The forgotten electrolyte in heart failure: serum chloride identifies a congestion phenotype with right ventricular dysfunction and hepatorenal involvement

Background

Right ventricular (RV) dysfunction and systemic venous congestion are major determinants of severity and prognosis in heart failure (HF). The pulmonary artery pulsatility index (PAPi) reflects RV–pulmonary arterial coupling, while the MELD-Na score reflects hepatorenal congestion. Serum chloride has emerged as a marker of neurohormonal activation, renal tubular adaptation, and diuretic responsiveness, but its relationship with RV dysfunction and systemic congestion phenotypes remains incompletely defined. We evaluated whether hypochloremia identifies a congestion-dominant HF phenotype characterized by RV dysfunction and multi-organ involvement.

Methods

We retrospectively analyzed 112 patients who underwent right heart catheterization. Echocardiographic, hemodynamic, and laboratory data were collected. Patients were stratified by median serum chloride (≤103 vs >103 mEq/L). RV dysfunction was defined as PAPi <3 and advanced systemic congestion as MELD-Na ≥15. Group comparisons assessed differences in hemodynamic and congestion markers. Receiver operating characteristic (ROC) and correlation analyses evaluated associations between chloride levels, PAPi, and MELD-Na.

Results

Demographic characteristics were similar between groups (age 58.1±13.4 vs 58.8±15.1 years, p=0.789). Patients with lower chloride demonstrated impaired RV function with lower PAPi (5.04±4.25 vs 6.89±5.14, p=0.049), reduced tricuspid annular plane systolic excursion (1.84±0.52 vs 2.21±0.48 cm, p<0.001), and higher pulmonary capillary wedge pressure (14.65±6.95 vs 11.92±5.37 mmHg, p=0.021). Left ventricular ejection fraction was also lower (49.4±17.7 vs 57.8±11.6%, p=0.003).

Markers of systemic congestion were significantly worse in the low chloride group, including higher MELD-Na (12.6±6.0 vs 8.5±2.9, p<0.001), higher NT-proBNP (2233±3034 vs 1074±2249 pg/mL, p=0.023), lower sodium (136.6±4.4 vs 141.3±2.0 mEq/L, p<0.001), and greater hepatorenal involvement with higher creatinine (1.02±0.36 vs 0.85±0.33 mg/dL, p=0.007), bilirubin (1.12±1.22 vs 0.62±0.37 mg/dL, p=0.004), and international normalized ratio (1.31±0.39 vs 1.15±0.30, p=0.014).

Patients with RV dysfunction (PAPi <3) had lower chloride levels (101 vs 104 mEq/L, p=0.010), while those with advanced congestion (MELD-Na ≥15) demonstrated markedly reduced chloride (93 vs 104 mEq/L, p<0.001). Chloride moderately discriminated RV dysfunction (AUC=0.65) but strongly discriminated advanced congestion (AUC=0.83). Chloride correlated positively with PAPi (r=0.24, p=0.015) and inversely with MELD-Na (r=−0.51, p<0.001). Results are presented in Table 1.

Conclusions

Hypochloremia is associated with RV dysfunction and advanced systemic congestion in HF. Serum chloride identifies a congestion-dominant phenotype characterized by impaired RV function and hepatorenal involvement and may serve as a simple and widely available marker of congestion physiology.