Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial

Importance The presumed proarrhythmic action of caffeineis controversial. Few studies have assessed the effect of high doses of caffeinein patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias. Objective To compare the effect of high-dose caffeineor placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test. Design, Setting, and Participants Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction Interventions Caffeine(100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffeeat 1-hour intervals, for a total of 500 mg of caffeineor placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated. Main Outcomes and Measures Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring. Results We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeineand placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P  = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P  = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test–derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeineingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeineconcentration compared with lower plasma levels ( P  = .91) or with the placebo group ( P  = .74). Conclusions and Relevance Acute ingestion of high doses of caffeinedid not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias. Trial Registration clinicaltrials.gov Identifier:NCT02045992