Increased Myocardial Stiffness in Patients with High Risk Left Ventricular Hypertrophy: The Hallmark of Stage-B HFpEF.

Michinari Hieda; Satyam Sarma; Christopher M Hearon; Katrin A Dias; Jose Martinez; Mitchel Samels; Braden Everding; Dean Palmer; Sheryl Livingston; Margot Morris; Erin Howden; Benjamin D Levine
Individuals with left ventricular hypertrophy (LVH) and elevated cardiac biomarkers in middle-age are at high risk for the development of heart failure with preserved ejection fraction (HFpEF). However, it is unknown what the pathophysiological underpinnings of this high risk state may be. We tested the hypothesis that patients with LVH and elevated cardiac biomarkers would demonstrate elevated LV myocardial stiffness when compared to healthy controls as a key marker for future HFpEF. Forty-six patients with LVH (LV septum >11 mm) and elevated cardiac biomarkers [NT-proBNP (>40 pg/ml) or TnT (>0.6 pg/ml)] were recruited, along with 61 age- and sexmatched (by cohort) healthy controls. To define LV pressure-volume relationships, right heart catheterization and 3D-echocardiography were performed while preload was manipulated using lower body negative pressure and rapid saline infusion. There were significant differences in body size, blood pressure, and baseline pulmonary capillary wedge pressure between groups (e.g., PCWP: LVH: 13.4 ± 2.7, vs. control: 11.7 ± 1.7mmHg, P<0.0001). The LV was less distensible in LVH than controls (smaller volume for the same filling pressure). When preload was expressed as transmural filling pressure (PCWP - RAP), LV myocardial stiffness was nearly 30% greater in LVH compared to controls (LVH stiffness constant: 0.053 ± 0.027, vs. controls: 0.042 ± 0.020, P=0.028). LV myocardial stiffness in patients with LVH and elevated biomarkers (stage-B HFpEF) is greater than age- and sex- matched controls, and thus appears to represent a transitional state from a "normal healthy-heart" to HFpEF. Although, LV myocardial stiffness of LVH patients is greater than that of healthy controls at this early stage, further studies are required to clarify whether interventions such as exercise training to improve LV compliance may prevent the full manifestation of the HFpEF syndrome in these high risk individuals. URL: Unique Identifiers: NCT03476785 and NCT02039154.Background:
ISSN 1524-4539
Published 23 Dec 2019
DOI 10.1161/CIRCULATIONAHA.119.040332
Type Journal Article