Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure.

Background: Lower serum chloride (Cl) is associated with mortality in heart failure patients and may be more prognostically relevant than sodium. However, the association of hemodynamics and Cl levels is unknown.

Methods: 438 sequential patients with advanced chronic heart failure (ACHF) underwent invasive hemodynamic assessment with measured serum Cl levels during an evaluation for ACHF. Patients were followed for death, heart transplant (HT), or ventricular assist device placement (VAD). A backwards regression model determined hemodynamic predictors of Cl (removal, P<0.1) with candidate variables: Fick cardiac index (FCI), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), mean arterial pressure (MAP), heart rate (HR), and pulmonary artery systolic pressure (PASP). All models were also adjusted for serum sodium and bicarbonate.

Results: In this cohort, the median Cl level was 102 [98-104]meq/L (range 86-113meq/L). Chloride was weakly correlated with FCI (rho 0.12, P=0.01) and MAP (rho 0.21, P<0.001); but not PCWP, RAP, HR or PASP (P>0.05 for all). In the multivariable model, FCI (beta 0.73meq/L/L/min/m, P=0.002) but not RAP (P=0.3) or MAP (P=0.2), remained associated with Cl. Lower Cl was associated with increased risk of death, HT, or VAD placement (HR 0.94/meq/L, 95% CI 0.89-0.99, P=0.01). However, this association was attenuated after additional adjustment for BUN (P=0.27) and PCWP and FCI (0.48).

Conclusions: Lower FCI, not lower MAP or higher cardiac filling pressures, was associated with lower chloride. Although lower chloride was associated with poor long-term outcomes, this risk attenuates with adjustment for more conventional clinical parameters.