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. 2024 Aug 19;20(16):1008-1017.
doi: 10.4244/EIJ-D-24-00247.

Changes in absolute coronary flow and microvascular resistance during exercise in patients with ANOCA

Michel Zeitouni  1 , Ghilas Rahoual  1 , Niki Procopi  1 , Frederic Beaupré  1 , Maxime Michon  1 , Clélia Martinez  1 , David Sulman  1 , Paul Guedeney  1 , Nadjib Hammoudi  1 , Eric Vicaut  2 , Stéphane Hatem  1 , Mathieu Kerneis  1 , Johanne Silvain  1 , Gilles Montalescot  1 , For The Action Group
Affiliations

Changes in absolute coronary flow and microvascular resistance during exercise in patients with ANOCA

Michel Zeitouni et al. EuroIntervention. .

Abstract

Background: Whether saline-induced hyperaemia captures exercise-induced coronary flow regulation remains unknown.

Aims: Through this study, we aimed to describe absolute coronary flow (Q) and microvascular resistance (Rμ) adaptation during exercise in participants with angina with non-obstructive coronary artery disease (ANOCA) and to explore the correlations between saline- and exercise-derived coronary flow reserve (CFR) and microvascular resistance reserve (MRR).

Methods: Rμ, Q, CFR and MRR were assessed in the left anterior descending artery using continuous thermodilution with saline infusion at 10 mL/min (rest), 20 mL/min (hyperaemia) and finally at a 10 mL/min infusion rate during stress testing with a dedicated supine cycling ergometer. An incremental workload of 30 watts every two minutes was applied. A saline-derived CFR (CFRsaline) cutoff <2.5 was used to identify coronary microvascular dysfunction (CMD).

Results: CFRsaline-defined CMD was observed in 53.3% of the participants (16/30). While cycling, these patients less of an ability to increase Q (7 [interquartile range [IQR] 30.5-103.0] vs 21 [IQR 5.8-45.0] mL/min/30 watts; p=0.01) due to a smaller decrease of Rμ (109 {IQR 32-286} vs 202 [IQR 102-379] Wood units [WU]/30 watts; p<0.01) as compared with the group with normal CFRsaline. In the overall population, CFRsaline and exercise-derived CFR (CFRexercise) were 2.70±0.90 and 2.85±1.54, respectively, with an agreement classification of 83.3%. A good correlation between saline and exercise techniques for both CFR (r=0.73; p<0.0001) and MRR (r=0.76; p<0.0001) was observed. Among participants with normal CFRsaline, 28.7% (4/14) had an impaired CFRexercise <2.5 at the peak of exercise due to a moderate and late decrease of Rμ.

Conclusions: Saline-induced hyperaemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate adaptation among participants with exercise-related CMD.

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Conflict of interest statement

M. Zeitouni received research grants and honorarium from Bayer, BMS-Pfizer, la Fédération Française de Cardiologie, Servier, AstraZeneca, Novo Nordisk, and Abbott. J. Silvain received research grants and honorarium from AstraZeneca, Bayer Healthcare SAS, Abbott Medical France SAS, Biotronik, Boehringer Ingelheim France, CSL Behring, Gilead Science, and Sanofi-Aventis France; and has been a stockholder of PharmaSeeds, Terumo France SAS, and Zoll. G. Montalescot received research grants and honorarium from Abbott, Amgen, AstraZeneca, Ascendia, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Boston Scientific, CeleCor, CSL Behring, Idorsia, Lilly, Novartis, Novo Nordisk, Opalia, Pfizer, Quantum Genomics, Sanofi, and Terumo. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Coronary physiological assessment using saline- and exercise-induced hyperaemia.
Absolute microvascular resistance (Rµ) and blood flow (Q) were assessed at rest (continuous saline infusion rate [Qi]=10 mL/min), after saline-induced hyperaemia (continuous Qi=20 mL/min) and at each step of exercise (continuous Qi=10 mL/min). Fractional flow reserve (FFR) and coronary flow reserve (CFR) were assessed after saline-induced hyperaemia and at each step of exercise, until exhaustion. The temperature of the infused saline (Ti) was recorded, as well as the the distal blood temperature after complete mixing (T). MRR: microvascular resistance reserve; Pa: aortic pressure; Pd: distal coronary pressure; W: watts; WU: Wood unit
Figure 2
Figure 2. Microvascular haemodynamic adaptation during physiological stress.
Coronary flow reserve (A), rate pressure product (B), microvascular resistance (C) and absolute coronary flow (D) are represented according to the percentage of the theoretical workload achieved by patients. The grey area denotes physical exercise and the orange area denotes saline-induced hyperaemia. WU: Wood unit
Figure 3
Figure 3. Haemodynamic profiles of patients with CFRsaline ≥2.5 and CFRexercise <2.5.
Coronary flow reserve (A), rate pressure product (B), microvascular resistance (C) and absolute coronary flow (D) are represented according to the percentage of the theoretical workload achieved by patients. The grey area denotes physical exercise and the orange area denotes saline-induced hyperaemia. CFRexercise: exercise-induced coronary flow reserve; CFRsaline: saline-induced coronary flow reserve; WU: Wood unit
Central illustration
Central illustration. Agreement between CFR as induced by saline infusion at 20 mL/min (CFRsaline) and by physiological exercise test (CFRexercise).
A) Procedure for saline-induced hyperaemia. B) Exercise-induced hyperaemia setup. C) Plots of the individual values of CFRsaline versus CFRexercise with their corresponding Bland-Altman plot (D). E) Plots of the individual values of MRRsaline versus MRRexercise with their corresponding Bland-Altman plot (F). CFR: coronary flow reserve; Fr: French; LAD: left anterior descending artery; MRRexercise: exercise-derived microvascular resistance reserve; MRRsaline: saline-derived MRR; Pd: distal coronary pressure; Q: absolute coronary flow; Qi: infusion rate of saline; Rµ: absolute microvascular resistance; SD: standard deviation; T: distal blood temperature after complete mixing with saline; Ti: temperature of the infused saline
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