3332Exercise training ameliorates vasodilator capacity of coronary microvessels in patients with vasospastic angina - A new therapeutic approach for the coronary functional disorder
Authors: Sugisawa J , Matsumoto Y , Suda A , Ota H , Tsuchiya S , Ohyama K , Takeuchi M , Shindo T , Ikeda S , Hao K , Kikuchi Y , Takahashi J , Takase K , Kohzuki M , Shimokawa H 
Published: October 2019

Abstract

Background
We have recently demonstrated that coronary vasospasm could develop in both epicardial coronary arteries and intramuscular coronary microvessels in patients with vasospastic angina (VSA). However, it remains to be examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients and if so, whether exercise training could ameliorate vasodilator capacity of coronary microvessels on the top of calcium channel blockers. The effectiveness of exercise training is established for organic coronary artery disease but remained to be examined for VSA.

Purpose
We thus examined whether vasodilator capacity of coronary microvessels is impaired in VSA patients without organic coronary stenosis using an adenosine-stress dynamic computed tomography perfusion (CTP) that can measure absolute value of myocardial blood flow (MBF). We also examined whether exercise training ameliorates not only vasodilator capacity of coronary microvessels but also exercise capacity and frequency of angina attack.

Methods
In the first protocol, we measured MBF using CTP in consecutive 32 VSA patients with acetylcholine-induced diffuse coronary spasm in the left anterior descending coronary arteries (LAD) and 12 non-VSA controls. In the second protocol, we conducted a randomized controlled trial (RCT; Exercise VSA trial, UMIN: ehz745.008423996), where 20 VSA patients were randomly assigned to either exercise group (Ex group: supervised exercise training session for 30-min using bicycle ergometer, once/week at the hospital and more than 3 times/week at home) or non-exercise group (Non-Ex group) (n=10 each) (Figure A). Before and 3 months after exercise training, we measured MBF with adenosine-stress dynamic CTP and peak VO2 by cardiopulmonary exercise tests, and also assessed angina attack with Seattle Angina Questionnaire (SAQ).

Results
In the first protocol, CTP showed that adenosine-stress MBF was significantly decreased in the VSA group compared with the non-VSA group (VSA, 137.2±6.6 vs. Non-VSA, 174.4±10.7 ml/100g/min, P<0.01) (Figure B), although patient characteristics were comparable between the 2 groups. In the second protocol, exercise training was performed safely in all patients, and RCT showed that MBF was significantly increased in the Ex group compared with the non-Ex group (Figures C, D), although patient characteristics were also comparable between the 2 groups. Furthermore, peak VO2 was significantly increased in the Ex group compared with the non-Ex group (Figure E), and frequency of angina was significantly decreased in the Ex group compared with the non-Ex group (Figure F). Finally, there was a significant positive correlation between the extents of the changes in peak VO2 and the SAQ score for angina frequency in the Ex group (P<0.01, R=0.67).
Figures

Conclusions
These results provide the first evidence that vasodilator capacity of coronary microvessels is impaired in VSA patients, which can be ameliorated by exercise training.