Circ Heart Fail. 2016 Aug;9(8). pii: e003180. doi: 10.1161/CIRCHEARTFAILURE.116.003180.
Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights.
Hanberg JS1, Rao V1, Ter Maaten JM1, Laur O1, Brisco MA1, Perry Wilson F1, Grodin JL1, Assefa M1, Samuel Broughton J1, Planavsky NJ1, Ahmad T1, Bellumkonda L1, Tang WH1, Parikh CR1, Testani JM2.
BACKGROUND:Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature.
METHODS AND RESULTS:Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46; P<0 .001="" b=""> with no incremental contribution from serum sodium0>
response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0 .001="" b="" in="" interventional="" pilot="" the="">lysine chloride0> supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L, and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type natriuretic peptide, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio.
CONCLUSIONS:Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters.
CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT02031354.
© 2016 American Heart Association, Inc.