Clinico-pathophysiological considerations in coronary microvascular disorders

Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

The value of ATP stress MCE in evaluating myocardial microvascular spasm -- a case report 1

We reported a patient with chest pain, but the coronary angiography was normal. ATP stress myocardial contrast electrocardiography(MCE) was performed. There was apical ventricular septal perfusion delay before ATP stress, and the perfusion delay areas were significantly reduced at the peak period, which was similar to the “reverse redistribution” perfusion characteristics of nuclear myocardium in coronary vasospasm, The areas of delayed perfusion in the recovery period were larger than that before stress, the increase of blood flow spectrum resistance in the distal segment of left anterior descending coronary artery and the occurrence of chest pain all showed that ATP induced myocardial microvascular spasm. The MCE perfusion characteristics and the changes of coronary spectrum had certain clinical value in the diagnosis of myocardial microvascular spasm.

Sex Differences in Coronary Function Test Results in Patient With Angina and Nonobstructive Disease

Introduction: Invasive coronary function testing (CFT) has become the recommended diagnostic tool to assess the various endotypes of coronary vasomotor dysfunction in patients with angina and no obstructive coronary artery disease (ANOCA), which has implications for therapy and prognosis. Although the expanding performance of CFT is leading to increased knowledge of coronary vasomotor dysfunction, little is known about sex-related differences in the results of comprehensive CFT.Methods: We conducted a prospective study of all consecutive patients with ANOCA that underwent clinically indicated CFT in a tertiary interventional from February 2019 to February 2021. CFT consisted of acetylcholine testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose CMD. CMD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) &lt; 2.0.Results: In total, 228 women and 38 men underwent CFT. No differences in traditional risk factors were seen, but women had a higher prevalence of migraine (45 vs. 14%, p = 0.001). Men more often had a history of percutaneous coronary intervention (12 vs. 49%, p = 0.001). We found no difference in clinical presentation. Coronary vasomotor dysfunction was present in 95% of men and 88% of women (p = 0.25), but males show more often epicardial spasm and less microvascular spasm than women (63 vs. 42% and 29 vs. 40% respectively, p = 0.039). Impaired CFR was more prevalent among females (6 vs 20%, p = 0.033). IMR [median of 23 (15–32) vs. 19 (13–25), p = 0.08] did not differ between the sexes.Conclusion: Men undergoing CFT show a comparable prevalence of coronary vascular dysfunction as women. However, men have a higher prevalence of epicardial spasm and a lower prevalence of microvascular spasm compared with women. An impaired CFR was more often present in women, with an equally impairment of IMR.

ATP stress MCE in evaluating coronary microvascular spasm: a case report

We report a case of coronary microvascular spasm assessed by ATP stress MCE (myocardial contrast electrocardiography). The patient had chest pain, but the coronary angiography was normal. There was apical ventricular septal perfusion delay before ATP stress, and the perfusion was significantly improved at peak stress, which was similar to the radionuclide myocardial perfusion characteristics of coronary microvascular spasm, In the recovery period, the flow spectrum resistance of the distal coronary artery of the left anterior descending artery increased compared with that before stress, which further confirmed that local coronary microvascular spasm was induced after vasodilation.

Rationale and Design of the Vasospastic Angina Treatment by Endothelin Receptor Antagonism (VERA) Trial

Background Pharmacological treatment of patients diagnosed with vasospastic angina (VSA) or microvascular angina (MVA) is challenging and often patients remain symptomatic. Endothelin (ET)-1 plays an important role in the regulation of the vascular tone and stimulation of ET-1 receptors can induce a potent and long-lasting vasoconstriction. Macitentan is a potent, inhibitor of the ETA receptor. Purpose This prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept trial is designed to investigate macitentan as a potential novel treatment for patients with VSA due to epicardial spasm or MVA due to microvascular spasm, together defined as coronary artery spasm (CAS).Methods and Results A total of 30 patients with CAS will receive treatment with either 10 mg of macitentan daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in random order. The primary outcome is the reduction in angina, calculated as (1) the frequency of angina attacks * severity (on a VAS scale 1-10); and (2) the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10) during medication use (macitentan or placebo) up to 2 weeks after discontinuation of the study medication. The primary analysis will assess the within-subject differences in the burden of anginal symptoms following treatment with macitentan versus placebo.Conclusions The VERA trial will be the first to evaluate the efficacy of the ETA receptor antagonist, macitentan, in the treatment of VSA due to epicardial spasm and MVA due to microvascular spasm.Trial Registration trialregister.nl, Identifier: NL7546. Registration date: 20 February 2019.

Intracoronary acetylcholine testing among 746 consecutive Japanese patients with angina-like chest pain and unobstructed coronary artery disease

Background Intracoronary acetylcholine (ACh) testing is useful for the detection of epicardial spasm (ES) and coronary microvascular spasm (CMS). Objectives We retrospectively analysed the incidence of ES and CMS in consecutive Japanese patients with unobstructed coronary artery disease. Methods From January 1991 to February 2019, we performed intracoronary ACh testing of 1864 patients. Among these patients, a total of 746 consecutive patients (254 women, mean age 64±11 years) who underwent first diagnostic angiography for suspected myocardial ischaemia and had unobstructed coronary arteries (&lt; 50%) were enrolled. ES was defined as ≥ 90% stenosis and usual chest symptoms and ischaemic ECG changes, while CMS was defined as &lt; 75% stenosis and usual chest symptoms and ischaemic ECG changes. Results We performed intracoronary ACh testing on both coronary arteries in 96% (716/746) of all subjects. Overall, ES was found in 329 patients (44%), whereas CMS was revealed in 40 patients (5%) including 4 patients with coexisting ES. In patients with ES, women made up 22%, and approximately three-quarters of the patients had resting chest pain. In contrast, women composed 65% (26/40) of those with CMS, and 15 patients with CMS had another chest symptom. CMS was frequently observed in the LCA but not the RCA. Electrical cardioversion was necessary for two patients. Conclusions CMS was recognized in only 5% of consecutive Japanese patients with unobstructed coronary artery disease, whereas ES was revealed in 44% of those patients. CMS was often observed in women and in the LCA.

Invasive Diagnosis of Coronary Functional Disorders Causing Angina Pectoris

Coronary vasomotion disorders represent a frequent cause of angina and/or dyspnoea in patients with non-obstructed coronary arteries. The highly sophisticated interplay of vasodilatation and vasoconstriction can be assessed in an interventional diagnostic procedure. Established parameters characterising adequate vasodilatation are coronary blood flow at rest, and, after drug-induced vasodilation, coronary flow reserve, and microvascular resistance (hyperaemic microvascular resistance, index of microcirculatory resistance). An increased vasoconstrictive potential is diagnosed by provocation testing with acetylcholine or ergonovine. This enables a diagnosis of coronary epicardial and/or microvascular spasm. Ischaemia associated with microvascular spasm can be confirmed by ischaemic ECG changes and the measurement of lactate concentrations in the coronary sinus. Although interventional diagnostic procedures are helpful for determining the mechanism of the angina, which may be the key to successful medical treatment, they are still neither widely accepted nor applied in many medical centres. This article summarises currently well-established invasive methods for the diagnosis of coronary functional disorders causing angina pectoris.

AB0439 CAPILLAROSCOPIC PATTERNS IN PATIENTS WITH SYSTEMIC SCLEROSIS-POLYMYOSITIS/DERMATOMYOSITIS (SSc-PM/DM) OVERLAP SYNDROME

Background:Impaired microcirculation is one of the leading factors in local and general pathogenesis of SSc. Widefield nail-fold video-capillaroscopy (NFVC) stands as the most informative and at the same time simple method used for evaluation of capillary circulation.Objectives:To identify characteristic and specific for SSc– PM/DM capillaroscopic features.Methods:Both hand II – V fingers of 68 pts with SSc-PM/DM were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms.Results:SSc-specific dilatations of capillary loops were the most common for SSc-PM/DM and were found in all pts; 50% of them had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (50%) and hemorrhages (51.5%), associated with generalized microvascular spasm in early disease and capillary sclerosis in advanced disease. The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 63% of examined nailfolds, branching bushy behavior of capillary loops and mega-capillaries predominated; architectural disorientation/disarrangement of capillary loops with formation of subcutaneous plexus was seen in more than 50% of them. Capillaroscopic changes consistent with active scleroderma pattern were present in 54 % and were associated with lab signs of inflammatory muscle syndrome and immunological disorders: giant capillaries (p<0.02), disorientation of capillary loops (p<0.02) and ramified/bushy capillaries (p<0.04) were significantly more frequent in patients with severe muscle syndrome, increased CPK, ANF -positivity and hemorrhages (p<0.03).Conclusion:Thus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combining features specific for SSc (capillary dilation, avascular areas, hemorrhages) and for PM/DM (bushy and giant capillaries, disorientation of capillary loops of the nailfold with formation of subcutaneous plexuses.)Disclosure of Interests:None declared

Myocardial Infarction with Nonobstructive Coronary Artery (MINOCA)

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is diagnosed in almost equal to 5 to 6% of patients who present with acute myocardial infarction (AMI). Causes of MINOCA are varied. Appropriate diagnosis and evaluation is important to uncover the correct cause and prescribe specific therapies to treat the underlying cause.Women with evidence of MINOCA are being increasingly recognized. The mechanisms underlying MINOCA, such as coronary microvascular spasm, represent a diagnostic and therapeutic challenge to medical fraternity, as there is neither a uniform nor comprehensive diagnostic strategy for accurate risk stratification, in the present scenario, for these patients.Here, we are reporting a case of MINOCA, which is rare and incompletely evaluated.