journal of Cardiovascular Magnetic Resonance volume 19, Article number: 103 (2017) point out this article


Background

Adenosine anxiety cardiovascular magnetic resonance (CMR) deserve to detect far-ranging coronary artery stenoses v high diagnostic accuracy. Caffeine is a nonselective vain inhibitor that adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, possibly yielding false-negative results. Much dispute exists around the affect of caffeine on adenosene myocardial perfusion imaging. Our research sought to investigate the impacts of caffeine on ischemia detection in patients through suspected or known coronary artery condition (CAD) experience adenosine stress CMR.

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Methods

Thirty patient with proof of myocardial ischemia on caffeine-naïve adenosine stress and anxiety CMR were prospectively enrolled and underwent repeat adenosine stress and anxiety CMR ~ intake of 200 mg caffeine. Both CMR exams were then contrasted for review of ischemic burden.

Results

Despite input of caffeine, no conversion of a optimistic to a an unfavorable stress study emerged on a every patient basis. Although we found significant lower ischemic load in CMR exams through caffeine contrasted to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based upon a 16-segment model, 3 segment on a 60-segment model, and 1 ml in total ischemic myocardial volume, p 




Patient characteristics

Of the n = 1247 screened patients, n = 288 gave informed consent to the examine protocol former adenosine tension CMR, check out Fig. 1. Of these, n = 46 demonstrated far-reaching myocardial ischemia, n = 16 were drop outs (n = 9 withdrew consent, n = 7 were revascularized before 2nd stress CMR could be performed). The staying n = 30 patients with far-ranging myocardial ischemia went back for one more CMR study with defined prior caffeine intake, watch Table 1.


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Caffeine levels and ischemic segments

Despite varying caffeine level (4.6 ± 2.2 mg/L) ~ 200 mg caffeine with 60 min time to attain maximum of plasma level <18>, no correlation could be found in between caffeine levels and also the variety of ischemic segments.


This is the very first study assessing the influence of caffeine top top the ischemic burden by a two-exam adenosine stress CMR protocol including both a caffeine-naïve CMR scan and also a repeat CMR scan after defined caffeine intake. Major findings are: 1) regardless of intake that caffeine former the repeat CMR exam, no conversion of an ischemic-positive to an ischemic-negative study could be it was observed in this high-risk population. 2) Although far-reaching differences in the extent of ischemic load were demonstrated between caffeine-naïve and post-caffeine CMR exams based on a 16-segment model, 60-segment model and also total ischemic volume, distinctions were small in absolute terms, and also no prognostic appropriate myocardial ischemia (≥2 segment in a 16-segment model) was missed despite intake of caffeine <26>. 3) A history of CAD appears to have actually no influence, since no far-reaching differences might be observed for patients with prior myocardial infarction, well-known CAD or ahead CABG vs. Patients v no history of CAD. 4) No correlation could be found in between serum caffeine levels and also the variety of ischemic segments.

Patient characteristics

In total, n = 30 topics were included in this study, Fig. 1; no patience had proof of caffeine throughout the time of the early CMR (all serum caffeine level 27, 28>.

Myocardial perfusion defect by visual interpretation on a dichotomous basis

Visual translate on a dichotomous basis (presence or lack of ischemia) revealed ischemia in both initial and also repeat adenosine CMR scans. Therefore, regardless of prior caffeine intake, adenosine stress and anxiety CMR still seems to it is in a an important diagnostic device for the detection of far-reaching CAD. This is in line with previous studies suggesting a negligible result of caffeine on the results of myocardial perfusion researches <13, 14>. Of note, on a per patient communication no pertinent ischemia to be missed despite the entry of caffeine. However, ischemic burden seems to be diminished after caffeine intake, Fig. 2.

Myocardial perfusion defect through segment and also total volume

Our observation that ischemic burden tends to be decreased after front caffeine intake can be shown by quantitative evaluation of the 16-segment model: 7.9 ± 3.5 segments verified myocardial ischemia there is no caffeine vs. 6.9 ± 3.5 segments after caffeine intake, p 19>. In contrast, Zoghbi et al. <14> studied the impact of one 8-oz. Cup the brewed caffeinated coffee (with a caffeine content differing from 25 mg come 240 mg) one hour prior to adenosine gated SPECT. Consequently, the latter study <14> demonstrated lower caffeine levels varying from 3.1 ± 1.6 mg/L, vice versa, in the current study patients verified caffeine levels in the range of 4.6 ± 2.2 mg/L, saying a unique effect the caffeine on coronary hyperemia. Our results are in line with a study from Namdar et al. <9>. They learned the effect of 200 mg caffeine (equivalent to our dose) ~ above myocardial blood circulation at rest and also exercise in healthy volunteers at normoxia and also during acute exposure to stimulated altitude through 15O–labeled H2O and also positron emissions tomography. They discovered that a sheep of two cups of coffee (200 mg caffeine) significantly decreased exercise-induced myocardial blood flow at normoxia and at hypoxia, arguing that exercise-induced hyperemic flow an answer may at the very least in part be antagonized through caffeine <9>.

Most of our patients had actually ischemic burden consisting of several myocardial segments, Figs. 2, 3 and 4. Data evaluation revealed 7.9 ± 3.5 ischemic segments without caffeine vs. 6.9 ± 3.5 ischemic segments with caffeine, identifying our patients cohort as a subset of very-high-risk patients, since an additional group could show <29> that patients v >5 ischemic (of 16) segments had actually a threat of an disadvantage CAD occasion of roughly 14%/year. Return our results emphasize that on a 16-segment design basis the influence of caffeine leader to a to decrease of ischemic burden by only 1 segment (7.9 ± 3.5 vs. 6.9 ± 3.5), these differences were far-reaching (p 26, 30, 31>. Therefore, caffeine-induced effects on myocardial ischemia might mask not only patients’ precise diagnosis but additionally his prognosis.

Interestingly, among our patients had only 2 ischemic segments in his caffeine-naïve exam, which is taken into consideration as a threshold because that moderate-severe myocardial ischemia <26>, indicating adverse outcome which could warrant more invasive diagnosis by coronary angiography. In this case, in spite of intake the caffeine in the follow-up exam, the repeat scan still prove 2 ischemic segments, pointing in the direction of the hypothesis that no prognostic appropriate myocardial ischemia is to let go by prior caffeine entry in one adenosine stress and anxiety CMR test. However, in cases in which only 2 the 16 myocardial segments room involved, prior caffeine could substantially rise the threat of a false-negative tension CMR or at least the probability to detect myocardial ischemia in just a single instead of 2 segments. At first sight, this can be a negligible difference. However, it is the clinical prestige to finding the true degree of ischemic burden not only for diagnostic but additionally for prognostic objectives <26, 32>, due to the fact that patients v zero or just one ischemic segment deserve to be for sure deferred native revascularizations and also show a favorable outcome on clinical treatment that does not differ native those patients through normal CMR perfusion studies <32>. Based on our findings, we should expect, that in reduced ischemic burden patients far-reaching ischemia would be missed, affecting not just prognostic assessment however the diagnosis itself.

In the 60-segment model, we discovered an even higher difference in ischemic segments between caffeine-naive and also caffeine adenosene CMR tension scans: 18.6 ± 8.7 vs. 15.7 ± 8.7 segments, p 2, 3 and also 4, underlining a low but far-reaching impact that caffeine ~ above the degree of ischemic burden in adenosine stress and anxiety CMR tests.

Patient subgroups

Subgroup analysis revealed the patients with no LGE contrasted to patients with ischemic LGE prove no significant differences in the variety of ischemic segments in their initial vs. Their repeat CMR scan with regard come the 16-segment model, p = 0.89, the 60-segment model, p = 0.46, and for the full quantified ischemic volume, p = 0.37, Table 3. This is that importance since one might argue that LGE in patients could interfere with the potential degree of myocardial ischemia especially in state of resolved perfusion defects. Similar results might be observed because that the ischemic burden in between the initial and also repeat CMR scan in patients without a history of CAD vs. Patient with known CAD v regard come the 16-segment model (p = 0.43), 60-segment design (p = 0.73), and total ischemic volume (p = 0.85). Likewise, in patients v no ahead coronary artery bypass graft (CABG) vs. Patients v prior CABG, segment of ischemia in a 16-segment model, 60-segment model, and total ischemic volume demonstrated no far-reaching differences between both CMR exams (p = 0.58, p = 0.18, p = 0.26, respectively). These results underline the the existence of caffeine itself appears to be the key driver the a decreased ischemic burden, independent from patient’s cardiac history.

Caffeine levels and ischemic segments

Despite differing caffeine level after comparable caffeine entry (200 mg each) in ~ our institution, no correlation could be found between caffeine levels and also the number of involved ischemic segments. This is in line v Lee et al. <13>, stating the the concentration that caffeine (at baseline or ~ supplementation) was not associated with percent defect reversibility. Furthermore, the quantity of readjust of caffeine levels from the initial CMR to the second CMR test after caffeine consumption had no impact on percent defect reversibility, p = 0.97. Reyes et al. <33> investigated 30 patient with recognized or doubt CAD with and without caffeine by clinically suggested myocardial perfusion imaging. They discovered that myocardial ischemia reduced by presence of caffeine through the typical use the 140 μg adenosine yet did not change significantly v the usage of the higher adenosine dose of 210 μg arguing that in patients through prior caffeine consumption the protocol might be switched come the higher adenosine dose. The reason for this finding can be the vain interaction between adenosine and caffeine, for this reason receptor blockade by caffeine might be surmounted by an enhanced dose of adenosine. However, the higher dose is no approved for use in the United states in imaging <1>.

Limitations

Since this is a single-center study, potential center-specific predisposition cannot be excluded. Furthermore, the outcomes of this research were increased in a population with extensive ischemic burden, and might no be moved to patients which show an ischemic burden consisting of only 1 or 2 myocardial segments. Therefore, our results cannot be generalised to all patients through CAD. Furthermore, quantification of ischemic burden by a 2D 3-slice strategy may be worse to a 3D complete coverage approach. However, our 3-slice technique is usual practice because that clinical routine, and also underlines the real-world character of this study.

We have actually not handle the ingestion of different caffeine amounts in order to detect a potential threshold at which caffeine reflects definite impact on the degree of ischemic burden. However, intention of our research was to reach far-reaching serum levels of caffeine to show the affect of caffeine ~ above myocardial ischemic burden. Furthermore, a previous research from Lee et al. <13> assessed adenosine-induced myocardial perfusion imaging defects end a broad variety of caffeine concentrations with SPECT, and also found no far-reaching caffeine effect.

Moreover, many of the previously mentioned studies are performed with SPECT since there is just scarce data around the impact of caffeine on adenosine stress CMR, i m sorry is known to have far better spatial resolution than SPECT. Therefore, no all the data can be applied to the an approach of CMR.

In this study, coronary angiography was provided as the gold traditional for the detection of significant CAD. Nevertheless, one must keep in mind that the sole anatomical existence of a stenosis does no always provide sufficient information concerning its hemodynamic relevance. Thus, functional assessment by intracoronary pressure wire (FFR) or intravascular ultrasound researches would have actually been highly desirable, however was not lugged out in this study.

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In high-risk patients with prior caffeine intake, we uncovered less ischemic burden on your adenosine tension CMR contrasted to their caffeine-naïve adenosine stress CMR study. Since these differences can it is in detected visually in a sample of only 30 patient in a statistically far-reaching way, the impact of caffeine in CMR diagnostic and also prognostic assessment can not be concerned as negligible. Therefore, we recommend patients reserved for adenosine stress and anxiety CMR to refrain from caffeine in stimulate to keep 1) the high diagnostic accuracy the adenosine tension CMR for the detection of far-reaching coronary stenosis, and 2) the high prognostic worth which is related to the dimension of ischemic burden.