Prior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how ...genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter-defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown.
We interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7-10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 95% confidence interval, 0.07-0.81; dose: hazard ratio: 0.14 95% confidence interval, 0.04-0.44). Greater reduction in exercise dose conferred greater reduction in VA (
=0.01 for trend). Patients without desmosomal mutations and those with primary-prevention ICDs benefited more from exercise reduction (
=0.16 and
=0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA.
Exercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are "gene-elusive" and those with primary-prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high-risk patients to alter decision-making regarding ICD implantation.
Background
Implantable defibrillators (ICD) are an important therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC) patients at high risk of sudden death. Given the high appropriate ICD ...therapy rate, some have argued that the mere act of implanting an ICD inflates the malignant arrhythmia rate in ARVC.
Objective
To report the arrhythmic course of ARVC patients without ICDs at the fulfillment of the 2010 Task Force Criteria and explore predictors of malignant ventricular arrhythmias.
Methods
We included 131 definite ARVC patients (age 32 ± 15 years, male 39%, proband 50%) either without ICDs (N = 47) or receiving an ICD at least 6 months after the fulfillment of the diagnostic criteria. The primary outcome was a composite of cardiac arrest (both resuscitated successfully and unsuccessfully) and sustained ventricular tachyarrhythmias (cycle length< 600 milliseconds, at least 30 seconds or requiring an intervention for termination).
Results
At the fulfillment of the diagnostic criteria, ICDs were not recommended to 59 (45%) patients and declined by 22 (17%) patients. Forty (31%) patients were not recognized as having ARVC by the treating physicians. Over 8 (interquartile interval: 3–12) years, 38 (29%) patients had primary outcomes (8 cardiac arrests 3 died and 30 sustained ventricular arrhythmias) while not having ICDs. The 1‐year and 5‐year event‐free survival was 92% and 72%. Spontaneous sustained ventricular arrhythmias, cardiac syncope, men, proband, and inducibility in electrophysiology study were significantly associated with the primary outcome.
Conclusion
In a contemporary cohort, a considerable risk of malignant arrhythmias existed in ARVC when ICDs were not implanted.
High-degree atrioventricular block (AVB) recovery in CS has been shown to be highly variable despite immunosuppressive treatment, with no reliable tool available to predict odds of reversibility. ...This study sought to evaluate the potential of combined fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and resting myocardial perfusion imaging (rMPI) to predict reversibility of newly diagnosed high-grade AVB in cardiac sarcoidosis (CS).
We performed a single-center, retrospective analysis of patients with CS presenting with high-grade AVB who underwent combined FDG-PET/CT and rMPI. The 2016 JCS and the 2014 HRS diagnostic criteria were used for the diagnosis of CS. Patients with a history of coronary artery disease or prior immunosuppressive treatment were excluded. Patients were divided into AVB recovery and non-recovery subgroups. CS disease staging was based on FDG-PET and rMPI findings: (Stage 0) normal FDG-PET and rMPI (Stage 1) positive FDG-PET and normal rMPI (Stage 2) positive FDG-PET with perfusion deficits on rMPI (Stage 3) normal FDG-PET with perfusion deficits on rMPI.
Twenty-seven patients, including 13 demonstrating AVB recovery, were identified. Eleven out of fourteen (78.6%) patients presenting with stage 1 CS demonstrated AVB recovery. Stage 1 CS was significantly more present in the recovery group compared to the non-recovery group (84.6% vs 21.4%, P = .002). Eleven presented with stage 2 CS, with only 2 (18.2%) recovering AV nodal conduction. Stage 2 CS presented more frequently in the non-recovery group (64.3% vs 15.4%, P = .020).
Combined FDG-PET and rMPI employed to stage CS disease presenting with high-degree AVB appears to have good performance for predicting likelihood of recovery.
Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family ...with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM_004415.4): c.877G>A, p.(Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life‐threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p = .04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 46% in cases vs. 449/1495 30% in gnomAD; p = .004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
Pacemakers and defibrillators were explanted post mortem in Canada, tested and resterilized, and implanted in patients in underserved countries. The incidence of infection at 2 years among patients ...with reused devices was not significantly different from that among matched control patients who received new devices.
Background Despite growing use of the subcutaneous implantable cardioverter-defibrillator (S- ICD ), its clinical role in arrhythmogenic right ventricular cardiomyopathy/dysplasia ( ARVC /D) patients ...remains undefined. We aim to elucidate the cardiac phenotype, implant characteristics, and long-term efficacy regarding appropriate therapy and complications in ARVC /D patients with an S- ICD implant. Methods and Results A transatlantic cohort of ARVC /D patients who underwent S- ICD implantation was analyzed for clinical characteristics, S- ICD therapy, and long-term outcome including device-related complications. The cohort included 29 patients (52% male, 76% probands, 59% with ARVC /D-associated mutation, 59% primary prevention no prior sustained ventricular arrhythmias, and 45% first-generation S- ICD devices). At implant, all inducible patients (27/29) had conversion of induced ventricular fibrillation. Two patients (7%) had superficial infections of the incision site that were treated conservatively. Over a median follow-up of 3.16 years (interquartile range: 2.21-4.51 years), all episodes (6 patients, 4% per year) of sustained ventricular arrhythmias were appropriately detected and treated. Six patients (21%) experienced 39 inappropriate shocks, with 3 requiring device explantation. Oversensing of noncardiac signal (n=4; especially myopotentials) and cardiac signal (n=4) was the most frequent etiology. No lead or device dislodgement, infection, skin erosion, or explantation related to need for antitachycardia pacing was noted. Conclusions S- ICD can effectively treat both induced and spontaneous ventricular arrhythmias in patients with ARVC /D. The rate of inappropriate shocks, although considerable, is comparable to that in ARVC /D patients treated with transvenous ICD s. When they occurred, inappropriate shocks were primarily due to cardiac and, uniquely, noncardiac oversensing. We suggest potential strategies for minimizing inappropriate therapy.
Background Diagnosis of congenital long-QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal-to-borderline resting QT interval. A 3-step algorithm based on exercise ...response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3-step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex-specific cutoffs beyond the resting QTc. Methods and Results We identified 208 LQTS likely pathogenic or pathogenic
or
variant carriers in the Canadian NLQTS (National Long-QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal-to-borderline range. The 4-minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4-minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1-minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1-minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients. Conclusions The 3-step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS.
An elevated resting heart rate has been associated with adverse cardiovascular outcomes. Its prognostic value has not specifically been examined in patients with atrial fibrillation.
The purpose of ...this study was to assess the relationship between resting heart rate measured in sinus rhythm and in atrial fibrillation and subsequent hospitalizations and death.
An analysis of individual patient-level data from subjects enrolled in the AFFIRM and AF-CHF trials was conducted to determine the impact of resting heart rate on hospitalizations and mortality. Separate analyses were performed in atrial fibrillation and sinus rhythm. A total of 7159 baseline ECGs (4848 in atrial fibrillation, 2311 in sinus rhythm) were analyzed in 5164 patients (34.8% female, age 68.2 ± 8.3 years).
During mean follow-up of 40.8 ± 16.3 months, 1016 patients died (668 cardiovascular deaths), and 3150 required at least 1 hospitalization (2215 cardiovascular). An elevated baseline heart rate in sinus rhythm was associated with increased all-cause mortality hazard ratio (HR) 1.24 per 10 bpm increase, 95% confidence interval (CI) 1.14-1.36, P < .0001. In contrast, a baseline heart rate in atrial fibrillation was not associated with mortality. However, compared to heart rates 90-114 bpm in atrial fibrillation, a heart rate >114 bpm was independently associated with all-cause (HR 1.18, 95% CI 1.06-1.31, P = .0018) and cardiovascular (HR 1.25, 95% CI 1.10-1.42, P = .0005) hospitalizations.
In patients with a history of atrial fibrillation, an elevated baseline heart rate in sinus rhythm is independently associated with mortality. In contrast, the baseline heart rate in atrial fibrillation is not associated with mortality but predicts hospitalizations.
Genetic heart diseases are common causes of sudden cardiac death (SCD) in the young and are typically divided into inherited cardiomyopathies and primary electrical heart diseases. Cardiomyopathies ...associated with risk of SCD include hypertrophic cardiomyopathy (HCM) and arrhythmogenic cardiomyopathy (ACM). The latter includes arrhythmogenic right ventricular cardiomyopathy (ARVC) as well as ACM primarily affecting the left ventricle, such as lamin cardiomyopathy. Primary electrical diseases more commonly seen in clinical practice include Brugada syndrome (BrS) and long QT syndrome (LQTS). Risk stratification of SCD is a central component of the management of patients with these genetic heart diseases. Numerous risk factors have been identified with variable degrees of scientific evidence. More recently, risk prediction models have been developed to estimate the absolute risk of sustained arrhythmias and SCD, to support clinicians and patients in decision making regarding prophylactic implantable cardioverter-defibrillators (ICDs). This paper provides a practical review of the current literature on risk stratification in ARVC and other ACMs, HCM, BrS, and LQTS, and summarises current recommendations for ICD use.
Les cardiopathies génétiques constituent une cause courante de mort cardiaque subite (MCS) chez les jeunes. Elles se divisent généralement en deux types : les cardiomyopathies héréditaires et les troubles de conduction primaires. Les cardiomyopathies associées au risque de MCS comprennent la cardiomyopathie hypertrophique (CMH) et la cardiomyopathie arythmogène (CMA). Cette dernière comprend la cardiomyopathie ventriculaire droite arythmogène (CVDA) ainsi que la CMA affectant principalement le ventricule gauche, comme la cardiomyopathie due à la lamine de type A mutée. Les troubles de conduction primaires les plus courants en pratique clinique comprennent le syndrome de Brugada (SB) et le syndrome du QT long (SQTL). La stratification du risque de MCS est un élément essentiel de la prise en charge des patients atteints de ces cardiopathies génétiques. De nombreux facteurs de risque ont été mis au jour avec un degré de certitude scientifique variable. Plus récemment, des modèles de prédiction du risque ont été mis au point pour estimer le risque absolu d’arythmie soutenue et de MCS afin d’aider les cliniciens et les patients à prendre des décisions touchant le recours prophylactique aux défibrillateurs cardioverteurs implantables (DCI). Dans le présent article de synthèse, nous abordons d’un point de vue pratique la littérature actuelle sur la stratification du risque dans les cas de CVDA ou d’autres CMA, de CMH, de SB et de SQTL. Nous résumons aussi les recommandations actuelles visant le recours aux DCI.
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