Effect of Atrial Fibrillation on Hypertrophic Cardiomyopathy
Abstract & Commentary
Synopsis: Atrial fibrillation is a frequent complication of hypertrophic cardiomyopathy that often represents a turning point in the clinical course of the disease. It remains to be demonstrated if aggressive antiarrhythmic therapy will alter this effect of atrial fibrillation on prognosis.
Source: Olivotto I, et al. Circulation. 2001;104: 2517-2524.
Olivotto and colleagues analyzed the prevalence and prognostic significance of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). Data from patients with HCM who were followed at 2 community-based HCM clinics (Florence, Italy, and Minneapolis, Minn) were combined yielding a study group of 480 patients. The mean duration of follow-up was 9.1 ± 6 years. The mean age at diagnosis was 45 ± 20 years. Patients were followed according to standard clinical practice at the time. Atrial fibrillation was documented based on ECG recordings and was classified as either exclusively paroxysmal, paroxysmal converting to chronic (ie, persistent), or exclusively chronic. For survival analysis, 3 modes of HCM -related deaths were defined: 1) sudden unexpected deaths; 2) heart failure-related deaths; and 3) stroke-related deaths.
AF was noted in 107 of the 480 patients. Twenty-five patients developed AF before the initial HCM diagnosis was made, and, for 18 of these, AF was the initial manifestation of HCM. The remaining 82 AF patients developed their arrhythmia 2 months to 29 years after the initial diagnosis of HCM. The overall prevalence of AF in the entire population was 22%. AF presented in a paroxysmal form in 77 patients, but in 32 of these it progressed to chronic AF despite aggressive attempts to maintain sinus rhythm with antiarrhythmic therapy. In those who progressed from paroxysmal to chronic AF, the average time for progression was 5.1 ± 3.5 years. AF prevalence increased progressively with age. More than 35% of the patients older than 60 years had some form of AF. However, AF was not exclusively seen in older patients. There were 39 patients who developed AF at 50 years of age or younger.
Predictors of AF among patients with sinus rhythm at the time of initial diagnosis included advanced age, advanced New York Heart Association class, and a left atrial dimension greater than 45 mm Hg. A family history of sudden death, a maximum left ventricular thickness of greater than 20 mm, and a left ventricular outflow tract gradient greater than 30 mm Hg were not independent predictors of AF.
During follow-up, 74 of the 480 patients died of HCM-related causes including 38 deaths (35%) among the 107 AF patients. In the latter group, there were 13 sudden deaths, 17 heart failure deaths, and 8 stroke-related deaths. Annual HCM-related mortality was 3% in AF patients compared with 1% in a control group of patients with similar other clinical characteristics who did not have AF. The excess risk was explained by increased mortality due to stroke and heart failure. There was no association between AF and any increased risk for sudden death. AF was associated with new or worsening symptoms in most patients. Over the long term, AF was associated with a substantial risk of progression to class III or class IV heart failure. Ischemic stroke was more frequent among AF patients than among controlled patients in sinus rhythm and resulted in 8 deaths and permanent disability in 11 additional patients. Analysis of therapy during follow-up suggested that warfarin reduced the risk of ischemic stroke. The efficacy of antiarrhythmic therapy in improving outcomes was not clearly shown. Olivotto et al concluded that AF is a frequent complication of HCM that often represents a turning point in the clinical course of the disease. It remains to be demonstrated if aggressive antiarrhythmic therapy will alter this effect of AF on prognosis.
Comment by John P. DiMarco, MD, PhD
This retrospective analysis of data from 2 community- based HCM treatment centers provides important information about the significance of AF in patients with HCM. The high prevalence of AF in HCM is undoubtedly due to a number of factors. The noncompliant ventricle seen in patients with HCM raises atrial pressures, and this produces atrial distention and fibrosis, the anatomic bases for AF. In addition, myocellular disarray may facilitate atrial arrhythmias in the same fashion that it produces the substrate for ventricular arrhythmias. The former mechanism is probably the major factor responsible for AF in the older patients, whereas the younger patients may have more of a primary arrhythmia.
AF eliminates the atrial component of ventricular filling and can produce rapid changes in hemodynamics in HCM patients with AF. In addition, poorly controlled ventricular rates will not allow adequate ventricular filling and can result in syncope, pulmonary edema, and even cardiac arrest. Unfortunately, the data in this paper do not suggest that standard antiarrhythmic therapy is particularly effective in preventing the development of chronic AF. However, the severity of the symptoms associated with AF in HCM patients makes vigorous attempts to identify those who will at least temporarily respond to antiarrhythmic drugs important. It remains to be seen however if we can devise an aggressive long-term antiarrhythmic therapy that can reverse the negative effect of AF on the diseased course in HCM patients.
Dr. DiMarco is Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville.