Spectrum and prognostic significance of arrhythmias on ambulatory Holter electrocardiogram in hypertrophic cardiomyopathy

ObjectivesThe goal of this study was to assemble a profile and assess the significance of arrhythmias in a nontertiary-based hypertrophic cardiomyopathy (HCM) cohort.BackgroundHypertrophic cardiomyopathy is associated with arrhythmia-related consequences, particularly sudden death. Ventricular tachyarrhythmias on Holter electrocardiograms (ECG) have been reported as markers for sudden death in highly selected HCM populations.MethodsWe assessed the profile of ventricular and supraventricular ectopy and bradyarrhythmia on ambulatory 24-h Holter ECG and also related these findings to clinical outcome in 178 HCM patients.ResultsOf the 178 study patients, 157 (88%) had premature ventricular complexes (PVCs), including 21 (12%) with ≥500 PVCs, 74 (42%) had couplets, 67 (37%) had supraventricular tachycardia (SVT), and 56 (31%) had nonsustained ventricular tachycardia (NSVT). Mean number of PVCs was 330 ± 763 (range 1 to 5,435) and increased with age (p < 0.01); NSVT was associated with greater left ventricular hypertrophy (p = 0.01) and severe symptoms (New York Heart Association functional classes III and IV) (p = 0.04); SVT occurred more commonly in patients with outflow obstruction (p = 0.02). Over a follow-up of 5.5 ± 3.4 years, 11 (6%) patients died suddenly (annual mortality rate, 1.1%) including 5 patients with NSVT. For sudden death, NSVT on Holter ECG had negative and positive predictive values of 95% and 9%, and sensitivity and specificity of 45% and 69%, respectively.ConclusionsIn this nontertiary-based HCM cohort, ventricular and supraventricular tachyarrhythmias were particularly frequent and demonstrated a broad spectrum on ambulatory (Holter) ECG. Paradoxically, despite such a highly arrhythmogenic substrate, sudden death events proved to be relatively uncommon. Ventricular tachyarrhythmias had a low positive and relatively high negative predictive value for sudden death in this HCM population

Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy

Background— End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results— Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients ≤40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3±3 years. Duration from onset of HCM symptoms to ES identification was considerable (14±10 years), but ES onset to death/transplantation was brief (2.7±2 years). ES occurred with similar frequency in patients with or without prior myectomy ( P =0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions— ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation

Hypertrophic Cardiomyopathy Is Predominantly a Disease of Left Ventricular Outflow Tract Obstruction

Background— Nonobstructive hypertrophic cardiomyopathy (HCM) has been regarded as the predominant hemodynamic form of the disease on the basis of assessment of outflow gradient under resting conditions. We sought to prospectively define the prevalence, clinical profile, and significance of left ventricular (LV) outflow tract obstruction under resting conditions and with physiological exercise in a large HCM cohort. Methods and Results— We prospectively analyzed 320 consecutive HCM patients (age, 47±17 years), measuring LV outflow gradient at rest, with Valsalva maneuver, and with exercise echocardiography. LV outflow obstruction was present at rest and/or with exercise in 225 patients (70%); 119 had rest gradients ≥50 mm Hg and were not exercised. Of the other 201 patients with gradients <50 mm Hg at rest (average, 4±9 mm Hg), 106 developed mechanical obstruction to LV outflow resulting from mitral valve–septal contact after exercise (80±43 mm Hg), including 76 with marked gradients ≥50 mm Hg and 46 with heart failure symptoms. The remaining 95 patients (30%) had no or small gradients (<30 mm Hg) both at rest and with exercise. Valsalva maneuver underestimated the presence and magnitude of exercise-induced obstruction. Conclusions— Among those patients who come to clinical evaluation, HCM is a predominantly obstructive disease in which LV outflow gradients, frequently associated with heart failure symptoms and often identified only with exercise, are evident in most patients (ie, 70%). Identification of LV outflow obstruction with exercise echocardiography may broaden management options in HCM by identifying symptomatic patients not otherwise regarded as potential candidates for septal reduction therapy. Assessment of subaortic gradients with exercise should be a routine component of the evaluation of HCM patients without outflow obstruction under resting conditions