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Original Investigation
December 2016

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

Author Affiliations
  • 1Postgraduate Program in Health Science: Cardiology and Cardiovascular Sciences, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
  • 2Department of Nutrition, Medical School, Federal University of Rio Grande do Sul, Porto Alegre
  • 3Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
  • 4Cardiovascular Division, University Hospital, Federal University of Santa Maria, Santa Maria, Brazil
  • 5medical student at Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
  • 6Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
JAMA Intern Med. 2016;176(12):1752-1759. doi:10.1001/jamainternmed.2016.6374
Key Points

Question  Is there a proarrhythmic action of caffeine in patients with heart failure?

Findings  In this randomized clinical trial, we evaluated the short-term effects of high-dose caffeine in patients with heart failure at increased risk for arrhythmic events. After 500 mg of caffeine administered over a 5-hour period, we found no statistically significant effect of caffeine ingestion on the frequency of ventricular or supraventricular ectopies, even during the physical stress of a treadmill test.

Meaning  These results challenge the intuitive perception that caffeine intake should be limited in patients with heart disease and at risk for arrhythmia.


Importance  The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias.

Objective  To compare the effect of high-dose caffeine or 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 <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015.

Interventions  Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or 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 caffeine and 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 caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74).

Conclusions and Relevance  Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias.

Trial Registration  clinicaltrials.gov Identifier: NCT02045992