Ischemia with non-obstructive coronary arteries is associated with increased risk of incident heart failure: a large registry-based imaging cohort

Introduction Ischemia with non-obstructive coronary arteries (INOCA) is increasingly identified in patients undergoing evaluation for suspected coronary artery disease (CAD). The risk of incident heart failure in patients with INOCA remains insufficiently characterized. Purpose To evaluate the risk of major adverse cardiovascular events (MACE) and heart failure hospitalization in patients with INOCA compared with non-ischemic individuals and patients with obstructive CAD. Methods In this retrospective registry-based cohort study, 26,412 consecutive patients undergoing cardiovascular magnetic resonance perfusion imaging (n=1,292) or myocardial scintigraphy (n=25,120) between 2010 and 2023 at two tertiary centres in southern Sweden were included. Coronary angiography data were retrieved from the SWEDEHEART SCAAR registry. INOCA was defined as reversible ischemia on functional imaging without significant obstructive coronary stenosis. Patients were categorized as no ischemia, INOCA, or obstructive CAD. Patients with history of heart failure, acute coronary syndrome, coronary angiography before index imaging, non-ischemic cardiomyopathy, or missing coronary angiography despite ischemia were excluded.The primary outcome was MACE, including cardiovascular death, stroke, or acute myocardial infarction within 3 years. The secondary outcome was incident heart failure hospitalization during the same follow-up period. Results Among 26,412 patients, 388 (1.5%) had INOCA, 23,017 (87%) had no ischemia, and 3,007 (11%) had CAD. During 3-year follow-up 2,943 MACE events and 321 heart failure hospitalizations occurred. Kaplan–Meier analysis demonstrated similar rates of MACE between INOCA and the non-ischemic group (Figure 1). There was a higher risk of heart failure in INOCA patients compared to non-ischemic individuals, with risk intermediate between non-ischemic individuals and patients with obstructive CAD (Figure 2). Non-proportional hazards were addressed using time-dependent Cox regression analyses (0–1.5 and 1.5–3 years), adjusted for age, sex, type 2 diabetes, and imaging modality. The association between INOCA and incident heart failure were more pronounced beyond 1.5 years of follow-up (HR 3.4, 95% CI 1.4–8.4), than during the first time interval (HR 2.5, 95% CI 0.9–6.8). Corresponding HRs for CAD were 3.8 (95% CI 2.8–5.3) in the first time interval, and 1.1 (95% CI 0.7–1.7) in the second time interval. Type 2 diabetes was independently associated with heart failure in both time intervals (HR 2.0 [95% CI 1.5–2.7] and HR 2.6 [95% CI 1.8–3.6]). Conclusion Patients with INOCA have a significantly higher risk of incident heart failure compared with non-ischemic individuals, with risk approaching that of patients with obstructive CAD over three years of follow-up. These findings challenge the perception of INOCA as a benign condition and underscore the need for improved clinical surveillance in this patient population.Figure 1Figure 2