Myocardial Tissue Characterization by CMR Captures Mechanistic Severity Beyond Filling Pressure in HFpEF: The...

Diastolic dysfunction (DD) in heart failure with preserved ejection fraction (HFpEF) reflects active relaxation (τ) and passive stiffness (β), conflated by end-diastolic pressure (EDP) and potentially requiring different therapies. Whether cardiac magnetic resonance (CMR) tissue mapping captures these beyond filling pressure is unknown.

This study aims to determine whether CMR tissue mapping (native T1 corrected for field strength and scanner [T1c], native T2 corrected for field strength and scanner [T2c]) captures τ and β as markers of mechanistic severity in HFpEF beyond EDP.

In this prospective multicenter study, patients with suspected HFpEF underwent CMR with sequence-corrected tissue mapping and invasive pressure-volume loop analysis. HFpEF was defined as EDP ≥16 mm Hg (n = 52). Age- and sex-matched control patients (n = 32) and healthy volunteers (n = 18) provided cross-group context. Eighteen catheterized symptomatic patients with normal resting EDP underwent handgrip provocation for a continuum analysis. Partial correlations adjusted T1c-β and T2c-τ associations for EDP.

T1c and T2c differed between HFpEF and matched control patients (Cliff's δ 0.74 and 0.80; both P < 0.001). Within HFpEF, T1c correlated with β (partial ρ = 0.47; P = 0.003) and T2c with τ (ρ = 0.35; P = 0.018), both conditional on EDP. Exploratory partitioning around medoids clustering on τ and β identified 2 phenotypes (mild DD [n = 24], severe DD [n = 28]; adjusted Rand index: 0.78) that separated T1c and T2c (both P < 0.001), whereas an EDP median split did not, consistent with tissue mapping reflecting mechanistic severity beyond filling pressure.

In invasively characterized HFpEF, CMR tissue mapping captures active relaxation impairment and passive stiffness conditional on filling pressure, robust to clinical covariate adjustment. The exploratory 2-phenotype partition is hypothesis-generating; prospective external validation, including treatment-response data, is required before clinical stratification. (Validation of CMR Against Invasive Heamodynamics in Patients With HFpEF [DECIPHER HFpEF]; NCT03251183).