A single center study that included 187 patients who presented with angina-like chest pain and nonobstructive coronary arteries on diagnostic angiography, has shown that co-existence of high microvascular resistance index (IMR) and vasospasm is associated with an increased incidence of major adverse cardiovascular events (MACE – defined as cardiac death, nonfatal myocardial infarction, and hospitalizations). Rho-kinase activation thought to underlie mechanisms leading to high IMR in this patient population.
The 187 patients included in the study had a median follow-up of 893 days.
The results of the study were published this month in Journal of American College of Cardiology (JACC). The authors found that IMR correlated with the incidence of cardiac events (hazard ratio: 1.05; 95% confidence interval: 1.02 to 1.09; p = 0.002) and receiver-operating characteristics (ROC) curve analysis revealed IMR of 18.0 as the best cut-off (sensitivity 90%, specificity 63.4%, negative predictive value 99.1%). Patients were divided into 4 groups based on presence or absence of vasospastic angina (VSA) and IMR < 18 or > 18. It was found that out these 4 groups, the group with vasospastic angina (VSA) and IMR greater than equal to 18 had the highest incidence of MACE (HR: 6.23, 95% CI : 1.21-118.48, p = 0.03). According to the authors, this highlights that patients with both enhanced coronary vasoconstrictive reactivity and reduced vasodilator function are at high risk for future MACE.
Subjects were selected based on the presence of main vessel luminal narrowing<70% and/or fractional flow reserve [FFR] >0.8 with further exclusion of patients who had cardiomyopathy, significant valvular diseases (e.g., aortic stenosis), previous coronary stent implantation, relative contraindication for provocation test (e.g., bronchial asthma), renal failure, poor general condition, and those who had unsuccessful procedures during physiological measurement and/or acetylcholine (Ach) provocation test. Ach provocation test was done to identify subjects suffering from vasospastic angina (VSA). Coronary flow was determined using variables such as coronary flow reserve (CFR), FFR and IMR measured subsequent to administration vasodilatory intracoronary isosorbide dintrate. The authors also assessed the role of rho-kinase activation on reduced cardiac vasodilation by administering fasudil, a rho-kinase inhibitor and then calculating the percent change in IMR from pre-fasudil exposed coronary arteries.
In patients with VSA, CFR was negatively correlated with IMR. Further, this negative correlation was also observed between CFR and percent change in IMR after intracoronary fasudil, thereby implicating a role of rho-kinase activation in increased microvascular resistance. This patient population remains at a higher risk for MACE despite receiving treatment with calcium channel blockers, nitrate and nicorandil. Since the coronary vessels in VSA have non-obstructive stenosis, microvascular dysfuntion underlies the bad prognosis seen in these patients.
The study has some limitations, the first being that the study was single-center which necessitates further multi-center studies in order to consolidate the findings. Secondly, there were only 10 MACE events in the cohort, which may have led to a reduction in the statistical power of the results. Third, only left anterior descending (LAD) was evaluated for physiological measurements of coronary blood flow and circumflex arteries were not used for this purpose. Fourth, 14% of patients with microvascular spasm were inaccurately classified into non-VSA group and did not have their hemodynamic profiling performed. Fifth, VSA is known to more commonly affect females and the present study included 60% men which may have produced discrepancies in findings. Lastly, information regarding the changes in medical therapy, adherence to the therapy, and symptom and/or quality of life (e.g., Seattle Angina Questionnaire) during the follow-up was not available to the investigators.