Right ventricular myocardial stiffness assessed by non-invasive shear wave elastography in HFpEF: a pre-specified substudy of PACIFIC-PRESERVED

Background Heart failure with preserved ejection fraction (HFpEF) is characterized by marked biological and structural heterogeneity, with myocardial stiffness considered a central pathophysiological determinant. However, in vivo assessment of regional myocardial mechanical properties remains limited, particularly at the right ventricular (RV) level. Shear wave elastography (SWE), based on high–frame rate echocardiography, enables non-invasive quantification of myocardial stiffness through measurement of shear wave propagation velocity. We aimed to determine whether RV myocardial stiffness identifies mechanical remodeling in HFpEF beyond conventional imaging parameters. Methods PACIFIC-PRESERVED is a prospective, deeply phenotyped cohort enrolling HFpEF, HFrEF, and control participants in a 3:2:1 ratio. Myocardial stiffness assessment was included as a pre-specified secondary objective in a dedicated imaging sub-study. Among 168 enrolled patients, 132 underwent SWE acquisition, and 126 (95.5%) had analyzable RV free wall shear velocity measurements (62 HFpEF, 41 HFrEF, 23 controls). SWE measurements were obtained using an innovative ultrasound probe in parasternal short-axis views (M-mode acquisition). Comprehensive multimodal phenotyping included echocardiography, cardiac magnetic resonance (CMR), and biological profiling. Results RV myocardial shear wave velocity differed significantly across groups (p<0.0001, Figure). HFpEF patients exhibited markedly higher RV shear velocity compared with controls (1.97±0.58 vs 1.40±0.32 m/s), consistent with increased myocardial stiffness. Values were similar between HFpEF and HFrEF (p=0.99). Fractional anisotropy did not differ between groups, consistent with the absence of overt myocardial architectural remodeling. Importantly, conventional RV functional parameters were preserved in HFpEF. CMR demonstrated similar RV volumes across groups, and RVEF in HFpEF (58±8%) did not differ from controls (61±6%; p=0.43), whereas it was reduced in HFrEF (50±11%; p<0.001). Similarly, TAPSE measured by cardiac echography was preserved in HFpEF (23±5 mm) as compared to controls (24±3 mm, p=0,19) but significantly reduced in HFrEF (20±6 mm, p=0.004). RV shear velocity did not correlate with RVEF, RV volumes, or TAPSE. Conclusions Assessment of RV myocardial stiffness by shear wave elastography is feasible and reproducible in a prospective HF cohort. Increased RV shear wave velocity is observed in both HFpEF and HFrEF compared with controls, despite preserved RV function in HFpEF. These findings suggest that SWE-derived RV stiffness represents a distinct and potentially early marker of myocardial involvement in heart failure, preceding overt RV functional impairment.