Association of albuminuria and right ventricular free wall strain in HFpEF and at-risk patients: a cardio-renal interaction in HFpEF

Introduction Heart failure (HF) affects approximately 60 million people worldwide, about half of whom have preserved ejection fraction (HFpEF) (1,2). HFpEF is a heterogeneous syndrome, and up to 40% of patients present with albuminuria, which has been associated with adverse outcomes (3,4). Previous studies have demonstrated a correlation between albuminuria and right ventricular dysfunction (RVD) in HFpEF (5). Since both RVD and albuminuria are linked to poor prognosis, a shared underlying mechanism may be assumed. Aim This study investigates the relationship between albuminuria and right ventricular free wall strain (RVFWS) in HFpEF patients compared to an at-risk cohort. Methods Patients from two prospective cohort studies at our Heart Centre were pooled. HFpEF was defined as a HFA-PEFF score ≥5 or invasively measured pulmonary capillary wedge pressure (PCWP) ≥15 mmHg at rest or ≥25 mmHg during peak exertion (7). The at-risk cohort included patients with chronic kidney disease (CKD) ≥G3 or >A1 and at least one cardiovascular risk factor (hypertension, hyperlipidemia, or diabetes mellitus), excluding those with prior HF diagnosis. Clinical, laboratory and echocardiographic parameters were collected and compared between the cohorts. Urinary albumin-to-creatinine ratio (UACR) was used as a measure of albuminuria and log-transformed due to right-skewed distribution. RVFWS was acquired from an RV-focused apical four-chamber view by analysing speckle-tracking echocardiography with TomTec software. RVD was defined as RVFWS ≥-20% or fractional area change (FAC) <35% (8). Results A total of 134 HFpEF and 138 at-risk patients were included. HFpEF patients were older and had a higher prevalence of atrial fibrillation, while estimated glomerular filtration rate was lower in the at-risk cohort (table 1). UACR levels did not differ significantly between groups. Multivariate linear regression showed an independent correlation between RVFWS and UACR in HFpEF (β = 1.1; 95% CI 0.46 - 1.8; P = 0.001, figure 1 and table 3), but not in at-risk patients. A similar correlation was seen for FAC and UACR in HFpEF, but not in at-risk patients (figure 2 and table 4). Logarithmic increases in UACR were associated with an increased risk for RVD by both RVFWS (OR 1.32; 95% CI 1.05 – 1.68; P=0.018, table 5) and FAC (OR 1.46; 95% CI 1.07 – 2.00; P=0.016, table 5). Patients with concurrent and RVD defined by RVFWS exhibited the highest mean E/E′ compared to those with neither abnormality (P < 0.046). Discussion RVFWS correlates independently with UACR in HFpEF but not in at-risk individuals, supporting a cardio-renal interaction specific to HFpEF (3,4). This association links albuminuria to subclinical RV dysfunction, both known predictors of adverse outcomes (5,9). Whether their effects on disease severity are additive and the underlying pathophysiological mechanisms remain to be determined and warrant further investigation.