Impact of Diabetes Mellitus on Ventricular Structure, Arterial Stiffness, and Pulsatile Hemodynamics in Heart Failure With Preserved Ejection Fraction

Background Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HFpEF, but its impact on left ventricular and arterial structure and function in HFpEF is unknown. Methods and Results We assessed the impact of diabetes mellitus on left ventricular cellular and interstitial hypertrophy (assessed with cardiac magnetic resonance imaging, including T1 mapping pregadolinium and postgadolinium administration), arterial stiffness (assessed with arterial tonometry), and pulsatile arterial hemodynamics (assessed with in‐office pressure‐flow analyses and 24‐hour ambulatory monitoring) among 53 subjects with HFpEF (32 diabetic and 21 nondiabetic subjects). Despite few differences in clinical characteristics, diabetic subjects with HFpEF exhibited a markedly greater left ventricular mass index (78.1 [95% CI, 70.4–85.9] g versus 63.6 [95% CI, 55.8–71.3] g; P=0.0093) and indexed extracellular volume (23.6 [95% CI, 21.2–26.1] mL/m2 versus 16.2 [95% CI, 13.1–19.4] mL/m2; P=0.0008). Pronounced aortic stiffening was also observed in the diabetic group (carotid‐femoral pulse wave velocity, 11.86 [95% CI, 10.4–13.1] m/s versus 8.8 [95% CI, 7.5–10.1] m/s; P=0.0027), with an adverse pulsatile hemodynamic profile characterized by increased oscillatory power (315 [95% CI, 258–373] mW versus 190 [95% CI, 144–236] mW; P=0.0007), aortic characteristic impedance (0.154 [95% CI, 0.124–0.183] mm Hg/mL per second versus 0.096 [95% CI, 0.072–0.121] mm Hg/mL per second; P=0.0024), and forward (59.5 [95% CI, 52.8–66.1] mm Hg versus 40.1 [95% CI, 31.6–48.6] mm Hg; P=0.0010) and backward (19.6 [95% CI, 16.2–22.9] mm Hg versus 14.1 [95% CI, 10.9–17.3] mm Hg; P=0.0169) wave amplitude. Abnormal pulsatile hemodynamics were also evident in 24‐hour ambulatory monitoring, despite the absence of significant differences in 24‐hour systolic blood pressure between the groups. Conclusions Diabetes mellitus is a key determinant of left ventricular remodeling, arterial stiffness, adverse pulsatile hemodynamics, and ventricular‐arterial interactions in HFpEF. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01516346.