Impact of Caffeine on Adenosine-Induced Myocardial Blood Flow and the Efficacy of Increasing Adenosine Dose to Overcome the Antagonistic Effect of Caffeine in Healthy Adults

Aims We aimed to investigate adenosine-induced increase in myocardial blood flow (MBF) during caffeine ingestion and restriction using cardiovascular magnetic resonance imaging (CMR)-based coronary sinus (CS) flow measurements and determine reliable indicators of stress adequacy. Methods and results Twenty healthy randomly assigned volunteers (10 males and 10 females, age 30±3 years) underwent two adenosine stress CMRs within 1 month on different days: 1 h after taking a caffeine tablet (in the first CMR) and placebo tablet (in the second CMR), after 24-h caffeine abstinence. The CS flow, ascending aortic flow, and native T1 of the myocardium and spleen were measured at rest and during adenosine infusion at increasing doses until the target heart rate (HR) (>10 beats/min [bpm]) was attained. At an adenosine dose of 120 µg/kg/min, lower MBF was observed with caffeine than with placebo (2.30±0.95 vs. 2.97±0.97 mL/min/g, p<0.001). Seven participants on caffeine and three on placebo required an increased dose of adenosine to achieve the target HR (p=0.012). Despite achieving the target HR, MBF was significantly lower with caffeine than with placebo (2.60±1.02 vs. 3.11±0.79 mL/min/g, p=0.012). Notably, only myocardial T1 correlated significantly with MBF in the caffeine (r=0.74, p<0.001) and placebo (r=0.52, p=0.018) phases. Conclusion Although the antagonistic effects of caffeine may slightly be overcome by increasing the adenosine dose, an HR increase >10 bpm may be an unreliable criterion for increasing doses of adenosine. Therefore, caffeine restriction is essential for myocardial perfusion imaging with adenosine. Trial registration UMIN-CTR, UMIN000029891, Registered 8 November 2017, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000034145