Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights

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

doi:10.1161/CIRCHEARTFAILURE.116.003180

Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

122 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

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 language	English
Article number	003180
Number of pages	12
Journal	Circulation-Heart failure
Volume	9
Issue number	8
DOIs	https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180
Publication status	Published - Aug-2016

Keywords

cardiorenal syndrome
chloride
diuretics
SODIUM RESTRICTION
SENSING MECHANISM
CHLORIDE
FUROSEMIDE
KINASES
TRIAL

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Hanberg, J. S., Rao, V., ter Maaten, J. M., Laur, O., Brisco, M. A., Wilson, F. P., Grodin, J. L., Assefa, M., Broughton, J. S., Planavsky, N. J., Ahmad, T., Bellumkonda, L., Tang, W. H. W., Parikh, C. R., & Testani, J. M. (2016). Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights. Circulation-Heart failure, 9(8), Article 003180. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180

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title = "Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights",

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 (chlorideConclusions-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.",

keywords = "cardiorenal syndrome, chloride, diuretics, SODIUM RESTRICTION, SENSING MECHANISM, CHLORIDE, FUROSEMIDE, KINASES, TRIAL",

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

note = "{\textcopyright} 2016 American Heart Association, Inc.",

year = "2016",

month = aug,

doi = "10.1161/CIRCHEARTFAILURE.116.003180",

language = "English",

volume = "9",

journal = "Circulation-Heart failure",

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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: Mechanistic Insights', Circulation-Heart failure, vol. 9, no. 8, 003180. https://doi.org/10.1161/CIRCHEARTFAILURE.116.003180

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T1 - Hypochloremia and Diuretic Resistance in Heart Failure

T2 - Mechanistic Insights

AU - Hanberg, Jennifer S.

AU - Rao, Veena

AU - ter Maaten, Jozine M.

AU - Laur, Olga

AU - Brisco, Meredith A.

AU - Wilson, F. Perry

AU - Grodin, Justin L.

AU - Assefa, Mahlet

AU - Broughton, J. Samuel

AU - Planavsky, Noah J.

AU - Ahmad, Tariq

AU - Bellumkonda, Lavanya

AU - Tang, W. H. Wilson

AU - Parikh, Chirag R.

AU - Testani, Jeffrey M.

PY - 2016/8

Y1 - 2016/8

N2 - 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 (chlorideConclusions-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.

AB - 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 (chlorideConclusions-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.

KW - cardiorenal syndrome

KW - chloride

KW - diuretics

KW - SODIUM RESTRICTION

KW - SENSING MECHANISM

KW - CHLORIDE

KW - FUROSEMIDE

KW - KINASES

KW - TRIAL

U2 - 10.1161/CIRCHEARTFAILURE.116.003180

DO - 10.1161/CIRCHEARTFAILURE.116.003180

M3 - Article

C2 - 27507113

SN - 1941-3289

VL - 9

JO - Circulation-Heart failure

JF - Circulation-Heart failure

IS - 8

M1 - 003180

ER -

Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights

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