Hypochloremia and diuretic resistance in heart failure

Jennifer S. Hanberg, Veena Rao, Jozine M. Ter Maaten, Olga Laur, Meredith A. Brisco, F. Perry Wilson, Justin L. Grodin, Mahlet Assefa, J. Samuel Broughton, Noah J. Planavsky, Tariq Ahmad, Lavanya Bellumkonda, W. H.Wilson Tang, Chirag R. Parikh, Jeffrey M. Testani

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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) with no incremental contribution from serum sodium (P=0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot, lysine chloride 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.

Original languageEnglish (US)
Article numbere003180
JournalCirculation: Heart Failure
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2016

Fingerprint

Diuretics
Chlorides
Heart Failure
Serum
Kidney
Renin
Sodium Chloride
Lysine
Weight Loss
Sodium
Sodium Potassium Chloride Symporter Inhibitors
Hyponatremia
Brain Natriuretic Peptide
Blood Urea Nitrogen
Furosemide
Osmolar Concentration
Epidemiologic Studies
Creatinine
Outpatients
Salts

Keywords

  • cardiorenal syndrome
  • chloride
  • diuretics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hanberg, J. S., Rao, V., Ter Maaten, J. M., Laur, O., Brisco, M. A., Wilson, F. P., ... Testani, J. M. (2016). Hypochloremia and diuretic resistance in heart failure. Circulation: Heart Failure, 9(8), [e003180]. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180

Hypochloremia and diuretic resistance in heart failure. / Hanberg, Jennifer S.; Rao, Veena; Ter Maaten, Jozine M.; Laur, Olga; Brisco, Meredith A.; Wilson, F. Perry; Grodin, Justin L.; Assefa, Mahlet; Broughton, J. Samuel; Planavsky, Noah J.; Ahmad, Tariq; Bellumkonda, Lavanya; Tang, W. H.Wilson; Parikh, Chirag R.; Testani, Jeffrey M.

In: Circulation: Heart Failure, Vol. 9, No. 8, e003180, 01.08.2016.

Research output: Contribution to journalArticle

Hanberg, JS, Rao, V, Ter Maaten, JM, Laur, O, Brisco, MA, Wilson, FP, Grodin, JL, Assefa, M, Broughton, JS, Planavsky, NJ, Ahmad, T, Bellumkonda, L, Tang, WHW, Parikh, CR & Testani, JM 2016, 'Hypochloremia and diuretic resistance in heart failure', Circulation: Heart Failure, vol. 9, no. 8, e003180. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180
Hanberg JS, Rao V, Ter Maaten JM, Laur O, Brisco MA, Wilson FP et al. Hypochloremia and diuretic resistance in heart failure. Circulation: Heart Failure. 2016 Aug 1;9(8). e003180. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180
Hanberg, Jennifer S. ; Rao, Veena ; Ter Maaten, Jozine M. ; Laur, Olga ; Brisco, Meredith A. ; Wilson, F. Perry ; Grodin, Justin L. ; Assefa, Mahlet ; Broughton, J. Samuel ; Planavsky, Noah J. ; Ahmad, Tariq ; Bellumkonda, Lavanya ; Tang, W. H.Wilson ; Parikh, Chirag R. ; Testani, Jeffrey M. / Hypochloremia and diuretic resistance in heart failure. In: Circulation: Heart Failure. 2016 ; Vol. 9, No. 8.
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