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.

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.

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.

Utility of Conventional Electrocardiographic Criteria in Patients With Idiopathic Ventricular Tachycardia.

OBJECTIVES: This study sought to determine the ability of conventional electrocardiographic (ECG) criteria to correctly differentiate idiopathic ventricular tachycardia (VT) from supraventricular tachycardia (SVT) with aberrancy. BACKGROUND: Previously reported VT ECG criteria were developed from cohorts of patients with structural heart disease and have not been applied to patients with idiopathic VT. METHODS: ECGs of 115 idiopathic VTs, 101 post-myocardial infarction (MI) VTs, and 111 wide QRS SVTs were analyzed using standard criteria. VT was diagnosed in patients when at least 1 criterion was met, SVT when no criteria were met, and indeterminate when there were conflicting criteria. RESULTS: Standard ECG criteria more frequently diagnosed VT in the post-MI group than the idiopathic group (95% vs. 82%, respectively; p < 0.01). Diagnosis in only 12 of the 111 SVT patients (11%) met the criteria for VT. All patients in the idiopathic VT group with right branch bundle block morphology who did not meet VT criteria demonstrated an rsR' pattern in V1 (consistent with SVT). Among idiopathic VT patients, Purkinje-associated VT had the lowest sensitivity for correct VT diagnosis in 13 of 23 patients (57%), septal sites of origin were correctly diagnosed in only 56 of 76 patients (74%), whereas nonseptal sites had a high sensitivity in 35 of 35 patients (100%; p < 0.005). CONCLUSIONS: Conventional ECG criteria have reduced sensitivity to distinguish VT from SVT with aberrancy in patients with idiopathic VT. This is most pronounced in VT originating from septal sites, particularly Purkinje sites and the septal outflow tract regions. Clinicians should be aware that application of conventional ECG criteria in idiopathic VT may underdiagnose VT.

Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel.

BACKGROUND: The etiology of conduction disturbances necessitating permanent pacemaker (PPM) implantation is often unknown, although familial aggregation of PPM (faPPM) suggests a possible genetic basis. We developed a pan-cardiovascular next generation sequencing (NGS) panel to genetically characterize a selected cohort of faPPM. MATERIALS AND METHODS: We designed and validated a custom NGS panel targeting the coding and splicing regions of 246 genes with involvement in cardiac pathogenicity. We enrolled 112 PPM patients and selected nine (8%) with faPPM to be analyzed by NGS. RESULTS: Our NGS panel covers 95% of the intended target with an average of 229x read depth at a minimum of 15-fold depth, reaching a SNP true positive rate of 98%. The faPPM patients presented with isolated cardiac conduction disease (ICCD) or sick sinus syndrome (SSS) without overt structural heart disease or identifiable secondary etiology. Three patients (33.3%) had heterozygous deleterious variants previously reported in autosomal dominant cardiac diseases including CCD: LDB3 (p.D117N) and TRPM4 (p.G844D) variants in patient 4; TRPM4 (p.G844D) and ABCC9 (p.V734I) variants in patient 6; and SCN5A (p.T220I) and APOB (p.R3527Q) variants in patient 7. CONCLUSION: FaPPM occurred in 8% of our PPM clinic population. The employment of massive parallel sequencing for a large selected panel of cardiovascular genes identified a high percentage (33.3%) of the faPPM patients with deleterious variants previously reported in autosomal dominant cardiac diseases, suggesting that genetic variants may play a role in faPPM.

Arrhythmias in the muscular dystrophies.

In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occurs with variable prevalence, mirroring the phenotypic variability seen among and within the various hereditary myopathies. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The noncardiac manifestations can lead to delayed recognition of symptoms, affect the decision to implant a prophylactic device, and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications.

Utilization rates of implantable cardioverter-defibrillators for primary prevention of sudden cardiac death: a 2012 calculation for a midwestern health referral region.

BACKGROUND: Utilization rates (URs) for implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death (PPSCD) are lacking in the community. OBJECTIVE: The purpose of this study was to establish the ICD UR in central Indiana. METHODS: A query run on 2 hospitals in a health information exchange database in Indianapolis identified patients between 2011 and 2012 with left ventricular ejection fraction (EF) ≤0.35. ICD eligibility and utilization were determined from chart review. RESULTS: We identified 1863 patients with at least 1 low EF study. Two cohorts were analyzed: 1672 patients without and 191 patients with International Classification of Diseases, Ninth Revision, Clinical Modification procedure code 37.94 for ICD placement. We manually reviewed a stratified (by hospital) random sample of 300 patients from the no-ICD procedure code cohort and found that 48 (16%) had no ICD but had class I indications for ICD. Eight of 300 (2.7%) actually had ICD implantation for PPSCD. Review of all 191 patients in the ICD procedure code cohort identified 70 with ICD implantation for PPSCD. The ICD UR (ratio between patients with ICD for PPSCD and all with indication) was 38% overall (95% confidence interval [CI] 28%-49%). URs were 48% for males (95% CI 34%-61%), 21% for females (95% CI 16%-26%, P = .0002 vs males), 40% for whites (95% CI 27%-53%), and 37% for blacks (95% CI 28%-46%, P = .66 vs whites). CONCLUSION: ICD UR is 38% among patients meeting class I indications, suggesting further opportunities for improving guideline compliance. This study also illustrates limitations in calculating ICD UR using large electronic repositories without hands-on chart review.

Change in cognitive function over 12 months among patients with an implantable cardioverter-defibrillator.

BACKGROUND: Patients with implantable cardioverter-defibrillators (ICDs) have decreased cognitive function associated with arrhythmic and/or cardiac disorders, such as ischemic cardiomyopathy. Little is known about changes in cognitive function over time among ICD patients. AIMS: The aim of this study was to evaluate baseline-to-12-month changes in cognitive function in memory (total recall and delayed recall), psychomotor speed, and executive function among ICD patients. METHODS: In this prospective study, 115 (mean [SD] age, 64.83 [9.06] years, 75% mean) and 77 ICD patients completed baseline and 12-month face-to-face interviews, respectively, which included neuropsychological tests to evaluate cognitive function. RESULTS: Patients who completed baseline and 12-month testing had decreased total and delayed recall memory (all P < .05). No significant changes from baseline to 12 months were observed in psychomotor speed (t = 0.33; P = .74) and executive function (t = -1.12; P = .27). Using 1.0 standard deviation or below the mean as a cutoff criterion, 12% to 22% of ICD patients had poor cognitive function over time. Particularly, at baseline, 17 (15%) and 15 (13%) of the 115 patients had poor memory in total and delayed recall, respectively. At 12 months, 12 (16%) and 9 (12%) of the 77 patients had poor memory in total and delayed recall, respectively. CONCLUSIONS: In this sample of patients with ICDs, memory was poor at baseline and decreased over 12 months. Future studies are indicated to determine how this change in memory influences outcomes such as medication adherence.

Arrhythmias in the muscular dystrophies.

The muscular dystrophies are a group of inherited diseases affecting skeletal muscle that also affect cardiac muscle. Cardiac involvement occurs as a degenerative process with fibrosis and fatty replacement of the myocardium. Electrophysiologists are asked to participate in the care of muscular dystrophy patients because of the risk of atrial arrhythmias, conduction disease, bradycardia, ventricular arrhythmias, and sudden death. Duchenne, Becker, and limb-girdle types 2C-2F and 2I are muscular dystrophies in which the development of a dilated cardiomyopathy is common. Arrhythmias and conduction disease occur after the development of the dilated cardiomyopathy. Patients are considered for pacemakers or implantable cardioverter-defibrillators on the basis of guidelines used for nonischemic cardiomyopathies. Myotonic types 1 and 2, Emery-Dreifuss, limb-girdle type 1B, and facioscapulohumeral muscular dystrophies present with conduction disease and associated arrhythmias and variably with a dilated cardiomyopathy. In myotonic type 1, Emery-Dreifuss, and limb-girdle type 1B muscular dystrophies, conduction abnormalities are frequent and often require pacing. Recent studies support the use of prophylactic implantable cardioverter-defibrillators rather than pacemakers. In all the muscular dystrophies, respiratory muscle involvement can impact quality and quantity of life and needs to be factored in when considering a prophylactic device.

A retrospective analysis of proceduralist-directed, nurse-administered propofol sedation for implantable cardioverter-defibrillator procedures.

BACKGROUND: There is controversy whether proceduralist-directed, nurse-administered propofol sedation (PDNAPS) is safe. OBJECTIVE: To assess the frequency of adverse events when PDNAPS is used for implantable cardioverter-defibrillator (ICD)-related procedures and to determine the patient and procedural characteristics associated with adverse events. METHODS: Consecutive ICD-related procedures using PDNAPS from May 2006 to July 2009 at a tertiary-care hospital were evaluated. Serious adverse events were defined as procedural death, unexpected transfer to an intensive care unit, respiratory failure requiring intubation/bag-mask ventilation, or hypotension requiring vasoconstrictor/inotrope support. Nonserious adverse events were defined as hypotension requiring fluid resuscitation or hypoxemia requiring augmented respiratory support with non-rebreather mask, oral airway, or jaw lift. RESULTS: Of 582 patients (age 64 ± 14 years, 72.3% males) undergoing ICD-related procedures using PDNAPS, 58 (10.0%) patients had serious adverse events with no procedural death and 225 (38.7%) had nonserious adverse events. Longer procedure duration (relative risk [RR] = 2.1 per hour; 95% confidence interval [CI] = 1.6-2.8; P < .001) and biventricular implant (RR = 2.7; CI = 1.4-5.3; P = .003) were independent predictors of serious adverse events. A longer procedure duration (RR = 1.4 per hour; CI = 1.1-1.7; P = .001), heart failure class (RR = 1.4 per 1 class; CI = 1.1-1.7; P = .002), and use of propofol infusion (RR = 3.5; CI = 2.2-5.7; P < .001) were independent predictors of nonserious adverse events. CONCLUSION: PDNAPS for shorter ICD procedures including single- and dual-chamber implants, generator changes, and defibrillation threshold testing have acceptable rates of serious adverse events and manageable nonserious adverse events and should be considered for further study. Biventricular implants and other complex procedures should be done with an anesthesiologist.

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.

Survival and CTG repeat expansion in adults with myotonic dystrophy type 1.

INTRODUCTION: An association is observed between the severity of myotonic dystrophy type 1 (DM1) and the genetic abnormality of cytosine-thymine-guanine (CTG) repeat expansion. It is unknown whether an association exists between survival and CTG repeat expansion. METHODS: In an adult 406-patient DM1 cohort, the phenotype, including survival age, was evaluated in relation to CTG repeat expansion. RESULTS: At study entry, age was 42 ± 12 (range 18-78) years, with a CTG repeat length of 629 ± 386 (range 54-1965). An inverse correlation was observed between CTG repeat length and the age at onset and younger DM1 phenotype. Over a follow-up of 9.2 ± 3.1 years, 118 (29.1%) patients died, including 60 of neuromuscular respiratory failure, 41 of cardiac causes, and 17 of non-neuromuscular, non-cardiac causes. There was an inverse relationship between all-cause survival and CTG length (relative risk 5.4 per log repeat, 95% confidence interval 2.9-10.2, P < 0.001). CONCLUSION: The data demonstrate a genotype-mortality association in DM1.

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.