Ischemia in non-obstructive CAD in Italy: the INOCA-IT multicenter registry

Abstract Background Despite increasing awareness, INOCA is underdiagnosed. Our study aims to assess the prevalence of INOCA in 3 centers in Northern, Central, and Southern Italy, stratifying patients based on coronary microvascular dysfunction (CMD), vasospastic angina (VSA), microvascular spasm (MSA), or non-cardiac origins (NCO), implementing tailored medical therapy and evaluating impact on angina severity, quality of life, and cardiac outcomes at 1 year. Methods The INOCA IT Multicenter Registry is a prospective, multicenter, single-arm clinical study that included patients presenting with CCS symptoms and/or positive stress tests, and non-obstructive CAD on coronary angiography.Invasive coronary functional testing was performed, assessing Coronary Flow Reserve (CFR), Index of Microvascular Resistance (IMR). Acetylcholine (ACh) spasm provocation test was also conducted to identify abnormal vasoreactivity. Patients were consequently classified into different INOCA endotypes and received personalized medical therapy. Patients underwent 1-year clinical follow-up. Results A total of 212 patients were enrolled, the mean age was 61±11 years and 60.4% were female. Overall, 64.2% of patients suffered from hypertension, 15.6% had diabetes, the mean BMI was 26.8±4.7 and 72.6% suffered from dyslipidemia. Most patients presented with typical chest pain (86.8%), the median Canadian Cardiovascular Society (CCS) grade was 2(IQR 2-3) and the median New York Heart Association (NHYA) class median 2 (IQR 1-2). At invasive coronary functional testing (mean CFR: 3.25±1.78, mean IMR 22.1±15.0), 22.6% of patients were diagnosed with CMD, 22.2% with VSA, 14.2% with MSA, 16.0% were affected by both CMD and VSA, 3.8% had both CMD and MVA, 21.2% patients had NCO symptoms.The prevalence of INOCA endotypes showed geographical differences: the first endotype in northern Italy was VSA (27.5%), CMD was the first in central Italy (28.9%), whereas most patients from southern Italy had chest pain of NCO (32.1%) – p for overall comparisons =0.028. The latter also had the highest prevalence of hypertension (83.9%vs52.5% and 61.8% in the other areas, p0.01) and dyslipidemia (85.7vs 65.0 and 71.1 in the other areas, p=0.026). Moreover, male patients were more frequently affected by VSA compared to other endotypes in northern Italy (37.5%, p for overall comparison=0.043). Finally, VSA was the most frequently misdiagnosed endotype upon non-invasive diagnostic work-up, with a false negative rate of 78.8%, whereas CMD was identified more frequently, with a true positive rate of 50%. The last patient was enrolled in March 2024, and 1-year follow will be available at the time of presentation. Conclusions This real-world analysis highlights the importance of providing accurate diagnosis and subsequent tailored therapy to INOCA patients with a safe and systematical approach. We expect to detect improved QOL and angina symptoms following optimization of medical therapy.