Ventricular arterial coupling in patients with ischemia but no obstructive coronary artery disease: novel insight into heart failure progression

Abstract

Abstract Background Ischemia with no obstructive coronary artery disease (INOCA) is prevalent in women and is associated with increased risk of developing heart failure with preserved ejection fraction (HFpEF). While the exact mechanism contributing to heart failure progression remains incompletely understood, we hypothesize that impaired ventricular-arterial coupling (VAC) plays a key role. Purpose To evaluate VAC across the INOCA-HFpEF continuum. Methods To accomplish our research objective, we leveraged cardiac magnetic resonance images from individuals with INOCA and HFpEF from the WISE Pre-HFpEF (NCT03876223) and WISE HFpEF (NCT02582021) studies, along with reference controls. Aortic pulse wave velocity (aPWV) was measured using velocity-encoded MRI, from the proximal ascending to distal descending aorta. Global longitudinal strain (GLS) was measured by feature tracking of horizontal and vertical long axis cine images. VAC was defined as the ratio between aPWV and GLS. To test for potential mediators, we assessed the relationship between VAC and age, risk factors, systolic blood pressure (SBP), diastolic blood pressure (DBP), myocardial perfusion reserve index (MPRI), LV end diastolic pressure (LVEDP), cardiac structure/function, and Kansas City Cardiomyopathy questionnaire (KCCQ). Results The baseline characteristics of the three study groups are described in the Table. Patients with INOCA had similar KCCQ scores as HFpEF patients, suggesting INOCA patients may have subclinical HFpEF. Consistent with our hypothesis, we observed a progressive impairment in VAC across the three groups (Controls vs INOCA vs HFpEF), being significantly worst in HFpEF(Figure). Importantly, VAC was inversely related with age, systolic/diastolic blood pressure, and LV mass index (R=-0.6, R=-0.4, R=-0.4, R=-0.3 respectively, all p <0.001). Conclusion The data herein support the hypothesis that VAC contributes to heart failure progression, with age, arterial blood pressure and LV mass being key determinants. That VAC was not yet significantly different between INOCA, and reference controls highlights an important opportunity for intervention to prevent heart failure progression.