracking principen, för bedömning av ejektionsfraktionen. Material och metod: 32 hjärtfriska testpersoner mellan 20–43 år inkluderades i tvärsnittsstudien. Apikala 4- och 2-kammarbilder insamlades ifrån testpersonerna och användes för beräkning av ejektionsfraktionen. Den manuella metoden Simpsons biplan grundas på operatörens utlinjering av endokardiet. Den automatiska funktionen a2Dq utgår ifrån 53 hjärtmodeller och placerar en region of interest automatiskt. Den semiautomatiska funktionen används genom att operatören modifierar region of interest men inte längden av vänsterkammaren. Resultat: Resultatet visade att det inte förelåg någon signifikant skillnad i mätvärdena av ejektionsfraktionen mellan de tre mätprinciperna. Den semiautomatiska och manuella metoden som är operatörsberoende hade likvärdiga mätresultat. Den automatiska funktionen erhöll totalt 6 mätvärden som hamnade utanför normalgränserna. Diskussion: Automatiska funktioner för bedömning av ejektionsfraktionen utvecklas snabbt och kräver utvärderingar. Automatiska mätningar har påvisats vara fördelaktiga då de inte är så tidskrävande som den manuella Simsons biplanmetoden. Tidsaspekten framhävs i de flesta studier dock på bekostnad av säkra mätresultat. Observationerna i denna studie påvisar att den automatiska funktionen inte är säker nog för användning. Konklusion: Enligt observationer ifrån denna studien rekommenderas att den automatiska funktionen ifrån Philips inte används.
Introduction: Ultrasound are soundwaves with frequencies above 20 000Hz. Piezoelectric crystals are used to generate sound waves that can be transmitted into the tissue and reflected back to the crystals to obtain an ultrasound image. The ejection fraction expresses how much blood the left ventricle pumps out with each contraction and is an important parameter for assessment of the hearts global systolic function. The recommended method Simpson´s biplane to assess ejection fraction is compared with Philips automatic function a2Dq, which is based on the principle of speckle tracking. Material and method: The study population included 32 tests subjects with age between 20-43 years old. The test subjects had no records of earlier heart pathologies. Apical 4- and 2-chamber images were collected for the purpose to measure the ejection fraction. The manual method Simpson´s biplane is based on the sonographers manual tracking of the endocardial border. The automatic function a2Dq is based on 53 heart models with different anatomy and physiology and applies a region of interest automatically along the endocardial border. The semi-automatic function allows the sonographer to adjust the region of interest but not the length of the chamber. Result: The result showed that there was no significant difference in the measured values of ejection fraction between the three different techniques. The semi-automatic and Simpson´s biplane method showed equivalent results. The automatic function showed a wide variance of measurements which resulted with a total of 6 measurement ended up below the normal values for ejection fraction. Discussion: Automatic functions for assessing the ejection fraction rapidly develops and requires validations. Automatic functions have shown to be advantageous as the are not as time-consuming as the manual Simpson´s biplane method. In most studies, however, the time aspect is emphasized at the expense of correct measurements results. The observations in this study show that the automatically function a2Dq from Philips are not providing correct measurements. Conclusion: According to observations in this study, it´s recommended that the automatic function from Philips shouldn’t be used.

INTRODUÇÃO: A doença de Chagas tem uma alta prevalência no Brasil e América Latina. Dentre as miocardiopatias (MCP), é a que evolui com pior prognóstico. A identificação precoce de disfunção sistólica de uma MCP é fundamental para o início do tratamento, assim como sua definição etiológica, sendo o ecocardiograma um dos métodos diagnósticos mais importantes na prática clínica. No entanto, mesmo que a análise da função sistólica global do ventrículo esquerdo (VE) demonstre fração de ejeção preservada, é possível já estar ocorrendo alguma anormalidade contrátil, não detectada pelos exames de rotina. A nova ferramenta ecocardiográfica denominada speckle tracking permite a análise de múltiplos parâmetros que compõem a dinâmica de contração do VE (deslocamento, velocidade de deslocamento, strain, strain rate, rotação e torção), caracterizando de forma integral a função sistólica. Trata-se de um método sensível com potencial para se detectar lesão miocárdica incipiente e auxiliar na definição etiológica de uma MCP dilatada. Um estudo detalhado da mecânica de contração do VE em doença de Chagas, ao longo de toda sua evolução, nunca foi realizado antes. OBJETIVO: Comparar os múltiplos parâmetros obtidos por speckle tracking da dinâmica de contração do VE com controles, desde a forma indeterminada da doença de Chagas até as fases mais avançadas da disfunção sistólica. MÉTODO: No período de janeiro de 2010 a agosto de 2013 estudamos pacientes chagásicos divididos em 04 grupos: Ch1A, forma indeterminada; Ch1B, fração de ejeção normal (FE >= 0,55), mas com alteração no eletrocardiograma; Ch2, MCP chagásica com disfunção sistólica discreta a moderada (FEVE 0,55- 0,30) e Ch3, MCP com disfunção importante (FEVE < 0,30). Indivíduos normais e pacientes com MCP de outras etiologias também foram estudados para compor o grupo controle, sendo pareados pela FEVE. Todos os pacientes foram submetidos ao ecocardiograma convencional com aquisição de imagens para speckle tracking. As imagens foram avaliadas para determinação de parâmetros da dinâmica ventricular por observador experiente usando software específico. RESULTADOS: Um total de 131 pacientes foram incluídos, 47 (36%) deles alocados em grupos de chagásicos. Dezesseis indivíduos chagásicos eram homens (34%). A média de idade variou de 54 a 56 anos para os grupos chagásicos e 37 a 50 anos para os controles. A exequibilidade global para análise por técnica de speckle tracking foi de 97%. Foi encontrada diferença significativa na análise de velocidade longitudinal global com menores valores no grupo Ch1A em relação aos controles normais, C1 (Ch1A, 3,33 ± 0,44 cm/s vs C1, 4,44 ± 0,78 cm/s; p < 0,001). Foram observadas reduções de todos os parâmetros da mecânica de contração do VE em paralelo ao comprometimento sistólico, tanto para as análises globais, quanto para segmento-a-segmento, em pacientes chagásicos e com MCP de outras etiologias. Foi observado um aumento paradoxal do deslocamento longitudinal global no grupo com disfunção sistólica importante (Ch3, 6,48 ± 1,57 mm vs C3, 4,63 ± 1,60 mm; p = 0,01). Essa tendência foi acompanhada pelas observações de maiores valores de deslocamento radial global apical (Ch3, 2,49 ± 0,83 mm vs C3, 1,54 ± 1,18 mm; p = 0,04). Na análise segmentar, foram evidenciados piores valores de deslocamento radial, strain e strain rate radiais em segmentos classicamente acometidos pela doença de Chagas (paredes inferior e inferolateral) e paradoxal aumento de valores destes parâmetros em outros segmentos, como nas paredes septal e anterior. CONCLUSÃO: A técnica de ecocardiografia com speckle tracking demonstrou redução dos parâmetros da dinâmica ventricular de pacientes chagásicos e não chagásicos em paralelo com a redução da fração de ejeção do ventrículo esquerdo. Em comparação com pacientes com MCP não chagásica, os pacientes com doença de Chagas apresentaram redução de deslocamento longitudinal e radial, strain e strain rate radiais em segmentos das paredes inferior e inferolateral com aumento paradoxal de outros (septal e anterior), caracterizando uma dinâmica de contração vicariante peculiar a esta MCP. Por fim, pacientes chagásicos na forma indeterminada apresentaram menor velocidade de contração longitudinal em comparação aos controles normais, o que pode ser indício de uma lesão miocárdica incipiente
INTRODUCTION: Chagas disease has a high prevalence in Brazil and Latin America. Among the cardiomyopathies (CMP), it evolves with the worst prognosis. Early identification of a CMP systolic impairment is critical to treatment initiation as well as its etiologic definition, and echocardiogram is one of the most important diagnostic methods in clinical practice. However, even if global analysis of left ventricle (LV) systolic function discloses a preserved ejection fraction, an ongoing contractile abnormality is already possible, not detected by routine tests. A new echocardiographic tool called speckle tracking allows an analysis of multiple parameters that comprise LV contraction dynamics (displacement, displacement velocity, strain and strain rate, rotation and twist), fully characterizing LV systolic function. It is a sensitive method with the potential to detect incipient myocardial injury and help to define the etiology of a dilated CMP. A detailed study of LV contraction mechanics in Chagas disease, throughout its evolution, has never been done before. OBJECTIVE: To compare multiple parameters of LV dynamics contraction obtained by speckle tracking with controls, since the indeterminate form of Chagas disease until later stages of systolic dysfunction. METHODS: From January 2010 to August 2013, we studied patients with Chagas disease divided into 04 groups: Ch1A, indeterminate form; Ch1B, normal ejection fraction (EF >= 0.55), but with electrocardiogram abnormalities; Ch2, chagasic CMP with mild to moderate systolic dysfunction (LVEF 0.55-0.30) and Ch3, CMP with severe dysfunction (LVEF < 0.30). Normal individuals and patients with other etiologies of CMP were also studied to compose the control group, and were matched by LVEF. All patients underwent echocardiography with conventional imaging added with speckle tracking imaging acquisition. Images were assessed to determine the parameters of dynamic ventricular by an experienced observer using specific software. RESULTS: A total of 131 patients were included, 47 (36 %) of them allocated in groups of Chagas disease. Sixteen chagasic individuals were men (34 %). The mean age ranged from 54 to 56 years for chagasic groups and 37 to 50 years for controls. The overall feasibility for analysis by speckle tracking technique was 97%. Significant difference was found in the analysis of global longitudinal velocity with lower values in group Ch1A compared with normal controls, C1 (Ch1A, 3.33 ± 0.44 cm/s vs C1, 4.44 ± 0.78 cm/s; p < 0.001). We observed a reduction of all parameters of LV contraction mechanics parallel to systolic impairment, both for global as for segment-to-segment analyses, in chagasic patients and in CMP with other etiologies. We also observed a paradoxical increase in global longitudinal displacement in the group with severe systolic dysfunction (Ch3, 6.48 ± 1.57 mm vs C3, 4.63 ± 1.60 mm; p = 0.01). This trend was followed by observations of higher values of apical global radial displacement (Ch3, 2.49 ± 0.83 mm vs C3, 1.54 ± 1.18 mm; p = 0.04). In segmental analysis, we observed worse values of radial displacement as well as radial strain and strain rate in segments classically affected by Chagas disease (inferior and inferolateral walls) and paradoxical increase of values of these parameters in other segments, such as in septal and anterior wall. CONCLUSION: The technique of echocardiography with speckle tracking disclosed a decrease in ventricular chagasic and non-chagasic dynamic parameters in parallel with the reduction in the ejection fraction of the left ventricle. Compared with patients with non-chagasic CMP, patients with Chagas disease had reduced longitudinal and radial displacement, radial strain and strain rate of segments into inferior and inferolateral walls with paradoxical increase in others (septal and anterior), comprising a dynamic vicarious contraction peculiar to this CMP. Finally, chagasic patients in the indeterminate form had a lower longitudinal velocity compared with normal controls, which may indicate an incipient myocardial injury

Background. Assessment of left ventricular (LV) function is a fundamental part of clinical cardiology, holding important diagnostic, prognostic and management implications. The most important advance in LV quantification over the last decade was the development of techniques aimed to quantify tissue motion and deformation from ultrasound images, such as tissue Doppler imaging (DTI) and two-dimensional speckle-tracking echocardiography (2DSTE). More recently, speckle-tracking algorithms have been applied to three-dimensional (3D) volumetric acquisitions of the LV (i.e. referred to as 3D speckle-tracking echocardiography, 3DSTE), making possible to analyze all LV myocardial strain components from the same dataset. At present, 3DSTE technology is a research tool in its infancy of development, and its potential clinical value still remains to be demonstrated. With respect to prior technologies (DTI and 2DSTE), 3DSTE comes with several advantages, but also with new challenges. It is currently unknown if the theoretical benefits of an additional third dimension to study the complex LV mechanics (no more “out-of-plane” motion of speckles, only a single acquisition needed etc) are not actually outweighted by the new technical challenges derived from using a volumetric acquisition of the LV (i.e. lower spatial and temporal resolution of speckles than with 2DSTE). A major concern of 2DSTE strain is the large intervendor variability of strain measurements provided by various commercially-available software packages. At present, it is unclear if a similar problem may affect also 3DSTE, and to what extent. Furthermore, despite researchers are increasingly employing 3DSTE to study various pathologic conditions, the reference values and normal pattern of LV myocardial strain in healthy adults by 3DSTE, as well as the possible influence of various clinical and technical factors on LV strain values are currently unknown. Finally, the validation process of 3DSTE is difficult due to the lack of adequate three-dimensional gold standard that can be applied noninvasively in human subjects to validate regional LV function in 3D. Therefore, there is a great need for rigorous validation work, methodological and intervendor standardization to be undertaken before its application in clinical settings. Methods and Results. Project design: single-centre, prospective, observational clinical study, aiming to explore the clinical feasibility and usefulness of LV 3D strain analysis using state-of-the-art commercially available 3DE equipment. The project involves a series of 4 clinical studies. The aim of the Study #1 was to assess the intervendor consistency and variability of LV 3D strain values between the two 3DSTE equipments commercially available: VividE9 (GE, Vingmed, Horten, Norway) and Artida (Toshiba Medical Systems Corporation, Tokyo, Japan) ultrasound systems. Sixty patients (38 ± 12 years, 64% males) with a wide range of LV end-diastolic volumes and ejection fractions were enrolled. Global longitudinal (3DLɛ), radial (3DRɛ), circumferential (3DCɛ) and area (3DAɛ) strain values were obtained offline using the corresponding proprietary software package. Overall, the intervendor agreement of 3DRɛ, 3DCɛ and 3DAɛ measured with Artida and VividE9 was poor. 3DLɛ showed the closest values between the two platforms (bias = 1.5%, limits of agreement (LOA) from −2.9 to −5.9%, P < 0.05). Artida provided significantly higher values of both 3DCɛ and 3DAɛ than VividE9 (bias = 6.6% for 3DCɛ, 6.0% for 3DAɛ and -24% for 3DRɛ respectively, P < 0.001). All 3D strain components showed good reproducibility (intraclass correlation coefficients: 0.82–0.98), except for 3DRɛ by Artida, which showed only a moderate reproducibility. Therefore, reference values should be identified for each system, and baseline and follow-up data in longitudinal studies should be obtained using the same 3DSTE equipment. The aim of the Study #2 was to assess the normative values for LV 3D strain in 218 healthy volunteers (age range 18-76, 57% women) by vendor-specific 3DSTE equipment (Vivid E9, 4D AutoLVQ software,). For comparison LV strain was also measured by vendor-specific 2DSTE software and by a vendor-independent 3DSTE software. Feasibility of global 3D strain analysis by 4D AutoLVQ was 89%, lower than 2DLε (95%) and similar to 2DCε (92%). Feasibility of segmental 3DSTE analysis ranged from 46% to 100%. Reference values of 3D strain parameters were identified according to gender and age group. 3DLε decreased, while 3DCε increased with ageing (p<0.001). Men had lower 3DLε, 3DRε, 3DAε and 2DLε than women (p<0.02). At stepwise multivariable linear regression analysis, demographic (age and gender), cardiac (LV size and mass) and technical (image quality and temporal resolution) factors accounted for the variance of LV 3D strain measurements. Since major inter-software differences in LV strain measurements were identified (p<0.001 for all), limits of normality for LV strain analysis by vendor-specific 3DSTE software should not be used interchangeably with those by 2DSTE or vendor-independent 3DSTE softwares. The aim of the Study #3 was to assess if LV deformation by 3D STE in patients after ST-elevation myocardial infarction (STEMI) could provide an accurate and objective assessment of infarct size and transmurality, in comparison with magnetic resonance with late gadolinium enhancement (LGE-CMR). A total of 77 STEMI patients were enrolled by 2D and 3D echo, and in 46 patients LGE-CMR studies were performed within 24 hours. The relative amount of DE tissue per segment was used to define transmural necrosis (51-100% DE). LV function was assessed from three apical LV 2D views by measuring 2DLε, and from 3D LV full-volume datasets, assessing visual wall motion score (WMS) and measuring 3DLε, 3DCε, 3DAε and 3DRε. Strain parameters were correlated with conventional indices of LV systolic function (LVEF) and infarct size (troponin I, WMSI, infarct size index at LGE-CMR). Despite a good accuracy for 2DLε and 3D strain parameters (AUC=0.81-0.73), visual wall motion assessment by experienced reader on good-quality 3D data sets (AUC=0.87) was found to be superior than strain quantification to predict transmural necrosis at LGE-CMR. The aims of the Study #4 to describe the LV myocardial mechanics in patients with hypertrophic cardiomyopathy (HCM) using 2DSTE and 3DSTE, and to compare it with the normal deformation pattern in healthy subjects. In 32 HCM pts and 32 age- and gender-matched controls, we analyzed peak global 2DLε and 3DLε, 3DCε, 3DRε, 3DAε. LV ejection fraction (LVEF), LV mass and outflow tract area (LVOTA) were measured by 3D echo. Symptomatic status was defined by NYHA class (II-IV). Although LVEF was similar in pts and controls (64±6% vs 62±4%, p=0.29), LV systolic strain was significantly impaired in pts (p<0.0001), except for 3DCε, which was only marginally lower. In HCM patients, all strain parameters were correlated with LV end-systolic volume (r=0.55 to 0.67), LVEF (r=-0.82 to -0.88) and mass (r=0.33 to 0.56). Symptomatic patients had more impaired 3DAε, 3DRε and 3DCε, but also had more LVOT obstruction and concentric remodelling, and higher E/e'. At ROC curve analysis, 3DAε, 3DRε and 3DCε had a good accuracy to identify symptomatic pts (AUCs 0.72-0.73). 3D LV mass had an inverse correlation with LV longitudinal deformation: r=-0.74 for 2DLε and -0.70 for 3DLε (p<0.001 for both). In HCM with preserved LVEF, the longitudinal strain was significantly reduced, however symptom development is multifactorial and related to the additional impairment of LV deformation in circumferential-radial direction. Conclusions. This project addressed several issues of of pivotal importance for 3DSTE. It provided a comprehensive analysis of 3DSTE measurement variability (intra- and inter-observer, at test-retest, inter-vendor and inter-software), and reported on the feasibility of 3DSTE in clinical setting and on the comparison with LV strain by 2DSTE. In addition, it is the first to report normal ranges of 3D strain parameters by 3DSTE using both vendor-specific and vendor-independent software packages. Finally, this project presents the added value of 3DSTE in comparison with previous methods for assessing LV function in 2 common pathologic conditions (acute STEMI, as the prototype of regional necrotic transmural injury; and HCM, as the prototype of myocardial disease with impaired longitudinal systolic mechanics despite preserved LVEF). This series of studies contributes with original data to the current scientific evidence-based knowledge on 3DSTE, which is essential for the development and appropriate use of this novel technology.
Introduzione. La valutazione della funzione ventricolare sinistra (VS) rappresenta una parte fondamentale della cardiologia clinica, per le sue notevoli implicazioni diagnostiche, prognostiche e di gestione dei pazienti. Il progresso più importante nell’analisi quantitative della funzione VS negli ultimi dieci anni è stato lo sviluppo di tecniche finalizzate a quantificare il movimento e la deformazione del tessuto miocardico con tecniche ecografiche, come il Doppler tissutale (DTI) e l’ecocardiografia speckle-tracking bidimensionale (2DSTE). Più di recente, gli algoritmi speckle-tracking sono stati applicati alle acquisizioni tridimensionali (3D) del VS (cioè ecocardiografia 3D speckle-tracking, 3DSTE), rendendo possibile l’analisi di tutte le componenti della deformazione miocardica del VS su un unico dataset. Oggi, la tecnologia 3DSTE è agli albori del suo sviluppo, ed il suo potenziale valore clinico resta ancora da dimostrare. Rispetto alle tecnologie precedenti (DTI e 2DSTE), il 3DSTE gode di diversi vantaggi, ma comporta anche nuove sfide. Al momento, non è ancora noto se i benefici teorici di una supplementare terza dimensione per studiare la complessa meccanica del VS (non più movimento "fuori-piano" degli speckles, un’unica acquisizione necessaria, ecc) non siano in realtà controbilanciate dalle nuove sfide tecniche derivanti dall'utilizzo di un acquisizione volumetrica del VS (cioè minor risoluzione spaziale e temporale del 3DSTE rispetto al 2DSTE). Una delle principali preoccupazioni con il 2DSTE è la grande variabilità delle misure di deformazione fra i vari software disponibili in commercio. Allo stato attuale, non è chiaro se un problema simile possa influire anche 3DSTE e, se sì, in quale misura. Inoltre, nonostante i ricercatori utilizzino sempre più frequentemente il 3DSTE per studiare varie condizioni patologiche, sono attualmente sconosciuti i valori di riferimento per la deformazione miocardica del VS mediante 3DSTE, così come la possibile influenza di vari fattori clinici e tecnici sui valori di deformazione VS ottenibili con 3DSTE. Infine, il processo di validazione del 3DSTE è difficile a causa della mancanza di un'adeguata metodica di riferimento tridimensionale che possa essere applicata in maniera non invasiva in soggetti umani per validare la funzione VS regionale in 3D. Pertanto, c’è bisogno di un grande e rigoroso lavoro di validazione, di standardizzazione metodologica e intervendor da iportare a termine prima della sua applicazione in ambito clinico. Metodi e Risultati. Progettazione: studio clinico mono-centrico, prospettico, osservazionale, con l'obiettivo di esplorare la fattibilità clinica e l'utilità dell’analisi della deformazone miocardica del VS utilizzando attrezzature 3DE allo stato dell’arte. Il progetto prevede una serie di 4 studi clinici. L'obiettivo dello Studio # 1 è stato quello di valutare la variabilità e la coerenza dei valori di deformazione VS tra le due apparecchiature 3DSTE disponibili in commercio: Vivid E9 (GE Vingmed, Horten, Norvegia) e Artida (Toshiba Medical Systems Corporation, Tokyo, Giappone). Per questo studio sono stati arruolati 60 pazienti (38 ± 12 anni, 64 % maschi) con una vasta gamma di volumi e frazioni di eiezione del VS. Lo strain longitudinale globale (3DLɛ), radiale (3DRɛ), circonferenziale (3DCɛ) e l'area strain (3DAɛ) sono stati ottenuti con il rispettivo software proprietario. Nel complesso, la concordanza del 3DRɛ, 3DCɛ e 3DAɛ misurati con Artida e Vivid E9 era scadente. Tra le varie component, il 3DLɛ ha mostrato i valori più vicini tra le due piattaforme (bias = 1,5 %, limiti di concordanza da -2,9 a -5,9%, p<0,05). Artida ha fornito valori significativamente più elevati di 3DCɛ e 3DAɛ rispetto a VividE9 (bias = 6,6% per 3DCɛ, 6,0% per 3DAɛ e -24% per 3DRɛ, rispettivamente, p <0,001). Tutti i componenti di deformazione 3D hanno mostrato una buona riproducibilità (coefficiente di correlazione intraclasse: 0,82-0,98), fatta eccezione per 3DRɛ da Artida, che ha mostrato solo una moderata riproducibilità. Pertanto, i valori di riferimento devono essere identificati per ogni apparechiatura 3DSTE, e i dati basali e di follow-up in studi longitudinali devono essere ottenuti utilizzando la stessa attrezzatura. L'obiettivo dello Studio #2 è stato quello di valutare i valori di riferimento per lo strain longitudinale 3D (3DLε) del VS in 218 volontari sani (età 18-76 , il 57% donne), misuarti con un softwares 3DSTE (Vivid E9 , software 4D AutoLVQ) . Per confronto, Lε è stato misurato utilizzando anche il software specifico per il 2DSTE, e un software 3DSTE independente dall’ecocardiografo che acquisisce i data set 3D. La fattibilità dello strain 3D con 4D AutoLVQ era 89%, essendo inferiore a quella del 2DLε (95%) e simile a quella del 2DCε (92%). La fattibilità di analisi 3DSTE segmentale variava dal 46% al 100%. Valori di riferimento dei parametri di deformazione 3D sono stati identificati in base al sesso e gruppo di età. 3DLε diminuiva, mentre 3DCε aumentava con l'invecchiamento (p<0.001). Gli uomini mostravano 3DLε, 3DRε, 3DAε e 2DLε minori rispetto alle donne (p<0,02). All'analisi multivariata di regressione lineare, i fattori demografici (età e sesso), cardiaci (volumi e massa VS) e tecnici (qualità dell'immagine e la risoluzione temporale) hanno indipendentemente contribuito alla varianza dello strain 3D. Tenendo conto dalle notevoli differenze inter-software nei valori di strain VS identificati (p<0,001 per tutti), i limiti di normalità per lo strain VS identificati con un software 3DSTE specifico non dovrebbero essere usati in modo intercambiabile con quelli di 2DSTE o di un software 3DSTE independente dal fornitore. L'obiettivo dello Studio #3 era di valutare se la deformazione VS mediante 3DSTE nei pazienti dopo infarto miocardico con sopraslivellamento ST (STEMI) potrebbe fornire una valutazione accurata e obiettiva delle dimensioni dell'infarto e della transmuralità della necrosi, in confronto con la risonanza magnetica con gadolinio (LGE - CMR). Un totale di 77 pazienti con STEMI sono stati arruolati con l’eco 2D e 3D, e in 46 pazienti sono stati eseguiti studi LGE - CMR entro 24 ore dall’esame ecocardiografico. La quantità relativa di DE per segmento è stata usata per definire la necrosi transmurale (51-100% DE). La funzione VS è stata valutata nelle 3 sezioni 2D apicali del VS, misurando il 2DLε, e dal volume di dati 3D, valutando il punteggio della cinetica segmentaria (WMS) e la misurazione del 3DLε, 3DCε, 3DAε e 3DRε. I parametri di deformazione del VS erano correlati con gli indici convenzionali di funzione sistolica VS (FEVS) e di estensione dell’infarto (troponina I, WMSI, dimensioni dell'infarto alla LGE - CMR). Nonostante una buona accuratezza dello 2DLε e dei parametri di deformazione 3D (AUC = 0,81-0,73), la valutazione visiva della cinetica regionale da parte di un osservatore esperto su immagini 3D di buona qualità (AUC = 0.87) è risultata essere sempre superiore rispetto al valore predittivo dello strain per identificare la necrosi transmurale alla LGE - CMR. Gli obiettivi dello Studio #4 erano di descrivere la funzione miocardica del VS nei pazienti con cardiomiopatia ipertrofica (HCM) mediante 2DSTE e 3DSTE, e di confrontarla con la deformazione VS normale di soggetti sani. In 32 pazienti con HCM e 32 controlli simili per età e per sesso, abbiamo analizzato il valore globale del 2DLε e del 3DLε, 3DCε, 3DRε, 3DAε. La frazione di eiezione (FEVS), la massa del VS e l'area del tratto di efflusso (LVOTA) sono stati misurati mediante eco 3D. Lo stato sintomatico è stato definito dalla classe NYHA (II - IV). Anche se LVEF era simile nei pazienti e nei controlli (64 ± 6 % vs 62 ± 4 %, p = 0,29), lo strain VS era significativamente ridotto nei pazienti (p < 0,0001), fatta eccezione per 3DCε, che era solo marginalmente più basso. Nei pazienti con HCM, tutti i parametri di deformazione erano correlati con il volume telesistolico del VS (r = 0,55-0,67), la FEVS (r = -0,82 a -0,88) e la massa VS (r = 0,33-0,56). I pazienti sintomatici avevano una riduzione maggiore del 3DAε , 3DRε e 3DCε, ma avevano anche più ostruzione dell’efflusso, un maggior rimodellamento concentrico ed un rapporto E/e ' più alto. All’analisi delle curve ROC, 3DAε, 3DRε e 3DCε hanno avuto una buona precisione per individuare i soggetti sintomatici (AUC 0,72-0,73). La massa 3D del VS mostrò una correlazione inversa con la deformazione longitudinale del VS: r = -0,74 per 2DLε e -0,70 per 3DLε (p < 0,001 per entrambi). In HCM con FEVS conservata, la deformazione longitudinale è risultata significativamente ridotta, tuttavia lo sviluppo dei sintomi è multifattoriale e relativo al deterioramento aggiuntivo della deformazione VS nella direzione circonferenziale – radiale. Conclusioni. Questo progetto ha affrontato diversi temi di importanza fondamentale per la validazione clinica dello 3DSTE. Ha fornito un'analisi completa della variabilità di misura mediante 3DSTE (intra- ed interosservatore, al test-retest, inter-macchina e inter-software), ha valutato la fattibilità del 3DSTE in ambiente clinico e confrontato I valori ottenuti con lo strain VS mediante 2DSTE. Inoltre, questo è il primo studio a definire i limiti di riferimento per lo strain 3D utilizzando sia software specifici che indipendenti dal fornitore. Infine, questo progetto presenta il valore aggiunto di 3DSTE rispetto ai precedenti metodi per la valutazione della funzione VS in 2 condizioni patologiche comuni (STEMI acuto, come prototipo di lesione transmurale regionale necrotica, e l’HCM, come prototipo di malattia miocardica con funzione sistolica longitudinale compromessa nonostante FEVS conservata). Questa serie di studi contribuisce con dei dati originali alle conoscenze attuali basate sull'evidenza scientifica sul 3DSTE, che è essenziale per lo sviluppo e l'uso appropriato di questa nuova tecnologia.

Ferramentas diagnósticas capazes de detectar envolvimento cardíaco precoce na doença de Chagas são necessárias. A técnica ecocardiográfica de rastreamento de pontos, ou speckle tracking echocardiography (STE) oferece condições para o diagnóstico precoce de lesão cardíaca por avaliar a deformação miocárdica (strain). O objetivo do estudo foi avaliar as alterações sequenciais de parâmetros estruturais e funcionais dos ventrículos na evolução da doença. Um total de 37 hamsters fêmeas (Mesocricetus auratus) adultas receberam, por via intraperitoneal, 35.000 formas tripomastigotas de Trypanosoma cruzi (grupo Chagas) e outras 20 receberam igual volume de solução salina (grupo controle). Ecocardiograma foi realizado imediatamente antes da infecção (exame basal) e repetido para avaliação das fases aguda (1 mês) e crônica (4, 6 e 8 meses após). Foram avaliados: diâmetros do ventrículo esquerdo (DDFVE e DSFVE), fração de ejeção (FEVE), strain longitudinal (GLS), circunferencial (GCS) e radial (GRS) do ventrículo esquerdo e TAPSE, índice de função sistólica do ventrículo direito. A avaliação das diferenças entre os dois grupos ao longo de tempo foi realizada por meio da análise de variância (ANOVA) para modelos mistos de medidas repetidas. Ao exame basal, os dois grupos apresentaram idade média de 89 ± 1 dias. Os animais do grupo controle apresentaram peso de 130 ± 15 gramas; frequência cardíaca de 204 ± 18 batimentos/minuto, enquanto os do grupo Chagas apresentaram peso de 143 ± 12 gramas e frequência cardíaca de 198 ± 18 batimentos/minuto. Os valores de peso foram significativamente diferentes (p= 0,004) entre os grupos, mas não os de frequência cardíaca. A fração de ejeção do ventrículo esquerdo foi de 64 ± 5 % no grupo controle e de 61 ± 5 % no grupo Chagas, p= 0,10, enquanto o GLS foi de -15,2 ± 2,7 % no grupo controle e de -14,2 ± 3,4 % no grupo Chagas, p= 0,25. Na evolução da doença, o grupo Chagas apresentou aumento do DSFVE significativamente maior do que o aumento mostrado pelo grupo controle (valor-p da interação grupos#tempo= 0,007); a FEVE mostrou queda progressiva ao longo do tempo no grupo Chagas, com diferença verificada entre os grupos a partir de 6 meses do exame basal (valor-p da interação grupos#tempo= 0,005). O GLS e o GCS dos animais do grupo Chagas apresentaram comportamento significativamente diferente ao longo do tempo em comparação com o grupo controle (valor-p da interação grupos#tempo= 0,003 para o GLS e < 0,001 para oGCS). Para ambos, a diferença entre os grupos é verificada a partir do primeiro mês, quando se detecta queda pronunciada desses parâmetros de deformação. O índice TAPSE do grupo Chagas apresentou comportamento significativamente diferente ao longo do tempo em comparação ao grupo controle (valor-p da interação grupos#tempo < 0,009), com diferença observada a partir do primeiro mês. Diante disso, os resultados revelam que o GLS e o GCS são os parâmetros mais sensíveis para a avaliação funcional do ventrículo esquerdo na fase aguda e na fase crônica da doença de Chagas no modelo estudado.
Diagnostic tools capable to detect early heart involvement in Chagas\' disease are necessary. The speckle tracking echocardiography (STE) provides conditions for early diagnosis of cardiac lesion by evaluating myocardial deformation (strain). The objective of this study was to evaluate the sequential changes of structural and functional parameters of the ventricles in the evolution of the disease. A total of 37 adult female hamsters (Mesocricetus auratus) were inoculated intraperitoneally with 35,000 trypomastigote forms of Trypanosoma cruzi (Chagas group) and another 20 received equal volume of saline solution (control group). Echocardiography was performed before the infection (baseline) and repeated for assessment of acute (1 month) and chronic (4, 6 and 8 months after) phases. Left ventricular end-diastolic (LVED), left ventricular end-systolic (LVES), left ventricular ejection fraction (LVEF) and longitudinal strain (GLS) were measured at parasternal long-axis view. Circumferential strain (GCS) and radial strain (GRS) were evaluated at short-axis view (mid-LV cavity). Tricuspid annular plane systolic excursion (TAPSE) was used to assess right ventricular function. The analysis of variance (ANOVA) for mixed models of repeated measures was used to evaluate the differences between the two groups over time. At baseline, the two groups had a mean age of 89 ± 1 days. The animals in the control group had a weight of 130 ± 15 grams; heart rate of 204 ± 18 beats/minute, while those in the Chagas group had a weight of 143 ± 12 grams and a heart rate of 198 ± 18 beats/minute. The weight values were significantly different (p = 0.004) between the groups, but not those of heart rate. Left ventricular ejection fraction was 64 ± 5% in the control group and 61 ± 5% in the Chagas group (p = 0.10), while GLS was -15.2 ± 2.7% in the control group and of -14.2 ± 3.4% in the Chagas group (p = 0.25). In the evolution of the disease, the Chagas group presented a significantly higher increase in the LVES than the increase shown by the control group (p-value of the interaction groups # time = 0.007); the LVEF showed progressive decrease over time in the Chagas group, with a difference between groups after 6 months of baseline examination (p-value of interaction groups # time = 0.005). The GLS and GCS of the animals of the Chagas group showed significantly different behavior over time compared to the control group (p-value of the interaction groups # time = 0.003 for GLS and <0.001 for GCS). For both, the difference between groups is verified from the first month, when a pronounced decrease of these deformation parameters is detected. The TAPSE index of the Chagas group presented a significantly different behavior over time compared to the control group (p-value of interaction groups # time <0.009), with difference observed from the first month. Therefore, the results indicate that GLS and GCS are the most sensitive parameters for left ventricle functional assessment in acute and chronic phases of an experimental model of Chagas disease.

Background: the right ventricle (RV) is a complex shaped cardiac chamber, whose pump function is mainly driven by a longitudinal deformation, as showed by anatomical studies. Conventional echocardiography showed several limitations in the analysis of RV size and function. RV systolic dysfunction is an important prognostic factor in several pathological condition, among which pulmonary hypertension (PH). However, the progression of RV mechanical changes that lead to the RV pump function impairment remains to be clarified. The new echocardiographic techniques, two dimensional-speckle tracking (2D-STE) and three-dimensional echocardiography (3DE), allow to investigate volumes, ejection fraction and myocardial mechanics of the RV. Moreover, we developed a custom-made software package that applied to the 3DE beutel of the RV allows to discriminate between the relative contribution of the longitudinal and radial displacement to the global RV pump function. Purpose: to value the mechanics of RV in healthy condition, in presence of systemic sclerosis (SSc), a condition predisposing to PH, and in presence of PH. Methods: we enrollled 270 healthy subjects, 75 patients affected by SSc (a pathological condition at high risk of PH), without PH, and 59 patients affected by PH (excluded PH type 2). Some of PH patients underwent to more than one echocardiograms, for a total of 81 exams. 57 age- and gender-matched healthy volunteers have been selected. All subjects underwent a complete echocardiogram, including dedicated 3DE acquisition of the RV. A dedicated software has been applied on apical 2D image of the RV in order to measure the longitudinal strain (LS) and the transversal displacement (TD) of both the free-wall (RVFW) and the interventricular septum (IVS). 3DE data sets of the RV have been analyzed by RV function 2.0 (TomTec) in order to obtain volumes and ejection fraction (RVEF). Then PH have been divided according to RV-EF: preserved (≥45%) or impaired (<45%). Finally, the 3DE RV beutels were analyzed by our custom made software package obtaining the longitudinal EF (LongEF) and radial EF (RadEF) and their relative contribution to RVEF by calculating the ratios LongEF/RVEF and RadEF/RVEF. Results: the analysis of the healthy volunteers provided reference values of RV volumes, ejection fraction, LS and TD. The 3DE RV beutel analysis showed that in healthy subjects the relative contribution of longitudinal and radial motion is equal. In SSc patients no significant differences about RV size and function have been demonstrated. PH patients showed significantly larger 3DE RV end-diastolic and end-systolic volumes (106±39 ml vs 67 ±14 ml and 65±33 vs 28±7 ml, respectively; p<0.0001), lower 3D RVEF (41±11% vs 58±4%; p<0.0001), lower LS values and impaired TD values than controls. Similarly, both LongEF and RadEF were lower (18±7% vs 27±4% and 15±7% vs 27±5%, respectively; p<0.0001) in PH patients. However, only the RadEF/RVEF appeared impaired (36±11 vs 47±6, p<0.0001), whereas LongEF/RVEF (47±9 vs 47±6, p=NS) was similar between pts and controls. Looking at the subgroup of patients with reduced RVEF, RV pump dysfunction was mainly driven by progressive reduction of the radial component of RV wall displacement. Conclusions: in healthy condition, the radial component of RV wall displacement is as important as the longitudinal one to determine global RV pump function. In patients with PH, the impairment of RV pump function seems to be mainly driven by the progressive reduction of RV radial displacement.
Presupposti: il ventricolo destro (VDx) è una cavità cardiaca di forma complessa la cui funzione di pompa in condizioni di normalità sembra essere determinata prevalentemente dall’accorciamento longitudinale. Tale affermazione deriva da studi anatomici che hanno mostrato come nella parete ventricolare destra, lo strato di fibre miocardiche longitudinali sia il più rappresentato. L’ecocardiografia convenzionale dimostra numerosi limiti nello studio delle dimensioni e della funzione del VDx, legati principalmente alla complessità della sua forma e meccanica. Tuttavia, la funzione ventricolare destra ha dimostrato essere un importante fattore prognostico in alcune condizioni patologiche, tra cui l’ipertensione polmonare (PH). E’ tuttora sconosciuta la sequenza di eventi che conducono alla disfunzione di pompa globale del VDx nei soggetti affetti da PH. Due metodiche ecocardiografiche di recente introduzione, lo speckle-tracking bidimensionale e l’ecocardiografia tridimensionale, permettono una più accurata valutazione delle dimensioni e funzione della cavità ventricolare destra. In particolare, consentono di valutare i volumi e la forma del VDx, la funzione di pompa globale e la sua meccanica miocardica, in termini di deformazione longitudinale e trasversale. Scopo dello studio: valutare la meccanica del ventricolo destro in condizioni di normalità ed in presenza di PH, definendo le alterazioni meccaniche che determinano la progressiva disfunzione di pompa globale del VDx che caratterizza la storia clinica dei pazienti affetti da PH. Materiali e metodi: sono stati arruolati 270 soggetti sani, 75 pazienti affetti da sclerosi sistemica (in quanto popolazione ad alto rischio di sviluppare PH) senza PH e 59 pazienti affetti da PH (esclusa PH tipo 2). In quest’ultimo gruppo alcuni soggetti sono stati sottoposti a più di un esame ecocardiografico, a distanza di tempo, per un totale di 81 ecocardiogrammi. Dalla popolazione di soggetti sani è stato scelto un campione di 57 soggetti sovrapponibile per età e sesso alle due popolazioni patologiche. Tutti i pazienti sono stati sottoposti ad almeno un ecocardiogramma completo, comprensivo di acquisizioni tridimensionali del VDx. Mediante un software dedicato da un’immagine bidimensionale dedicata per il VDx è stata eseguita l’analisi speckle tracking che ha permesso di valutare lo strain longitudinale e la deformazione trasversale della parete libera e del setto interventricolare. Il data set tridimensionale è stato analizzato mediante un software dedicato che ha permesso di misurare i volumi e la frazione di eiezione del VDx. Il beutel tridimensionale così ottenuto è stato successivamente analizzato con un software ad hoc che ha permesso di stimare separatamente il contributo longitudinale e radiale alla genesi della frazione di eiezione del VDx. Risultati: dall’analisi del gruppo di soggetti sani sono stati ottenuti i valori di normalità di volume telediastolico e telesistolico, frazione di eiezione, strain longitudinale e displacement trasversale del VDx. Dall’analisi del beutel tridimensionale del VDx è emerso che la deformazione longitudinale e radiale contribuiscono in eguale misura alla funzione di pompa globale del VDx. I soggetti affetti da sclerosi sistemica hanno dimostrato valori leggermente superiori di pressione sistolica in arteria polmonare e resistenze vascolari polmonari totali rispetto ai soggetti sani, seppure senza raggiungere i criteri patologici. Invece, i valori di dimensione e funzione del VDx sono risultati sovrapponbili rispetto ai controlli sani. I pazienti affetti da PH hanno dimostrato volumi del VDx sensibilmente superiori con una ridotta frazione di eiezione. Le componenti longitudinale e radiale della frazione di eiezione sono risultate entrambe ridotte, ma in particolare il contributo relativo radiale ha dimostrato essere quello maggiormente alterato. Per quanto riguarda la meccanica miocardica, lo strain longitudinale della parete libera e del setto interventricolare è risultato ridotto ed anche la deformazione trasversale globale è risultata alterata. In particolare nei soggetti con PH, soprattutto la meccanica del setto interventricolare ha dimostrato di essere alterata, con una minore entotà di spostamento sistolico dello stesso verso il centro della cavità ventricolare sinistra. Dividendo i pazienti con PH in due gruppi (con frazione di eiezione conservata e frazione di eiezione ridotta), è stato possibile dimostrare che tutti i parametri di funzione e deformazione del VDx sono maggiormente alterati nel secondo gruppo. Tuttavia, mentre il contributo longitudinale alla frazione di eiezione è risultato preservato, il contributo radiale ha dimostrato di essere significativamente ridotto. Conclusioni: in condizioni di normalità la funzione ventricolare destra sembra essere determinata in egual misura dalla deformazione longitudinale e radiale. In presenza di ipertensione polmonare, il progressivo deterioramento della funzione di pompa del VDx è veicolata prevalentemente da una riduzione del contributo radiale.

A doença arterial coronária é importante e prevalente manifestação da aterosclerose. A avaliação da função diastólica pelos parâmetros mitrais obtidos com Doppler ecocardiográfico possui limitações nos coronariopatas com fração de ejeção do ventrículo esquerdo (FEVE) preservada. Nestes, a disfunção diastólica, independentemente da FEVE, associa-se a maior incidência de desfechos desfavoráveis. A elevação da pressão diastólica final (PD2) do ventrículo esquerdo (VE) é a principal consequência fisiológica da disfunção diastólica. A pesquisa por melhores formas de determinação da PD2 do VE estendeu-se às modernas técnicas ecocardiográficas de quantificação da mecânica cardíaca. O objetivo deste estudo é correlacionar as medidas de deformação miocárdica, obtidas pelo speckle-tracking ecocardiográfico bidimensional, com a medida invasiva da PD2 do VE em pacientes com insuficiência coronariana e FEVE preservada. Métodos: foram avaliados 81 coronariopatas (idade: 61 ±8 anos) com FEVE >50%, encaminhados para cineangiocoronariografia eletiva, 40 destes com PD2 elevada (>16 mm Hg). Todos os indivíduos foram submetidos à avaliação ecocardiográfica convencional imediatamente antes do cateterismo e subsequente avaliação offline, com ecocardiografia speckle tracking (EST) para obtenção de medidas sistólicas e diastólicas de strain e strain rate circunferenciais e longitudinais, e estudo rotacional do VE. Foram analisadas as variáveis diastólicas da EST, tanto de forma isolada, quanto combinada com a velocidade da onda E ao Doppler. Resultados: Comparativamente, os pacientes do grupo com PD2 do VE elevada (n=40) mostraram aumento do volume indexado do átrio esquerdo (22 ±6 mL vs 26 ±8,26 mL p=0,04), velocidade da onda E (65 ±15 cm/s vs 78 ±20 cm/s p=0,02), relação E/e\' médio (8,14 ±2,0 vs 11,54 ±2,7 p=0,03) e relação E/strain rate global circunferencial (SRGC) pico E (39 cm vs 46 cm p <0,01). Nos 81 pacientes a correlação de Spearman com a medida invasiva da PD2 do VE foi de 0,56 para a relação E/e\' (p=0,03) e de 0,43 para a relação E/ESRGC pico E (p<0,01). A área sob a curva ROC foi significativa em ambas, sendo 0,83 e 0,73 respectivamente (p<0,05). Conclusão: A relação E/SRGC pico E é capaz de identificar elevação da PD2 do VE em coronariopatas com FEVE preservada, com menor desempenho que a relação E/e\'.
Introduction: Coronary artery disease (CAD) is important and prevalent manifestation of atherosclerosis. The assessment of diastolic function by mitral Doppler echocardiographic parameters has limitations in patients with CAD and preserved left ventricular ejection fraction (LVEF). Diastolic dysfunction is associated with higher incidence of unfavorable outcomes in these patients, regardless of LVEF. The increase in left ventricle end-diastolic pressure (LVEDP) is the main physiological consequence of diastolic dysfunction. The search for better ways of determining the LVEDP extended to the quantitative evaluation of cardiac mechanics with the modern echocardiographic techniques. The aim of this study is to correlate the invasive mesures of LVEDP and myocardial deformation measurements obtained by the two-dimensional speckle-tracking echocardiography in patients with coronary artery disease and preserved LVEF. Methods: 81 CAD patients (age: 61 ± 8 years) with LVEF >50%, scheduled for elective coronary angiography were evaluated, 40 of these with high LVEDP (>16 mm Hg). All subjects underwent conventional echocardiography immediately before catheterization and subsequent offline assessment with speckletracking echocardiography (STE) to obtain systolic and diastolic values of circumferential and longitudinal strain and strain rate, and rotational LV study. Diastolic variables of EST were analyzed both isolated and combined with the speed of the transmitral Doppler E wave. Results: Patients in the group with the high LVEDP (n =40) showed increased left atrial volume index (22 ± 6 mL vs 26 ± 8.26 mL p =0.04), E wave velocity (65 ± 15 cm/s vs 78 ±20 cm/s p = 0.02), E/e\' (average) ratio ( 8.14 ± 2.0 vs 11.54 ± 2.7 p = 0.03) and E/global circumferential strain rate (GCSR) peak E (39 cm vs 46 cm p <0.01). In 81 patients, Spearman\'s correlation with the invasive measurement of LVEDP was 0,56 (p =0.03) for the E/e\' ratio and 0.43 for the E/GCSR peak E (p <0.01). The area under the ROC curve was significant for both (p < 0.05): 0.83 and 0.73 respectively. Conclusion: The E/GCSR peak E ratio is able to identify elevated LVEDP in CAD patients with preserved LVEF, with less performance than the E/e\' ratio.

Ventricular arrhythmias (VA) are a frequent precursor to sudden cardiac death (SCD) in patients with structural heart disease (SHD). Patients with SHD are at risk of recurrent ventricular tachycardia (VT), which generally occurs due to re-entry within and around the presence of an arrhythmogenic scar. Therefore, scarred myocardium forms the necessary substrate for arrhythmogenesis to occur. A scar may occur due to obstructive coronary artery disease, causing ischaemic cardiomyopathy (ICM), or from cardiac injury due to several other causes, including inflammatory, infiltrative, toxin-mediated, or genetic heart disease, termed non-ischaemic cardiomyopathy (NICM). An implantable cardioverting defibrillator (ICD) can abort SCD from recurrent VAs. However, they do not stop VAs from occurring in the first place. Anti-arrhythmic drugs (AADs) may reduce the frequency and burden of VAs but have limited efficacy. Some have a narrow therapeutic window or the potential for multiorgan toxicity and can be poorly tolerated. Catheter ablation (CA) is a class I indication for treating sustained monomorphic VT refractory to AADs. CA reduces VT burden, the number of defibrillator therapies, greater freedom from recurrent ventricular arrhythmia, and improves quality of life. However, recurrences can be experienced in up to 50% of patients with SHD-related VT. Some reasons for the failure of CA include reliable identification of critical components of substrate that can harbour VAs both in sinus rhythm and during ongoing VT using electroanatomic mapping (EAM) and imaging techniques, as well as limitations in assessing intraprocedural endpoints. Further refinement of electroanatomic mapping techniques is required to improve the efficacy of CA. This thesis aims to expand on current techniques for substrate identification and methods to improve the efficacy of VA ablation procedures.

Background：Aortic stenosis (AS) is the commonest valve disease in the West. Aortic valve replacement (AVR) remains the only available management for AS and results in improved symptoms and recovery of ventricular functions. In addition, it is well known that AVR results in disruption of LV function mainly in the form of reversal of septal motion as well as depression of right ventricular (RV) systolic function. The aim of this thesis was to study, in detail, the early and mid-term response of ventricular function to AVR procedures (surgical and TAVI) as well as post operative patients’ exercise capacity. Methods：We studied LV and RV function by Doppler echocardiography and speckle tracking echocardiography (STE) in the following 4 groups; (1) 30 severe AS patients (age 62±11 years, 19 male) with normal LV ejection fraction (EF) who underwent AVR, (2) 20 severe AS patients (age 79±6 years, 14 male) who underwent TAVI, (3) 30 healthy controls (age 63±11 years, 16 male), (4) 21 healthy controls (age 57±9 years, 14 male) who underwent exercise echocardiography. Results: After one week of TAVI, the septal radial motion and RV tricuspid annulus peak systolic excursion (TAPSE) were not different from before, while surgical AVR had significantly reversed septal radial motion and TAPSE dropped by 70% compared to before. The extent of the reversed septal motion correlated with that of TAPSE (r=0.78, p<0.001) in the patients as a whole after AVR and TAVI (Study I). Compared with controls, the LV twist function was increased in AS patients before and normalized after 6 months of surgical AVR. In controls, the LV twist correlated with LV fractional shortening (r=0.81, p<0.001), a relationship which became weak in patients before (r=0.52, p<0.01) and after AVR (r=0.34, p=ns) (Study II). After 6 months of surgical AVR, the reversed septal radial motion was still significantly lower than before. The septal peak displacement also decreased and its time became prolonged. In contrast, the LV lateral wall peak displacement increased and the time to peak displacement was early. The accentuated lateral wall peak displacement correlated with the septal peak displacement time delay (r=0.60, p<0.001) and septal-lateral time delay (r=0.64, p<0.001) (Study III). In 21 surgical AVR patients who performed exercise echocardiography, the LV function was normal at rest but different from controls with exercise. At peak exercise, oxygen consumption (pVO2) was lower in patients than controls. Although patients could achieve cardiac output (CO) and heart rate (HR) similar to controls at peak exercise, the LV systolic and early diastolic myocardial velocities and strain rate as well as their delta changes were significantly lower than controls. pVO2 correlated with peak exercise LV myocardial function in the patients group only, and the systolic global longitudinal strain rate (GLSRs) at peak exercise was the only independent predictor of pVO2 in multivariate regression analysis (p=0.03) (Study IV). Conclusion: Surgical AVR is an effective treatment for AS patients, but results in reversed septal radial motion and reduced TAPSE. The newly developed TAVI procedure maintains RV function which results in preservation of septal radial motion. In AS, the LV twist function is exaggerated, normalizes after AVR but loses its relationship with basal LV function. While the reversed septal motion results in decreased and delayed septal longitudinal displacement which is compensated for by the accentuated lateral wall displacement and the time early. These patients remain suffering from limited exercise capacity years after AVR.

Objetivo: O principal propósito do estudo foi pesquisar a disfunção ventricular esquerda subclínica em pacientes com lúpus eritematoso sistêmico juvenil (LESJ) através da técnica de speckle-tracking bidimensional. Foi investigada ainda uma possível correlação entre o comprometimento da deformação miocárdica e o SLEDAI-2K (Systemic Lupus Erithematosus Disease Activity Index 2000), bem como a presença de fatores de risco cardiovascular, tanto tradicionais como ligados à doença. Métodos: 50 pacientes assintomáticos do ponto de vista cardiovascular e 50 controles saudáveis (14,74 vs. 14,82 anos, p=0.83) foram avaliados pelo ecocardiograma convencional e pelo speckle-tracking bidimensional. Resultados: Apesar da fração de ejeção normal, os pacientes apresentaram redução de todos os parâmetros de deformação miocárdica longitudinal e radial, quando comparados aos controles: strain de pico sistólico longitudinal [-20,3 (-11 a -26) vs. -22 (-17,8 a -30.4) %, p < 0,0001], strain rate de pico sistólico longitudinal [-1,19 ± 0,21 vs. -1,3 ± 0,25 s-1, p=0,0005], strain rate longitudinal na diástole precoce [1,7 (0,99 a 2,95) vs. 2 (1,08 a 3,00) s-1 , p=0,0034], strain de pico sistólico radial [33,09 ± 8,6 vs. 44,36 ± 8,72%, p < 0,0001], strain rate de pico sistólico radial [1,98 ± 0,53 vs. 2,49 ± 0,68 s-1, p < 0,0001] e strain rate radial na diástole precoce [-2,31 ± 0,88 vs. -2,75 ± 0,97 s-1, p=0,02]. O strain de pico sistólico circunferencial [-23,67 ± 3,46 vs. - 24,6 ± 2,86%, p=0,43] e o strain rate circunferencial na diástole precoce [2 (0,88 a 3,4) vs. 1,99 (1,19 a 3,7) s-1, p=0,88] foram semelhantes em pacientes e controles. Apenas o strain rate de pico sistólico circunferencial [-1,5 ± 0,3 vs. -1,6 ± 0,3 s-1, p=0,036] mostrou-se reduzido no LESJ. Uma correlação negativa foi identificada entre o strain de pico sistólico longitudinal e o SLEDAI-2K (r = - 0,52; p < 0,0001) e também o número de fatores de risco cardiovascular por paciente (r = -0,32, p=0,024). Conclusões: Foi evidenciada disfunção sistólica e diastólica subclínica de ventrículo esquerdo no LESJ através da técnica de speckle-tracking bidimensional. A atividade da doença e a exposição aos fatores de risco cardiovascular provavelmente contribuíram para o comprometimento da deformação miocárdica nesses pacientes
Objectives: The main purpose of the study was to investigate left ventricular (LV) subclinical systolic and diastolic dysfunction in childhood-onset systemic lupus erythematosus (c-SLE) patients using two-dimensional speckletracking (2DST) echocardiography. We also interrogated possible correlations between impairment of myocardial deformation and the SLE Disease Activity Index 2000 (SLEDAI-2K), as well as the presence of traditional and disease-related cardiovascular risk factors (CRFs). Method: A total of 50 asymptomatic patients and 50 controls (age 14.74 vs. 14.82 years, p = 0.83) were evaluated by standard and 2DST echocardiography. Results: Despite a normal ejection fraction (EF), there was reduction in all parameters of LV longitudinal and radial deformation in patients compared to controls: peak longitudinal systolic strain [-20.3 (-11 to -26) vs. -22 (-17.8 to -30.4)%, p < 0.0001], peak longitudinal systolic strain rate [-1.19 ± 0.21 vs. -1.3 ± 0.25 s-1, p = 0.0005], longitudinal strain rate in early diastole [1.7 (0.99-2.95) vs. 2 (1.08-3.00) s-1, p = 0.0034], peak radial systolic strain [33.09 ± 8.6 vs. 44.36 ± 8.72%, p < 0.0001], peak radial systolic strain rate [1.98 ± 0.53 vs. 2.49 ± 0.68 s-1, p < 0.0001], and radial strain rate in early diastole [-2.31 ± 0.88 vs. -2.75 ± 0.97 s-1, p = 0.02]. Peak circumferential systolic strain [- 23.67 ± 3.46 vs. -24.6 ± 2.86%, p=0.43] and circumferential strain in early diastole [2 (0,88 a 3,4) vs. 1,99 (1,19 a 3,7) s-1, p=0.88 ] were similar between patients and controls, although peak circumferential systolic strain rate [-1.5 ± 0.3 vs. -1.6 ± 0.3 s-1, p = 0.036] was reduced in c-SLE. Further analysis of patients revealed a negative correlation between LV peak longitudinal systolic strain and SLEDAI-2K(r= -0.52, p < 0.0001) and also between LV PLSS and the number of CRFs per patient (r = -0.32, p = 0.024). Conclusions: 2DST echocardiography has identified subclinical LV deformation impairment in c-SLE patients. Disease activity and cumulative exposure to CRFs contribute to myocardial compromise

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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Um dos principais desafios na miocardiopatia chagásica é a detecção de alterações precoces na função ventricular esquerda. A avaliação do strain pelo speckle tracking na ecocardiografia bidimensional (2-D ST) é um novo método com aplicações em diversas doenças cardíacas, tendo sido validado para pacientes com infarto do miocárdio em comparação à ressonância magnética cardíaca (RMC). Neste estudo, avaliamos a hipótese de que o strain global longitudinal (SGL) possui um valor incremental à fração de ejeção (FE) pelo método de Simpson para predição de fibrose miocárdica na RMC, em pacientes portadores de doença de Chagas (DC). Métodos: Estudo observacional, com um total de 58 pacientes portadores de DC. Todos os pacientes foram submetidos à realização de ecocardiograma convencional e com strain pelo speckle tracking, além de RMC. Resultados: A análise da curva ROC mostrou que tanto a SGL (área sob a curva: 0,78, p = 0,001) quanto a fração de ejeção (área sob a curva: 0,82, p < 0,001) tiveram significância estatística na detecção de fibrose. Em relação á porcentagem de fibrose, uma alta correlação foi observada tanto com a FE pela ecocardiografia (r = - 0,70, p < 0,001) quanto com o SGL (r = 0,64, p < 0,001). Contudo, quando ajustado pela regressão linear múltipla, o SGL perdeu a significância estatística como preditor independente de fibrose miocárdica (p = 0.111). Conclusões: SGL não possui valor incremental em relação à FE na predição de fibrose miocárdica em pacientes portadores de DC.
One of the most challenging issues of chronic Chagas disease is to provide earlier detection of heart involvement. Two-dimensional speckle tracking (2-D ST) echocardiography, a new imaging modality with useful applications in several cardiac diseases, has been validated for subjects with myocardial infarction against cardiac magnetic resonance (CMR). Here we hypothesize that the longitudinal global strain (LGS) has an incremental value to ejection fraction for predicting myocardial fibrosis in subjects with Chagas disease. Methods: This observational study comprised 58 subjects with Chagas disease, confirmed by two positive serologic tests. All subjects underwent conventional Doppler echocardiogram plus speckle tracking strain, and cardiac magnetic resonance. Results: The ROC curve analysis revealed that both LGS (Area under the curve: 0.78, p = 0.001) and ejection fraction (Area under the curve: 0.82, p < 0.001) were significant predictors of myocardial fibrosis. Regarding the percentage of fibrosis, a high correlation was observed with both ejection fraction assessed by echocardiography (r = - 0.70, p < 0.001) and LGS (r = 0.64, p < 0.001). However, when adjusted through multiple linear regression, the LGS lost statistical significance as a predictor of myocardial fibrosis (p = 0.111). Conclusions: LGS has no incremental value to conventional ejection fraction measurement in the prediction of myocardial fibrosis in subjects with Chagas disease.

Introduction and Objectives: The adverse remodeling of the left ventricle (LV) after ST-elevation acute myocardial infarction (STEMI) is a complex phenomenon characterized by different phases. Firstly, the infarct expands during the healing process through thinning and enlargement of necrotic area; secondarily, there is a global LV volume increase and systolic dysfunction that involves the remote myocardium through hypertrophy, apoptosis and interstitial collagen deposition. Several studies found a close correlation between infarct size and LV remodeling; others associated the adverse remodeling with the following development of congestive heart failure, ventricular arrhythmias and cardiovascular death. The ability of novel echocardiographic parameters of myocardial strain to predict the extent and transmurality of myocardial necrosis after STEMI suggests their possible role in predicting the subsequent LV remodeling. In this thesis, we report the results of a prospective study aimed to determine the predictive value of the various two- (2D) and threedimensional (3D) strain components for LV remodeling and clinical outcome in patients with first recanalized STEMI. Methods: We enrolled a consecutive cohort of 64 patients treated with a primary percutaneous coronary intervention after first STEMI, at a single centre. All patients underwent a comprehensive 2D and 3D echocardiogram at pre-discharge and after 13±2 months to assess LV volumes and function. 2D and 3D strain components were measured by speckle tracking analysis. LV adverse remodeling was defined as relative increase of end-systolic volume >15% respect to basal measurement. Results: Seventeen (27%) patients showed unfavourable remodeling at the follow-up visit. Among clinical data, peak Troponin I value and Killip class at admission were significantly related to adverse remodeling. Pre-discharge less negative 2D- and 3D peak global longitudinal (GL) and 3D end-systolic global area (GA) strain resulted independent determinants of unfavourable LV remodeling. Using ROC curves, a 2D GL strain less negative than a cut-off value of -14.2% showed a sensibility of 73% and a specificity of 61% to predict unfavourable LV remodeling (AUC 0.74, 95% CI 0.61-0.87; p=0.005). Predischarge 2D GL strain was also predictive, at limits of significance, of the composite clinical end point (death, overt heart failure and unstable angina) (p=0.057). Conclusions: Despite optimal medical therapy, LV negative remodeling remains a relatively frequent process after a STEMI, at a mid-term follow-up. Predischarge 2D- 3D GL and GA strain are significant predictors of unfavourable LV remodeling and adverse clinical outcome in patients with first recanalized STEMI. The measurement of these non-invasive, reproducible and unexpensive parameters of LV myocardial function helps to select a sub-population of survivors STEMI patients who may need a closer follow-up and a more aggressive management.
Introduzione e obiettivi: Il rimodellamento avverso del ventricolo sinistro (VS) dopo un infarto miocardico acuto con sopraslivellamento del tratto ST (STEMI) è un fenomeno complesso caratterizzato da diverse fasi. Dapprima l’espansione infartuale avviene durante il periodo di cicatrizzazione attraverso l’assottigliamento e dilatazione della regione necrotica; successivamente vi è un rimodellamento globale del VS che coinvolge il cosiddetto miocardio remoto tramite ipertrofia eccentrica, apoptosi e deposizione di fibre collagene interstiziali. Diversi studi hanno trovato una stretta correlazione fra entità e transmuralità della necrosi miocardica con il rimodellamento del VS; altri hanno associato il rimodellamento avverso con lo sviluppo di insufficienza cardiaca congestizia, aritmie ventricolari e morte cardiovascolare. La capacità dei nuovi indici di deformazione miocardica (strain) di stimare l’estensione e transmuralità di necrosi dopo uno STEMI suggerisce il loro possibile ruolo predittivo di rimodellamento avverso del VS. In questa tesi, vengono riportati i risultati di uno studio prospettico volto a determinare la capacità dei diversi indici di strain bi- (2D) e tridimensionali (3D) nel predire il rimodellamento avverso del VS e la prognosi clinica in pazienti affetti da infarto miocardico acuto e sottoposti a ricanalizzazione percutanea. Metodi: Abbiamo arruolato 64 pazienti trattati con angioplastica primaria per primo STEMI, in un singolo centro. Tutti i pazienti sono stati sottoposti ad ecocardiogramma 2D e 3D predimissione e dopo un periodo medio di 13 ± 2 mesi, per la stima dei volumi e frazione di eiezione del VS. Sono stati inoltre determinati gli strain globali 2D e 3D del ventricolo sinistro misurati con la tecnica speckle tracking. Il rimodellamento avverso del VS è stato definito come incremento relativo del volume telesistolico >15% rispetto alla misura predimissione. Risultati: In diciassette (27%) pazienti è stato documentato un rimodellamento avverso del VS all’ecocardiogramma di follow-up. Fra i dati clinici analizzati, il picco di troponina I e la classe Killip all’ingresso sono stati significativamente correlati a rimodellamento avverso del VS. Un valore ridotto (meno negativo) degli strain longitudinale 2D e 3D e dell’area strain 3D sono risultati predittori indipendenti di rimodellamento avverso del VS. Dall’analisi delle curve ROC, un valore di strain longitudinale 2D meno negativo di -14.2% ha mostrato una sensibilità ed una specificità del 73% e 61% rispettivamente nel prevedere il rimodellamento avverso del VS (AUC 0.74, 95% CI 0.61-0.87; p=0.005). L’entità dello strain longitudinale 2D predimissione è stata inoltre correlata ad un end-point composito di morte cardiovascolare, scompenso cardiaco ed angina instabile (p=0.057). Conclusioni: Nonostante terapia medica ottimale, il rimodellamento avverso del VS dopo STEMI risulta un evento relativamente frequente ad un follow-up di medio termine. Gli strain longitudinali 2D e 3D ed area strain 3D del VS, valutati predimissione, sono risultati indicatori di rimodellamento avverso del ventricolo sinistro e prognosi clinica sfavorevole in una coorte di pazienti affetti da primo infarto miocardico acuto, sottoposto a ricanalizzazione mediante angioplastica primaria. La misura non invasiva, riproducibile e a basso costo di questi parametri di funzione sistolica del ventricolo sinistro può aiutare nell’individuare una sottopopolazione di soggetti sopravvissuti ad uno STEMI che necessitano di uno stretto monitoraggio clinico ed un trattamento più aggressivo.

Intensive training is associated with hemodynamic changes that typically induce an enlargement of cardiac chamber. Despite LA dilatation in athletes has been interpreted as a benign adaptation, little evidence is available. The aim of this thesis is to demonstrate that LA size changes in response to alterations in loading conditions and to analyse atrial myocardial function in athletes through the application of novel echocardiographic techniques. We found that top-level athletes exhibit a dynamic morphological and functional LA remodelling, induced by training, with an increase in reservoir and conduit volumes, but stable active volume. Training causes an increase in biatrial volumes which is accompanied by normal filling pressures and stiffness. These changes in atrial morphology are not associated with respective electrical changes. Extending the evidence from adult athletes to children, we found that training-induced atrial remodelling can occur in the early phases of the sports career and is associated with a preserved biatrial function. Finally, in a meta-analysis study of the available evidence we demonstrated that atrial function and size are not affected by aging. In conclusions, athlete’s heart is characterized by a physiological biatrial enlargement. This adaptation occurs in close association with LV cavity enlargement, is dynamic and reversible. This increase in biatrial size is not intrinsically an expression of atrial dysfunction. Indeed, in athletes the atria are characterized by a preserved reservoir function, normal myocardial stiffness, and dynamic changes in response to different loading conditions.

A doença aterosclerótica coronariana tem um grande impacto na morbidade e mortalidade em todo mundo. A terapia cardíaca com ondas de choque consiste em uma nova opção potencial para o tratamento de pacientes com doença coronariana crônica e angina refratária. No presente estudo, avaliamos os efeitos das ondas de choque na mecânica do ventrículo esquerdo, avaliados pela ecocardiografia com speckle tracking, assim como nos sintomas clínicos e isquemia miocárdica em pacientes com angina refratária. Estudamos, prospectivamente, 19 pacientes com angina refratária submetidos à terapia com ondas de choque com 3 sessões de tratamento por semana, realizados na primeira, quinta e nona semanas, totalizando 9 semanas de tratamento. A mecânica do ventrículo esquerdo foi avaliada por meio da determinação do strain longitudinal global e segmentar. A perfusão miocárdica foi analisada por cintilografia de perfusão miocárdica com Tecnécio-99m Sestamibi, para determinação do summed stress score (SSS). Parâmetros clínicos foram mensurados pelo escore de angina da Canadian Cardiovascular Society (CCS), escore de insuficiência cardíaca da New York Heart Association (NYHA) e qualidade de vida pelo Seattle Angina Questionnaire (SAQ). Todos os dados foram mensurados antes do início do tratamento e 6 meses após a terapia com ondas de choque. Os nossos resultados demonstraram que as ondas de choque não ocasionaram efeitos colaterais importantes e os pacientes apresentaram melhora significativa dos sintomas. Antes do tratamento, 18 (94,7%) pacientes se apresentavam com angina CCS classe III ou IV, e 6 meses após houve redução para 3 (15,8%) pacientes (p = 0,0001), associada à melhora no SAQ (38,5%; p < 0,001). Treze (68,4%) pacientes estavam em classe funcional III ou IV da NYHA antes do tratamento, com redução significativa para 7 (36,8%); p = 0,014. Nenhuma alteração foi observada no SSS global basal no acompanhamento de 6 meses (15,33 ± 8,60 versus 16,60 ± 8,06, p = 0,155) determinado pela cintilografia miocárdica. No entanto, houve redução significativa no SSS médio dos segmentos isquêmicos tratados (2,1 ± 0,87 pré versus 1,6 ± 1,19 pós-terapia, p = 0,024). O strain longitudinal global do ventrículo esquerdo permaneceu inalterado (-13,03 ± 8,96 pré versus -15,88 ± 3,43 pós-tratamento; p = 0,256). Também não foi observada alteração significativa no strain longitudinal segmentar do ventrículo esquerdo pela ecocardiografia com speckle tracking. Concluímos que a terapia com ondas de choque é um procedimento seguro para tratamento de pacientes com angina refratária, que resulta em melhor qualidade de vida, melhora na perfusão miocárdica dos segmentos tratados e preservação da mecânica ventricular esquerda
Coronary atherosclerotic disease represents a major impact on morbidity and mortality worldwide. Cardiac shock wave therapy is a new potential option for the treatment of patients with chronic coronary disease and refractory angina. In the present study, we sought to determine the effects of shock wave therapy on the left ventricular mechanics, evaluated by speckle tracking echocardiography, as well as on myocardial perfusion and symptoms of patients with refractory angina. We prospectively studied 19 patients undergoing shock wave therapy with 3 sessions per week, on the 1st, 5th and 9th weeks, for a total of 9 weeks of treatment. The left ventricular mechanics was evaluated by global longitudinal strain using the speckle tracking echocardiography. Myocardial perfusion was assessed by myocardial scintigraphy with Technetium-99m Sestamibi, for determination of summed stress score (SSS). Clinical parameters were evaluated by the Canadian Cardiovascular Society (CCS) angina score, New York Heart Association (NYHA ) heart failure score and quality of life by the Seattle Angina Questionnaire (SAQ). All data were measured prior to the treatment and 6 months after shock wave therapy. Our results demonstrated that shock wave therapy did not cause significant side effects and improved symptoms. Before treatment, 18 patients (94.7%) had CCS class III or IV angina, and 6 months later there was a reduction to 3 (15.8%), p = 0.0001, associated with improvement in SAQ ( 38.5%, p < 0.001). Thirteen (68.4%) were in NYHA class III or IV before treatment, with a significant reduction to 7 (36.8%); p = 0.014. No change was observed in the global SSS at 6-months follow-up (from 15.33 ± 8.60 baseline to 16.60 ± 8.06 post-treatment, p = 0.155). However, there was a significant reduction in the mean SSS of the treated ischemic segments (2.1 ± 0.87 pre versus 1.6 ± 1.19 post therapy, p = 0.024). The global longitudinal strain remained unchanged (-13.03 ± 8.96 pre versus -15.88 ± 3.43 6 months post-treatment, p = 0.256). In the same way, no significant difference was observed in the longitudinal strain of the left ventricular segments. We concluded that shock wave therapy is a safe procedure for the treatment of patients with refractory angina, resulting in better quality of life, improved myocardial perfusion of the treated segments, and preservation of left ventricular mechanics

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O “coração atleta” é o termo designado para caracterizar as adaptações cardíacas funcionais e anatômicas secundárias ao treinamento físico intenso e prolongado em humanos e animais. O ecocardiograma desempenha papel fundamental em distinguir as adaptações fisiológicas secundárias ao exercício, outrossim, as recentes técnicas introduzidas como Speckle Tracking (Ste) têm permitido obter informações relevantes a respeito da função cardíaca em humanos atletas. Desta forma, objetivou-se avaliar por meio do ecocardiograma, a estrutura e função sistólica do ventrículo esquerdo de cães praticantes de pastoreio há no mínimo quatro meses, cinco a seis vezes por semana, de quatro a oito horas por dia. Para tanto, 31 cães foram divididos em dois grupos: grupo pastoreio (GP, n=15) e grupo sedentário (GS, n=16), avaliados em um único momento, em repouso, e posteriormente submetidas a análise de variância, multivariada (ANOVA), dois por dois, em nível de significância à 95% (p<0,05) e tendência à 90% (p<0.1). Os cães do GP apresentaram maiores valores de diâmetro interno do ventrículo esquerdo ao final da sístole (GP: 2,72 ± 0,09; GS: 2,43 ± 0,09; P<0,034) indicando predomínio isotônico desta atividade. O volume sistólico apresentou-se maior no GP (GP: 28,51 ± 2,20; GS: 22,13 ± 2,17; P<0,049), enquanto o índice de performance miocárdica do ventrículo esquerdo (GP: 0,37 ± 0,03; GS: 0,46 ± 0,03; P<0,028) e o movimento sistólico septal (GP: 0,13 ± 0,01; GS: 0,15 ± 0,01; P<0,044) foram menores em relação ao GS, indicando melhor função cardíaca sisto-diastólica nos cães de pastoreio. Por meio da técnica Ste foi possível observar diminuição dos valores de strain e ou strain rate de alguns segmentos nos cães do GP, nos sentidos radial, circunferencial, longitudinal e transversal em relação ao GS, indicando menor necessidade de deformação miocárdica para a manutenção da função sistólica. Os resultados encontrados indicam que as variáveis ecocardiográficas convencionais (estruturais e funcionais), teciduais e provenientes da técnica STe, foram complementares e fundamentais para a compreensão das adaptações cardiovasculares em cães de pastoreio.
The "athlete's heart" is the term designed to characterize functional and anatomic cardiac adaptations secondary to intense and prolonged physical training in humans and animals. The echocardiogram plays a fundamental role in distinguishing the physiological adaptations secondary to exercise, also, the recent techniques introduced as Speckle Tracking Echocardiography have allowed us to obtain relevant information regarding cardiac function in human athletes. The aim of this study was to evaluate the structure and systolic function of the left ventricle of dogs practicing herding for at least four months, five to six times a week, from four to eight hours a day using echocardiography. For this, 31 dogs were divided into two groups: herding group (GP, n=15) and sedentary group (GS, n=16), evaluated in a single moment, at rest, and then submitted the multivariate analysis of variance (ANOVA), two by two, at the level of significance at 95% (p<0,05) and tendency to 90% (p<0.1). The GP dogs showed higher values of internal diameter of the ventricle at the end of systole (GP: 2,72 ± 0,09; GS: 2,43 ± 0,09; P<0,034), indicating isotonic predominance of this activity. At respect functional adaptations variables, systolic volume was higher in GP (GP: 28,51 ± 2,20; GS: 22,13 ± 2,17; P<0,049), differently from myocardial performance index of the left ventricle (GP: 0,37 ± 0,03; GS: 0,46 ± 0,03; P<0,028) and septal systolic moviment to GS (GP: 0,13 ± 0,01; GS: 0,15 ± 0,01; P<0,044). By means of the Ste technique, it was possible to observe a decrease in the strain and or strain rate values in GP dogs, in the radial, circumferential, longitudinal and transverse directions in relation to GS, indicating a lower need for myocardial deformation to maintain systolic function. The results indicate that the conventional echocardiographic variables (structural and functional) and tissue, obtained by the STe technique, were complementary and essential for the understanding of cardiovascular adaptations in herding dogs.

Desde o primeiro relato a Doença de Chagas permanece endêmica na América Latina com 18 milhões de pessoas cronicamente infectadas e, aproximadamente, 200.000 novos casos por ano. Doença parasitária causada por Trypanosoma cruzi, tem como transmissor \"natural\" da doença um inseto hematófago, o Reduris (barbeiro). Este inseto se torna infectado ao ingerir o sangue de um animal ou indivíduo infectado com o Trypanosoma cruzi. O contágio ocorre basicamente nas áreas rurais nas quais o homem, frequentemente, está em contato com hospedeiros e vetores ao destruir a mata nativa. Apesar da infecção geralmente ocorrer nos primeiros anos de vida, os pacientes infectados podem manifestar os sinais e sintomas da cardiopatia chagásica até 20 anos mais tarde. O custo propriamente dito e o sofrimento humano representados pela Doença de Chagas são grandes. Medicamentos, internações hospitalares frequentes e tratamento com dispositivos de alto custo (ex: marcapasso/ cardiodesfibrilador). Com quadro clínico insidioso, os pacientes podem apresentar insuficiência cardíaca franca, eventos tromboembólicos, arritmias ventriculares, dor torácica atípica e morte súbita. Seu diagnóstico baseia-se em epidemiologia positiva, anamnese, exame físico, alterações eletrocardiográficas, radiológicas e testes sorológicos. O envolvimento cardíaco é a principal causa de morte, sendo que a fisiopatologia e a evolução clínica da doença não são completamente compreendidas e a estratificação de risco permanece um desafio. A presença de disfunção miocárdica associada ou não à doença arterial aterosclerótica vem acompanhada de áreas de fibrose miocárdica e tem se mostrado como importante fator de pior prognóstico. A Ressonância Magnética Cardíaca (RMC) é um método já consagrado na detecção de fibrose miocárdica pela técnica de realce tardio (RT). Os objetivos dessa tese são: 1-Correlacionar o strain miocárdico nos segmentos do ventrículo esquerdo com as áreas de realce tardio detectadas na Ressonância Magnética Cardíaca, 2- Correlacionar o strain global do ventrículo esquerdo avaliado pela técnica de Speckle Tracking com a extensão de fibrose (numero de segmentos) avaliada pela Ressonância Magnética Cardíaca; 3- Comparar a Fração de ejeção avaliada pelo Ecocardiograma bidimensional e a Ressonância Magnética Cardíaca em pacientes com cardiopatia chagásica crônica; 4- Avaliar se existe relação entre a fração de ejeção avaliada pelo ecocardiograma bidimensional e a extensão de fibrose (número de segmentos) pela Ressonância Cardíaca. Foram selecionados 31 pacientes com o diagnóstico confirmado de Doença de Chagas. 27 pacientes que respeitaram os critérios de inclusão e exclusão, e que assinaram o termo de consentimento livre e esclarecido realizaram Ressonância Magnética Cardíaca com a técnica de realce tardio. De todos os pacientes selecionados, 27 completaram o protocolo da RMC e realizaram em sequencia o Ecocardiograma transtorácico para avaliar o strain miocárdico (speckle tracking) em intervalo máximo de 5 dias. Todos que completaram o protocolo não apresentaram efeitos adversos e os exames foram considerados interpretáveis. Para calcular a amostra de pacientes necessária, os cálculos foram feitos pela estatística de teste t, com distribuição t de Student, para comparação entre duas médias, com poder de teste de 80% e nível de significância de 5%, o que resultou numa estimativa de tamanho mínimo de amostra de 22 lesões por grupo (44 lesões) para que seja possível identificar diferenças significativas em todas as regiões numa amostra com medidas de mesmo comportamento que as observadas em Yajima et al e Jitsuo Higaki et al. Com isso, a amostra mínima seria de 22 pacientes. Para avaliar a concordância entre variáveis quantitativas, utilizou-se o coeficiente de concordância de Lin com intervalo de confiança (IC) 95% estimado segundo método Bootstrap. O coeficiente de concordância de Lin (Rc) combinada precisão e acurácia para determinar se observações desviam-se significativamente da linha de perfeita concordância (linha de 45 graus com origem no 0 dos eixos x e y). O coeficiente de Kappa de Cohen com IC 95% foi utilizado em analises de concordância para variáveis categóricas. Valores de p foram calculados utilizando-se método exato. Os critérios de Landis & Koch foram utilizados na interpretação dos coeficientes de concordância, assim definidos: (a) quase-perfeita, para valores de 0,81 a 1,00; (b) substancial, para valores de 0,61 a 0,80; (c) moderada, para valores entre 0,41 e 0,60; (d) regular, para valores entre 0,21 e 0,40; (d) discreta, para valores de 0 a 0,20. As estimações de intervalos de confiança 95% via bootstrap basearam-se em 1000 replicações. Estimativas de sensibilidade, especificidade, valores preditivo positivo e negativo com IC95% foram determinados. Variáveis quantitativas foram comparadas entre 2 grupos independentes utilizando-se testes não-paramétrico de Mann-Whitney com métodos exatos de cálculo do valor-p. Variáveis quantitativas comparadas com Mann-Whitney foram descritas com mediana e intervalo interquartil. Dado o reduzido tamanho de amostra, analise de regressão logística binaria univariada foi conduzida utilizando método exato. Para covariável quantitativa foi testada, a suposição de linearidade com o log-odds no modelo de regressão logística através da construção de \"Smoothed Scatter Plots\". Quando suposição não foi satisfeita, covariável originalmente quantitativa foi dicotomizadas segundo a mediana da distribuição. Odds ratios e seus respectivos intervalos de confiança 95% foram estimados. Analises de correlação entre variáveis quantitativas foram conduzidas utilizando-se coeficiente de correlação de Spearman(rho)(com IC95%). Forte correlação foi definida como |rho| >=0.70; correlação moderada para 0.5 <= |rho| <0.7 ; correlação fraca a moderada para 0.3<= |rho| <0.5; e fraca para |rho| <0.3. Normalidade foi avaliada com a inspeção visual de histogramas e aplicação do teste de normalidade Shapiro-Wilks. Todos os valores de p apresentados são do tipo bilateral: p < 0.05 e 0.05= 55% como normal e <55% alterada, comparamos à extensão de fibrose- numero de segmentos- ( realce tardio) pela CMR. Observou-se uma diferença marginalmente significativa na comparação das medianas do numero de segmentos com realce tardio na CMR entre os 2 grupos (p=0.064). ¹based on exact Mann-Whitney test. Comparamos também a fração de ejeção do ventrículo esquerdo pela RMC e pelo Ecocardiograma transtorácico utilizando o método de Simpson. Ao nível de significância de 5% (coeficiente de Lin), observou-se uma quase perfeita concordância entre FEVE pela Ressonância Magnética Cardíaca e FEVE pelo Ecocardiograma transtorácico utilizando em ambos o método de Simpson. (Rc = 0.9335 IC95% 0.878-0.957; N=27).
Since the first report, Chaga\'s disease remains endemic in Latin America with 18 million chronically infected people and approximately 200,000 new cases per year. Parasitic disease caused by Trypanosoma cruzi, is \"natural\" transmitter disease of a hematophagous insect, the Reduris (barber). This insect becomes infected by ingesting blood of an animal or individual infected with Trypanosoma cruzi. The infection occurs primarily in rural areas where men often are in touch with hosts and vectors by destroying the native forest. Despite the infection usually occurs early in life, infected patients may exhibit signs and symptoms of Chagas disease 20 years later. The cost itself and human suffering represented by Chagas disease are a public issue. Medication, frequent hospitalization and treatment with costly devices (eg pacemaker / defibrillator) are frequently necessary. With insidious clinical signs and symptons, patients may present with heart failure, thromboembolic events, ventricular arrhythmias, atypical chest pain and sudden death. Its diagnosis is based on positive epidemiology, history, physical examination, electrocardiographic, radiological and serological changes. Cardiac involvement is the leading cause of death, and the pathophysiology and clinical course of the disease are not fully understood and the risk stratification remains a challenge. The presence of myocardial dysfunction with or without atherosclerotic arterial disease is accompanied by myocardial fibrosis areas and has been an important factor of poor prognosis. Cardiac Magnetic Resonance (CMR) is a method already established in the detection of myocardial fibrosis by delayed gadolinium enhancement technique (DGE). The objectives of this thesis are: 1-To correlate myocardial strain in left ventricular segments with areas of late enhancement detected in Cardiac Magnetic Resonance, 2- correlate the global left ventricular strain measured by Speckle Tracking technique with fibrosis extension (number of segments) evaluated by Cardiac Magnetic Resonance; 3- Compare the ejection fraction assessed by Two-dimensional echocardiography and cardiac Magnetic Resonance in patients with chronic cardiac Chagas\' disease; 4- To assess whether there is a relationship between the ejection fraction assessed by two-dimensional echocardiography and fibrosis extension (number of segments) by CMR. We selected 31 patients with confirmed diagnosis of Chagas\' disease. 27 patients who complied with the inclusion and exclusion criteria, and who signed the informed consent , performed Cardiac Magnetic Resonance with late gadolinium enhancement (DGE) technique. Of all the selected patients, 27 completed the RMC protocol and were in sequence directed to the transthoracic echocardiogram to assess myocardial strain (speckle tracking) in maximum interval of 5 days. Everyone who completed the protocol showed no adverse effects and the tests were considered interpretable. To calculate the sample required patients, we used the test statistic t, with t Student distribution for comparison between two averages, with the power to test 80% and 5% significance level, which resulted in an estimate minimum sample of 22 injuries per group size (44 injuries) so you can identify significant differences in all regions in a sample with the same measures of behavior than those observed in Yajima et al and Jitsuo Higaki et al. Thus, the minimum sample size would be 22 patients. To evaluate the correlation between quantitative variables, we used the Lin\'s concordance coefficient (1,2) with a confidence interval (CI) 95% estimated second method Bootstrap (4). The correlation coefficient Lin (Rc) combines precision and accuracy to determine if observations deviate significantly from perfect correlation line (45 degree line with origin 0 of the x and y axes). Cohen\'s kappa coefficient with 95% (3) was used for analysis of agreement for categorical variables. P values were calculated using the exact method. The Landis and Koch criteria (5) were used in the interpretation of correlation coefficients defined as follows: (a) quasi-perfect for values 0.81 to 1.00; (b) substantial amounts of 0.61 to the 0.80; (c) Moderate to values between 0.41 and 0.60; (d) regular, to between 0.21 and 0.40; (d) mild to values from 0 to 0.20. The estimation of 95% confidence intervals by bootstrap based on 1000 replicates. Quantitative variables were compared between two independent groups using non-parametric Mann-Whitney test with exact methods of calculating the p-value. (6-8) Quantitative variables compared with Mann-Whitney were described as median and interquartile range. Given the small sample size, regression analysis univariate binary logistic regression was conducted using exact method (9-11). For quantitative covariate was tested, the linearity assumption with the log-odds in the logistic regression model by building \"Smoothed Scatter Plots\". (9) When assumption was not met, originally quantitative covariate was dichotomized according to the median of the distribution. Odds ratios and their 95% confidence intervals were estimated. All significance probabilities (p values) presented are the bilateral type and values less than 0.05 considered statistically significant. The R (R Foundation, Vienna, Austria) software was used for statistical analysis of data. In order to measure the correlation between the results of both tests in the study were calculated sensitivity, specificity, positive predictive value and negative predictive value considering the CMR as the gold standard. Results: Of the 27 study patients have a average age of 53.1 + - 7.0 years and median of 54 years. 08 (29.7%) men and 19 (70.3%) women. The average ejection fraction by echocardiography was 55.1 + - 14.7%, and by Cardiac Magnetic Resonance was 55.8 + - 13.4%. The total number of evaluated segments was 453 (98.7%), with no interpretation performed in only 6 segments (1.3%) on echocardiography, a total of 459 segments. Delayed enhancement by Cardiac Magnetic Ressonance was found in 61 segments analyzed. In the order \"side\" 86 segmets registered an altered strain. As the gold standard the delayed enhancement in the MRC, compared to segment studied segment. We take into account the literature describing the prevalence of fibrosis in patients with chronic Chagas\' heart disease of approximately 40%. With this data we obtained a sensitivity of 95%, specificity 91%, positive predictive value of 88.6% and a negative predictive value of 96.6%. Correlating the Global Longitudinal Strain (SGL) and extent (number of segments with delayed enhancement by CMR) of fibrosis in this study, no difference was observed in the number of segments of medians in the CMR compared between Strain Global Longitudinal groups - Normal x changed (p = 0.287, exact Mann-Whitney). Using as an ejection fraction of the left ventricle limits > = 55% as normal and < 55% changed, compared to the extent of fibrose- number of segments- (delayed enhancement) by CMR. There was a marginally significant difference when comparing the median number of segments with delayed enhancement on CMR between the 2 groups (p = 0.064). ¹based on exact Mann-Whitney test. We also compared the ejection fraction of the left ventricle by CMR and transthoracic echocardiography using the Simpson method. At a significance level of 5% (Lin coefficient), there was an almost perfect correlation between LVEF by Cardiac Magnetic Resonance and LVEF by using transthoracic echocardiography in both the Simpson method. (Rc = 0.9335 95% CI 0878-0957; N = 27)

Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

Lors de la systole, le ventricule gauche (VG) se déforme suite à la contraction des cardiomyocytes. De part l’orientation en spirale des fibres myocardiques, ces déformations incluent un mouvement de torsion, la base et l’apex du VG tournant dans des sens opposés. L’emmagasinement d’énergie élastique par ce mécanisme et surtout sa restitution très précoce en début de diastole jouent un rôle clé dans le remplissage ventriculaire gauche. Les objectifs de ce travail ont été d’étudier les adaptations mécaniques ventriculaires gauche en se focalisant sur le rôle de la torsion 1) lors d’un exercice d’intensité croissante chez le sujet sédentaire jeune, 2) suite à l’entrainement aérobie au repos et lors d’un exercice d’intensité croissante et, 3) concomitantes aux dysfonctions cardiaques observées après un exercice épuisant de longue durée. Pour cela, nous avons effectué des échocardiographies au repos et/ou lors d’épreuves d’effort d’intensité croissante en incluant l’utilisation d’un nouvel outil échocardiographique basé sur le "speckle tracking" (STE). Nos résultats soulignent le rôle clé de la torsion dans le couplage systole – diastole à l’effort. De plus, nos résultats montrent une modification des adaptations mécaniques ventriculaires gauche à l’effort en parallèle à l’amélioration de la fonction diastolique chez les sportifs entrainés en endurance aérobie. Enfin, la dysfonction ventriculaire gauche transitoire observée après un exercice épuisant de longue durée est caractérisée par une diminution et un décalage dans le temps de la torsion, limitant probablement la diminution précoce des pressions intraventriculaires gauche et donc le remplissage. L’ensemble de ces résultats mettent en évidence, d’une part, l’intérêt de l’évaluation par STE de la mécanique ventriculaire gauche au repos et à l’effort, et d’autre part le rôle clé du mécanisme de torsion – détorsion dans l’explication de fonctions diastoliques améliorées ou altérées
During systole, contraction of cardiomyocytes induces left ventricular (LV) strains. Moreover, the helical orientation of myofibers induces LV torsion consequently to LV basal and apical rotations. LV torsion stores energy in elastic component that is released very early in diastole and constitutes a key factor of LV filling. The aims of this thesis were to characterize LV mechanicals adaptations focussing on the role of LV torsion 1) during a progressive exercise test in healthy sedentary subjects, 2) induced by aerobic training at rest and during a progressive exercise test and, 3) concomitant with cardiac dysfunctions after prolonged and strenuous exercise. We used a novel echocardiographic tool, based on Speckle Tracking (STE), in order to evaluate LV function at rest and/or during a progressive exercise test. Our results underlined the key role of LV torsion in systolic – diastolic coupling during exercise. Moreover, our results showed an alteration of LV mechanical adaptation paralleling the enhancement of diastolic function during effort in aerobic trained subjects. At last, transient LV dysfunction after prolonged and strenuous exercise was associated with decreased and delayed LV torsion, probably limiting the early drop of LV intraventricular pressures and thus LV filling. All together, these results underlined the usefulness to evaluate LV mechanics at rest and during effort by STE, and point out the key role of twisting – untwisting mechanism in improved or depressed LV diastolic function

Bakgrund: Ekokardiografi har en betydande roll i diagnostisering av vänster kammare. Genom undersökning av segmentell och global longitudinell strain samt strain rate kan regional och global kinetik bedömas. Vid kontraktion och relaxation deformeras myokardiet varvid segmentell strain mäter deformationen av respektive segment uttryckt i procent medan strain rate mäter hastigheten av deformationen. Genom summering av medelvärdet från alla segment erhålls global longitudinell strain. Syfte: Syftet med studien var att jämföra ultraljudbaserade segmentell och global strain samt strain rate i vänster kammare. Jämförelse har gjorts mellan mätningar utförd av erfaren biomedicinsk analytiker samt mindre erfarna biomedicinska analytikerstudenter. Metod: Kvantitativ studie där 10 testpersoner undersökts ekokardiografiskt. Bildtagningen och mätresultaten insamlades med Siemens Acuson SC2000. Sammanställning av insamlade mätvärden gjordes på Microsoft Excel och Microsoft Word i diagram och tabeller. För jämförelse av strain segmentellt och globalt samt strain rate har analysmetoden Related-Samples Wilcoxon Signed Rank Test använts. Resultat: Resultatet visade enbart en statistisk signifikant skillnad (p <0,05) vid segmentell strain i basala segmenten i apikala projektioner mellan erfaren biomedicinsk analytiker och student 1. Konklusion: Datamaterialet är inte tillräckligt för att kunna generalisera resultatet till en större population. Det behövs fortsatta studier inom området för att dra en mer säkerställd slutsats.
Background: Echocardiography has a major role for assessment of the left ventricle. By using segmental and global longitudinal strain and strain rate both regional and global kinetics can be assessed. Segmental strain measures deformation of the myocardium as strain rate measures the velocity of the deformation. By summing the average from all segments, global longitudinal strain is obtained. Purpose:  To compare heart ultrasound-based segmental and global strain and strain rate in the left ventricle. Comparisons have been made between experienced biomedical laboratory scientist and less experienced biomedical laboratory scientist’s students. Method: Quantitative study were 10 test subjects have been examined echocardiographically. Imaging and measurements were collected with Siemens Acuson SC2000. Compilation of collected measurements were made on Microsoft Excel and Microsoft Word in charts and tables. For comparison of segmental and global strain and strain rate the analysis method Related-Samples Wilcoxon Signed Rank Test were used. Result: The result shows only one statistically significant difference (p <0.05) of segmental strain in the basal segments of apical projections between experienced biomedical laboratory scientist and student 1.  Conclusion: The data material is not enough to generalize the result to a larger population. Further studies are needed to draw a more secure conclusion.

Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome. Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient >40mmHg or valve area <1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) <50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients. Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p<0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p< 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p<0.001), presence of restrictive LV filling (p<0.001), raised PSPAP (p<0.001) and CABG (p=0.037). However, only EF<40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p<0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p<0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p<0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p<0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p<0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p<0.001 for both). LVEF increased (from 45±1 to 54±2%;p<0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p<0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p<0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index<=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p<0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p<0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p<0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p<0.001). Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.

Background:Left ventricular function is particularly important to investigate since it has prognostic significance in some heart diseases such as aortic stenosis. One of the relatively new methods to evaluate this is deformation analysis that can produce a measure of global longitudinal strain with speckle-tracking.  Objective:The objective was to examine the possibility of measuring left ventricular longitudinal function in patients with aortic stenosis from ECG-gated computed tomography images with the new software Segment CT and investigate prevalence of its reduction. Additionally, a second objective was to evaluate the feasibility of global longitudinal strain analysis from ECG-gated computed tomography in comparison with echocardiography and ejection fraction in a subset of patients.  Material and methods:This study included 97 patients with severe aortic stenosis who underwent evaluation before planned treatment with transcatheter aortic valve implantation during 2016-2017 at Uppsala Hospital. Global strain was calculated from ECG-gated computed tomography and echocardiography with dedicated software. Results:Left ventricular function measured by global strain was impaired in all patients while ejection fraction was decreased in 31 %. Mean global longitudinal strain by ECG-gated computed tomography was -6.46±3.51 % and by echocardiography -10.69±4.23 %. The mean difference between the methods was 4.23 %, which was statistically significant (p=0.02) while the correlation was good (r=0.74). Conclusions:The strain analysis of ECG-gated computed tomography images was successful in less than a half of the patients. The results of the two methods showed good correlation but not agreement, further research is thus needed with a higher number of patients.

he thesis deals with proposal of an algorithm and implementation of a program that tracks a motion of the heart muscle in the captured ultrasound video of the heart. The point position estimation is calculated by optical flow method. The Active Shape Model method is used to confirm the accuracy of point's position tracking. The user annotates desired structure of the heart arch first and the application displays new points which represent a new deformed heart shape.

L'activité physique régulière est bénéfique pour la santé cardiovasculaire. Cependant, destravaux ont rapporté des dysfonctions cardiaques après des exercices physiques prolongés (EPP) tels que les marathons ou les triathlons longue distance type "Ironman". Ces dysfonctions sont souvent associées à des dommages myocardiques. Récemment, des études échocardiographiques ont suggéré que ces dysfonctions étaient associées à des baisses de contractilité et de relaxation myocardiques.Toutefois, l'atteinte myocardique après un EPP reste à ce jour controversée et les mécanismes sousjacents de ces dysfonctions demeurent inconnus. Dans ce contexte, le but de ce travail de doctorat a été de vérifier la diminution de contractilité et/ou de relaxation du myocarde après un EPP ii) d'évaluer l'implication de la voie ß-adrénergique et du stress oxydant dans l'altération de la fonction cardiaque.Pour cela, une première approche clinique, basée sur l'utilisation de l'échocardiographie cardiaque haute résolution (et plus particulièrement une technique de pointe, le "Speckle TrackingEchocardiography") nous a permis d'appréhender la fonction myocardique par l'intermédiaire de l'évaluation des déformations et de la torsion du ventricule gauche pendant le cycle cardiaque. Une deuxième approche fondamentale, chez l'animal, nous a permis d'évaluer la fonction cardiaque après un EPP chez le rat au niveau de l'organe entier et de l'organe isolé dans des conditions basale et de stress (ß-adrénergique). Des investigations complémentaires ont été réalisées sur le tissu myocardique pour évaluer le stress oxydant (GSH/GSSG, MDA) et des marqueurs de dommages cellulaires cardiaques (troponines I) après avoir bloqué la NAD(P)H oxydase (Nox), enzyme fortement impliquée dans la production d'espèces réactives dérivées de l'oxygène au niveau cardiaque. Les résultats de ces travaux montrent clairement, chez l'Homme et l'animal, des baisses de contractilité et de relaxation myocardiques associées à une augmentation des marqueurs de dommages cellulaires cardiaques après un EPP. Alors que la voie ß-adrénergique ne semble pas être impliquée dans ces dysfonctions, nos résultats indiquent que le stress oxydant joue un rôle majeur, puisque lorsque la Nox est bloquée, la fonction cardiaque est majoritairement restaurée après l'EPP.

Background: Coarctation of the aorta (CoA) is a congenital heart disease which represents a narrowing of the proximal descending aorta, hence increasing pressure afterload to the left ventricle (LV). Conventional treatment of native CoA is surgical repair, however potential recurrence or other related complications e.g. aortic rupture, heart failure and cerebrovascular events are common. Thus, lifelong follow-up of these patients is required. Echocardiography is the most patient’s friendly method to evaluate CoA and in particular its effect on LV function. Moreover, the novel speckle tracking echocardiography (STE) is an important method to assess subclinical LV dysfunction, a technique that promises better evaluation of LV function in these patients. The aims of this thesis were to review the literature on LV function in children with CoA using myocardial deformation imaging technologies, hence, to better understand the current knowledge and vagueness of the scientific evidence. We also aimed to study the effect of early CoA repair on the structure and function of LV and ascending aorta. In addition, we wished to establish in a meta-analysis format normal values of speckle tracking derived strain and strain rate values. Methods: Study 1. We have systematically searched the PubMed, and studies that fulfilled the inclusion criteria were critically analyzed and presented on a narrative form. Study 2 and 3. In addition to conventional echocardiographic measures of LV and ascending aorta, we measured longitudinal strain and strain rate of the LV using a vendor independent software, TomTec. We have also measured the aorto-septal angle (AoSA). Data was compared with normal healthy controls. Study 4. Electronic databases were systematically searched and suitable studies were meta analyzed using Comprehensive meta-analysis version 3 software. Results: Study 1. In 7/4945 included articles, 123 and 76 patients with congenital aortic stenosis (CAS) and CoA were reported, respectively. Normal conventional LV function, with subclinical myocardial dysfunction were reported in all studies before intervention. After intervention, a consistent improvement of myocardial deformation parameters was documented, even though not reaching normal values. Study 2. In 21 patients with CoA, LV function significantly improved after intervention (p <0.001), however normal values were not reached even at medium-term follow-up (p = 0.002). Medium-term longitudinal strain correlated with pre intervention LV ejection faction (EF) (r = 0.58, p = 0.006). Medium-term subnormal values were more frequently associated with Bicuspid aortic valve (BAV) (33.3% vs. 66.6%; p <0.05). Study 3. AoSA was abnormally wide before intervention, in particular at peak ejection in the descending aorta (p <0.0001), and correlated with CoA pressure gradient. After intervention, AoSA normalized and significantly correlated with the increase of LV cavity function and overall LV deformation parameters. Study 4. In a meta-analysis of 28/282 studies including 1192 subjects, strain and strain rate values were established. Longitudinal strain normal mean values varied from -12.9 to -26.5 (mean, -20.5; 95 % CI, -20.0 to -21.0). Normal mean values of circumferential strain varied from -10.5 to -27.0 (mean, -22.06; 95 % CI, -21.5 to -22.5). Radial strain normal mean values varied from 24.9 to 62.1 (mean, 45.4; 95 % CI, 43.0 to 47.8). Meta-regression showed LV end-diastolic diameter as a significant determinant of variation of longitudinal strain. Longitudinal systolic strain rate was significantly determined by age and radial strain was influenced by the type of vendor used. Conclusion: The systematic review showed subclinical LV dysfunction in children with CoA before and after correction. However, since most of the patients were operated at an older age and had preserved LV EF, the effect of early intervention on LV function was only speculated. Our children with CoA who were operated at an earlier age showed LV subclinical dysfunction even at medium- term after intervention while the AoSA returned to normal shortly after intervention. Lower longitudinal strain values were found in patients with LV dysfunction (LV EF <50%) before intervention and BAV. Finally, normal range values for strain and strain rate have been established and seem to be influenced by patients’ age, LV end-diastolic diameter and vendor used.

The general purpose of this thesis is to establish capability and accuracy of speckle tracking echocardiography (STE) in assessing left atrial (LA), left ventricular (LV) and right ventricular (RV) function and their correlation with myocardial fibrosis, filling pressure and clinical outcomes in advanced heart failure (HF) patients before and after heart transplantation (HT). I demonstrated that HT recipients had impaired LV twist dynamics in the form of reduced rotation twist angle and untwist rate but time to peak twist was not different from the age matched controls and other cardiac surgical patients. With a longitudinal study conducted on patients with refractory HF, the best prognostic power has been shown by RV strain analysis. Among the indexes of LV function, the LV ejection fraction (LVEF) demonstrated the lowest diagnostic accuracy; instead LV global circumferential strain (GCS) showed a better sensitivity and specificity than LV global longitudinal strain (GLS). When analyzing the relationship between different severity of myocardial fibrosis and LV cavity function, the strongest function parameter that correlated with severity of myocardial fibrosis was GLS. In contrast, none of diastolic LV function or even measures of exercise capacity correlated with myocardial fibrosis. In patients with end-stage HF, global peak atrial longitudinal strain (PALS), an index of atrial reservoir function was dependent by pulmonary capillary wedge pressure (PCWP) and LV fibrosis, but not influenced by LV systolic function. Results from this study confirm previous evidence of correlation between impaired global PALS and increased PCWP.

La radiothérapie (RT), traitement adjuvant du cancer du sein, est associée à un risque accru de pathologies cardiovasculaires plusieurs années post-RT. L'identification de signes précoces de cardiotoxicité et la mise en évidence de leurs liens avec la dose de rayonnements ionisants absorbée par le cœur pourraient favoriser la prédiction de la survenue de pathologies cardiovasculaires et améliorer la prévention chez les patientes à risque.Cette thèse s’appuie sur la cohorte BACCARAT constituée d’une centaine de patientes traitées par RT du sein, sans chimiothérapie et suivies jusqu’à 24 mois post-RT. Une reconstitution individuelle des doses absorbées par le cœur, le ventricule gauche (VG) et les artères coronaires a été réalisée.Les signes précoces de cardiotoxicité sont définis par la quantification des dysfonctions cardiaques infracliniques mesurées par échocardiographies et par la mesure de l’évolution des concentrations d’un panel de biomarqueurs circulants potentiellement impliqués dans la cardiotoxicité.Avec un suivi de 6 mois, l’analyse des données a permis de montrer une relation dose-réponse entre une dysfonction ventriculaire gauche infraclinique caractérisée par une diminution >10% de l’indice de contractilité myocardique (longitudinal strain) et la dose moyenne absorbée par le VG. L’ajout de la mesure de l’altération précoce en fin de RT du taux de fibrinogène à la dose au VG permettait une amélioration de la prédiction du risque
Radiation therapy (RT), an adjuvant treatment for breast cancer, is associated with an increased risk of cardiovascular disease several years after RT. Identifying early signs of cardiotoxicity and their relationship to the dose of ionizing radiation absorbed by the heart could help predict the occurrence of cardiovascular disease and improve prevention in patients at risk.This thesis is based on the BACCARAT cohort that included a hundred of patients treated with breast RT without chemotherapy and followed during 24 months post-RT. An individual reconstitution of the doses absorbed by the heart, the left ventricle (LV) and the coronary arteries was performed.Early signs of cardiotoxicity were defined by subclinical cardiac dysfunctions evaluated by echocardiography and by changes in the concentrations of a panel of circulating biomarkers potentially involved in cardiotoxicity.With an intermediate follow-up of 6 months, the analysis of data showed a dose-response relationship between subclinical left ventricular dysfunction characterized by a >10% decrease in the myocardial contractility index (longitudinal strain) and the average dose absorbed by the LV. The alteration of fibrinogen levels at the end of RT, combined with the LV dose, improved risk prediction (based on longitudinal strain)

L’athlète entrainé est un modèle physiologique d’adaptation cardiaque extrême où il est parfois difficile de faire la distinction entre le remodelage cardiaque adaptatif induit par l’exercice physique et certaines cardiomyopathies débutantes. L’échocardiographie est l’examen d’imagerie de premier choix pour l’étude du cœur d’athlète au repos et à l’effort. Les développements semi-récents du speckle tracking et de l’imagerie tridimensionnelle (3D) ont montré un intérêt clinique dans la description de la réponse cardiaque à l’exercice. Toutefois certains aspects techniques nécessitent d’être investigués. De plus, les outils de post-traitement actuels ne permettent qu’une évaluation incomplète de l’hémodynamique cardiaque et de l’analyse morphofonctionnelle régionale. Dans un premier temps, à l’aide d’un modèle expérimental mimant l’échocardiographie de stress, nous avons démontré la validité du speckle tracking pour l’étude de la déformation régionale dans une large gamme de fréquences de déformation en comparaison à la technique de référence par sonomicrométrie. Secondairement, nous avons étudié chez des sujets volontaires sans cardiopathie avérée (athlètes et non athlètes) une méthode de quantification non invasive des gradients de pressions intraventriculaires (GPIVs) pour l’évaluation de la fonction systolique et diastolique ventriculaire gauche (VG), qui est basée sur le post-traitement des données de vitesses de flux intra cavitaires acquises en mode TM Doppler couleur. Nous avons montré que cet indice hémodynamique était facilement accessible, et bien corrélé au mécanisme de succion VG. L’analyse des mesures de GPIVs a mis en évidence une variabilité inter-constructeur qui était principalement liée aux différences de résolution de l’image Doppler couleur. Enfin, en utilisant une approche échocardiographique multiparamétrique (speckle tracking, GPIV, et volumes 3D), nous nous sommes intéressés à caractériser la relation physiologique entre le type d’entrainement physique et le remodelage cardiaque gauche et droit au sein d’une équipe de footballeurs canadiens suivie de manière longitudinale. L’analyse régionale des modifications morphologiques et fonctionnelles du ventricule droit (VD) induites par l’exercice chronique a été réalisée à l’aide d’un nouvel algorithme de post- traitement des acquisitions 3D permettant une segmentation tripartite (apex, chambre d’admission, chambre d’éjection) des volumes VD en échocardiographie. En conclusion, les outils de post-traitement échocardiographique étudiés dans ce travail pour l’analyse globale et régionale de la fonction et de la morphologie cardiaques semblent applicables au cœur d’athlète et pourraient avoir un intérêt dans la caractérisation du remodelage cardiaque physiologique à l’exercice
The trained athlete is a physiological model of extreme cardiac adaptation for whom the distinction between adaptive cardiac remodeling induced by chronic exercise and certain early cardiomyopathies can be difficult to assess. Echocardiography is the first-choice imaging modality to evaluate the athlete’s heart at rest and during exercise. Semi-recent developments in speckle tracking and 3D ultrasound imaging have shown clinical interest in the echocardiographic description of the athlete’s heart. However, some technical aspects require further investigation. Moreover, current post-treatment tools provide only a partial analysis of cardiac hemodynamics and regional myocardial function. Using an experimental model mimicking stress echocardiography, we first demonstrated the validity of speckle tracking in comparison to sonomicrometry to measure regional deformation in a large range of deformation rates. Secondly, we studied in volunteers without heart disease (athletes and non- athletes) the reliability of a method to assess non-invasively the left ventricular (LV) systolic and diastolic intraventricular pressure gradients (IVPGs) based on post-processing of intracardiac flow velocity data acquired using color Doppler M-mode. This hemodynamic index was highly feasible and well correlated with LV suction. Analysis of IVPG measurements revealed inter-vendor variability which was mainly related to differences in color Doppler image resolution. Finally, using a multiparametric echocardiographic approach (speckle tracking, IVPGs, and 3D volumes), we studied the physiological relationship between the type of exercise training and the left and right cardiac remodeling among a Canadian football team followed longitudinally. The regional analysis of right ventricular (RV) morphological and functional changes induced by chronic exercise was performed using a new computational method based on 3D echocardiography that volumetrically parcellated the RV into three segments (apex, outlet, and inlet). In conclusion, our workhas shown that the echocardiographic post-processing tools studied for the global and regional analysis of cardiac function and morphology apply to the athlete’s heart and could be useful in the characterization of the exercise-induced cardiac remodeling

Le diabète est aujourd’hui la 7ème cause de mortalité dans le monde. Dans cette population, la cardiomyopathie diabétique est la principale cause de morbi-mortalité. Le développement de cette complication débutant dès l’apparition du diabète, un dépistage et une prise en charge précoces de cette pathologie sont donc de première importance et sont les deux objectifs visés par ces travaux. La première étude que nous avons réalisée a permis de démontrer l’utilité d’une évaluation compréhensive de la fonction régionale myocardique gauche par 2D speckle-tracking imaging, en conditions de stress à la dobutamine, dans le dépistage précoce de la cardiomyopathie diabétique chez des patients diabétiques de type 2 asymptomatiques. La deuxième partie de ces travaux a, quant à elle, donné lieu à deux études. L’étude clinique a permis de mettre en évidence une amélioration de la réponse au stress de la fonction régionale myocardique après 3 mois de supplémentation en vitamine D3 chez des patients carencés. L’étude expérimentale a, pour sa part, souligné les effets bénéfiques sur le remodelage et la fonction cardiaques de cette supplémentation, en prévention secondaire, dans un modèle murin de diabète de type 2 induit par un régime gras et sucré. Par ailleurs, cette étude a mis en lumière l’implication potentielle d’une modulation des taux myocardiques en espèces lipotoxiques par la vitamine D3 dans ces effets. L’ensemble de ces travaux de thèse a ainsi permis, d’une part, de proposer une technique de dépistage des signes précoces d’altération de la fonction cardiaque chez le patient diabétique de type 2 et, d’autre part, de montrer les effets bénéfiques d’une supplémentation en vitamine D3 dans ce contexte
Diabetes has reached the 7th place in the world’s top ten mortality causes. In this population, morbi-mortality mainly originates from diabetic cardiomyopathy. This complication evolving from the onset of diabetes, early diagnosis and care are of paramount importance and are the two purposes of this work. In our first study, we demonstrated the relevance of a comprehensive 2D speckle-tracking imaging analysis, under dobutamine stress, in unmasking early left ventricular regional myocardial dysfunction in a population of asymptomatic type 2 diabetic patients. In the second part of this work, we performed two studies. In the first one, we brought to light an improvement of regional myocardial function response to dobutamine stress after a three-month vitamin D3 supplementation protocol, in deficient patients. The second study was performed in a mouse model of diet-induced type 2 diabetes. In this last work, we put forward the beneficial effects of vitamin D3 supplementation, in secondary prevention, on cardiac remodeling and function. These cardioprotective effects may be, at least in part, on account of modulatory effects of vitamin D3 on myocardial lipotoxic species levels. This whole work allow us to propose a tool enabling recognition of early cardiac function impairments in type 2 diabetic patients and to demonstrate the beneficial effects of vitamin D3 supplementation in this context