Association of microvascular dysfunction with cardiovascular outcomes in heart failure with preserved ejection fraction

Abstract

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a disease that portends an increased risk of morbidity and mortality. Studies have reported an association between HFpEF and microvascular dysfunction, however this association and its prognostic significance remain unclear. The purpose of this meta-analysis is to evaluated the association of microvascular dysfunction with cardiovascular outcomes in patients with HFpEF. Methods A literature search was conducted for studies evaluating the association between microvascular dysfunction measured with global myocardial flow reserve (GMFR) and coronary flow reserve (CFR) and major adverse cardiovascular events (MACE) in patients with HFpEF. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. The minimum follow up duration was one year. Results A total of 5 studies with 448 patients (252 with HFpEF, 196 healthy controls) met inclusion criteria for evaluation of the association of GMPR with HFpEF. Patients with HFpEF had a significantly lower GMPR compared to healthy controls (SMD -0.83, 95% CI -1.03,-0.63; p<0.01). Heterogeneity was moderate: Chi2=9.5, df=4, I2 = 58%. Only 2 studies were identified that reported on the evaluation of CFR in patients with HFpEF so meta-analysis could not be reliably performed. A total of 4 studies with 591 HFpEF patients (284 with reduced CFR and 307 with normal CFR) met inclusion for evaluating the association with MACE. Mean follow-up was 36 months. Patients with impaired CFR <2.0 had significantly higher risk of MACE compared to patients with normal CFR (OR 8.89, 95% CI 3.77-20.92; P<0.01). Heterogeneity was low: Chi2=4.77, df=3, I2=37%. Conclusion Patients with HFpEF have significant microvascular disease compared to patients without HFpEF, which is associated with an increased risk of MACE. Additional high-quality studies are required to further elucidate this association and determine the utility of targeted medical therapy.