Supplemental Material for: Right Ventricular Free Wall Strain Is Associated with Low-Grade Albuminuria in HFpEF: A Cross-Sectional Cohort Study

Methods

Patients with HFpEF (LVEF ≥50%, HFA-PEFF score ≥5 or invasively elevated filling pressures) and patients of a CKD comparator cohort (CKD ≥G3 or >A1 and ≥1 CV risk factor, without diagnosed HF) were pooled from two cross-sectional cohort studies for this analysis. All patients underwent comprehensive assessment including albuminuria and RVFWS measurement. Albuminuria was categorized by KDIGO stage (A1/A2/A3).

RVD was defined by RVFWS ≥ -20%, RV FAC <35% or TAPSE <17 mm. We examined the association between RVFWS and albuminuria using a multivariate linear model with a cohort interaction term and cohort-specific models. Model robustness was assessed by elastic-net regression, bootstrap internal validation, E-value and by adding NT-proBNP, neutrophile count, pulmonary artery systolic pressure and urinary α1-microglobulin individually in separate sensitivity models.

Inter- and intra-observer reproducibility of RVFWS was quantified.</p><p dir="ltr">Results: In total, 119 HFpEF and 133 CKD patients were identified. In HFpEF, RVFWS was more impaired (-22.5% vs. -25.7%, p < 0.001) and RVD more prevalent (30% vs. 16%). Median UACR lay within the KDIGO A1 range in both cohorts.

More impaired RVFWS was associated with higher UACR in HFpEF (adjusted UACR ratio 1.55 per 5% less-negative strain, 95% CI 1.17-2.04, p=0.002) but not in the CKD cohort (p=0.380), with a significant cohort interaction (p=0.002). The association persisted after adjustment in sensitivity models, and RVFWS was retained by penalized regression. Inter- and intra-observer agreement of RVFWS was moderate-to-good (ICC 0.71 and ICC 0.69, respectively).</p><p dir="ltr">Conclusion: In ambulatory HFpEF patients with predominantly low-grade albuminuria, RVFWS is associated with UACR independently of clinical confounders, an association not observed in a CKD cohort with CV risk factors and not attenuated after adjustment for estimated PASP. </p>