title: Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT02045992.
authors.affiliation: Postgraduate Program in Health Science: Cardiology and Cardiovascular Sciences, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Priccila
authors.initials: P
authors.lastname: Zuchinali
authors.affiliation: Department of Nutrition, Medical School, Federal University of Rio Grande do Sul, Porto Alegre.
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Souza
authors.affiliation: Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Maurício
authors.initials: M
authors.lastname: Pimentel
authors.affiliation: Cardiovascular Division, University Hospital, Federal University of Santa Maria, Santa Maria, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Chemello
authors.affiliation: medical student at Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Zimerman
authors.affiliation: medical student at Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Giaretta
authors.affiliation: Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Joyce
authors.initials: J
authors.lastname: Salamoni
authors.affiliation: Postgraduate Program in Health Science: Cardiology and Cardiovascular Sciences, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Bianca
authors.initials: B
authors.lastname: Fracasso
authors.affiliation: Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil6Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Leandro I
authors.initials: LI
authors.lastname: Zimerman
authors.affiliation: Postgraduate Program in Health Science: Cardiology and Cardiovascular Sciences, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil3Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil6Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Rohde
mesh_terms: D018880:Atrial Premature Complexes / Q000503:physiopathology*; D001794:Blood Pressure / Q000502:physiology; D002110:Caffeine / Q000008:administration & dosage* / Q000097:blood; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005080:Exercise Test; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D013599:Systole / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D018879:Ventricular Premature Complexes / Q000503:physiopathology*
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine