Dysfunction in the ßII spectrin-dependent cytoskeleton underlies human arrhythmia.

BACKGROUND: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked to cardiac pathologies, including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction and cardiac electric activity is not well understood and often overlooked in the cardiac arrhythmia field. METHODS AND RESULTS: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that ßII spectrin, an actin-associated molecule, is essential for the posttranslational targeting and localization of critical membrane proteins in heart. ßII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/ßII spectrin interaction, leading to severe human arrhythmia phenotypes. Mice lacking cardiac ßII spectrin display lethal arrhythmias, aberrant electric and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, ßII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes, including the Na/Ca exchanger, ryanodine receptor 2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in ßII spectrin-deficient mice. CONCLUSIONS: Our findings identify ßII spectrin as critical for normal myocyte electric activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology.

Poorer outcomes associated with more invasive lead management strategies for Abbott Riata® leads: a large, multicenter experience.

BACKGROUND: Over 100,000 Abbott Riata® were implanted in the United States before they were recalled in 2010. There are still a significant number of Abbott Riata® leads in use, and it is unclear how these leads should be managed at the time of generator change or lead malfunction. Although data comparing both Sprint Fidelis® and Abbott Riata® leads in this setting is available, there are no multicenter comparative studies of outcomes for various lead management strategies, including lead extraction (LE), lead abandonment/revision (LA), and generator change (GC) only at the time of device at elective replacement interval (ERI) for Abbott Riata® leads. METHODS: A retrospective, multicenter study was undertaken to compare short-term outcomes (major complications-MC, death, extended or re-hospitalizations within 60 days-RH, lead malfunction-LM) and total outcomes (short-term outcomes & lead malfunction during follow-up) of patients with Riata® leads undergoing LE, LA, or GC. RESULTS: 152 patients (65 ± 13 years, 68% male) were followed for a mean 33 ± 30 months following intervention. Out of 166 procedures, 13 patients underwent LE, 16 patients underwent LA, and 137 patients underwent GC. There was 1 major complication in each group, yielding an event rate of 7.7% for LE, 6.3% for LA, and 0.7% for GC cohorts. There were significantly more short-term and total adverse outcomes in the group of patients getting LE and LA versus GC only (38.5% & 31.3% vs 7.3%, P < 0.001). Total Riata® lead dwell time follow-up was 17,067 months. A total of 3 Riata® lead malfunctions were noted during long-term follow-up. Inappropriate shocks were similar between LE 7.7% (1/13), LA 6.3% (1/16). and GC 11.0% (4/136); P = 0.57. CONCLUSIONS: There were more short-term and total adverse outcomes in more invasive management strategies (LE and LA) versus GC alone. The failure rate of Riata® leads was substantially lower compared to previous reports. Therefore, we recommend only performing battery exchange when a device with an active Riata® lead is at ERI, unless there is malfunction of the Riata® lead noted on testing. There were significantly more short-term adverse outcomes in the lead extraction (5/13) and lead abandonment/revision (5/16) groups than the generator only (8/137) group (P < 0.001). GIB - Gastrointestinal bleed, CHF - congestive heart failure, NSTEMI - non-ST elevation MI.

2022 HRS expert consensus statement on evaluation and management of arrhythmic risk in neuromuscular disorders.

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs.

Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1.

BACKGROUND: Sudden death can occur as a consequence of cardiac-conduction abnormalities in the neuromuscular disease myotonic dystrophy type 1. The determinants of the risk of sudden death remain imprecise. METHODS: We assessed whether the electrocardiogram (ECG) was useful in predicting sudden death in 406 adult patients with genetically confirmed myotonic dystrophy type 1. A patient was characterized as having a severe abnormality if the ECG had at least one of the following features: rhythm other than sinus, PR interval of 240 msec or more, QRS duration of 120 msec or more, or second-degree or third-degree atrioventricular block. RESULTS: Patients with severe abnormalities according to the entry ECG were older than patients without severe abnormalities, had more severe skeletal-muscle impairment, and were more likely to have heart failure, left ventricular systolic dysfunction, or atrial tachyarrhythmia. Such patients were more likely to receive a pacemaker or an implantable cardioverter-defibrillator during the follow-up period. During a mean follow-up period of 5.7 years, 81 patients died; there were 27 sudden deaths, 32 deaths from progressive neuromuscular respiratory failure, 5 nonsudden deaths from cardiac causes, and 17 deaths from other causes. Among the 17 patients who died suddenly in whom postcollapse rhythm was evaluated, a ventricular tachyarrhythmia was observed in 9. A severe ECG abnormality (relative risk, 3.30; 95% confidence interval [CI], 1.24 to 8.78) and a clinical diagnosis of atrial tachyarrhythmia (relative risk, 5.18; 95% CI, 2.28 to 11.77) were independent risk factors for sudden death. CONCLUSIONS: Patients with adult myotonic dystrophy type 1 are at high risk for arrhythmias and sudden death. A severe abnormality on the ECG and a diagnosis of an atrial tachyarrhythmia predict sudden death. (ClinicalTrials.gov number, NCT00622453.)

Pacemaker and implantable cardioverter-defibrillator use in a US myotonic dystrophy type 1 population.

INTRODUCTION: We assessed implant rates, indications, characteristics, and outcomes in patients with the neuromuscular disease, myotonic dystrophy type 1 (DM1) receiving a pacemaker or an implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: Device use was evaluated in a prospective, multicenter registry of 406 genetically confirmed adult patients followed for 9.5 ± 3.2 years. Forty-six (11.3%) had or received a pacemaker and 21 (5.2%) received an ICD. Devices were primarily implanted for asymptomatic conduction abnormalities and left ventricular (LV) systolic dysfunction. However, 7 (15.2%) pacemakers were implanted for third-degree atrioventricular block and 6 (28.6%) ICDs were implanted for ventricular tachyarrhythmias (ventricular tachycardia [VT] or fibrillation [VF]). Patients receiving devices were older and more frequently had heart failure, LV systolic dysfunction, atrial tachyarrhythmias, and ECG conduction abnormalities compared to nondevice patients. Five (10.9%) pacemaker patients underwent upgrade to an ICD, 3 for LV systolic dysfunction, 1 for VT/VF, and 1 for progressive conduction disease. Seventeen (27.4%) of the 62 patients with devices were pacemaker-dependent at last follow-up. Three (14.3%) ICD patients had appropriate therapies. Twenty-four (52.2%) pacemaker patients died including 13 of respiratory failure and 7 of sudden death. Seven (33.3%) ICD patients died including 2 of respiratory failure and 3 of sudden death. The patients with ICDs and sudden death all had LV systolic dysfunction and 1 death was documented due to inappropriate therapies. CONCLUSIONS: DM1 patients commonly receive antiarrhythmia devices. The risk of VT/VF and sudden death suggests that ICDs rather than pacemakers should be considered for these patients.

Burnout and Well-Being Among Cardiology Fellowship Program Directors.

OBJECTIVES: The third annual Cardiovascular Diseases (CV) Fellowship Program Directors (PDs) Survey sought to understand burnout and well-being among CV fellowship PDs. BACKGROUND: Physician burnout is a common phenomenon. Data on burnout among cardiologists, specifically CV PDs, remain limited. METHODS: The survey contained 8 questions examining satisfaction, stress, and burnout among CV fellowship PDs. Burnout was defined based on the self-reported presence of ≥1 symptom of burnout, constant feelings of burnout, or complete burnout. RESULTS: Survey response rate was 57%. Most respondents were men (78%) and 54% represented university-based programs. Eighty percent reported satisfaction with their current job as PD, and 96% identified interactions with fellows as a driver of their satisfaction. Forty-five percent reported feeling a great deal of stress from their job. Stress was higher among women PDs, early-career PDs, and PDs of larger and university-based programs. Twenty-one percent reported some symptoms of burnout, and only 36% reported enjoyment without stress or burnout. Rates of enjoyment without stress or burnout were higher among men and late-career PDs, PDs of smaller programs, and PDs of community-based programs. Seventeen percent of PDs reported a high likelihood of resigning in the next year, of which the most common reason was the tasks of PDs were becoming overwhelming. CONCLUSIONS: Most CV fellowship PDs are satisfied with their position, but stress and burnout remain common. Women PDs, early-career PDs, and PDs of larger, university-based programs demonstrate more adverse markers of well-being. Opportunities exist to support CV fellowship PDs in their critical role.

Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a neurologic disorder with known cardiac involvement, including left ventricular systolic dysfunction (LVSD), heart failure (HF), atrioventricular and intraventricular conduction system disease, and sudden death. We studied the prevalence of these conditions and associated findings in a large population with DM1. METHODS: History, physical examination, genetic testing, and electrocardiography were performed on 406 patients with DM1, and cardiac imaging was performed on 180 (44.3%) of these patients. RESULTS: Left ventricular systolic dysfunction and clinical HF were found in 34 (18.9%) of 180 and in 23 (5.7%) of 406 of enrolled subjects, respectively, yielding an overall prevalence of LVSD/HF in 41 (10.1%) of 406. Increasing age, male sex, electrocardiographic conduction abnormalities, presence of atrial and ventricular arrhythmias, and implanted devices were all significantly associated with LVSD/HF, whereas cytosine-thiamine-guanine repeat length and neuromuscular severity score were not. The interval≥240 milliseconds (relative risk 4.1, 95% CI 1.7-9.6, P=.001) and QRS duration≥120 milliseconds (relative risk 4.2, 95% CI 2.0-8.5, P<.001) were significant predictors of LVSD/HF. The presence of LVSD/HF was also significantly associated with all-cause death (relative risk 3.9, 95% CI 2.3-6.4, P<.001) and cardiac death (relative risk 5.7, 95% CI 2.6-12.4, P<.001). CONCLUSIONS: A significant prevalence of LVSD/HF exists in patients with DM1. The presence of LVSD/HF in DM1 is significantly associated with all-cause and cardiac death.

Management and long-term outcomes associated with recalled implantable cardioverter-defibrillator leads: A multicenter experience.

BACKGROUND: No comparative study of outcomes in Riata and Sprint Fidelis leads undergoing lead extraction (LE), lead abandonment (LA), and generator change only (GC) has been published. OBJECTIVES: Determine outcomes (major complications [MC]; death, extended hospitalization, or rehospitalization within 60 days [RH]; lead malfunction) of LE, LA, and GC for recalled leads. METHODS: Retrospective, multicenter, comparative study. RESULTS: A total of 298 LE, 85 LA, and 310 GC were performed. In the clinical setting of a lead intervention, there was no difference in a composite of MC, death, RH, lead revision, inappropriate shocks, or device infection between LE and LA groups (15% vs 22%, P = .140). In the clinical setting of a device at elective replacement interval (ERI), there were significantly more acute events at 60 days (MC, death, and RH) in the LE and LA groups at 15.4% (4) and 15.4% (4), and this was significantly (P = .017) higher than the GC group at 5.1% (16). There was no difference (P = 1.000) in the composite of MC, death, RH, lead malfunction, lead revisions, device infections, or inappropriate shocks between LE, LA, and GC groups at 15.4% (4), 15.4% (4), and 17.4% (54), respectively. Following generator change, 14 of 175 Fidelis leads and 3 of 135 Riata leads failed over a total of 12,714 months of follow-up. CONCLUSIONS: The failure rate of recalled leads was substantially lower compared to previous reports. It may be prudent to perform generator change only when the device is at ERI, especially when the recalled lead has historical performance that likely outweighs the risks of extraction/abandonment.

Program Directors Survey on Diversity in Cardiovascular Training Programs.

BACKGROUND: Women and minorities are under-represented in cardiovascular disease (CVD) specialties. It remains unknown how characteristics of the CVD learning environment affect diversity and how program directors (PDs) approach these critical issues. OBJECTIVES: The second annual Cardiovascular PD Survey aimed to investigate characteristics of the CVD learning environment that may affect diversity and strategies PDs use to approach these issues. METHODS: The survey contained 20 questions examining U.S.-based CVD PD perceptions of diversity in CVD and related characteristics of the CVD fellowship learning environment. RESULTS: In total, 58% of PDs completed the survey. Responding programs demonstrated geographic diversity. The majority were university-based or -affiliated. A total of 86% of PDs felt diversity in CVD as a field needs to increase, and 70% agreed that training programs could play a significant role in this. In total, 89% of PDs have attempted to increase diversity in fellowship recruitment. The specific strategies used were associated with PD sex and the presence of under-represented minority trainees in the program. PDs identified lack of qualified candidates and overall culture of cardiology as the 2 most significant barriers to augmenting diversity. A majority of programs have support systems in place for minority fellows or specific gender groups, including procedures to report issues of harassment or an unsafe learning environment. PDs identified shared best practices for recruitment and implicit bias training, among others, as important resources in their efforts to support diversity in CVD training. CONCLUSIONS: Diversity is important to CVD PDs. They are striving to increase it in their programs through recruitment and strategies directed toward the fellowship learning environment. The CVD community has opportunities to standardize strategies and provide national resources to support PDs in these critical efforts.

Clinical Care Recommendations for Cardiologists Treating Adults With Myotonic Dystrophy.

Myotonic dystrophy is an inherited systemic disorder affecting skeletal muscle and the heart. Genetic testing for myotonic dystrophy is diagnostic and identifies those at risk for cardiac complications. The 2 major genetic forms of myotonic dystrophy, type 1 and type 2, differ in genetic etiology yet share clinical features. The cardiac management of myotonic dystrophy should include surveillance for arrhythmias and left ventricular dysfunction, both of which occur in progressive manner and contribute to morbidity and mortality. To promote the development of care guidelines for myotonic dystrophy, the Myotonic Foundation solicited the input of care experts and organized the drafting of these recommendations. As a rare disorder, large scale clinical trial data to guide the management of myotonic dystrophy are largely lacking. The following recommendations represent expert consensus opinion from those with experience in the management of myotonic dystrophy, in part supported by literature-based evidence where available.

Principles of electroanatomic mapping.

Electrophysiologic testing and radiofrequency ablation have evolved as curative measures for a variety of rhythm disturbances. As experience in this field has grown, ablation is progressively being used to address more complex rhythm disturbances. Paralleling this trend are technological advancements to facilitate these efforts, including electroanatomic mapping (EAM). At present, several different EAM systems utilizing various technologies are available to facilitate mapping and ablation. Use of these systems has been shown to reduce fluoroscopic exposure and radiation dose, with less significant effects on procedural duration and success rates. Among the data provided by EAM are chamber reconstruction, tagging of important anatomic landmarks and ablation lesions, display of diagnostic and mapping catheters without using fluoroscopy, activation mapping, and voltage (or scar) mapping. Several EAM systems have specialized features, such as enhanced ability to map non-sustained or hemodynamically unstable arrhythmias, ability to display diagnostic as well as mapping catheter positions, and wide compatibility with a variety of catheters. Each EAM system has its strengths and weaknesses, and the system chosen must depend upon what data is required for procedural success (activation mapping, substrate mapping, cardiac geometry), the anticipated arrhythmia, the compatibility of the system with adjunctive tools (i.e. diagnostic and ablation catheters), and the operator's familiarity with the selected system. While EAM can offer significant assistance during an EP procedure, their incorrect or inappropriate application can substantially hamper mapping efforts and procedural success, and should not replace careful interpretation of data and strict adherence to electrophysiologic principles.

Consensus-based care recommendations for adults with myotonic dystrophy type 1.

PURPOSE OF REVIEW: Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. RECENT FINDINGS: The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. SUMMARY: The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.

Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a postinfarction heart failure canine model.

BACKGROUND: Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects. METHODS AND RESULTS: We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048), increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8+/-13.6 mm Hg (P=0.02). CONCLUSIONS: Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.

Prognostic importance of wall motion abnormalities in patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator.

Patients with extensive regional wall motion abnormalities are predisposed to development of ventricular tachyarrhythmia. The prognostic effect of this in patients with an implantable cardioverter-defibrillator (ICD) and coronary artery disease (CAD) is not known. Echocardiographic left ventricular systolic indexes, wall motion score index (WMSI), and extent of regional akinesia in 140 patients (65 +/- 10 years old; 92% men) with an ICD and CAD were studied. Arrhythmic events requiring ICD therapy and causing death (n = 41, 29%) were recorded over a mean follow-up of 1.4 +/- 0.8 years. Left ventricular basal fractional shortening, ejection fraction, global WMSI, and extent of akinesia, especially in the inferoposterior regions of a right coronary artery territory, were univariate predictors (all p values <0.05). Global WMSI (hazard ratio 2.18, 95% confidence interval 1.03 to 4.65, p = 0.04) and fractional shortening (hazard ratio 0.93, 95% confidence interval 0.88 to 1.00, p = 0.04) were multivariate predictors. Global WMSI (p = 0.04) and > or =2 right coronary region akinetic segments (p = 0.05) provided incremental risk prediction to left ventricular ejection fraction in a global risk-assessment model (chi-square p = 0.001). Presence of right coronary region akinesia better identified those at increased risk of events (p = 0.02) compared with the presence of left anterior descending region akinesia (p = 0.2), independent of systolic function. In conclusion, global WMSI and left ventricular basal fractional shortening were important additional risk predictors of ICD events in CAD. Global WMSI and right coronary region inferoposterior akinesia provided independent and incremental risk assessment to left ventricular ejection fraction and improved identification of those at increased risk of ICD-related events in patients with ischemic cardiomyopathy.