1. Introduction
Caffeine is a central nervous system stimulant and is the most widely consumed psychoactive drug with approximately 80% of adults consuming it in the United States [1] . Caffeine acts as a cognitive enhancer through increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP), and can be found in many forms including coffee, energy drinks, oral pills, and injectables [2] .
Heart arrhythmias are irregular heartbeats that can cause cardiovascular events including heart failure, strokes, and myocardial infarctions. About 48 out of 100,000 adults have ventricular arrhythmias, abnormal heart beats in the lower chambers of the heart [3] . Heart arrhythmias occur when the electrical signals that control the heart’s beating are not functioning properly. They can be tachycardias (fast heartbeats), bradycardias (slow heartbeats), or irregular beats (atrial fibrillation (AF)) [4] . Caffeine is linked to tachycardia, which is a risk factor for supraventricular tachycardias, AF, and ventricular arrhythmias due to very rapid heartbeats [5] . Caffeine can also cause other cardiovascular problems such as hypertension [6] .
It is hypothesized that there is a dose-dependent relationship between caffeine and heart arrhythmias, but the exact relationship between the two has not been established. In addition to heart rhythm issues, caffeine can also spike blood pressure and cause cerebrovascular accidents and myocardial infarctions [6] . One in four people consumes caffeine sources three or more times a day. Given its vast and high consumption, there is a need to better understand the relationship between caffeine and arrhythmia [7] . The purpose of this study was to characterize the relationship between caffeine intake and heart arrhythmias.
2. Methods
A comprehensive medical literature search was conducted utilizing the search terms “caffeine arrhythmia” on PubMed. The search was limited to publications of randomized clinical trials, meta-analysis, and systematic reviews recently published in English since 2010. Studies must have discussed caffeine and its impact on heart arrhythmias. Studies not published in English, literature review type manuscripts, and studies that did not discuss both caffeine and heart arrhythmias were excluded from this medical literature review.
Parameters of interest include the author/study name, study type, intervention, primary endpoints of included study, results, and key study conclusions. The impact of caffeine consumption on a cardiovascular related outcome and any safety considerations were also recorded (Figure 1 and Table 1).
3. Results
After initial screening, 26 studies that met the search terms were identified, of which 13 met the inclusion criteria. A total of 13 studies were eligible and relevant for this medical review, of which 7 were randomized controlled clinical trials, 3 were meta analyses, and 3 were systematic reviews.
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Table 1. Summary of selected clinical studies assessing the impact of caffeine on heart rhythms.
Table Legend: VA = Ventricular arrhythmias; AF = Atrial Fibrillation; HFrEF = Heart failure with reduced ejection fraction; CI = confidence interval; RR = relative risk; VPM = Ventricular premature beats; SUN = Seguimiento Universidad de Navarra; PREDIMED = Prevencion con Dieta Maditerranea; HFrEF = heart failure and left ventricular systolic dysfunction; HR = heart rate; Atrial Fibrillation Effect on Quality of Life = AFEQT; LQTS = long qt syndrome; QTc = corrected QT interval; ED = energy drinks; SVES = supraventricular extrasystoles; ECG = electrocardiographic.
3.1. Caffeine Consumption and Atrial Fibrillation
Several studies evaluated the impact of caffeine consumption and risk of AF. A meta-analysis suggested that 40 - 180 mg of caffeine consumption through coffee sources did not increase risk of AF [8] . Additionally, 436 mg of caffeine daily reduced risk of AF [8] . One study had similar findings that caffeine consumption reduced risk of AF [9] . The dose response analysis suggested that there is a 6% decrease in AF risk per 300 mg/d increase in caffeine consumption (no upper limit evaluated) [9] . Another study also depicted a reduced risk of AF with low caffeine consumption (Odds Ratio 0.85, 95% CI 0.78 to 0.92, I(2) = 0%) [10] . The cohort study suggested that caffeine consumption did not result in higher chance of AF. Both cohorts depicted an inverse effect of moderate caffeine consumption and risk of AF [11] .
Oral caffeine administration did not increase the risk of AF in patients who underwent heart valve surgery with cardiopulmonary bypass. However, caffeine was linked to a higher risk of postoperative nausea and vomiting [12] . One randomized controlled trial depicted that AF triggers did not affect Atrial Fibrillation Effect on Quality of Life (AFEQT) and did not result in AF [13] .
3.2. Caffeine Consumption and Ventricular and Supraventricular Arrhythmias
Other studies have evaluated the relationship of caffeine consumption on supraventricular arrhythmias and tachycardias. In one study, 500 mg of caffeine was administered to patients with heart failure with reduced ejection fraction (HFrEF), however, it did not cause an increase in ventricular or supraventricular premature beats [14] . Furthermore, caffeine intake had no effect on heart rhythm, supraventricular tachycardia (SVT), or tachycardias [15] . However, it did lead to an increase in systolic and diastolic blood pressure [15] . Conversely, energy drink (ED) consumption increased the number of supraventricular extrasystoles in children and adolescents [16] . ED consumption lowered HR but did not affect QTc intervals and no dangerous arrhythmias were observed [16] . ED consumption can also alter ECG in some populations (underaged) [17] .
Additional studies evaluated various ventricular arrhythmias including premature ventricular contractions and atrial arrhythmias. One study suggested that caffeine consumption did not result in more premature atrial contractions, however, there was an increase in the number of premature ventricular contractions [18] . However, a study evaluating the impact of caffeine on ventricular arrhythmias found an insignificant relationship between caffeine intake and frequency of ventricular premature beats [19] . Energy drink consumption, including caffeine, did cause QTc prolongation in some patients, and also increased blood pressure [20] .
4. Discussion
A majority of the included studies suggest that caffeine does not increase the incidence of heart arrhythmias or other heart rhythm conditions. Studies evaluating the consumption of caffeine and risk of AF stated that caffeine did not increase the risk. Some studies even found that caffeine had an inverse effect on incidence of AF and had a protective effect. However, the level of caffeine consumption needed to elicit these effects is unclear as all studies used different dosages. One study stated that this protective effect happens with low caffeine consumption, whereas another study stated that AF risk was reduced with high caffeine consumption hence it is difficult to tell the ideal amount of caffeine to reduce AF risk [8] . A meta-analysis depicted that moderate caffeine intake reduced AF risk in both of the study cohorts [13] . Hence, the specific dosage of caffeine to reduce AF is not clearly defined. Furthermore, caffeine did not increase AF risk in the postoperative period in patients who underwent heart valve surgery with cardiopulmonary bypass. This is also applicable to HFrEF patients [14] . Studies investigating the impact of caffeinated energy drinks showcased a different trend of results with ED consumption leading to some long QT syndrome patients experiencing dangerous QTc changes upon intake, these results could also be because of other substances found in energy drinks such as taurine [20] . Among children, ED also changed electrocardiogram (ECG) in certain populations such as underaged individuals. Some minors may also develop malignant dysrhythmias after ED consumption. It is important to take into account as ED brand and exact quantity was not mentioned [16] .
One study showed caffeine did not increase the incidence of heart arrhythmias, which is similar to other review articles and papers [21] .However, caffeine does cause an increase in systolic and diastolic blood pressure, which can lead to hypertension. One study suggested that people with hypertension have a 50% increased chance of developing AF [22] . Future studies should evaluate the exact pathophysiology of caffeine and its impact on heart rhythms.
Although the majority of the evaluated studies suggest there is no significant impact of caffeine consumption on heart arrhythmias, there are certain populations at risk of heart arrhythmia issues. Minors are an “at risk” population when caffeine consumption from EDs can lead to malignant dysrhythmias and altered ECG [17] . Caffeine should also be avoided by patients diagnosed with LQTS because it causes an increase in QTc [20] . Caffeine can also lead to other cardiovascular issues such as increases in systolic and diastolic blood pressure, which can cause myocardial infarctions. Caffeine consumption was also seen to cause nausea and vomiting in the postoperative period in some patients [12] . These patient populations should proceed with caution when deciding to drink caffeine and how much. Additionally, other adverse effects of caffeine consumption including GI disturbances, tachycardia, and heart palpitations should be considered before use.
Limitations to this study include the small number (13) of studies that were eligible for this medical literature review. Only a handful of medical arrhythmia conditions were evaluated, with the majority of the studies looking at AF. However, this may be a reflection of the most common heart arrhythmia as opposed to study homogeneity. Additionally, a few studies evaluated EDs’ impact on heart rhythm, however the effects of ED consumption cannot be directly attributable solely to caffeine. Many EDs contain other ingredients for example carnitine, taurine, etc., which may also impact heart arrhythmias. Additionally, the dosages evaluated in each of these studies varied, limiting generalizability of this review. Future studies should evaluate various caffeine doses and incidence of heart arrhythmias in large, randomized controlled clinical trials. The method of caffeine administration and exact dosage used should be controlled. Additional studies should evaluate the heart arrhythmia risk in patients with predisposing cardiac conditions and/or other special populations. Studies should also have a large sample size to see caffeine impact on heart arrhythmias on a more diverse range of patients.
5. Conclusion
This medical literature review evaluated the relationship between caffeine and heart arrhythmias. Most studies evaluated have not found a significant association between caffeine and arrhythmia, while certain populations such as children and patients diagnosed with LQTS may be at risk. Moreover, some studies suggested that caffeine may be cardioprotective, but the exact dosage of consumption to elicit this effect is not clear. Future research is needed to fully elucidate the potential benefits of caffeine. Future studies could focus on FDA doses of caffeine (low, moderate, high) in order to generalize caffeine intake, caffeine’s short term and long-term impact on heart arrhythmias in individuals of different demographics should be conducted to identify at-risk individuals.