Nadolol decreases the incidence and severity of ventricular arrhythmias during exercise stress testing compared with β1-selective β-blockers in patients with catecholaminergic polymorphic ventricular tachycardia

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disease predisposing to malignant ventricular arrhythmias.ObjectiveWe aimed to explore the incidence and severity of ventricular arrhythmias in patients with CPVT before the initiation of β-blocker treatment, when treated with β1-selective β-blockers, and when treated with nadolol.MethodsIn this study, 34 patients with CPVT were included (mean age 34 ± 19 years; 15 (44%) women; 30 (88%) ryanodine receptor 2 variant positive). We performed 3 bicycle exercise stress tests in each patient: (1) before the initiation of β-blocker treatment, (2) after >6 weeks of treatment with β1-selective β-blockers and (3) after >6 weeks of treatment with nadolol. We recorded resting and maximum heart rates and the most severe ventricular arrhythmia occurring. Severity of arrhythmias was scored as 1 point for no arrhythmias or only single ventricular extrasystoles, 2 points for >10 ventricular extrasystoles per minute or bigeminy, 3 points for couplets, and 4 points for nonsustained ventricular tachycardia or sustained ventricular tachycardia.ResultsResting heart rate was similar during treatment with nadolol and β1-selective β-blockers (54 ± 10 beats/min vs 56 ± 14 beats/min; P = .50), while maximum heart rate was lower during treatment with nadolol compared with β1-selective β-blockers (122 ± 21 beats/min vs 139 ± 24 beats/min; P = .001). Arrhythmias during exercise stress testing were less severe during treatment with nadolol compared with during treatment with β1-selective β-blockers (arrhythmic score 1.6 ± 0.9 vs 2.5 ± 0.8; P < .001) and before the initiation of β-blocker treatment (arrhythmic score 1.6 ± 0.9 vs 2.7 ± 0.9; P = .001); however, no differences were observed during treatment with β1-selective β-blockers compared with before the initiation of β-blocker treatment (arrhythmic score 2.5 ± 0.8 vs 2.7 ± 0.9; P = .46).ConclusionThe incidence and severity of ventricular arrhythmias decreased during treatment with nadolol compared with during treatment with β1-selective β-blockers. β1-Selective β-blockers did not change the occurrence or severity of arrhythmias compared with no medication

Cardiac Mechanical Alterations and Genotype Specific Differences in Subjects With Long QT Syndrome

AbstractObjectivesThis study aimed to explore systolic and diastolic function and to investigate genotype-specific differences in subjects with long QT syndrome (LQTS).BackgroundLQTS is an arrhythmogenic cardiac ion channelopathy that traditionally has been considered a purely electrical disease. The most commonly affected ion channels are the slow potassium channel, IKs (KCNQ1 gene/LQT1), and the rapid potassium channel, IKr (KCNH2 gene/LQT2). Recent reports have indicated mechanical abnormalities in patients with LQTS.MethodsWe included 192 subjects with genotyped LQTS (139 LQT1, 53 LQT2). Healthy persons of similar age and sex as patients served as controls (n = 60). Using echocardiography, we assessed systolic function by left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and contraction duration (16 LV segments). Mechanical dispersion was calculated as standard deviation of contraction duration. Time difference between contraction duration and QT interval from electrocardiography (ECG) was defined as electromechanical time difference. We assessed diastolic function by transmitral filling velocities, early diastolic myocardial velocity (e′), and left atrial volume index (LAVI). Heart rate corrected QT interval (QTc) was assessed from 12-lead ECG.ResultsSystolic function by GLS was reduced in subjects with LQTS compared with healthy controls (−22.1 ± 2.1% vs. −23.0 ± 2.0%, p = 0.01), and GLS was worse in subjects with LQT2 compared with subjects with LQT1 (p = 0.01). Subjects with LQTS had longer contraction duration (426 ± 41 ms vs. 391 ± 36 ms, p < 0.001) and more dispersed contractions (33 ± 14 ms vs. 21 ± 7 ms, p < 0.001) compared with healthy controls. Diastolic function was also reduced in subjects with LQTS compared with healthy controls; e′ was lower (10.7 ± 2.7 cm/s vs. 12.5 ± 2.0 cm/s, p < 0.001), and LAVI was increased (30 ± 8 ml/m2 vs. 26 ± 5 ml/m2, p = 0.01), also when adjusted for age and other possible confounders.ConclusionsSubjects with LQTS had a consistent reduction in both systolic and diastolic function compared with healthy controls. Differences in myocardial function between subjects with LQT1 and subjects with LQT2 may indicate that mechanical alterations in LQTS are genotype specific

Arrhythmogenic right ventricular cardiomyopathy (ARVC)- Impact of exercise on cardiac outcome, differential diagnoses and risk stratification of arrhythmic events

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease with risk of ventricular arrhythmia, heart failure and sudden cardiac death. We investigated 110 mutation-positive ARVC subjects (37 athletes). Athletic activity was associated with impaired myocardial function and increased frequency of ventricular arrhythmia in individuals with ARVC. Athletic activity may aggravate and accelerate cardiac disease in ARVC. Right ventricular outflow tract ventricular tachycardia (RVOT-VT) is supposed to be a benign disease, while ARVC is a far from a benign disease. Discrimination between early phase ARVC and RVOT-VT can be challenging. In totally 165 patients, we showed that individuals with early phase ARVC had worse impact on the RV and lower amount of premature ventricular beats compared to RVOT-VT patients. These new parameters may help correct diagnosis in patients with unclear phenotypes. Prediction of arrhythmic events in early phase ARVC is challenging. We investigated early risk markers to improve risk stratification in 162 ARVC subjects. In early ARVC, signal averaged ECG and RV parameters were early risk markers. A combination of new echocardiographic and electrical parameters improved risk stratification in early ARVC

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

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

Harmful effects of exercise intensity and exercise duration in patients with arrhythmogenic cardiomyopathy

Objectives The goal of this study was to explore the association between exercise duration versus exercise intensity and adverse outcome in patients with arrhythmogenic cardiomyopathy (AC). Background Vigorous exercise aggravates and accelerates AC, but there are no data assessing the harmful effects of exercise intensity and duration in these patients. Methods Exercise habits at time of diagnosis were recorded by standardized interviews in consecutive AC patients. Exercise >6 metabolic equivalents was defined as high intensity, and exercise duration was categorized as long if above median. Life-threatening ventricular arrhythmia (VA) was defined as aborted cardiac arrest, documented sustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy. Results We included 173 AC patients (53% probands; 44% female; 41 ± 16 years of age). Median weekly exercise duration was 2.5 h (interquartile range: 2.0 to 5.5 h), and 91 patients (52%) reported high-intensity exercise. VA had occurred in 83 patients (48%) and was more prevalent in patients with high-intensity exercise than low-intensity exercise (74% vs. 20%, p < 0.001), and more prevalent in long-duration than short-duration exercise (65% vs. 31%, p < 0.001). High-intensity exercise was a strong and independent marker of VA, even when adjusted for the interaction with long-duration exercise (odds ratio: 3.8; 95% confidence interval: 1.3 to 11.0, p < 0.001), whereas long-duration exercise was not. Conclusions High-intensity exercise was a strong and independent marker of life-threatening VA in AC patients, independent of exercise duration. AC patients could be advised to restrict their exercise intensity

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