2023
Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Packer M, Wilcox C, Testani J. Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes. Circulation 2023, 148: 354-372. PMID: 37486998, PMCID: PMC10358443, DOI: 10.1161/circulationaha.123.064346.Peer-Reviewed Original ResearchConceptsSGLT2 inhibitorsProximal renal tubulesRenal tubulesProximal tubular effectHeart failure outcomesHeart failure eventsSodium-hydrogen exchanger 3Renal tubular sodiumProgressive volume lossLong-term treatmentReabsorption of glucoseTreatment-related changesChronic diuresisPharmacological toleranceTubular effectsClinical courseFractional excretionHeart failureTubular sodiumCardioprotective effectsRenal compensationDiuretic effectIndividual patientsDurable improvementDegree of upregulation
2018
Perturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT
Grodin JL, Testani JM, Pandey A, Sambandam K, Drazner MH, Fang JC, Tang WHW. Perturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT. European Journal Of Heart Failure 2018, 20: 1436-1443. PMID: 29893446, DOI: 10.1002/ejhf.1229.Peer-Reviewed Original ResearchConceptsSerum chloride levelsLoop diuretic useHeart failureSerum chlorideCause deathDiuretic useEjection fractionMultivariable Cox proportional hazards modelsCardiac Function Heart FailureCox proportional hazards modelAldosterone Antagonist TrialHeart failure hospitalizationPrimary composite endpointLower serum chlorideProportional hazards modelSerum chloride concentrationChloride levelsSpironolactone useCardiovascular deathFailure hospitalizationMultivariable adjustmentComposite endpointLoop diureticsClinical outcomesHazards modelHemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure
Grodin JL, Mullens W, Dupont M, Taylor DO, McKie PM, Starling RC, Testani JM, Tang WHW. Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure. International Journal Of Cardiology 2018, 252: 112-116. PMID: 29249420, DOI: 10.1016/j.ijcard.2017.11.024.Peer-Reviewed Original ResearchConceptsPulmonary capillary wedge pressureAdvanced chronic heart failureFick cardiac indexPulmonary artery systolic pressureRight atrial pressureVentricular assist device placementHeart transplantHeart rateHeart failureSerum chlorideHigher cardiac filling pressuresPoor long-term outcomesSerum Cl levelsCapillary wedge pressureCardiac filling pressuresChronic heart failureAdvanced heart failureInvasive hemodynamic assessmentHeart failure patientsRisk of deathLong-term outcomesLower serum chlorideConventional clinical parametersBackward regression modelAssociation of hemodynamics
2017
Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction
Ferreira JP, Girerd N, Duarte K, Coiro S, McMurray JJ, Dargie HJ, Pitt B, Dickstein K, Testani JM, Zannad F, Rossignol P. Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction. Circulation Heart Failure 2017, 10: e003500. PMID: 28159825, DOI: 10.1161/circheartfailure.116.003500.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedBiomarkersChloridesComorbidityDatabases, FactualFemaleHeart FailureHumansKaplan-Meier EstimateLinear ModelsMaleMiddle AgedMyocardial InfarctionNonlinear DynamicsPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicRetrospective StudiesRisk AssessmentRisk FactorsSodiumStroke VolumeVentricular Dysfunction, LeftVentricular Function, LeftConceptsHeart failureAcute myocardial infarctionSerum chlorideMyocardial infarctionPrognostic informationPrognostic variablesSodium levelsReduced left ventricular functionLow sodiumReduced ejection fractionLeft ventricular functionLower serum chlorideSignificant prognostic informationRelevant prognostic informationSerum chloride levelsPost-myocardial infarctionLow sodium levelsMore comorbiditiesCause mortalitySystolic dysfunctionCardiovascular mortalityEjection fractionVentricular functionClinical outcomesMortality rate
2016
Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF)
Grodin JL, Sun JL, Anstrom KJ, Chen HH, Starling RC, Testani JM, Tang WH. Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF). The American Journal Of Cardiology 2016, 119: 78-83. PMID: 27816115, PMCID: PMC5161696, DOI: 10.1016/j.amjcard.2016.09.014.Peer-Reviewed Original ResearchConceptsAcute heart failureSerum Cl levelsHeart failureClinical outcomesDiuretic responseAcute heart failure trialsRenal Optimization Strategies EvaluationShort-term clinical responseCumulative sodium excretionLoop diuretic doseHeart Failure TrialLong-term mortalitySerum chloride levelsCystatin C changesDiuretic dosePostdischarge outcomesSodium excretionCl levelsClinical responseRenal functionDiuretic efficiencyFailure TrialAdditional adjustmentCystatin CTherapeutic implicationsHypochloremia and Diuretic Resistance in Heart Failure
Hanberg JS, Rao V, Maaten J, Laur O, Brisco MA, Wilson F, Grodin JL, Assefa M, Broughton J, Planavsky NJ, Ahmad T, Bellumkonda L, Tang WH, Parikh CR, Testani JM. Hypochloremia and Diuretic Resistance in Heart Failure. Circulation Heart Failure 2016, 9: e003180. PMID: 27507113, PMCID: PMC4988527, DOI: 10.1161/circheartfailure.116.003180.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersChloridesConnecticutCross-Sectional StudiesDown-RegulationDrug ResistanceFemaleFurosemideHeart FailureHumansKidneyMaleMiddle AgedOdds RatioPilot ProjectsProspective StudiesReninRisk FactorsSodiumSodium Potassium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeConceptsDiuretic resistanceHeart failureCare centerSerum chloridePro-B-type natriuretic peptideChloride supplementationRenal free water excretionB-type natriuretic peptidePoor diuretic responsePlasma renin activityPlasma renin concentrationHeart failure cohortFree water excretionRecent epidemiological studiesBasic science evidenceBlood urea nitrogenSerum chloride levelsFurosemide equivalentsNeurohormonal activationRenin activityRenin concentrationCreatinine ratioLoop diureticsDiuretic responseSerum sodiumHypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure
Ter Maaten JM, Damman K, Hanberg JS, Givertz MM, Metra M, O'Connor CM, Teerlink JR, Ponikowski P, Cotter G, Davison B, Cleland JG, Bloomfield DM, Hillege HL, van Veldhuisen DJ, Voors AA, Testani JM. Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure. Circulation Heart Failure 2016, 9: e003109. PMID: 27507112, DOI: 10.1161/circheartfailure.116.003109.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAged, 80 and overBiomarkersChloridesDisease ProgressionDiureticsDown-RegulationDrug ResistanceFemaleHeart FailureHospitalizationHumansKaplan-Meier EstimateLinear ModelsMaleMiddle AgedMultivariate AnalysisProportional Hazards ModelsRisk FactorsTime FactorsTreatment OutcomeXanthinesConceptsAcute heart failureMEq/L.Heart failureDay 14Serum chloridePoor diuretic responseHours of admissionLower serum chlorideBlood urea nitrogenSerum chloride levelsAHF therapiesDiuretic resistancePROTECT trialNeurohormonal activationMultivariable adjustmentRenal functionHospital admissionMultivariable analysisDiuretic responseDiuretic responsivenessDiuretic targetChloride levelsUrea nitrogenHypochloremiaChloride homeostasisHypochloraemia is strongly and independently associated with mortality in patients with chronic heart failure
Testani JM, Hanberg JS, Arroyo JP, Brisco MA, Ter Maaten JM, Wilson FP, Bellumkonda L, Jacoby D, Tang WH, Parikh CR. Hypochloraemia is strongly and independently associated with mortality in patients with chronic heart failure. European Journal Of Heart Failure 2016, 18: 660-668. PMID: 26763893, PMCID: PMC5471359, DOI: 10.1002/ejhf.477.Peer-Reviewed Original ResearchConceptsChronic heart failureHeart failureSerum chlorideSerum sodiumLow serum sodiumHeart failure pathophysiologyGreater disease severityBEST trialDiuretic dosesSerum chloride valuesRenal functionWorsened survivalPrognostic importanceAdverse outcomesUnivariate analysisHyponatraemiaHypochloraemiaPatientsDisease severityMortalityAdditional researchFailureChloride valuesCritical roleSodiumImportance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure
Grodin JL, Verbrugge FH, Ellis SG, Mullens W, Testani JM, Tang WH. Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure. Circulation Heart Failure 2016, 9: e002453. PMID: 26721916, PMCID: PMC4702267, DOI: 10.1161/circheartfailure.115.002453.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkersChloridesChronic DiseaseCoronary AngiographyDown-RegulationFemaleHeart FailureHumansKaplan-Meier EstimateMaleMiddle AgedMultivariate AnalysisPrognosisProportional Hazards ModelsProspective StudiesRisk AssessmentRisk FactorsTime FactorsWater-Electrolyte BalanceWater-Electrolyte ImbalanceConceptsChronic heart failureStable chronic heart failureHeart failureLower serum chlorideSerum chlorideMortality riskElective diagnostic coronary angiographyLow serum chloride levelLong-term prognostic valueAdjusted mortality riskDiagnostic coronary angiographySerum chloride levelsAdjusted riskCause mortalityElectrolyte abnormalitiesCoronary angiographyStable patientsPrognostic implicationsPrognostic valueMultivariable modelChloride levelsSodium levelsPatientsChloride homeostasisMortality
2015
Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure
Grodin JL, Simon J, Hachamovitch R, Wu Y, Jackson G, Halkar M, Starling RC, Testani JM, Tang WH. Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure. Journal Of The American College Of Cardiology 2015, 66: 659-666. PMID: 26248993, DOI: 10.1016/j.jacc.2015.06.007.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureSerum chloride levelsDecompensated heart failureSerum sodium levelsHeart failureSodium levelsADHF cohortMultivariable risk-adjusted analysisMultivariable risk adjustmentChronic heart failureLong-term mortalityRisk-adjusted analysisChloride levelsElectrolyte abnormalitiesConsecutive patientsPrognostic roleSerum sodiumPrognostic significancePrognostic valueValidation cohortCleveland ClinicClinical significanceRisk adjustmentCohortMortality