Combination of ECG and Echocardiography for Identification of Arrhythmic Events in Early ARVC

OBJECTIVES: The aim of this study was to investigate early markers of arrhythmic events (AEs) and improve risk stratification in early arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: AEs are frequent in patients with ARVC, but risk stratification in subjects with early ARVC is challenging. METHODS: Early ARVC disease was defined as possible or borderline ARVC diagnosis according to the ARVC Task Force Criteria 2010. We performed resting and signal averaged electrocardiogram (ECG). Using echocardiography, we assessed right ventricular (RV) outflow tract diameter and right ventricular basal diameter (RV diameter). Global longitudinal strain and mechanical dispersion (MD) from strain echocardiography were assessed in both the right and left ventricle. AEs were defined as documented ventricular tachycardia, cardiac syncope, or aborted cardiac arrest. RESULTS: Of 162 included subjects with ARVC (41 ± 16 years of age, 47% female), 73 had early ARVC, including mutation positive family members not fulfilling definite ARVC diagnosis. AEs occurred in 15 (21%) subjects with early ARVC. Those with AEs in early disease had larger RV diameter (40 ± 4 mm vs. 37 ± 5 mm), more pronounced RVMD (39 ± 15 ms vs. 26 ± 11 ms), and more pathological signal averaged ECGs compared with those without AEs (all p ≤ 0.05). Adding measurements of RV diameter and RVMD to electrical parameters improved identification of subjects with AEs compared with electrical parameters alone (p = 0.05). CONCLUSIONS: ECG parameters, RV diameter, and RVMD were markers of previous arrhythmic events in patients with early ARVC. A combination of electrical and echocardiographic parameters improved identification of subjects with AEs in early ARVC disease. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. KEYWORDS: arrhythmic risk; arrhythmogenic right ventricular cardiomyopathy; echocardiography; signal averaged ECG; ventricular arrhythmia

Echocardiographic comparison between left ventricular non-compaction and hypertrophic cardiomyopathy

Background: Modern imaging technology has improved detection of left ventricular non-compaction cardiomyopathy (LVNC). Hypertrophic cardiomyopathy (HCM) shares morphological features with LVNC, but prognosis and treatment strategies differ between LVNC and HCM. Methods and results: Weaimed to compare global and regional LV myocardial function in LVNC and HCM.We hypothesized that apical function is reduced in LVNC due to the embryonic reduced compaction of the apex. We studied 25 patients with LVNC (47 ± 14 years) according to current criteria, 50 with HCM (47 ± 14 years) and 50 healthy individuals (49 ± 19 years). By echocardiography, we assessed maximal wall thickness (MWT) and LV ejection fraction (EF). Numbers of trabeculations were counted from 3 apical views. Global longitudinal strain by speckle tracking echocardiography was calculated froma 16 LV segments model. LV basal (6 segments) and apical (4 segments) longitudinal strainswere averaged.MWTwas thinner, EF lower and trabeculationswere more pronounced in LVNC compared to HCM(all p b 0.001) butwith no significantly differences in LV global longitudinal strain (−15.1± 6.1 vs.−16.8±3.7, p=0.14). Function by longitudinal strain increased significantly frombase to apex in HCM(−14.9±4.3% vs.−19.5±4.7%, p b 0.001) and in healthy controls (−20.0±1.9% vs. −21.8 ± 2.9%, p b 0.001), but not in LVNC (−14.7 ± 6.4% vs. −15.7 ± 7.2%, p = 0.35). Conclusions: Increased number of trabeculations, thinnerMWT and lower EF were characteristics of LVNC. Myocardial function was homogeneously reduced in LVNC,while an apical to basal gradient with relatively preserved apical function was present in HCM. These characteristics may help to discriminate between LVNC and HCM

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

Life-threatening arrhythmic presentation in patients with arrhythmogenic cardiomyopathy before and after entering the genomic era; a two-decade experience from a large volume center

Background: Arrhythmogenic cardiomyopathy (AC) is an inheritable progressive heart disease with high risk of life-threatening ventricular arrhythmia (VA). We aimed to explore the prevalence of VA as presenting event in patients with AC over two decades, symptoms preceding VA and compare the clinical presentations and rate of AC-diagnosis over time. Methods: We included consecutive AC-patients from our tertiary referral center. We recorded clinical history, VA (aborted cardiac arrest, sustained ventricular tachycardia or appropriate implantable cardioverter-defibrillator therapy), cardiac symptoms preceding VA in AC, and compared the history of patients diagnosed before and after implementation of genetic testing. Results: We included 179 consecutive AC-patients and mutation-positive family members (95 [53%] probands, 84 [45%] female, 49 ± 17 years), 33 (18%) diagnosed before and 146 (82%) after genetic testing became available. VA led to the AC-diagnosis in 46 (26%), and was less prevalent after implementation of genetic testing (17[52%] vs. 29[20%], p < 0.001), also when adjusted for proband status (Adjusted OR 2.7, 95% CI 1.1–6.7, p = 0.03). Yearly rate of AC-diagnosis increased after implementation of genetic testing in probands (2.7 ± 1.3 vs. 6.8 ± 4.3, p = 0.01) and family members (0.7 ± 1.1 vs. 7.7 ± 5.9, p = 0.002). Most patients with VA (92%) reported cardiac symptoms prior to event, and exercise-induced syncope was the strongest marker of subsequent VA (Adjusted OR 5.3, 95% CI 1.7–16.4, p = 0.004). Conclusion: VA led to AC-diagnosis in 46% of probands and was preceded by cardiac symptoms in the majority of cases. Yearly rate of AC-diagnoses increased after the implementation of genetic testing and life-threatening presentation of AC-disease seemed to decrease

Comparison of patients with early phase arrhythmogenic right ventricular cardiomyopathy and right ventricular outflow tract ventricular tachycardia

Aims: Differentiation between early-phase arrhythmogenic right ventricular cardiomyopathy (ARVC) and right ventricular outflow tract (RVOT)-ventricular tachycardia (VT) can be challenging, and correct diagnosis is important. We compared electrocardiogram (ECG) parameters and morphological right ventricular (RV) abnormalities and investigated if ECG and cardiac imaging can help to discriminate early-phase ARVC from RVOT-VT patients. Methods and results: We included 44 consecutive RVOT-VT (47+14 years) and 121 ARVC patients (42+17 years). Of the ARVC patients, 77 had definite ARVC and 44 had early-phase ARVC disease. All underwent clinical examination, ECG, and Holter monitoring. Frequency of premature ventricular complexes (PVC) was expressed as percent per total beats/24 h (%PVC), and PVC configuration was recorded. By echocardiography, we assessed indexed RV basal diameter (RVD), indexed RVOT diameter, and RV and left ventricular (LV) function. RV mechanical dispersion (RVMD), reflecting RV contraction heterogeneity, was assessed by speckle-tracking strain echocardiography. RV ejection fraction (RVEF) was assessed by cardiac magnetic resonance imaging (CMR). Patients with early-phase ARVC had lower %PVC by Holter and PVC more frequently originated from the RV lateral free wall (both P , 0.001). RVD was larger (21+3 vs. 19+2 mm, P , 0.01), RVMD was more pronounced (22+15 vs. 15+13 ms, P ¼ 0.03), and RVEF by CMR was decreased (41+8 vs. 49+4%, P , 0.001) in early-phase ARVC vs. RVOT-VT patients. Conclusion: Patients with early-phase ARVC had structural abnormalities with lower RVEF, increased RVD, and pronounced RVMD in addition to lower %PVC by Holter compared with RVOT-VT patients. These parameters can help correct diagnosis in patients with unclear phenotypes

Number of pregnancies and subsequent phenotype in a cross-sectional cohort of women with arrhythmogenic cardiomyopathy

Aims We aimed to assess the relation between number of pregnancies and cardiac structure, function, and arrhythmic events in women with arrhythmogenic cardiomyopathy (AC). Methods and results We included female AC patients in a cross-sectional study. Number of pregnancies and pregnancy related symptoms were recorded. Ventricular arrhythmias were defined as aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Right and left ventricular dimensions and function, including strain analyses, were assessed by echocardiography and magnetic resonance imaging. We created a new AC severity score to grade the severity of AC disease. We included 77 women (age 47 ± 16, 43 probands and 34 AC mutation positive female relatives), 19 ± 14 years after last pregnancy. Median number of pregnancies was 2 (0–4); 19 had no previous pregnancies, 16 had 1 pregnancy, 30 had 2, and 12 had ≥3 pregnancies. Presence of a definite AC diagnosis (P = 0.36), severity of AC disease (P = 0.53), and arrhythmic events (P = 0.25) did not differ between groups of pregnancies. Number of pregnancies was related to increased right ventricular outflow tract diameter in single variable analyses [odds ratio (OR) 1.76, 95% confidence interval (CI) 1.08–2.87; P = 0.02], but not when adjusted for body surface area and age (OR 1.56, 95% CI 0.91–2.66; P = 0.11). The number of pregnancies was not associated with any other measures of cardiac structure and function. Conclusion Higher number of pregnancies did not seem to relate to a worse phenotype in women with AC

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 ± 16 years, 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 ≥4 h/week during ≥6 years 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 b 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 âVigorous exercise in patients with hypertrophic cardiomyopathyâ [1]. The current article presents supplementary data on collection and analyses of exercise parameters and genetic data in the original research article. Keywords: Hypertrophic cardiomyopathy, Exercise, Genetics, Arrhythmi

Arrhythmia initiation in catecholaminergic polymorphic ventricular tachycardia type 1 depends on both heart rate and sympathetic stimulation

Aims: Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) predisposes to ventricular tachyarrhythmias (VTs) during high heart rates due to physical or psychological stress. The essential role of catecholaminergic effects on ventricular cardiomyocytes in this situation is well documented, but the importance of heart rate per se for arrhythmia initiation in CPVT1 is largely unexplored. Methods and results: Sixteen CPVT1 patients performed a bicycle stress-test. Occurrence of VT triggers, i.e. premature ventricular complexes (PVC), depended on high heart rate, with individual thresholds. Atrial pacing above the individual PVC threshold in three patients did not induce PVCs. The underlying mechanism for the clinical observation was explored using cardiomyocytes from mice with the RyR2-R2474S (RyR2-RS) mutation, which exhibit exercise-induced VTs. While rapid pacing increased the number of Ca2+ waves in both RyR2-RS and wild-type (p<0.05), β-adrenoceptor (βAR) stimulation induced more Ca2+ waves in RyR2-RS (p<0.05). Notably, Ca2+ waves occurred despite decreased sarcoplasmic reticulum (SR) Ca2+ content in RyR2-RS (p<0.05), suggesting increased cytosolic RyR2 Ca2+ sensitivity. A computational model of mouse ventricular cardiomyocyte electrophysiology reproduced the cellular CPVT1 phenotype when RyR2 Ca2+ sensitivity was increased. Importantly, diastolic fluctuations in phosphorylation of RyR2 and SR Ca2+ content determined Ca2+ wave initiation. These factors were modulated towards increased propensity for arrhythmia initiation by increased pacing rates, but even more by βAR stimulation. Conclusion: In CPVT1, VT propensity depends on individual heart rate thresholds for PVCs. Through converging data from clinical exercise stress-testing, cellular studies and computational modelling, we confirm the heart rate-independent pro-arrhythmic effects of βAR stimulation in CPVT1, but also identify an independent and synergistic contribution from effects of high heart rate

Strain echocardiography improves prediction of arrhythmic events in ischemic and non-ischemic dilated cardiomyopathy

Background Recent evidence suggests that an implantable cardioverter defibrillator (ICD) in non-ischemic cardiomyopathy (NICM) may not offer mortality benefit. We aimed to investigate if etiology of heart failure and strain echocardiography can improve risk stratification of life threatening ventricular arrhythmia (VA) in heart failure patients. Methods This prospective multi-center follow-up study consecutively included NICM and ischemic cardiomyopathy (ICM) patients with left ventricular ejection fraction (LVEF) <40%. We assessed LVEF, global longitudinal strain (GLS) and mechanical dispersion (MD) by echocardiography. Ventricular arrhythmia was defined as sustained ventricular tachycardia, sudden cardiac death or appropriate shock from an ICD. Results We included 290 patients (67 ± 13 years old, 74% males, 207(71%) ICM). During 22 ± 12 months follow up, VA occurred in 32(11%) patients. MD and GLS were both markers of VA in patients with ICM and NICM, whereas LVEF was not (p = 0.14). MD independently predicted VA (HR: 1.19; 95% CI 1.08–1.32, p = 0.001), with excellent arrhythmia free survival in patients with MD 70 ms had highest VA incidence with an event rate of 16%/year. Conclusion Patients with NICM and normal MD had low arrhythmic event rate, comparable to the general population. Patients with ICM and MD >70 ms had the highest risk of VA. Combining heart failure etiology and strain echocardiography may classify heart failure patients in low, intermediate and high risk of VA and thereby aid ICD decision strategies