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

Julio A Chirinos, Priyanka Bhattacharya, Anupam Kumar, Elizabeth Proto, Prasad Konda, Patrick Segers, Scott R Akers, Raymond R Townsend, Payman Zamani, Julio A Chirinos, Priyanka Bhattacharya, Anupam Kumar, Elizabeth Proto, Prasad Konda, Patrick Segers, Scott R Akers, Raymond R Townsend, Payman Zamani

Abstract

Background Heterogeneity in the underlying processes that contribute to heart failure with preserved ejection fraction ( HF p EF ) is increasingly recognized. Diabetes mellitus is a frequent comorbidity in HF p EF , but its impact on left ventricular and arterial structure and function in HF p EF 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 HF p EF (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 HF p EF . Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 01516346.

Trial registration: ClinicalTrials.gov NCT01516346.

Keywords: arterial stiffness; diabetes mellitus; heart failure with preserved ejection fraction; hemodynamics; left ventricular hypertrophy; magnetic resonance imaging; myocardial fibrosis.

Figures

Figure 1
Figure 1
Measurement and signal averaging of central pressure and flow using arterial tonometry and Doppler echocardiography.
Figure 2
Figure 2
Quantification of the aortic input impedance spectrum, aortic characteristic impedance, and wave separation analysis. Pb indicates backward pressure; Pf, forward pressure; Zin, input impedance.
Figure 3
Figure 3
Assessment of ambulatory central blood pressure and pulsatile hemodynamics.
Figure 4
Figure 4
Comparison of key cardiovascular parameters of left ventricular (LV) hypertrophy and cellular and interstitial expansion between diabetic and nondiabetic subjects. DM indicates diabetes mellitus.
Figure 5
Figure 5
Differences in aortic pulsatile hemodynamics assessed via pressure‐flow analyses, between diabetic and nondiabetic subjects. DM indicates diabetes mellitus; PP, pulse pressure; PWV, pulse wave velocity; Zc, characteristic impedance.
Figure 6
Figure 6
Differences in ambulatory blood pressure (BP) and pulsatile hemodynamics between diabetic and nondiabetic subjects. All units are in mm Hg. DBP indicates diastolic BP; DM, diabetes mellitus; PP, pulse pressure; SBP, systolic BP.

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