Prediction of Life-Threatening Ventricular Arrhythmia in Patients With Arrhythmogenic Cardiomyopathy: A Primary Prevention Cohort Study.

OBJECTIVES: This study aimed to identify clinical, electrocardiographic (ECG) and cardiac imaging predictors of first-time life-threatening ventricular arrhythmia in patients with arrhythmogenic cardiomyopathy (AC). BACKGROUND: The role of clinical, electrocardiographic, and cardiac imaging parameters in risk stratification of patients without ventricular arrhythmia is unclear. METHODS: We followed consecutive AC probands and mutation-positive family members with no documented ventricular arrhythmia from time of diagnosis to first event. We assessed clinical, electrocardiographic, and cardiac imaging parameters according to Task Force Criteria of 2010 in addition to left ventricular (LV) and strain parameters. High-intensity exercise was defined as >6 metabolic equivalents. RESULTS: We included 117 patients (29% probands, 50% female, age 40 ± 17 years). During 4.2 (interquartile range [IQR]: 2.4 to 7.4) years of follow-up, 18 (15%) patients experienced life-threatening ventricular arrhythmias. The 1-, 2-, and 5-year incidence was 6%, 9%, and 22%, respectively. History of high-intensity exercise, T-wave inversions ≥V3, and greater LV mechanical dispersion were the strongest risk markers (adjusted hazard ratio [HR]: 4.7 [95% confidence interval (CI): 1.2 to 17.5]; p = 0.02, 4.7 [95% CI: 1.6 to 13.9]; p = 0.005), and 1.4 [95% CI: 1.2 to 1.6] by 10-ms increments; p < 0.001, respectively). Median arrhythmia-free survival in patients with all risk factors was 1.2 (95% CI: 0.4 to 1.9) years, compared with an estimated 12.0 (95% CI: 11.5 to 12.5) years in patients without any risk factors. CONCLUSIONS: History of high-intensity exercise, electrocardiographic T-wave inversions ≥V3, and greater LV mechanical dispersion were strong predictors of life-threatening ventricular arrhythmia. Patients without any of these risk factors had minimal risk, whereas ≥2 risk factors increased the risk dramatically. This may help to make decisions on primary preventive implantable cardioverter defibrillator (ICD) therapy.

Vigorous exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: We aimed to investigate if history of vigorous exercise was associated with changes in left ventricular morphology, left ventricular function and ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy genotype positive, phenotype negative (Genotype+ LVH-) and in phenotype positive (HCM LVH+). METHODS: In this cross sectional study we included 187 subjects (age 49±16years, 89(48%) female, 121(65%) HCM LVH+ and 66 (35%) Genotype+ LVH-) who answered a questionnaire on physical activity history. Exercise ≥6 metabolic equivalents was defined as vigorous. Subjects with a history of vigorous exercise ≥4h/week during ≥6years were defined as athletes. All underwent echocardiography and Holter monitoring. VAs were defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia. RESULTS: In both Genotype+ LVH- and HCM LVH+, lifetime vigorous exercise correlated with larger left ventricular end-diastolic volume (rho 0.44 and 0.38 respectively, both p<0.001). Lifetime vigorous exercise correlated with increased left ventricular mass in Genotype+ LVH- (rho 0.28, p=0.03), but not in HCM LVH+ (p=0.53). Left ventricular systolic function was similar between athletes and non-athletes in Genotype+ LVH- and HCM LVH+. HCM LVH+ athletes had lower E/e' (p=0.03) and higher e' (p=0.02) compared to non-athletes, while this difference was not observed in Genotype+ LVH-. Lifetime vigorous exercise was similar among HCM LVH+ with and without VAs (p=0.89). CONCLUSIONS: Increased lifetime vigorous exercise was associated with larger left ventricular volumes in hypertrophic cardiomyopathy, but correlated to left ventricular mass only in Genotype+ LVH-. Vigorous exercise was associated with favorable diastolic function in HCM LVH+, and was not associated with VAs.

Data on exercise and cardiac imaging in a patient cohort with hypertrophic cardiomyopathy.

Data presented in this paper are supplementary material to our study "Vigorous exercise in patients with hypertrophic cardiomyopathy" [1]. The current article presents supplementary data on collection and analyses of exercise parameters and genetic data in the original research article.

Ventricular structure in ARVC: going beyond volumes as a measure of risk.

BACKGROUND: Altered right ventricular structure is an important feature of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), but is challenging to quantify objectively. The aim of this study was to go beyond ventricular volumes and diameters and to explore if the shape of the right and left ventricles could be assessed and related to clinical measures. We used quantifiable computational methods to automatically identify and analyse malformations in ARVC patients from Cardiovascular Magnetic Resonance (CMR) images. Furthermore, we investigated how automatically extracted structural features were related to arrhythmic events. METHODS: A retrospective cross-sectional feasibility study was performed on CMR short axis cine images of 27 ARVC patients and 21 ageing asymptomatic control subjects. All images were segmented at the end-diastolic (ED) and end-systolic (ES) phases of the cardiac cycle to create three-dimensional (3D) bi-ventricle shape models for each subject. The most common components to single- and bi-ventricular shape in the ARVC population were identified and compared to those obtained from the control group. The correlations were calculated between identified ARVC shapes and parameters from the 2010 Task Force Criteria, in addition to clinical outcomes such as ventricular arrhythmias. RESULTS: Bi-ventricle shape for the ARVC population showed, as ordered by prevalence with the percent of total variance in the population explained by each shape: global dilation/shrinking of both ventricles (44 %), elongation/shortening at the right ventricle (RV) outflow tract (15 %), tilting at the septum (10 %), shortening/lengthening of both ventricles (7 %), and bulging/shortening at both the RV inflow and outflow (5 %). Bi-ventricle shapes were significantly correlated to several clinical diagnostic parameters and outcomes, including (but not limited to) correlations between global dilation and electrocardiography (ECG) major criteria (p = 0.002), and base-to-apex lengthening and history of arrhythmias (p = 0.003). Classification of ARVC vs. control using shape modes yielded high sensitivity (96 %) and moderate specificity (81 %). CONCLUSION: We presented for the first time an automatic method for quantifying and analysing ventricular shapes in ARVC patients from CMR images. Specific ventricular shape features were highly correlated with diagnostic indices in ARVC patients and yielded high classification sensitivity. Ventricular shape analysis may be a novel approach to classify ARVC disease, and may be used in diagnosis and in risk stratification for ventricular arrhythmias.

[Catecholaminergic polymorphic ventricular tachycardia]. / Katekolaminerg polymorf ventrikkeltakykardi.

BACKGROUND: CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT. MATERIAL AND METHODS: The literature reviewed was identified through a non-systematic search in PubMed. RESULTS: Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved. INTERPRETATION: CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

AIM: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. METHODS AND RESULTS: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. CONCLUSION: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.