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. 2021 Dec 3;17(11):e925-e931.
doi: 10.4244/EIJ-D-21-00453.

Linear concentration-response relationship of serum caffeine with adenosine-induced fractional flow reserve overestimation: a comparison with papaverine

Hideaki Tanaka  1 , Hidenari Matsumoto, Haruya Takahashi, Masahiro Hosonuma, Shunya Sato, Kunihiro Ogura, Yosuke Oishi, Ryota Masaki, Koshiro Sakai, Teruo Sekimoto, Seita Kondo, Hiroaki Tsujita, Shigeto Tsukamoto, Arihiro Sumida, Natsumi Okada, Kazuo Inoue, Toshiro Shinke
Affiliations

Linear concentration-response relationship of serum caffeine with adenosine-induced fractional flow reserve overestimation: a comparison with papaverine

Hideaki Tanaka et al. EuroIntervention. .

Abstract

Background: Caffeine intake from one cup of coffee one hour before adenosine stress tests, corresponding to serum caffeine levels of 3-4 mg/L, is thought to be acceptable for non-invasive imaging.

Aims: We aimed to elucidate whether serum caffeine is independently associated with adenosine-induced fractional flow reserve (FFR) overestimation and their concentration-response relationship.

Methods: FFR was measured using adenosine (FFRADN) and papaverine (FFRPAP) in 209 patients. FFRADN overestimation was defined as FFRADN - FFRPAP. The locally weighted scatterplot smoothing (LOWESS) approach was applied to evaluate the relationship between serum caffeine level and FFRADN overestimation. Multiple regression analysis was used to determine independent factors associated with FFRADN overestimation.

Results: Caffeine was ingested at <12 hours in 85 patients, at 12-24 hours in 35 patients, and at >24 hours in 89 patients. Multiple regression analysis identified serum caffeine level as the strongest factor associated with FFRADN overestimation (p<0.001). The LOWESS curve demonstrated that FFRADN overestimation started from just above the lower detection limit of serum caffeine and increased approximately 0.01 FFR unit per 1 mg/L increase in serum caffeine level with a linear relationship. The 90th percentile of serum caffeine levels for the ≤12-hour, the 12-24-hour, and the >24-hour groups corresponded to FFRADN overestimations by 0.06, 0.03, and 0.02, respectively.

Conclusions: Serum caffeine overestimates FFRADN values in a linear concentration-response manner. FFRADN overestimation occurs at much lower serum caffeine levels than those that were previously believed. Our results highlight that standardised caffeine control is required for reliable adenosine-induced FFR measurements.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Comparisons among subgroups according to the time from the last caffeine intake. A) Serum caffeine level. B) FFRADN overestimation. FFRADN overestimation was defined as FFRADN−FFRPAP. FFRADN: fractional flow reserve value associated with adenosine; FFRPAP: fractional flow reserve value associated with papaverine
Figure 2
Figure 2
Distribution of FFRPAP values. FFRPAP: fractional flow reserve value associated with papaverine.
Central illustration
Central illustration
Relationship between serum caffeine level and FFRADN overestimation. FFRADN overestimation was defined as FFRADN−FFRPAP. The black line represents a locally weighted scatterplot smoothing curve. The red line corresponds to the 90th percentile of serum caffeine level for the ≤12-hour caffeine intake group (5.741 mg/L), the blue to the 12-24-hour group (2.722 mg/L), and the green to the >24-hour group (1.050 mg/L). FFRADN: fractional flow reserve value associated with adenosine; FFRPAP: fractional flow reserve value associated with papaverine
See this image and copyright information in PMC

Comment in

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