Serial sodium values and adverse outcomes in heart failure with preserved ejection fraction.
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ABSTRACT: Objective
The purpose of our study is to examine whether serial measurements of serum sodium values after diagnosis identify a higher-risk subset of patients with heart failure with preserved ejection fraction.Methods
We identified 50,932 subjects with HFpEF with 759,577 recorded sNa measurements (mean age 72 ± 11 years) using a validated algorithm in the VA national database from 2002 to 2012. We examined the association of repeated measures of sNa with mortality using a multivariable Cox proportional hazards model.Results
After a median follow-up of 2.9 years (IQR: 1.2-5.4), 19,011 deaths occurred. After adjusting for age, sex, race, BMI, glomerular filtration rate, potassium, coronary artery disease, hypertension, hyperlipidemia, atrial fibrillation, pulmonary disease, diabetes, anemia, and medications, we found J-shaped associations of serum sodium with mortality. HRs for all-cause mortality were 2.48 (95% CI: 2.38-2.60) for the sNA 115.00-133.99 category; and 1.40 (95% CI: 1.35-1.46) for the sNA 143.00-175.00 category compared to the 137.01-140.99 category (ref). We used generalized estimating equation-based negative binomial regression to compute the incidence density ratios (IDR) to examine days hospitalized for heart failure and for all causes. There were a total of 1,275,614 days of all-cause hospitalization and 104,006 days of heart-failure hospitalization. The IDRs for the lowest sNA group were 2.03 (95% CI: 1.90-2.18) for all-cause hospitalization and 1.73 (95% CI: 1.39-2.16) for heart-failure hospitalization.Conclusions
Our findings suggest that monitoring of serum sodium values during longitudinal follow-up can identify HFpEF patients at risk of adverse outcomes.
SUBMITTER: Imran TF
PROVIDER: S-EPMC8077233 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RationaleAbnormalities in nitric oxide signaling play a pivotal role in heart failure with preserved ejection fraction (HFpEF). Intravenous sodium nitrite, which is converted to nitric oxide in vivo, improves hemodynamics in HFpEF, but its use is limited by the need for parenteral administration. Nitrite can also be administered using a novel, portable micronebulizer system suitable for chronic use.ObjectiveDetermine whether inhaled nitrite improves hemodynamics in HFpEF.Methods and resultsIn a double-blind, randomized, placebo-controlled, parallel-group trial, subjects with HFpEF (n=26) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise before and after treatment with inhaled sodium nitrite (90 mg) or placebo. The primary end point was the pulmonary capillary wedge pressure during exercise. Before study drug administration, HFpEF subjects displayed an increase in pulmonary capillary wedge pressure with exercise from 20±6 to 34±7 mm Hg (P<0.0001). After study drug administration, exercise pulmonary capillary wedge pressure was substantially improved by nitrite as compared with placebo (baseline-adjusted mean 25±5 versus 31±6 mm Hg; analysis of covariance P=0.022). Inhaled nitrite reduced resting pulmonary capillary wedge pressure (-4±3 versus -1±2 mm Hg; P=0.002), improved pulmonary artery compliance (+1.5±1.1 versus +0.6±0.9 mL/mm Hg), and decreased mean pulmonary artery pressures at rest (-7±4 versus -3±4 mm Hg; P=0.007) and with exercise (-10±6 versus -5±6 mm Hg; P=0.05). Nitrite reduced right atrial pressures, with no effect on cardiac output or stroke volume.ConclusionsAcute administration of inhaled sodium nitrite reduces biventricular filling pressures and pulmonary artery pressures at rest and during exercise in HFpEF. Further study is warranted to evaluate chronic effects of inhaled nitrite in HFpEF.Clinical trial registrationThis single center randomized clinical trial is registered at clinicaltrials.gov (NCT02262078).
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