Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

doi:10.1016/j.ahj.2004.04.008

American Heart Journal

Volume 148, Issue 4, October 2004, Pages 590-595

https://doi.org/10.1016/j.ahj.2004.04.008 Get rights and content

Abstract

Background

Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route.

Methods

FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 μg as boli) and a standard intravenous infusion of 140 μg/kg/min were administered in a randomized fashion.

Results

Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-μg intracoronary bolus and 140-μg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-μg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-μg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration.

Conclusions

This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 μg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 μg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.

Section snippets

Study population

A total of 50 patients were prospectively enrolled. The study population consisted of 40 men and 10 women with a mean age of 66 years (SD ± 8 years; range, 52–76 years). Most patients had normal left ventricular function, and only intermediate coronary lesions were assessed. Exclusion criteria included acute coronary syndromes, prior myocardial infarction in the territory supplied by the target vessel, diffuse coronary stenoses, and atrioventricular conduction abnormalities in the

Patient characteristics

All 50 patients were included in the analysis. Demographic data are presented in Table I. Procedural success was 100% for advancing the pressure wire distal to the stenosis. There were no procedure-related complications. Several systemic adverse effects (Table II) were observed during intravenous adenosine administration, whereas intracoronary boli elicited an asymptomatic transient atrioventricular block in as much as 16% of patients. Thirty-two patients (64%) underwent percutaneous coronary

Discussion

This study suggests that the administration of very high intracoronary adenosine boli is safe. Although a dose-response relationship is observed with higher intracoronary doses, intravenous adenosine was more potent in achieving maximal hyperemia. This is of particular relevance in subjects with borderline FFR results (0.75–0.80). In such cases, an overestimation of FFR and an underestimation of lesion severity, because of suboptimal hyperemia, would result in false-negative values, with the

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Impact of increasing dose of intracoronary adenosine on peak hyperemia duration during fractional flow reserve assessment
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Fractional Flow Reserve (FFR) is currently indicated as a first line strategy for the functional assessment of intermediate coronary stenoses. However, the protocol for inducing hyperemia still lacks standardization. Intracoronary adenosine boli, with a progressive increase to high-dosage, have been proposed as a sensitive and accurate strategy for the classification of coronary stenoses, although being potentially affected by the achievement of plateau of the effect and by a less prolonged and stable hyperemia as compared to intravenous administration. Therefore, the aim of the present study was to define the conditioning parameters and assess the impact of increasing-dose intracoronary adenosine on peak hyperemia duration in patients undergoing FFR for intermediate coronary stenoses.
FFR was assessed in patients with intermediate (40 to 70%) lesions by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 μg, with dose doubling at each step). Hyperemic duration was defined as the time for the variation form minimum FFR ± 0.02 and time to recovery till baseline values.
We included 87 patients, undergoing FFR evaluation of 101 lesions. Mean peak hyperemia duration and time to recovery significantly increased with adenosine doses escalation (p = 0.02 and p < 0.001). Peak hyperemia duration and time to recovery with 1440 μg adenosine were 14.5 ± 12.6 s and 45.2 ± 30.7 s, respectively. Hyperemia duration was not related to Quantitative Coronary Angiography (QCA) parameters or FFR values. In fact, a similar increase in the time of hyperemic peak was noted when comparing patients with positive or negative FFR (p_between = 0.87) or patients with lesions < or ≥20 mm (p_between = 0.92) and lesions involving left main coronary or proximal left anterior descending artery (LAD) (p_between = 0.07). A linear relationship was observed between time to recovery and FFR variations, with a greater time to baseline required in patients with FFR ≤ 0.80 (p = 0.003) and in lesions ≥ 20 mm (p = 0.006), but not in LAD/LM lesions (p = 0.55).
The present study shows a progressive raise in the duration of peak hyperemia and time to recovery, after the administration of increasing doses of intracoronary adenosine for the assessment of FFR. Therefore, considering the potential advantages of a high-dose adenosine protocol, allowing a more prolonged hyperemia and a more precise and reliable measurement of FFR, further larger studies with such FFR strategy should certainly be advocated to confirm its safety and benefits, before its routinely use recommendation.
Contrast Fractional Flow Reserve (cFFR): A pragmatic response to the call for simplification of invasive functional assessment
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To review the current approaches to simplify functional assessment of coronary stenosis with particular regard for contrast Fractional Flow Reserve (cFFR).
Maximal hyperaemia to assess FFR is perceived as time-consuming, costly, unpleasant for the patient and associated with side effects. Resting indexes, like Pd/Pa and iFR, have been proposed to circumvent the use of vasodilators as well as an approach based on the administration of contrast medium to induce coronary vasodilation, the cFFR. Contrast FFR can be obtained quickly, at very low cost in the absence of substantial side effects. Among these alternative indexes, cFFR shows the best correlation with FFR, reduces the use of adenosine even more than a hybrid resting approach but has not yet been tested in a randomized, controlled trial with clinical end-points.
cFFR represents a cheap, safe and effective alternative to FFR, able to facilitate the dissemination of a functional approach to myocardial revascularization.
Meta-Analysis of Head-to-Head Comparison of Intracoronary Versus Intravenous Adenosine for the Assessment of Fractional Flow Reserve
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Citation Excerpt :
All statistical calculations were performed using Review Manager Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Of the 47 records initially screened, 11 studies met the inclusion criteria6–16 (Figure 1, Table 1). The included studies contained a total of 587 patients who underwent invasive evaluation for suspected coronary artery disease and 621 lesions.
Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100 μg) or high-dose IC adenosine (≥100 μg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80 μg) and 5 studies high-dose boluses (120 to 600 μg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p = 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p = 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifying hemodynamically significant coronary stenosis and is better tolerated by the patients.
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Coronary artery disease is the underlying condition responsible for ischemic heart disease. It is imperative for cardiologists to understand coronary physiology in health and disease states. Invasive methods for determining the hemodynamic significance of coronary lesions observed on coronary angiography include coronary flow reserve and fractional flow reserve. The hemodynamic principles behind these techniques and their application to the clinical assessment of patients with ischemic heart disease will be discussed in this chapter.
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Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

Abstract

Background

Methods

Results

Conclusions

Section snippets

Study population

Patient characteristics

Discussion

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Am Heart J

Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses

N Engl J Med

Beyond morphologynew coronary physiologic approaches to interventions

G Ital Cardiol

Comparison of intravenous adenosine to intracoronary papaverine for calculation of pressure-derived fractional flow reserve

Cathet Cardiovasc Diagn

Effects of adenosine on human coronary circulation

Circulation

Effect of intravenous and intracoronary adenosine 5'-triphosphate as compared with adenosine on coronary flow and pressure dynamics

Circulation