Valve Burden–Related Cardiac Remodeling in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Valvular regurgitation is a frequent but underrecognized feature of ADPKD. Although traditionally viewed as a benign finding, emerging evidence indicates that even mild valvular lesions can contribute to chronic volume load, potentially leading to early cardiac remodeling before overt dysfunction. Given the systemic connective tissue abnormalities inherent in ADPKD, valvular degeneration could represent part of the disease spectrum. However, whether such valvular abnormalities translate into measurable subclinical remodeling has not been well clarified. We aimed to determine whether the cumulative number of regurgitant valves correlates with echocardiographic indices of remodeling and whether global systolic and right ventricular functions remain preserved.

We retrospectively analyzed 99 patients with ADPKD who underwent comprehensive transthoracic echocardiography at a tertiary nephrology center. Valvular involvement (≥mild) of the mitral, aortic, tricuspid, or pulmonary valve was counted (range 0–4) to define the number of regurgitant valves (Num). Echocardiographic parameters included left ventricular mass index (LVMI), left atrial volume index (LAVI), E/e′ ratio (LV filling pressure), right atrial enlargement (RA_enlarged), left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic pressure (RVSP). Multivariable linear and logistic regression models were adjusted for age and sex. Analyses involving Num were performed among evaluable patients with complete valve grading.

In univariate analysis, patients with any valvular regurgitation had significantly higher LVMI than those without (80.9 ± 23.5 vs. 55.6 ± 5.9 g/m²; p = 0.020), supporting the association between valvular involvement and structural remodeling. Among evaluable patients with complete valve grading (n = 24), 79% had ≥1 regurgitant valve and 50% had ≥2, indicating that multivalvular involvement is not uncommon in ADPKD. Each additional regurgitant valve was associated with a significant increase in LVMI (+8.24 g/m² per valve; 95% CI 1.74–14.74; p = 0.016), independent of age and sex (Figure). Right atrial enlargement was associated with tricuspid regurgitation (OR 4.46; 95% CI 1.10–18.0; p = 0.036), and mitral regurgitation tended to correlate with elevated E/e′ ≥14 (OR 3.03; p = 0.095). Aortic regurgitation showed a nonsignificant trend toward higher LVMI (+12.2; p = 0.13). Despite these structural alterations, cardiac systolic and right ventricular functions remained preserved: LVEF (β = +0.59, p = 0.39), TAPSE (β = +2.29, p = 0.27), and RVSP (β = −0.17, p = 0.76). This pattern indicates that structural rather than functional remodeling predominates in early ADPKD, consistent with a burden-dependent continuum of cardiac involvement.

Valvular regurgitation, often regarded as a benign comorbidity, may in fact represent an early cardiac manifestation of systemic connective tissue involvement in ADPKD. Our findings demonstrate that the cumulative valvular burden correlates with left ventricular hypertrophy, marking the onset of structural remodeling even before measurable systolic dysfunction. Valve-specific associations (TR → RA enlargement; MR → diastolic load) support chamber-consistent remodeling pathways, suggesting that valvular lesions are not incidental but pathophysiologically relevant. Recognizing these subtle changes may help identify patients at risk of progressive cardiac remodeling. Accordingly, routine echocardiographic surveillance focusing on valvular burden and early chamber remodeling may contribute to proactive risk stratification and timely cardioprotective management in ADPKD, even in patients without overt heart failure or reduced ejection fraction.