Abstract

Background: The bicarbonate (HCO3 - ) buffer system plays a crucial role in maintaining acid-base homeostasis, and HCO3 - levels are affected by multiple factors in heart failure. Recently, a sub-analysis of the ADVOR trial for acute heart failure revealed that patients with elevated serum HCO3 - levels experienced beneficial effects of decongestion by acetazolamide. However, the significance of HCO3 - levels in chronic heart failure has not been fully understood. Aim: We sought to clarify whether HCO3 - levels have clinical relevance or prognostic impact in patients with chronic heart failure. Methods and Results: We conducted a prospective study involving hospitalized patients with stage C/D heart failure and measured HCO3 - levels in arterial blood gas samples prior to discharge. We enrolled a total of 718 patients (mean 68.3 years old and 62.1% male), with neutral pH ranging from 7.35 to 7.45, and found that 132 (18.4%) had HCO3 - levels exceeding 26 mmol/L. Patients with HCO3 - > 26 mmol/L were more likely to be male and to use loop diuretics, and had higher serum sodium, as well as lower potassium levels, compared to those with HCO3 - < 26 mmol/L, whereas there were no differences in B-type natriuretic peptide levels or left ventricular ejection fraction between the two groups. In a Kaplan-Meier analysis, patients with HCO3 - > 26 mmol/L had lower event-free survival rates from cardiac deaths and decompensated heart failure as well as the composite of the cardiac events over a median follow-up period of 1540 days ( Figure ). In a multivariable Cox proportional hazard model after adjusting confounding variables, the presence of HCO3 - > 26 mmol/L was independently associated with increased risks of the composite of cardiac events (hazard ratio, 1.64; P < 0.01). Conclusion: Elevated HCO3 - levels may indicate enhanced proximal nephron activation and resistance to loop diuretics, which predicted adverse outcomes in patients with chronic heart failure, even within a normal pH range.

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