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1
Schlenker, E. H., and M. Goldman. "Aspartic acid administered neonatally affects ventilation of male and female rats differently." Journal of Applied Physiology 61, no. 2 (August 1, 1986): 780–84. http://dx.doi.org/10.1152/jappl.1986.61.2.780.
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In this study ventilation was evaluated in 12-mo-old male and female rats who had received large doses of aspartic acid neonatally. Rats of both sexes treated with aspartic acid were obese, stunted, and exhibited hypogonadism. Although metabolic rates of the aspartic acid-treated rats were not different compared with sex-matched controls, ventilatory patterns were different. Aspartic acid-treated females breathed with a smaller tidal volume (VT), higher frequency (f), and similar minute ventilation (VE) compared with control females. This pattern is commonly observed in many patients who are obese. The aspartic acid-treated females responded to hypercapnic and hypoxic challenges by increasing f more than VT. Tissue pocket gases (PCO2 and PO2) of aspartic acid-treated females were normal. In contrast, aspartic acid-treated males hypoventilated compared with control males. Tissue pocket gas values suggested that aspartic acid-treated males were hypoxemic and hypercapnic. Moreover, the response of aspartic acid-treated males to hypercapnia was parallel to but was less than that of control male rats. The ventilatory response of aspartic acid-treated male rats to hypoxia was blunted. This study has shown that neonatal administration of aspartic acid causes a decreased ventilation and blunted response to hypoxia in adult male but not female rats.
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Pandit, Paresh B., Kee H. Pyon, Sherry E. Courtney, Sandra E. England, and Robert H. Habib. "Lung resistance and elastance in spontaneously breathing preterm infants: effects of breathing pattern and demographics." Journal of Applied Physiology 88, no. 3 (March 1, 2000): 997–1005. http://dx.doi.org/10.1152/jappl.2000.88.3.997.
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Reported values of lung resistance (Rl) and elastance (El) in spontaneously breathing preterm neonates vary widely. We hypothesized that this variability in lung properties can be largely explained by both inter- and intrasubject variability in breathing pattern and demographics. Thirty-three neonates receiving nasal continuous positive airway pressure [weight 606–1,792 g, gestational age (GA) of 25–33 wk, 2–49 days old] were studied. Transpulmonary pressure was measured by esophageal manometry and airway flow by face mask pneumotachography. Breath-to-breath changes in Rl and El in each infant were estimated by Fourier analysis of impedance (Z) and by multiple linear regression (MLR). Rl MLR (Rl MLR = 0.85 × Rl Z −0.43; r 2= 0.95) and El MLR(El MLR = 0.97 × El Z + 8.4; r 2 = 0.98) were highly correlated to Rl Z and El Z, respectively. Both Rl(mean ± SD; Rl Z = 70 ± 38, Rl MLR = 59 ± 36 cmH2O ⋅ s ⋅ l−1) and El (El Z = 434 ± 212, El MLR = 436 ± 210 cmH2O/l) exhibited wide intra- and intersubject variability. Regardless of computation method, Rl was found to decrease as a function of weight, age, respiratory rate (RR), and tidal volume (Vt) whereas it increased as a function of RR ⋅ Vt and inspiratory-to-expiratory time ratio (Ti/Te). El decreased with increasing weight, age, Vt and female gender and increased as RR and Ti/Te increased. We conclude that accounting for the effects of breathing pattern variability and demographic parameters on estimates of Rland El is essential if they are to be of clinical value. Multivariate statistical models of Rl and Elmay facilitate the interpretation of lung mechanics measurements in spontaneously breathing infants.
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van Campen, C. (Linda) M. C., and Frans C. Visser. "Female Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome or Idiopathic Chronic Fatigue: Comparison of Responses to a Two-Day Cardiopulmonary Exercise Testing Protocol." Healthcare 9, no. 6 (June 5, 2021): 682. http://dx.doi.org/10.3390/healthcare9060682.
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Introduction: Multiple studies have shown that peak oxygen consumption is reduced in the majority of ME/CFS patients, using the golden standard for measuring exercise intolerance: cardiopulmonary exercise testing (CPET). A 2-day CPET protocol has shown different results on day 2 in ME/CFS patients compared to sedentary controls. No comparison is known between ME/CFS and idiopathic chronic fatigue (ICF) for 2-day CPET protocols. We compared ME/CFS patients with patients with chronic fatigue who did not fulfil the ME/CFS criteria in a male population and hypothesized a different pattern of response would be present during the 2nd day CPET. Methods: Fifty-one female patients with ICF completed a 2-day CPET protocol and were compared to an age/sex-matched group of 50 female ME/CFS patients. Measures of oxygen consumption (VO2), heart rate (HR), systolic and diastolic blood pressure, workload (Work), and respiratory exchange ratio (RER) were collected at maximal (peak) and ventilatory threshold (VT) intensities. Results: Baseline characteristics for both groups were similar for age, BMI, BSA, and disease duration. A significance difference was present in the number of patients with fibromyalgia (seven ME/CFS patients vs zero ICF patients). Heart rate at rest and the RER did not differ significantly between CPET 1 and CPET 2. All other CPET parameters at the ventilatory threshold and maximum exercise differed significantly (p-value between 0.002 and <0.0001). ME/CFS patients showed a deterioration of performance on CPET2 as reflected by VO2 and workload at peak exercise and ventilatory threshold, whereas ICF patients showed improved performance on CPET2 with no significant change in peak workload. Conclusion: This study confirms that female ME/CFS patients have a reduction in exercise capacity in response to a second day CPET. These results are similar to published results in female ME/CFS populations. Patients diagnosed with ICF show a different response on day 2, more similar to sedentary and healthy controls.
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Pintao, Maria Carolina, Irene D. Bezemer, Andrea Aparecida Garcia, Marieke C. H. de Visser, Carine J. M. Doggen, Pieter H. Reitsma, and Frits Rosendaal. "Copy Number Variation of PROS1 and Protein S Deficiency Are Rare in a Population-Based Case-Control Study On Venous Thrombosis (MEGA study)." Blood 114, no. 22 (November 20, 2009): 3166. http://dx.doi.org/10.1182/blood.v114.22.3166.3166.
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Abstract Abstract 3166 Poster Board III-106 Protein S (PS) deficiency increases the risk of venous thrombosis (VT) in family studies, but it has been difficult to estimate the risk in population-based studies. Moreover, the genetic basis of PS deficiency is only poorly understood as in about 50% of PS deficient families no mutations are found by exon-targeted sequencing of the PS gene PROS1. Further, the laboratory diagnosis of PS deficiency is complicated by physiological variation due to age and sex, as well as interference by pregnancy, use of hormones and medication and vitamin K deficiency. We recently showed with the multiplex ligation-dependent probe amplification (MLPA) methodology, that whole or partial deletion of PROS1 explained PS deficiency in around 40% of point mutation-negative French PS deficient families. Here, we analyzed PS deficiency in the MEGA (Multiple Environmental and Genetic Assessment) study to verify whether gross gene deletions or duplications are also common in unselected individuals with venous thrombosis. The MEGA study included 5000 patients with a first episode of deep VT or pulmonary embolism and 5000 controls. Questionnaires and DNA samples were taken for every participant and blood was collected in around half of patients and controls. Total PS (tPS) was measured in plasma by ELISA. For analysis, vitamin K users were excluded yielding 2198 patients and 2904 controls. The mean tPS (±SD) was 102.6 U/dL (±19.1) in patients and 100.8 U/dL (±19.7) in controls. OR and 95% confidence interval were computed to estimate the relative risk of thrombosis. PS was not a risk factor for thrombosis in the MEGA study when deciles were used to calculate OR neither when lowest 2.5% or 1% PS levels was examined (data not shown). We then randomly analyzed DNA samples from 2270 participants out of 10000 individuals (1395 patients and 875 controls) by MLPA to look for copy number variations (CNVs). In only one individual an abnormal MLPA pattern was found and the test was repeated confirming results. This individual, a female patient of 66 years who was not using estrogens, was heterozygous for a deletion of the complete PROS1 gene. Her tPS was 64.3 U/dL, which was below the 2.5th percentile (tPS = 65.3 U/dL) of the total MEGA control group. To check if the frequency of CNVs in PROS1 was indeed low in the MEGA, we zoomed in on PS deficiency by selecting DNA from individuals with low tPS (cuttof: mean tPS -2SD of the total MEGA control group), not excluding vitamin K users. This selection yielded 404 individuals, out of which 198 had been previously analyzed in the first round. MLPA was performed for the remaining 206 individuals and no new CNV was found in PROS1. In conclusion, PS deficiency was not a risk factor for VT in this population-based study and deletions or duplications in PROS1 were not common. This is in contrast with previous data from family-based studies but in accordance with the fact that the genetic basis of PS deficiency and its risk for VT outside of a family setting was also not evident in other studies. Disclosures No relevant conflicts of interest to declare.
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Liakhovskyi, V. I., O. O. Kyzymenko, O. H. Krasnov, O. I. Krasnov, and T. V. Horodova-Andrieieva. "OPTIMIZATION OF THE VACUUM-ASSISTED TREATMENT FOR COMPLICATIONS OF DIABETIC FOOT SYNDROME." Medical and Ecological Problems 23, no. 5-6 (December 16, 2019): 15–19. http://dx.doi.org/10.31718/mep.2019.23.5-6.02.
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The nature of reparative and morphological changes in wounds was examined against the background of vacuum therapy in the comprehensive treatment of purulent and necrotic lesions of diabetic foot syndrome. We conducted comprehensive examination and treatment of 107 patients with DFS of grade II-IV according to Meggit-Wagner. The average age of patients was 53.2–4.3 years; there were 39 (36.4%) male and 68 (63.6%) female patients. Depending on the methods of topical treatment, patients were divided into two groups. The main group consisted of 55 (51.4%) subjects who underwent vacuum therapy during the topical treatment, and the comparison group comprised 52 (48.6%) patients who received standardized local treatment depending on the course of the wound process. In addition to the clinical studies, all patients underwent a comprehensive laboratory and instrumental examination, as well as measuring the area and pH of wounds on the 1st, 4th, 7th, 10th and 13th day after surgery. The analysis of the obtained results gives ground to establish that at a certain level of pH, there is a corresponding cytological pattern. The wide range of fluctuations in the pH of the wound medium in patients with purulent and necrotic lesions of diabetic foot syndrome leads to corresponding changes in cells, which is manifested by a long-lasting inflammatory process. In the main group, the rate of wound reduction was greatest on the 8th-10th days, and in the comparison group – on the 14th-15th days. Inpatient treatment was 14.2 bed-days in the main group and 23.5 ± 2.9 in the comparison group (p <0.05), respectively. Therefore, there is an acceleration of positive changes in clinical manifestations, cytological, morphological and pH-metric pattern against the background of conducting VT for an average of 5-7 days. The use of vacuum therapy makes it possible to accelerate the transition to the second phase of the wound process, which affects not only the time of treatment but also the outcome – preservation of the lower extremity in patients with diabetic foot syndrome.
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Benjamin, Charlotte C., Alex Rowlands, and Gaynor Parfitt. "Patterning of Affective Responses During a Graded Exercise Test in Children and Adolescents." Pediatric Exercise Science 24, no. 2 (May 2012): 275–88. http://dx.doi.org/10.1123/pes.24.2.275.
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Past studies have shown the patterning of affective responses during a graded exercise test (GXT) in adult and male adolescent populations, but none have explored the patterns in adolescent girls or younger children. This study explored the patterning of affective responses during a GXT in adolescents and younger children. Forty-nine children (21 male and 28 female) aged between 8–14 years (10.8 ± 1.8 years) completed a GXT. Ventilatory threshold (VT) was identified. At the end of each incremental step, participants reported affective valence. Results revealed that affective valence assessed by the Feeling Scale (FS) significantly declined from the onset of exercise until the point of VT in the younger children, but remained relatively stable in the adolescents. Exercise above the VT brought about significant declines in affective valence regardless of age or sex, but the decrease was significantly greater in adolescents. Results suggest it may be preferable to prescribe lower exercise intensities (below VT) for children, compared with adolescents, to ensure a positive affective response.
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Shlevkov, N. B., H. F. Salami, V. G. Kiktev, and S. F. Sokolov. "New ECG criteria for differential diagnosis of wide QRS complex tachycardias with right bundle branch block pattern." Terapevticheskii arkhiv 91, no. 4 (April 15, 2019): 83–89. http://dx.doi.org/10.26442/00403660.2019.04.000210.
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Aim. To evaluate standard 12-lead ECG indices for the differential diagnosis of wide QRS tachycardias with right bundle branch block (RBBB) pattern. Materials and methods. Study analyses the 244 ECG indices in 111 patients (79 males and 32 females, age 53±17 years) with RBBB tachycardias, who underwent electrophysiological studies. First step includes retrospective analysis of QRS characteristics in 20 patients with ventricular tachycardias (VT), 24 pts with aberrant supraventricular tachycardias (SVT+RBBB) and 14 pts with antidromic SVTs (WPW). ROC- and multifactorial analyses were performed to develop diagnostic ECG algorithms. The prognostic accuracy of the algorithms was subsequently evaluated on a prospective group of patients with RBBB tachycardias (n=53). Results and discussion. ECG criteria of RBBB VTs were: 1) the presence Q-wave in lead II, 2) the duration interval R(peak)-S(end) >100 ms in lead V5. ECG criteria for antidromic SVTs with RBBB were: 1) the duration of the R wave in lead I ≥80 ms, 2) the absence of split (M-sharp) R-waves in lead V2, 3) the absence notch in ascending S wave in lead aVL. The accuracy of the algorhythm for diagnostic of VTs with RBBB was 83% (sensitivity 100%, specificity 73%). The accuracy of the algorhythm for diagnostic of antidromic SVTs with RBBB was 91% (sensitivity 85%, specificity 96%). Conclusion. The proposed algorithms are based on new ECG criteria for the differential diagnosis of wide QRS complexes tachycardias with RBBB pattern, unlike the previous algorithms.
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Efficace, Fabio, Paola Fazi, Francesco Rodeghiero, Gianluca Gaidano, Piercarla Schinco, Monica Carpenedo, Alessandro Rambaldi, et al. "Health-Related Quality of Life in Patients with Primary Immune Thrombocytopenia Compared with the General Population." Blood 120, no. 21 (November 16, 2012): 2056. http://dx.doi.org/10.1182/blood.v120.21.2056.2056.
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Abstract Abstract 2056 Background: Recent international guidelines (Rodeghiero F, et al. Blood 113:2386–93, 2009) emphasize the importance of health-related quality of life (HRQOL) in patients with primary immune thrombocytopenia (pITP) and are advocating for more research in this area. However, very little research has been conducted on HRQOL of these patients. Aim: The main objective of this study was to identify specific limitations of HRQOL in pITP patients (ie, chronic, persistent and newly diagnosed patients) in comparison with their peers from the general population. Also, socio-demographic and clinical factors were considered to evaluate HRQOL impairment. Patients and Methods: Data were gathered through an ongoing multicenter observational study that recruits p-ITP patients. HRQOL was the primary endpoint of the study and was assessed with Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. Two summary scores, namely the physical component summary (PCS) and the mental component summary (MCS) are derived from a weighted combination of the eight scales. Mean SF-36 scores were compared to available national general population reference values and analyses were adjusted for age and gender. Based on previous research, eight points were considered to be a minimally important difference (MID) for the first eight SF-36 scales, while a difference of two points was judged as MID for the PCS and the MCS scores. A score difference at least equal to MID was considered as a clinically meaningful difference. Socio-demographic, clinical and laboratory data were also collected to investigate their association with HRQOL outcomes. Univariate and multivariate linear regression analyses were used. Results: To date of the 256 pITP patients included in this study, 69%, 16% and 15%, were diagnosed with chronic, persistent and newly diagnosed pITP respectively. Present analysis is based on 175 patients with HRQOL data currently available. At study participation, mean age of patients was 54 years (67% female and 33% male). At least one comorbidity was present in 53% of patients. The median time from initial diagnosis to study entry was 0.3, 8 and 77 months respectively for newly diagnosed, persistent and chronic patients. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P<.001), GH (P=.01), SF (P=.002), RE (P=.002). The largest clinically meaningful difference (Δ=13.4 points) was found for the RP domain with mean scores of 58.3 vs. 71.7 respectively for pITP patients and the general population. Age specific comparisons, (18–54, 55–64 and >65 years) suggested an almost uniform pattern in all scales with worse outcomes between pITP patients and population controls among the youngest groups. Statistically and clinically meaningful differences (ie, >8 points) were found in five out of the eight scales of the SF-36 in the youngest group of patients (18–54 years), when compared with their peers, while these differences were not present in the other age group categories. Comorbidity was the main factor influencing HRQOL by independently predicting worse HRQOL outcomes across all domains of the SF-36. SF-36 mean score differences in patients with or without comorbidity, were more than twice the magnitude of a clinically meaningful difference for PF and RP, being respectively: 69.7 vs. 87 and 51.3 vs. 68 points. Conclusions: This study suggests that HRQOL of p-ITP patients is far from optimal. In particular, role limitations (i.e., in work or other daily activities) due to physical health seems the major constraint faced by these patients when compared to their peers in the general population. Comorbidity seems the major factor associated with a poorer HRQOL profile. These findings need to be confirmed with a larger sample size and will eventually help guide the development of patient-centered supportive care programs. Disclosures: No relevant conflicts of interest to declare.
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Efficace, Fabio, Michele Baccarani, Massimo Breccia, Giuliana Alimena, Gianantonio Rosti, Giorgio Lambertenghi Deliliers, Claudia Baratè, et al. "Health-Related Quality of Life In Patients with Chronic Myeloid Leukemia Undergoing First Line Treatment with Imatinib for at Least Three Years Compared with the General Population. A Multicenter Study Including 448 Patients." Blood 116, no. 21 (November 19, 2010): 2273. http://dx.doi.org/10.1182/blood.v116.21.2273.2273.
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Abstract Abstract 2273 Background: While Imatinib (IM) has revolutionized treatment for chronic myeloid leukemia (CML), demonstrating outstanding survival figures, currently no data exist on mid to long term impact of disease burden and therapy from the patients’ perspective. Aim: The main objective of this study is to identify specific limitations of quality of life (QoL) in CML survivors who are undergoing first line treatment with IM in comparison with controls from the general population. Patient-reported symptom prevalence was also investigated. Patients and methods: Patients were recruited in 26 centers, randomly selected to geographically represent the whole study country. Patients selection criteria included: being in treatment with IM for at least three years and being in complete cytogenetic response at the time of study entry. All patients were invited by their treating physicians in the hospital to participate and all consenting patients were requested to complete a Health Survey Packet at home. Pre-paid reply envelopes were also provided with the request to send back completed Surveys to an independent National coordinating Data Center. Generic QoL was assessed with the SF-36 that consists of 36 items covering eight generic health status/QoL domains: physical functioning (PF), role limitations due to physical health (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations due to emotional problems (RE), and mental health (MH). All scales ranging between 0 and 100 with higher scores representing better outcomes. A previously devised patient-reported CML Symptom Checklist was used to investigate 9 symptoms of possible major concern in these patients. Mean SF-36 scores were compared to available national general population reference values and all analyses were adjusted for age and gender. Statistical comparisons were all adjusted for multiple testing. Differences in mean scores were expressed in Cohen effect sizes (ES; with 0.2, 0.5, and 0.8 indicating small, medium, and large ES, respectively) and clinical significance. Results: Between March and December 2009, 448 patients were recruited in a large national-based survivorship project. Patients’ compliance was optimal with 94% of patients (N=421) returning a valid Health Survey Packet to the National coordinating Data center. At study participation, mean age of patients was 56 years (59% male and 41% female) and median time of IM therapy was 5 years. Seventy-seven percent of patients were receiving standard dose of 400 mg and 43% had at least one comorbidity. Age and gender adjusted comparisons with general population norms revealed worse outcomes for the following scales: RP (P<.001; ES=0.3), GH (P<.001; ES=0.4) and RE (P=.01; ES=0.2). The largest clinically meaningful difference (Δ=12.3 points) was found for the RP domain with mean scores of 61.4 vs. 73.7 respectively for the CML and the general population. Age specific comparisons, adjusted by gender, (55-64; 65–74 and >75 years) suggested an almost uniform pattern in all scales with worse outcomes between CML patients and population controls among the youngest groups. GH was significantly worse in younger patients (55-64) (P=.03; ES=0.4) and no differences were found in the older age groups compared with population norms. Prevalence of reported symptoms (with any level of concern) was: fatigue (82%); problems with muscular cramps (78%); problems with musculoskeletal pain (72%); problems with edema (70%); skin problems (47%); diarrhea (43%); headache (39%); abdominal discomfort and nausea (28%). Conclusion: This study suggests that while still being on treatment with IM for years, CML patients might expect to have a QoL profile broadly similar to that of general population in many areas. However, role limitations (i.e., in work or other regular daily activities) due to physical health seem the major constraint faced by these patients; there is also an indication that younger patients might be those experiencing major limitations. Additional analyses will be undertaken to ascertain the impact of symptoms and other laboratory and clinical data on specific QoL domains. Such unique patient-reported data supplements conventional information on clinical efficacy of IM and may support both clinicians and patients in making more informed treatment decisions in this area. Disclosures: Rosti: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol M. Squibb: Honoraria, Speakers Bureau; Roche: Speakers Bureau.
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Belhassen, Bernard, Mikael Laredo, Rob W. Roudijk, Giovanni Peretto, Guy Zahavi, Srijita Sen-Chowdhry, Nicolas Badenco, et al. "The prevalence of left and right bundle branch block morphology ventricular tachycardia amongst patients with arrhythmogenic cardiomyopathy and sustained ventricular tachycardia: insights from the European Survey on Arrhythmogenic Cardiomyopathy." EP Europace, September 7, 2021. http://dx.doi.org/10.1093/europace/euab190.
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Abstract Aims In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. Methods and results Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients’ clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51–185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). Conclusion RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.
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Lee, Sharen, Wing Tak Wong, Ian Chi Kei Wong, Chloe Mak, Ngai Shing Mok, Tong Liu, and Gary Tse. "Ventricular Tachyarrhythmia Risk in Paediatric/Young vs. Adult Brugada Syndrome Patients: A Territory-Wide Study." Frontiers in Cardiovascular Medicine 8 (June 11, 2021). http://dx.doi.org/10.3389/fcvm.2021.671666.
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Introduction: Brugada syndrome (BrS) is a cardiac ion channelopathy with a higher prevalence in Asia compared to the Western populations. The present study compared the differences in clinical and electrocardiographic (ECG) presentation between paediatric/young (≤25 years old) and adult (>25 years) BrS patients.Method: This was a territory-wide retrospective cohort study of consecutive BrS patients presenting to public hospitals in Hong Kong. The primary outcome was spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF).Results: The cohort consists of 550 consecutive patients (median age of initial presentation = 51 ± 23 years; female = 7.3%; follow-up period = 83 ± 80 months), divided into adult (n = 505, mean age of initial presentation = 52 ± 19 years; female = 6.7%; mean follow-up period = 83 ± 80 months) and paediatric/young subgroups (n = 45, mean age of initial presentation = 21 ± 5 years, female = 13.3%, mean follow-up period = 73 ± 83 months). The mean annual VT/VF incidence rate were 17 and 25 cases per 1,000 patient-year, respectively. Multivariate analysis showed that initial presentation of type 1 pattern (HR = 1.80, 95% CI = [1.02, 3.15], p = 0.041), initial asymptomatic presentation (HR = 0.26, 95% CI = [0.07, 0.94], p = 0.040) and increased P-wave axis (HR = 0.98, 95% CI = [0.96, 1.00], p = 0.036) were significant predictors of VT/VF for the adult subgroup. Only initial presentation of VT/VF was predictive (HR = 29.30, 95% CI = [1.75, 492.00], p = 0.019) in the paediatric/young subgroup.Conclusion: Clinical and ECG presentation of BrS vary between the paediatric/young and adult population in BrS. Risk stratification and management strategies for younger patients should take into consideration and adopt an individualised approach.
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Nakamura, Takashi. "Abstract 12149: Impact of Elevated Cardiac Troponin and Increased Fibrosis on Clinical Manifestations in Hypertrophic Cardiomyopathy." Circulation 130, suppl_2 (November 25, 2014). http://dx.doi.org/10.1161/circ.130.suppl_2.12149.
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Introduction: Recently, in patients with hypertrophic cardiomyopathy (HCM), an abnormal serum concentration of cardiac troponin (cTn), which is a sensitive marker of myocyte injury, was reported to be an independent predictor of the adverse outcome. In addition, late gadolinium-enhancement (LGE) cardiac magnetic resonance (CMR) imaging, which has been used to uniquely characterize the extent of myocardial fibrosis, has prognostic value in HCM. However, the relationship between myocyte injury, fibrosis, and clinical events/manifestations remains unclear. Hypothesis: A combined analysis using cTn and LGE by CMR may help to identify the clinical events/manifestations in patients with HCM. Methods: Eighty-seven HCM patients receiving regular outpatient treatment underwent CMR (cine and LGE imaging). LV myocardial fibrosis mass index (FMI) was quantified and the distribution/pattern of LGE was analyzed using 17 segment model. Serum cTnI was measured within a week around CMR testing. cTnI elevation was defined as ≥ 0.05ng/mL. Clinical events were defined as heart failure (HF) admission, ventricular tachycardia (VT), atrial fibrillation, and syncope. Results: In total patients, mean age was 65.7 ± 15.0 years old and female patients were 41.4%. HF and VT events were observed in 22 (25%) and 16 (18%) patients, respectively. Both elevated cTnI and higher FMI were associated with the combined clinical events (P<0.01 and P<0.05, respectively). Elevated cTnI was associated not with HF (P=0.06), but with VT (P<0.001). In contrast, higher FMI was associated with HF (P=0.01), but not with VT (P=0.67). A grouping according to both cTnI and FMI showed the good stratification for clinical events as shown in the figure. Conclusions: In HCM patients, both cTn and FMI were significant markers for clinical events in HCM patients. In particular, elevated cTn was strongly associated with VT. Combined analysis of cTn and CMR may be useful in clinical practice for HCM.
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Trifunovic Zamaklar, D., G. Krljanac, M. Asanin, L. Savic-Spasic, J. Vratonjic, N. Arnautovic, S. Aleksandric, M. Vorkapic, L. Cucic, and I. Mrdovic. "Can analysis of myocardial mechanic help me to predict heart failure development in my STEMI patient whose EF is equal or above 50% after pPCI?" European Heart Journal - Cardiovascular Imaging 22, Supplement_1 (January 1, 2021). http://dx.doi.org/10.1093/ehjci/jeaa356.042.
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Abstract Funding Acknowledgements Type of funding sources: None. onbehalf PREDICT-VT In spite of contemporary STEMI management, heart failure (HF) develops in 4% up to 28% of pPCI-treated patients, with the highest incidence in the first year. Left ventricular ejection fraction (EF) is strong predictor predominately for HFrEF development, but risk stratification in case of preserved post pPCI EF (i.e. EF ≥ 50%) is still challenging. Aim the current study is a sub-study of PREDICT-VT study (NCT03263949). Its aim is to define clinical and "echocardiographic" profile of STEMI patient at risk to develop HF despite preserved post pPCI EF, including not only conventional echocardiographic data, but data from myocardial mechanic analysis obtained by early speckle tracking echocardiography. Methods in 307 consecutive pts enrolled in PREDICT-VT study early echocardiography (5 ± 2 days after pPCI) was done and included LA and multilayer LV deformation analysis with longitudinal (L), radial (R) and circumferential (C) strain (S; %) and strain rate (SR, 1/sec), calculation of LV index of post systolic shortening for longitudinal (PSS LS) and circumferential (PSS CS) strains and thorough analysis of LV rotation mechanic. Results From 242 patients who completed 1-year follow-up, 109 pts (45 %) had post pPCI EF ≥50%. Of those patients 34 (31%) became NYHA ≥ 2 or died during 1-year follow-up (MACE+ group). Patients with MACE were older (63 ± 8 vs 55 ± 10, p < 0.001), more frequently were female (47% vs 27%; p = 0.036) and more frequently had hypertension (40% vs 20%; p = 0.025). There were no significant differences in LV EF ( 56.5 ± 4.8% vs 56.3 ± 4.8 %; p = 0.849) and from conventional echo parameters only differences in E/A ratio (0.75 ± 0.24 vs 0.92 ± 0.32; p = 0.015) and MAPSE (1.54 ± 0.40 vs 1.36 ±0.27; p = 0.015) reached statistical significance. Surprisingly, there were no significant differences neither in LV longitudinal, nor circumferential deformations. However, LV radial deformation was significantly impaired in MACE+ pts both during systole (global radial strain: 16.4 ± 7.1 vs 21.1 ± 10.3; p = 0.008; end-systolic radial strain 13.1 ± 7.3 vs 18.1 ± 9.9; p = 0.005), early (radial SR E: -1.27 ± 0.66 vs 1.59 ± 0.79; p = 0.044) and late (radial SR A: -0.94 ± 0.41 vs -1.20 ± 0.59, p = 0.011) diastole. LV rotation was not significantly impaired, but slowed and delayed both during systole (time to peak systolic apical rotation (ms) 168 ± 86 vs 128 ± 70; p = 0.022) and diastole (rotation rate of LV base during early diastole (°/sec): 38.3 ± 27.4 vs 55.0 ± 31.5, p = 0.008; time to maximal LV untwisting rate (ms) 580 ± 210 vs 484 ± 154; p = 0.044), despite no differences in HR. Conclusion STEMI patients who will develop heart failure despite preserved post pPCI EF might have different clinical profile and different pattern of deviation in LV mechanic (predominately involving radial and rotational mechanic) and can be detected by contemporary echocardiographic techniques.
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Tzou, Wendy S., David F. Katz, Ryan G. Aleong, William H. Sauer, and David P. Kao. "Abstract 18718: Trends, Predictors, and Regional Variation in Use of Catheter Ablation Among 184,443 Hospitalizations for Ventricular Tachycardia." Circulation 132, suppl_3 (November 10, 2015). http://dx.doi.org/10.1161/circ.132.suppl_3.18718.
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Introduction: Catheter radiofrequency ablation (RFA) is used increasingly for treatment of ventricular tachycardia (VT), but little is known about utilization patterns. Hypothesis: Regional trends in VT hospitalization and RFA,and patient characteristics associated with VT RFA vary. Methods: Hospital discharge data was obtained from state agencies in California, New York, New Jersey, Vermont, New Hampshire, West Virginia, Colorado, and Texas from 1994-2012. All records with primary diagnosis of VT (ICD9-CM 427.1) were analyzed. Population-adjusted hospitalization rates were estimated using US Census Bureau data. In hospitals performing VT RFA, patient characteristics associated with RFA were identified using multivariate logistic regression. Results: In total, 184,443 hospitalizations for VT were reported; 11,941/136,437 (8.8%) admitted to VT ablation hospitals underwent RFA. Annual VT hospitalization rates varied from 10-17/100,000 in California (CA) and Texas (TX) to 20-30 in New York and New Jersey (NJ). VT ablation/hospitalization frequency varied from 9% in NJ to 18% in CA and TX. Positive predictors of undergoing VT RFA were female gender, non-white race, admission from home, and atrial flutter. Negative predictors included advancing age, non-private insurance, atrial fibrillation, anemia, coronary artery disease, heart failure, hypertension, and shock on admission (Figure, A). Higher RFA rates for women were driven by more patients without structural heart disease compared to men (Figure, B). Non-white patients were more likely to undergo RFA irrespective of structural heart disease. Conclusion: Significant regional variations exist in VT hospitalization and ablation rates. Also of note, women and non-white patients were more likely to undergo ablation, which may have reflected important differences in cardiac disease substrate.
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Rossetti, A., R. L. H. Spatjens, S. R. Seyen, A. T. J. Helderman-Van Den Enden, A. A. M. Wilde, and P. G. A. Volders. "P933Novel missense variant in DPP6 in familial ventricular fibrillation." EP Europace 22, Supplement_1 (June 1, 2020). http://dx.doi.org/10.1093/europace/euaa162.186.
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Abstract Funding Acknowledgements This work was supported by an ESC Research Grant to A.R., and by The Netherlands CardioVascular Research Initiative (CVON PREDICT2), Den Haag, The N Background The DPP6 gene, encoding dipeptidyl aminopeptidase-like protein-6, has been associated with familial ventricular fibrillation (VF) and early repolarization. The DPP6 protein is part of the macromolecular Ito-channel complex and functionally expressed in ventricular myocytes (VM) and Purkinje cells (PC). Here we report a novel missense variant in DPP6 identified in a family with sudden cardiac death/arrest due to VF. Purpose To examine the consequences of the novel DPP6 variant c.821G > A, p.(R274H) for cardiac Ito and their potential contribution to a VF substrate. Methods: Clinical Co-segregation of DPP6-R274H with major adverse cardiac events in the family members was investigated. Ambulatory ECGs, echocardiograms, exercise tests and ICD recordings were systematically analyzed. Cellular Chinese hamster ovary cells were transiently transfected with Ito α and β subunits in order to mimic the VM (Kv4.3 + KChIP2) or the PC phenotype (Kv4.3 + NCS1). Additionally, DPP6 wild type (WT) or variant was transfected. Ito was assessed by patch clamping. Results: Clinical DPP6-R274H, affecting a conserved region in the extracellular protein domain segregated with an autosomal dominant pattern of inheritance. The female index patient experienced first VF at 17 years, and subsequent ICD therapy, after her brother had died suddenly at 13 years. Both carriers were also known with mitral-valve prolapse (MVP), but otherwise without structural heart disease. A third sibling without arrhythmia, but with mild MVP, did not carry the DPP6 variant. No other pathogenic mutations were found by next generation sequencing in the index patient. ECGs of the index patient revealed dynamic early repolarization, U waves with varying amplitudes and pause-dependent prominence, and >8000/24 h superimposed premature ventricular complexes (PVCs) and (non)sustained VT. PVCs (QRS duration 120 ms) displayed both a left posterior (80%) and anterior (20%) fascicular origin. PVC burden was higher during daytime and exercise, with pause-dependent occurrence. Cellular In the PC model DPP6-R274H markedly decreased Ito density (at +30 mV: 291 pA/pF vs 995 pA/pF in WT; p < 0.001), whereas it did not in the VM model. In VM, but not in PC, Ito inactivation was slowed by the variant (Tau at 0 mV: 91 ms vs 49 ms in WT; p < 0.001). Conclusions The novel DPP6 variant R274H has differential effects on Ito in cellular models of VM versus PC. Our main finding of a loss-of-function in the PC model combined with a slowed Ito inactivation in the VM phenotype may exaggerate electrical heterogeneity, especially at the PC-VM junction. Ito loss in PC would prolong action-potential duration and promote early afterdepolarizations, consistent with the dynamic patterns of T-U-dispersion and (fascicular) ectopy in the index case. Mechano-electric influences by the MVP further promote arrhythmogenesis.
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Sabbag, A., B. Essayagh, C. Antoine, G. Benfari, J. Malouf, S. Asirvatham, H. Michelena, and M. Enriquez-Sarano. "650The arrhythmic mitral valve prolapse: presentation and outcome." EP Europace 22, Supplement_1 (June 1, 2020). http://dx.doi.org/10.1093/europace/euaa162.351.
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Abstract Background The majority of patients with of Mitral-valve-prolapse (MVP) have a excellent prognosis. Until recently most cases of mortality were thought to be related to mitral regurgitation and left ventricular dysfunction. The concept of the arrhythmic MVP emerged to describe cases of sudden cardiac death (SCD) in the presence of isolated MVP yet it’s phonotype remains incompletely and inconsistently defined. Purpose To analyze the prevalence, severity and characteristics of ventricular-arrhythmia (VA), to determine it’s phenotypical context and independent impact on outcome in patients with MVP. Methods A cohort of 595 (65 ± 16 years, 278 female) consecutive patients with MVP and comprehensive clinical, arrhythmia (24hour-Holter) and Doppler-echocardiographic characterization, was identified and long-term outcome analyzed. Results VA was frequent, present in 43% of patients with at least ventricular ectopy≥5%, but was most often moderate (ventricular-tachycardia—VT 120-179bpm) in 27% and rarely severe (VT≥180/min) in 8.6%. Presence of VA was associated with older age, male sex, bileaflet-prolapse, marked leaflet redundancy, mitral-annulus-disjunction (MAD), larger left-atrium and left ventricular end-systolic diameter, and T-wave-inversion/ST-depression (all P ≤ 0.001). Severe VA was independently associated with presence of MAD, leaflet-redundancy and T-wave-inversion/ST-depression (all P < 0.0001) but not with mitral regurgitation severity or ejection-fraction. Outcome primary endpoint of overall survival after arrhythmia diagnosis (8-year 87 ± 2%) was strongly associated with arrhythmia-severity (8-year 90 ± 2% for no/trivial arrhythmia, 85 ± 3% for mild/moderate and 76 ± 7% for severe arrhythmia. P = 0.02, Figure). Excess-mortality was substantial for severe-arrhythmia (univariate-hazard-ratio 2.70[1.27-5.77], P = 0.01 vs. no/trivial arrhythmia), even adjusted comprehensively including for MVP-characteristics (adjusted-hazard-ratio 2.94[1.36-6.36], P = 0.006) ). Conclusions This large cohort of isolated consecutive MVP characterized with 24-hour-Holter monitoring, clinical and Echocardiographic assessment, demonstrates that VA are frequent with MVP but rarely severe. The arrhythmic MVP was independently and strongly associated with specific ECG and morphologic patterns, particularly ST-T changes, MAD presence and marked leaflet redundancy, suggestive of a specific arrhythmic MVP phenotype, independently of MR-severity. Arrhythmia, particularly severe, is associated with long-term excess-mortality, independently of any other characteristics, including MR severity and LVEF. These findings lay the foundation for novel risk-stratification of MVP for the conduct of prospective controlled studies evaluating the management of MVP high-risk patients. Figure – Impact on survival of ventricular arrhythmia Overall survival of MVP stratified by ventricular arrhythmia (Panel A) or ventricular arrhythmia severity (Panel B) throughout follow-up. Abstract Figure.
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Kraus, S. M., P. Samuels, N. Laing, M. Ntsekhe, A. Chin, S. M. Moosa, K. Sliwa, and N. Ntusi. "6133Profile of cardiomyopathy patients in Cape Town - pilot phase the IMHOTEP Study." European Heart Journal 40, Supplement_1 (October 1, 2019). http://dx.doi.org/10.1093/eurheartj/ehz746.0158.
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Abstract Background Cardiomyopathies pose a great challenge because of poor prognosis and high prevalence in LMIC with limited access to specialised care. Little is known about the clinical profile of cardiomyopathy in Africa. Purpose Delineation of clinical presentation and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy. Method The African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) is a prospective multi-centre, hospital-based study and aims to investigate the clinical characteristics, aetiology, genetics, management and outcomes of cardiomyopathies in Africans. Results Assessment of the first 99 adult cases showed that dilated cardiomyopathy (DCM; n=67) was commonest, followed by hypertrophic (HCM; n=13), left ventricular noncompaction (LVNC; n=11), restrictive (RCM; n=4) and arrhythmogenic (ARVC; n=4) cardiomyopathies. Idiopathic DCM (22%) and peripartum cardiomyopathy (16%) accounted for the majority (Figure). A family history of cardiomyopathy or SCD was reported in 20% of cases. Mean age of presentation was 37±12 years. Most patients (96%) were symptomatic at presentation. NYHA class III/IV was more frequently seen in DCM (61%), RCM (50%) and LVNC (64%), whereas syncope was more common in ARVC (50%) and HCM (23%). VT and aborted cardiac arrest were reported in 7% and 3%, respectively. Onset of symptoms in the peripartum period was observed in 47% of women. Beta-blockers and ACE-inhibitors were prescribed in 77% and 78%, respectively, however optimal dosing was achieved in ≤14% of patients at a median time of 5.4 months after symptom onset. CMR was performed in 67 (68%) cases (Table) and contributed diagnostically in a third of cases. Late gadolinium enhancement (LGE) was observed in 92%. In DCM, linear mid-wall and subendocardial patterns of LGE were seen in 95% and 8% of patients respectively – a much higher percentage than previously reported in the literature. CMR volumetric and functional assessment DCM, n=38 HCM, n=11 ARVC, n=3 RCM, n=4 LVNC, n=11 LVEF (%) 27±15 78±7 55±5 52±7 32±17 LVEDV/BSA (ml/m2) 150±40 80±17 98±12 59±13 155±52 LV mass/BSA (g/m2) 82±23 102±35 74±3 71±14 88±31 RVEF (%) 34±15 68±10 22±15 49±18 33±15 RVEDV/BSA (ml/m2) 104±37 68±15 189±27 56±8 106±51 All continuous variables presented as mean ± standard deviation. Cardiomyopathy diagnosis (n=99) Conclusion IMHOTEP is the first multi-centre registry for cardiomyopathy in Africa. Preliminary data suggests an earlier age of onset with female predominance compared to other cohorts, and DCM is the predominant form of cardiomyopathy in Africa. Acknowledgement/Funding NEWTON FUND NON-COMMUNICABLE DISEASE - South African Medical Research Council (SAMRC/GSK)