2022
The impact of induction therapy on mortality and treated rejection in cardiac transplantation: A retrospective study
Bellumkonda L, Oikonomou EK, Hsueh C, Maulion C, Testani J, Patel J. The impact of induction therapy on mortality and treated rejection in cardiac transplantation: A retrospective study. The Journal Of Heart And Lung Transplantation 2022, 41: 482-491. PMID: 35094919, DOI: 10.1016/j.healun.2022.01.008.Peer-Reviewed Original ResearchConceptsInduction therapyCause mortalityOutcome measuresLeft ventricular assist device therapyT-cell depleting agentsVentricular assist device therapyDual organ transplantsRoutine induction therapySecondary outcome measuresTime of transplantationPrimary outcome measureCox regression modelPropensity score adjustmentRisk of rejectionPrior transplantCardiac transplantationHeart transplantationUNOS databaseAdult patientsOverall survivalDevice therapyMedian ageRetrospective studyReceptor antagonistReduced odds
2021
Multinephron Segment Diuretic Therapy to Overcome Diuretic Resistance in Acute Heart Failure: A Single-Center Experience
Cox ZL, Sarrell BA, Cella MK, Tucker B, Arroyo JP, Umanath K, Tidwell W, Guide A, Testani JM, Lewis JB, Dwyer JP. Multinephron Segment Diuretic Therapy to Overcome Diuretic Resistance in Acute Heart Failure: A Single-Center Experience. Journal Of Cardiac Failure 2021, 28: 21-31. PMID: 34403831, DOI: 10.1016/j.cardfail.2021.07.016.Peer-Reviewed Original ResearchConceptsAcute heart failureDiuretic resistanceDiuretic therapyHeart failureUrine outputSerum chemistryRenal replacement therapySingle medical centerSingle-center experienceAHF cohortDiuretic classesHospital mortalityTotal cohortKidney functionSerum sodiumCarbonic anhydrase inhibitorsProspective studyReplacement therapyCase-level evidenceRetrospective analysisMedical CenterDay 7Own controlTherapyPatientsRisk stratification of patients listed for heart transplantation while supported with extracorporeal membrane oxygenation
Ivey-Miranda JB, Maulion C, Farrero-Torres M, Griffin M, Posada-Martinez EL, Testani JM, Bellumkonda L. Risk stratification of patients listed for heart transplantation while supported with extracorporeal membrane oxygenation. Journal Of Thoracic And Cardiovascular Surgery 2021, 165: 711-720. PMID: 34167814, DOI: 10.1016/j.jtcvs.2021.05.032.Peer-Reviewed Original ResearchMeSH KeywordsAdultExtracorporeal Membrane OxygenationHeart TransplantationHeart-Assist DevicesHumansRenal DialysisRetrospective StudiesRisk AssessmentTreatment OutcomeConceptsHeart transplantMajor risk factorRisk factorsPosttransplantation mortalityHT recipientsMembrane oxygenationGood long-term prognosisSevere cardiogenic shockOrgan Sharing databaseLong-term prognosisExtracorporeal membrane oxygenationMinor risk factorsVentricular assist deviceCardiogenic shockHeart transplantationRecipient ageIndependent predictorsPrimary outcomeSharing databaseMechanical ventilationRisk stratificationUnited NetworkAdult candidatesECMOAbsence of recovery
2020
Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease
Verbrugge FH, Martens P, Testani JM, Tang WHW, Kuypers D, Bammens B. Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease. Cardiorenal Medicine 2020, 10: 402-414. PMID: 33120398, DOI: 10.1159/000509741.Peer-Reviewed Original ResearchMeSH KeywordsHeart FailureHumansPrognosisRenal DialysisRenal Insufficiency, ChronicRetrospective StudiesSodium Potassium Chloride Symporter InhibitorsConceptsDiuretic efficiencyCause mortalityMedian timeKidney diseaseChronic kidney disease severityLoop diuretic doseLoop diuretic therapyAcute kidney injuryRetrospective cohort studyChronic kidney diseaseRenal replacement therapyOnset of dialysisKidney disease severityCKD patientsDiuretic doseDiuretic therapyFurosemide usersKidney injuryKidney transplantationCohort studyCreatinine clearanceDialysis initiationPrognostic impactLoop diureticsUrine outputDifferential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes
Ivey-Miranda JB, Kunnirickal S, Bow L, Maulion C, Testani JM, Jacoby D, Kransdorf EP, Bellumkonda L. Differential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes. Journal Of Cardiac Failure 2020, 27: 40-47. PMID: 32750489, DOI: 10.1016/j.cardfail.2020.07.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultGraft RejectionHeart FailureHeart TransplantationHumansIsoantibodiesRetrospective StudiesRisk FactorsConceptsPanel reactive antibodyCause mortalityReactive antibodiesClass IClass II panel reactive antibodiesAdult heart transplant patientsPost-heart transplant outcomesClass IIRejection-related mortalityHeart transplant patientsOrgan Sharing dataHeart transplantationTransplant outcomesTransplant patientsSensitized patientsUnited NetworkIsolated elevationHigh riskGroup 2Group 1High mortalityCombined elevationGroup 4MortalityPatientsSodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series
Griffin M, Riello R, Rao VS, Ivey-Miranda J, Fleming J, Maulion C, McCallum W, Sarnak M, Collins S, Inzucchi SE, Testani JM. Sodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series. ESC Heart Failure 2020, 7: 1966-1971. PMID: 32476296, PMCID: PMC7373933, DOI: 10.1002/ehf2.12759.Peer-Reviewed Original ResearchMeSH KeywordsDiabetes Mellitus, Type 2DiureticsHeart FailureHumansRetrospective StudiesSodium-Glucose Transporter 2 InhibitorsConceptsAcute decompensated heart failureSodium-glucose cotransporter 2 inhibitorsGlucose cotransporter 2 inhibitorsDecompensated heart failureCotransporter 2 inhibitorsType 2 diabetesSGLT-2iBlood pressureHeart failureUrine outputYale-New Haven HospitalWeight lossIncidence of hypokalaemiaSGLT-2i initiationSGLT-2i therapyGlucose-lowering medicationsHeart failure outcomesCohort of patientsAverage weight lossDiuretic dosingDiuretic resistanceAdjunctive therapyWorsened survivalDiuretic efficiencyDiuretic monotherapyA Time-Updated, Parsimonious Model to Predict AKI in Hospitalized Children
Sandokji I, Yamamoto Y, Biswas A, Arora T, Ugwuowo U, Simonov M, Saran I, Martin M, Testani JM, Mansour S, Moledina DG, Greenberg JH, Wilson FP. A Time-Updated, Parsimonious Model to Predict AKI in Hospitalized Children. Journal Of The American Society Of Nephrology 2020, 31: 1348-1357. PMID: 32381598, PMCID: PMC7269342, DOI: 10.1681/asn.2019070745.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAdolescentChildChild, HospitalizedChild, PreschoolElectronic Health RecordsFemaleHumansInfantMachine LearningMaleRetrospective StudiesConceptsExternal validation cohortValidation cohortElectronic health recordsSevere AKIClinical risk stratification toolDevelopment of AKIHealth recordsRisk stratification toolInternal validation cohortLength of stayCharacteristic curveElectronic medical recordsNeonatal AKIInpatient mortalitySecondary outcomesHospital admissionPrimary outcomeHospitalized childrenCreatinine valuesMedical recordsStudy populationAKICohortChildrenPredictive variablesReal World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure A U.S. Center’s Experience
Griffin M, Soufer A, Goljo E, Colna M, Rao VS, Jeon S, Raghavendra P, D'Ambrosi J, Riello R, Coca SG, Mahoney D, Jacoby D, Ahmad T, Chen M, Tang WHW, Turner J, Mullens W, Wilson FP, Testani JM. Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure A U.S. Center’s Experience. JACC Heart Failure 2020, 8: 199-208. PMID: 32035891, PMCID: PMC7814403, DOI: 10.1016/j.jchf.2019.10.012.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureHypertonic saline administrationHypertonic saline therapyHypertonic salineSaline administrationSaline therapyDiuretic efficiencyUrine outputSerum sodiumWeight lossAcute decompensated heartDecompensated heart failureCohort of patientsTotal urine outputReal-world safetyU.S. academic medical centersAcademic medical centerLarge U.S. academic medical centerDiuretic doseCenter experienceHeart failureMetabolic derangementsPrimary analytic approachRespiratory statusClinical variablesAccess and Outcomes Among Hypertrophic Cardiomyopathy Patients in a Large Integrated Health System
Thomas A, Papoutsidakis N, Spatz E, Testani J, Soucier R, Chou J, Ahmad T, Darr U, Hu X, Li F, Chen ME, Bellumkonda L, Sumathipala A, Jacoby D. Access and Outcomes Among Hypertrophic Cardiomyopathy Patients in a Large Integrated Health System. Journal Of The American Heart Association 2020, 9: e014095. PMID: 31973610, PMCID: PMC7033886, DOI: 10.1161/jaha.119.014095.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCardiomyopathy, HypertrophicCause of DeathConnecticutDelivery of Health Care, IntegratedFemaleHealthcare DisparitiesHeart Disease Risk FactorsHospitalizationHumansMaleMiddle AgedOutcome and Process Assessment, Health CareReferral and ConsultationRetrospective StudiesRisk AssessmentSocial ClassSocial Determinants of HealthTreatment OutcomeConceptsSpecialty careHCM patientsCare cohortHypertrophic cardiomyopathyYale New Haven Health SystemLarge integrated health systemHealth systemBackground Hypertrophic cardiomyopathyRetrospective cohort studySocioeconomic statusPatients' socioeconomic statusHigher socioeconomic status groupsHypertrophic cardiomyopathy patientsIntegrated health systemSpecialty care accessSocioeconomic status groupsMedical insurance providersCardiomyopathy clinicCause deathLSES patientsCause hospitalizationCause mortalityNoncardiac causesCohort studySecondary outcomes
2019
Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure The 3T Trial
Cox ZL, Hung R, Lenihan DJ, Testani JM. Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure The 3T Trial. JACC Heart Failure 2019, 8: 157-168. PMID: 31838029, PMCID: PMC7058489, DOI: 10.1016/j.jchf.2019.09.012.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedChlorothiazideDiureticsDose-Response Relationship, DrugDouble-Blind MethodDrug Therapy, CombinationFemaleFollow-Up StudiesFurosemideHeart FailureHumansInfusions, IntravenousMaleMetolazoneMiddle AgedProspective StudiesRetrospective StudiesTolvaptanTreatment OutcomeConceptsAcute heart failureLoop diuretic resistanceDiuretic resistanceHigh-dose loop diuretic therapyLoop diuretic therapyDouble-blinded trialInfusion of furosemideCombination diureticsDiuretic strategyDiuretic therapyOral metolazoneTolvaptan therapyDiuretic efficacyHeart failurePrimary outcomePatientsLimited evidenceWeight lossTherapyChlorothiazideMetolazoneTolvaptanDiureticsInfusionCohortEffect on Survival of Concurrent Hemoconcentration and Increase in Creatinine During Treatment of Acute Decompensated Heart Failure
Griffin M, Rao VS, Fleming J, Raghavendra P, Turner J, Mahoney D, Wettersten N, Maisel A, Ivey-Miranda JB, Inker L, Tang WHW, Wilson FP, Testani JM. Effect on Survival of Concurrent Hemoconcentration and Increase in Creatinine During Treatment of Acute Decompensated Heart Failure. The American Journal Of Cardiology 2019, 124: 1707-1711. PMID: 31601358, PMCID: PMC6959849, DOI: 10.1016/j.amjcard.2019.08.034.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureDecompensated heart failureHeart failureImproved survivalHigher loop diuretic dosesLoop diuretic dosesNet fluid lossPlasma volume reductionAggressive decongestionAggressive diuresisPostdischarge survivalDiuretic dosesPostdischarge outcomesSerum creatinineHospital treatmentHospital parametersBetter survivalCreatinineHemoconcentrationPatient carePatientsSurvivalLonger lengthVolume reductionTreatmentA simple real-time model for predicting acute kidney injury in hospitalized patients in the US: A descriptive modeling study
Simonov M, Ugwuowo U, Moreira E, Yamamoto Y, Biswas A, Martin M, Testani J, Wilson FP. A simple real-time model for predicting acute kidney injury in hospitalized patients in the US: A descriptive modeling study. PLOS Medicine 2019, 16: e1002861. PMID: 31306408, PMCID: PMC6629054, DOI: 10.1371/journal.pmed.1002861.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAged, 80 and overConnecticutDecision Support TechniquesElectronic Health RecordsFemaleHospital MortalityHumansInpatientsMaleMiddle AgedPatient AdmissionPredictive Value of TestsPrognosisRenal DialysisRetrospective StudiesRisk AssessmentRisk FactorsSeverity of Illness IndexTime FactorsConceptsAcute kidney injuryImminent acute kidney injuryElectronic health recordsKidney injuryHospital 1Prediction of AKIRenal replacement therapyOptimal treatment strategyLaboratory dataReceiver operator characteristic curveInternal validation setAKI occurrenceAKI severityHospitalized adultsMedical comorbiditiesOverall cohortAdverse eventsHospitalized patientsSurgical wardsSignificant morbidityReplacement therapyExternal validation data setsHospital 2Hospital 3Study hospitalLeft atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy
Latif SR, Nguyen VQ, Peters DC, Soufer A, Henry ML, Grunseich K, Testani J, Hur DJ, Huber S, Mojibian H, Dicks D, Sinusas AJ, Meadows JL, Papoutsidakis N, Jacoby D, Baldassarre LA. Left atrial fibrosis correlates with extent of left ventricular myocardial delayed enhancement and left ventricular strain in hypertrophic cardiomyopathy. The International Journal Of Cardiovascular Imaging 2019, 35: 1309-1318. PMID: 30790116, DOI: 10.1007/s10554-019-01551-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAtrial Function, LeftAtrial RemodelingCardiomyopathy, HypertrophicContrast MediaFemaleFibrosisHeart AtriaHeart VentriclesHumansHypertrophy, Left VentricularMagnetic Resonance Imaging, CineMaleMiddle AgedOrganometallic CompoundsPredictive Value of TestsRetrospective StudiesVentricular Dysfunction, LeftVentricular Function, LeftVentricular RemodelingConceptsLA fibrosisLV-LGEHypertrophic cardiomyopathyLA-LGELV fibrosisLV parametersLV end-diastolic volumeSetting of HCMAldosterone system inhibitionLate gadolinium enhancement (LGE) sequencesLV global strainLeft ventricular massEnd-diastolic volumeLeft atrial fibrosisMaximum wall thicknessFibrosis correlatesRenin-AngiotensinVentricular strainMedication usageAtrial fibrosisLV remodelingVentricular massLV massSystem inhibitionDiastolic volume
2018
Enhancing the prediction of acute kidney injury risk after percutaneous coronary intervention using machine learning techniques: A retrospective cohort study
Huang C, Murugiah K, Mahajan S, Li SX, Dhruva SS, Haimovich JS, Wang Y, Schulz WL, Testani JM, Wilson FP, Mena CI, Masoudi FA, Rumsfeld JS, Spertus JA, Mortazavi BJ, Krumholz HM. Enhancing the prediction of acute kidney injury risk after percutaneous coronary intervention using machine learning techniques: A retrospective cohort study. PLOS Medicine 2018, 15: e1002703. PMID: 30481186, PMCID: PMC6258473, DOI: 10.1371/journal.pmed.1002703.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedClinical Decision-MakingData MiningDecision Support TechniquesFemaleHumansMachine LearningMaleMiddle AgedPercutaneous Coronary InterventionProtective FactorsRegistriesReproducibility of ResultsRetrospective StudiesRisk AssessmentRisk FactorsTime FactorsTreatment OutcomeConceptsPercutaneous coronary interventionNational Cardiovascular Data RegistryRisk prediction modelAKI eventsAKI riskCoronary interventionAKI modelMean ageCardiology-National Cardiovascular Data RegistryAcute kidney injury riskAKI risk predictionRetrospective cohort studyIdentification of patientsCandidate variablesAvailable candidate variablesCohort studyPCI proceduresPoint of careBrier scoreAmerican CollegeData registryPatientsCalibration slopeInjury riskSame cohortThe prognostic role of different renal function phenotypes in patients with acute heart failure
Palazzuoli A, Ruocco G, Pellicori P, Incampo E, Di Tommaso C, Favilli R, Evangelista I, Nuti R, Testani JM. The prognostic role of different renal function phenotypes in patients with acute heart failure. International Journal Of Cardiology 2018, 276: 198-203. PMID: 30503187, DOI: 10.1016/j.ijcard.2018.11.108.Peer-Reviewed Original ResearchConceptsAcute heart failureBUN increaseHeart failureIndependent predictorsPrognostic roleAdverse outcomesGlomerular filtration rate reductionBlood nitrogen ureaSigns of HFRenal function deteriorationBUN changeClinical congestionEffective decongestionFunction deteriorationRenal functionSerum creatininePoor outcomePrognostic relevanceComplete resolutionClinical signsPatientsNitrogen ureaHospitalizationBUNOutcomesOutcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis
Brisco‐Bacik M, Maaten J, Houser SR, Vedage NA, Rao V, Ahmad T, Wilson FP, Testani JM. Outcomes Associated With a Strategy of Adjuvant Metolazone or High‐Dose Loop Diuretics in Acute Decompensated Heart Failure: A Propensity Analysis. Journal Of The American Heart Association 2018, 7: e009149. PMID: 30371181, PMCID: PMC6222930, DOI: 10.1161/jaha.118.009149.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedCause of DeathDose-Response Relationship, DrugFemaleFollow-Up StudiesGuideline AdherenceHeart FailureHumansInjections, IntravenousMaleMetolazonePropensity ScoreRetrospective StudiesSodium Chloride Symporter InhibitorsSodium Potassium Chloride Symporter InhibitorsStroke VolumeSurvival RateTreatment OutcomeUnited StatesConceptsHigh-dose loop diureticsAcute decompensated heart failureDecompensated heart failureLoop diureticsRenal functionPropensity adjustmentHeart failureCommon electronic medical recordIntravenous loop diureticsLoop diuretic dosePropensity-adjusted analysisThiazide-type diureticsControl trial dataElectronic medical recordsDiuretic doseDiuretic strategyCause mortalityAdverse eventsBaseline characteristicsSecondary outcomesThiazide diureticsResults PatientsDischarge diagnosisMedical recordsDiuretics
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
Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance
Palazzuoli A, Testani JM, Ruocco G, Pellegrini M, Ronco C, Nuti R. Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance. International Journal Of Cardiology 2016, 224: 213-219. PMID: 27657476, DOI: 10.1016/j.ijcard.2016.09.005.Peer-Reviewed Original ResearchConceptsLower diuretic efficiencyChronic kidney diseaseDiuretic efficiencyAdverse eventsDose administrationAcute decompensated heart failureDecompensated heart failureAdverse event ratesDiuretic doseWRF occurrenceRenal dysfunctionClinical characteristicsRenal functionHeart failureHD patientsMultivariable analysisClinical statusPrognostic significanceAdverse outcomesContinuous administrationKidney diseaseDE patientsLD patientsBest modalityPatientsEfficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone
Cardinale M, Altshuler J, Testani JM. Efficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone. Pharmacotherapy The Journal Of Human Pharmacology And Drug Therapy 2016, 36: 843-851. PMID: 27321568, DOI: 10.1002/phar.1787.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdministration, IntravenousAdultAgedChlorothiazideDiureticsFemaleHeart FailureHumansMaleMetolazoneMiddle AgedRetrospective StudiesConceptsAcute decompensated heart failureIntravenous chlorothiazideUrine outputIndex doseOral metolazoneLoop diureticsHigh-dose loop diureticsAdministration of chlorothiazideDecompensated heart failurePrimary end pointRetrospective cohort studyTertiary care hospitalFurosemide equivalentsHospital mortalityImproved diuresisDiuretic dosesLast doseMedian doseCohort studyCare hospitalHeart failureMultiple dosesInstitutional protocolInadequate responseOwn controlHypochloraemia 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 roleSodium