Introduction: Right ventricular (RV) dysfunction identifies pulmonary arterial hypertension (PAH) patients at increased risk of mortality. Currently, few widely available biomarkers are associated with RV dysfunction in PAH. Serum chloride, a commonly measured laboratory value, is used to prognosticate left ventricular systolic heart failure patients, but the link between serum chloride, RV dysfunction, exercise capacity, and mortality in PAH patients is unexplored.
Methods: We performed a longitudinal observational study of 203 PAH patients to determine if hypochloridemia is associated with markers of RV function, exercise capacity, and survival in PAH. Serum chloride levels were measured at the time of referral. Hypochloridemia was defined as the lowest quartile of chloride levels in our study cohort. Data on clinical characteristics, six-minute walk distance (6MWD), hemodynamics, and cardiovascular mortality were collected.
Results: Hypochloridemia was significantly associated with higher right atrial pressures (11±1 vs 8±0.4 mm Hg, p=0.01), natural log transformation of serum NT pro-BNP levels (7.2±0.2 vs 6.5±0.1, p=0.03), and decreased six-minute walk distance (272±32 vs 353±14 meters, p=0.02). There was no difference in the severity of pulmonary vascular disease between patient with and without hypochloridemia (mPAP: 48±2 vs 46±1 mm Hg, p=0.42 and PVR: 10±1 vs 9±1 WU, p=0.26). Finally, hypochloridemia was associated with increased cardiovascular mortality (median survival: 7.6 vs 16.1 years, p=0.02)(Figure).
Conclusion: Hypochloridemia identifies PAH patients with worse RV dysfunction, reduced exercise capacity, and increased risk of cardiovascular mortality.