Diabetic phenotype and prognosis of patients with heart failure and preserved ejection fraction in a real life cohort

Abstract

Background Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, with several underlying etiologic and pathophysiologic factors. The presence of diabetes might identify an important phenotype, with implications for therapeutic strategies. While diabetes is associated with worse prognosis in HFpEF, the prognostic impact of glycemic control is yet unknown. Hence, we investigated phenotypic differences between diabetic and non-diabetic HFpEF patients (pts), and the prognostic impact of glycated hemoglobin (HbA1C). Methods We prospectively enrolled 183 pts with HFpEF (78 ± 9 years, 38% men), including 70 (38%) diabetics (type 2 diabetes only). They underwent 2D echocardiography (n = 183), cardiac magnetic resonance (CMR) (n = 150), and were followed for a combined outcome of all-cause mortality and first HF hospitalization. The prognostic impact of diabetes and glycemic control were determined with Cox proportional hazard models, and illustrated by adjusted Kaplan Meier curves. Results Diabetic HFpEF pts were younger (76 ± 9 vs 80 ± 8 years, p = 0.002), more obese (BMI 31 ± 6 vs 27 ± 6 kg/m2, p = 0.001) and suffered more frequently from sleep apnea (18% vs 7%, p = 0.032). Atrial fibrillation, however, was more frequent in non-diabetic pts (69% vs 53%, p = 0.028). Although no echocardiographic difference could be detected, CMR analysis revealed a trend towards higher LV mass (66 ± 18 vs 71 ± 14 g/m2, p = 0.07) and higher levels of fibrosis (53% vs 36% of patients had ECV by T1 mapping > 33%, p = 0.05) in diabetic patients. Over 25 ± 12 months, 111 HFpEF pts (63%) reached the combined outcome (24 deaths and 87 HF hospitalizations). Diabetes was a significant predictor of mortality and hospitalization for heart failure (HR: 1.72 [1.1–2.6], p = 0.011, adjusted for age, BMI, NYHA class and renal function). In diabetic patients, lower levels of glycated hemoglobin (HbA1C < 7%) were associated with worse prognosis (HR: 2.07 [1.1–4.0], p = 0.028 adjusted for age, BMI, hemoglobin and NT-proBNP levels). Conclusion Our study highlights phenotypic features characterizing diabetic patients with HFpEF. Notably, they are younger and more obese than their non-diabetic counterpart, but suffer less from atrial fibrillation. Although diabetes is a predictor of poor outcome in HFpEF, intensive glycemic control (HbA1C < 7%) in diabetic patients is associated with worse prognosis.

Effect of diabetes mellitus on the development of left ventricular contractile dysfunction in women with heart failure and preserved ejection fraction

“…The underlying mechanisms of the adverse effect of DM on LV systolic function are not fully understood. HFpEF comorbid with DM could induce a broad context of metabolic disorder, oxidative stress, and a systemic inflammatory state, resulting in excitation-contraction coupling impairment, extracellular matrix fibrosis, and microvasculature dysfunction, thereby promoting myocardial contractility impairment [ 3 , 23 , 26 ]. Based on the observation in our study that DM has a greater adverse effect on LV contractility in women than in men, the decline in the estrogen level at menopause together with the presence of DM may be responsible for this difference [ 27 ].…”

“…Moreover, comorbid cardiovascular risk factors, such as DM, represent other major factors responsible for LV remodeling in HFpEF development [20]. In recent studies comparing HFpEF patients with and without DM, those with DM seem to present with increased LVM [21][22][23]. Nevertheless, the sex differences in LV remodeling in the context of DM are unclear.…”

Sex Differences of the Diabetic Heart

“…Kim et al (2019) also show that the impact of diabetes on long-term mortality and HF readmission seems to be greater in females than in males. Women represent ∼60% of patients having HF with preserved ejection fraction (HFpEF) whether they present with diabetes or not, but T2D women are younger, more obese, have worse renal function, lower prevalence of atrial fibrillation, and decreased hemoglobin levels (Lejeune et al, 2021). Importantly, HFpEF is more prevalent in women than in men, who preferentially exert HF with reduced ejection fraction (Beale et al, 2019;Dewan et al, 2019).…”

Impact of myocardial scars on left ventricular deformation in type 2 diabetes mellitus after myocardial infarction by contrast-enhanced cardiac magnetic resonance

“…Cardiac magnetic resonance (CMR) imaging, which has been widely used in the last decades in clinical practice, provides information on various characteristics of cardiac structure, function, and myocardial tissue [ 10 – 12 ]. CMR tissue tracking has been used to measure myocardial deformation [ 13 ].…”