Enhanced External Counterpulsation for the Treatment of Angina With Nonobstructive Coronary Artery Disease.

Angina and nonobstructive coronary artery disease (ANOCA) is associated with poor outcomes and limited treatment options. Enhanced external counterpulsation (EECP) is a noninvasive treatment that involves applying external inflatable cuffs to the lower extremities to increase blood flow during diastole, followed by deflation during systole. Although EECP is approved for treatment in patients with refractory angina due to obstructive coronary artery disease, its effectiveness in treating patients with ANOCA with refractory angina is limited to small studies. We assessed the efficacy of EECP treatment in patients with ANOCA (defined as ≤50% stenosis in any major epicardial vessels) with refractory anginaby measuring changes in Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test, Duke Activity Status Index (DASI), Seattle Angina Questionnaire 7 (SAQ7), and weekly anginal episodes pre-EECP and post-EECP treatment. A total of 101 patients with ANOCA with CCS class III/IV angina completed a full course of EECP treatment at 2 large EECP centers. In 101 patients with ANOCA the mean age (SD) of 60.6 (11.3) years and 62.4% of the cohort were women. We found significant improvements post-EECP treatment in CCS angina class (mean (SD) 3.4 (0.5) to 2.4 (2.9), p <0.001), 6-minute walk test (median 1200 (IQR 972 to 1411) to 1358 (1170 to 1600), p <0.001), DASI (mean (SD) 15.2 (11.6) to 31.5 (16.3), p <0.001), SAQ7 (mean (DS) 36.2 (24.7) to 31.5 (16.3), p <0.001), and weekly anginal episodes (mean (SD) 5.3 (3.5) to 2.4 (2.9), p <0.001). After EECP treatment, 71 patients (70.3%) had an improvement of ≥1 CCS angina class, including 33 (32.7%) patients improving by ≥2 CCS classes. In conclusion, in patients with ANOCA, EECP therapy reduces CCS angina class and improves exercise tolerance and capacity; and should be considered a part of optimal medical therapy.

INOCA/ANOCA: Mechanisms and novel treatments.

Angina or ischemia with no obstructive coronary disease (ANOCA/INOCA) is a common but under-treated condition due to poorly understood pathophysiologic mechanisms, limited diagnostic tools, and lack of proven targeted therapy. Coronary microvascular dysfunction (CMD) occurs when the microvasculature inadequately perfuses the myocardium under stress, or at rest in the case of microvascular spasm resulting in ANOCA/INOCA. Coronary functional angiography (CFA) measures endothelial independent microvascular dysfunction (coronary flow reduction <2.5) in response to adenosine and endothelial dependent microvascular dysfunction (lack of dilation and/or constriction) to acetylcholine testing as well as epicardial and microvascular spasm. Current treatment for coronary microvascular dysfunction is limited to renin-angiotensin system (RAS) inhibitors and statins as well as antianginal medications. Novel therapies targeting the underlying pathology are under development and include the coronary sinus reducer, CD34+ stem cell therapy, and novel pharmacologic agents such as sGC stimulators or endothelin-receptor blockers. We review the current understanding of pathophysiology, diagnostic tools, and novel therapies for coronary microvascular dysfunction in ANOCA/INOCA.