Microvascular Disease in Patients With Diabetes With Heart Failure and Reduced Ejection Versus Preserved Ejection Fraction

Abstract

Microvascular complications are common among patients with diabetes mellitus (DM). The presence of heart failure (HF) is presumed to be due to macrovascular disease (typically HF with reduced ejection fraction [HFrEF] following myocardial infarction). We hypothesized that HF with preserved ejection fraction (HFpEF) in patients with DM may be a manifestation of microvascular disease compared with HFrEF. The objective of this study was to examine the prevalence and association with clinical outcome of microvascular complications in patients with HF and DM. RESEARCH DESIGN AND METHODS We investigated the prevalence, association with clinical outcome, and cardiac structure and function of microvascular (neuropathy, nephropathy, and retinopathy) complications of DM in 2,800 prospectively enrolled participants with HF and DM (561 with HFpEF) from the Asian Sudden Cardiac Death In Heart Failure (ASIAN-HF) registry. RESULTS A total of 601 (21.5%) participants with DM had microvascular complications. Participants with DM and any (one or more) microvascular complications were more likely to have HFpEF (odds ratio 1.70 [95% CI 1.15-2.50]; P = 0.008). Furthermore, the likelihood of having HFpEF increased with an increasing number of microvascular complications (P trend < 0.001). Microvascular complications were associated with more left ventricular (LV) hypertrophy and a greater reduction in quality of life in HFpEF than HFrEF (P interaction < 0.001 for all). Compared with participants with DM and without microvascular complications, the adjusted hazard ratio for the composite outcome of all-cause death or HF hospitalization was 1.35 (95% CI 1.04-1.76) for participants with DM and microvascular complications regardless of HF type (P interaction = 0.112). CONCLUSIONS Diabetic microvascular disease is more common, and related to greater LV remodeling, more impairment of quality in life, and similar adverse outcomes, in participants with HFpEF compared with HFrEF. HFpEF may be a clinical manifestation of microvascular disease in DM. In patients with diabetes mellitus (DM), microvascular disease is traditionally recognized as the presence of neuropathy, retinopathy, or nephropathy (1). In contrast, cardiac involvement in DM is usually categorized as macrovascular disease; namely, epicardial coronary artery disease with myocardial infarction leading to heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with DM are increasingly

Cellular and Molecular Differences between HFpEF and HFrEF: A Step Ahead in an Improved Pathological Understanding

“…It is present in both HFpEF and HFrEF (Table 1) [23,24,106], as shown by a similar loss in cardiac microvascular density [23,24]. However, comorbidities can differentially affect endothelial function, with microvascular complications being more prevalent in HFpEF than in HFrEF [22]. Besides being more severe in HFpEF, endothelial dysfunction happens earlier in the progression of HFpEF.…”

“…Remodelling differences in HFrEF and HFpEF can be explained by structural differences in the cardiomyocytes, with thinner and more elongated cardiomyocytes, lower myofibrillar density, and reduced cardiomyocyte passive stiffness (F passive ) in cardiac biopsies of HFrEF patients compared to HFpEF patients [54]. Comorbidities found in both HFrEF and HFpEF also differentially alter the structure of the heart; T2DM, for example, causes a more pronounced left ventricular hypertrophy and worsened quality of life in HFpEF compared to HFrEF [22]. Furthermore, increased cardiomyocyte size in the HFpEF biopsies correlates with lower myocardial PKG activity and cGMP concentration [130].…”

Sex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure

“…However, our models adjusted for the competing risk of death. This suggests that other CV risk factors not included in our study (e.g., microvascular disease [ 30 ]) may be more strongly associated with higher age in women than men. Furthermore, it is known that women have higher systolic and diastolic LV elastance than men at a given age, and the differences (particularly for end-diastolic elastance) are accentuated with aging ( 31 , 32 ), which could potentially explain stronger associations of age with incident HF in women.…”

Regional adiposity and heart failure with preserved ejection fraction

“…26,27 Diabetes is also associated with LV remodelling, ventricular hypertrophy, and cardiac microvascular disease, likely contributing to the development of HFpEF among patients with diabetes. 28 Clinical outcomes are also worse among patients with diabetes treated with insulin in HFpEF. 29 The link between obesity and diabetes are likely driven by inhibited glucose transport and uptake into muscle cells caused by insulin resistance and reduced insulin sensitivity in the setting of glucotoxicity.…”