2024
Serial direct sodium removal in patients with heart failure and diuretic resistance
Rao V, Ivey‐Miranda J, Cox Z, Moreno‐Villagomez J, Ramos‐Mastache D, Neville D, Balkcom N, Asher J, Bellumkonda L, Bigvava T, Shaburishvili T, Bartunek J, Wilson F, Finkelstein F, Maulion C, Turner J, Testani J. Serial direct sodium removal in patients with heart failure and diuretic resistance. European Journal Of Heart Failure 2024, 26: 1215-1230. PMID: 38556717, DOI: 10.1002/ejhf.3196.Peer-Reviewed Original ResearchConceptsDiuretic resistanceCardiorenal syndromeHeart failureLoop diureticsDiuretic withdrawalHigh-dose loop diureticsN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideGrowth differentiation factor 15Carbohydrate antigen 125Differentiation factor 15Sodium removalRandomized controlled studyCardiorenal parametersDiuretic doseSoluble ST2Natriuretic peptideMedian timeDiuretic responseKidney injuryPeritoneal membraneElectrolyte handlingKidney functionDiureticsInterleukin-6
2021
Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure
Cox ZL, Rao VS, Ivey-Miranda JB, Moreno-Villagomez J, Mahoney D, Ponikowski P, Biegus J, Turner JM, Maulion C, Bellumkonda L, Asher JL, Parise H, Wilson PF, Ellison DH, Wilcox CS, Testani JM. Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure. European Heart Journal 2021, 42: 4468-4477. PMID: 34529781, PMCID: PMC8599022, DOI: 10.1093/eurheartj/ehab620.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureSpontaneous natriuresisDiuretic resistanceHeart failureSodium reabsorptionUrine collectionSpot urine sodium concentrationsIntravenous loop diureticsNeutral sodium balanceAcute heart failureDecompensated heart failureRenal sodium reabsorptionSubgroup of patientsUrine sodium concentrationSpot urine samplesDiuretic therapySodium aviditySodium excretionUrine sodiumCreatinine ratioLoop diureticsDiuretic administrationSodium balanceNatriuresisHealthy volunteersUse of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA‐REG OUTCOME trial
Pellicori P, Fitchett D, Kosiborod MN, Ofstad AP, Seman L, Zinman B, Zwiener I, Wanner C, George J, Inzucchi SE, Testani JM, Cleland JGF. Use of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA‐REG OUTCOME trial. European Journal Of Heart Failure 2021, 23: 1085-1093. PMID: 34031968, PMCID: PMC11497224, DOI: 10.1002/ejhf.2220.Peer-Reviewed Original ResearchConceptsUse of LDDiagnosis of HFHeart failureLoop diureticsHF diagnosisEMPA-REG OUTCOME trialType 2 diabetes mellitusSigns of congestionCardiovascular eventsCardiovascular mortalityOutcome trialsDiabetes mellitusPatient subgroupsPatientsDiagnosisHigh rateOutcomesMellitusT2DMDiureticsSymptomsMortalityBaselineTrialsNatriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure
Rao VS, Ivey-Miranda JB, Cox ZL, Riello R, Griffin M, Fleming J, Soucier R, Sangkachand P, O'Brien M, LoRusso F, D'Ambrosi J, Churchwell K, Mahoney D, Bellumkonda L, Asher JL, Maulion C, Turner JM, Wilson FP, Collins SP, Testani JM. Natriuretic Equation to Predict Loop Diuretic Response in Patients With Heart Failure. Journal Of The American College Of Cardiology 2021, 77: 695-708. PMID: 33573739, PMCID: PMC8114781, DOI: 10.1016/j.jacc.2020.12.022.Peer-Reviewed Original ResearchConceptsLoop diuretic administrationDiuretic therapyNatriuretic responseDiuretic administrationSodium outputAcute decompensated heart failureDecompensated heart failureHeart failure admissionsDaily urine outputSpot urine samplesNet fluid outputNet fluid lossPathway cohortHeart failureLoop diureticsUrine outputDiuretic responseResidual congestionFluid outputTherapyCohortWeight lossAdditional studiesUrine samplesExcellent discrimination
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 ResearchConceptsDiuretic 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 outputMechanisms of Diuretic Resistance Study: design and rationale
Cox ZL, Fleming J, Ivey‐Miranda J, Griffin M, Mahoney D, Jackson K, Hodson DZ, Thomas D, Gomez N, Rao VS, Testani JM. Mechanisms of Diuretic Resistance Study: design and rationale. ESC Heart Failure 2020, 7: 4458-4464. PMID: 32893505, PMCID: PMC7754741, DOI: 10.1002/ehf2.12949.Peer-Reviewed Original ResearchAcute decompensated heart failureDiuretic resistanceDiuretic responseUrine collectionCombination diuretic therapyLoop diuretic administrationLoop diuretic doseLoop diuretic resistanceDecompensated heart failureProspective patient cohortPhysical exam findingsSpot urine collectionADHF hospitalizationsDiuretic doseDiuretic therapyHF outcomesBaseline bloodCommon complicationPatient characteristicsProspective cohortHeart failureLoop diureticsDiuretic administrationUrine biomarkersExam findingsPathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure
Wilcox CS, Testani JM, Pitt B. Pathophysiology of Diuretic Resistance and Its Implications for the Management of Chronic Heart Failure. Hypertension 2020, 76: 1045-1054. PMID: 32829662, PMCID: PMC10683075, DOI: 10.1161/hypertensionaha.120.15205.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic heart failureDiuretic resistanceHeart failureHigh daily salt intakeDiuretic-resistant patientsSequential nephron blockadeDaily salt intakeHypochloremic metabolic alkalosisLoop of HenleMultiple diureticsRenal nervesReflex activationLoop diureticsSalt intakeRecurrent hospitalizationsVolume overloadPathophysiological mechanismsSingle doseSodium outputMetabolic alkalosisPharmacokinetic mechanismsDistal tubulesDiureticsProximal tubulesRenal tubulesDiuretic Therapy for Patients With Heart Failure JACC State-of-the-Art Review
Felker GM, Ellison DH, Mullens W, Cox ZL, Testani JM. Diuretic Therapy for Patients With Heart Failure JACC State-of-the-Art Review. Journal Of The American College Of Cardiology 2020, 75: 1178-1195. PMID: 32164892, DOI: 10.1016/j.jacc.2019.12.059.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHeart failureDiuretic therapyElevated intracardiac filling pressuresRobust clinical trial evidenceFailure JACC StateIntracardiac filling pressuresUse of diureticsClinical trial evidenceCornerstone of treatmentConstellation of signsMajor clinical challengeExtracellular fluid volumeDiuretic pharmacokineticsDiuretic regimenDiuretic resistanceLoop diureticsPoor prognosisTrial evidenceOutpatient settingJACC StateFilling pressureClinical challengeDiureticsRenal physiologyTherapyEffect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure
Cox ZL, Sury K, Rao VS, Ivey-Miranda JB, Griffin M, Mahoney D, Gomez N, Fleming JH, Inker LA, Coca SG, Turner J, Wilson FP, Testani JM. Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure. Journal Of Cardiac Failure 2020, 26: 402-409. PMID: 32007554, PMCID: PMC7798124, DOI: 10.1016/j.cardfail.2020.01.019.Peer-Reviewed Original ResearchConceptsAcute kidney injuryFractional excretionHeart failureLoop diureticsDecompensated heart failureFurosemide equivalentsKidney injuryProspective cohortDiuretic administrationDiuretic responsePeak diuresisDiuretic effectFEUreaDiureticsPatientsDiagnostic superiorityHospital systemExcretionMagnitude of changeDegree of changeBaselineDistribution of changesFENaDiuresisFailureFirst-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution
Rao VS, Turner JM, Griffin M, Mahoney D, Asher J, Jeon S, Yoo PS, Boutagy N, Feher A, Sinusas A, Wilson FP, Finkelstein F, Testani JM. First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution. Circulation 2020, 141: 1043-1053. PMID: 31910658, PMCID: PMC7331276, DOI: 10.1161/circulationaha.119.043062.Peer-Reviewed Original ResearchConceptsStandard PD solutionExperimental heart failureHeart failurePD solutionsAdverse eventsPeritoneal dialysisSignificant discomfortSodium removalEnd-stage renal diseaseEnd pointElevated right atrial pressureMaintenance of euvolemiaPrimary end pointSecondary end pointsRight atrial pressureHuman proofLoss of responseSolute removalPorcine experimentsAtrial pressureRenal diseaseLoop diureticsSerum electrolytesHuman studiesPeritoneal membraneEvaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology
Mullens W, Damman K, Testani JM, Martens P, Mueller C, Lassus J, Tang WHW, Skouri H, Verbrugge FH, Orso F, Hill L, Ural D, Lainscak M, Rossignol P, Metra M, Mebazaa A, Seferovic P, Ruschitzka F, Coats A. Evaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal Of Heart Failure 2020, 22: 584-603. PMID: 31908120, DOI: 10.1002/ejhf.1697.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGlomerular filtration rateHeart failureKidney functionFiltration rateRenal functionSerum creatinineAcute heart failure episodeGuideline-directed medical therapyImproved long-term outcomesCardio-renal dysfunctionCardio-renal interactionsAcute heart failureChronic heart failureHeart Failure AssociationHeart failure careHeart failure stateHeart failure episodesAppropriate clinical contextLong-term outcomesRenal function assessmentFurther treatment strategiesNeurohumoral blockersLoop diureticsMedical therapyWorse outcomes
2019
Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure
Charokopos A, Griffin M, Rao VS, Inker L, Sury K, Asher J, Turner J, Mahoney D, Cox ZL, Wilson FP, Testani JM. Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure. Clinical Journal Of The American Society Of Nephrology 2019, 14: cjn.11600918. PMID: 31010938, PMCID: PMC6500945, DOI: 10.2215/cjn.11600918.Peer-Reviewed Original ResearchConceptsDiuretic efficiencyHeart failureAlbumin levelsDiuretic excretionDiuretic doseInpatient cohortUrine albuminOutpatient cohortLoop diureticsIL-6Higher urine albuminLoop diuretic doseUrinary albumin levelsLow serum albuminPlasma IL-6Heart failure cohortHuman heart failureDiuretic resistanceSuccessful decongestionDiuretic treatmentSystemic inflammationKidney functionSite of actionSerum albuminSodium outputDiuretic Resistance in Heart Failure
Gupta R, Testani J, Collins S. Diuretic Resistance in Heart Failure. Current Heart Failure Reports 2019, 16: 57-66. PMID: 30762178, PMCID: PMC6431570, DOI: 10.1007/s11897-019-0424-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAcute heart failureLoop diuretic doseHeart failureDiuretic doseLoop diureticsChronic heart failureUrine sodium concentrationDiuretic resistanceNatriuretic responseDiuretic efficiencyInpatient stayPrognostic valueFuture trialsDiuretic responsivenessAdditional biomarkersTailored therapyDiureticsSodium concentrationTherapyCurrent literatureAdministrationDoseOverview of mechanismsRecent studiesDR
2018
Early urine electrolyte patterns in patients with acute heart failure
Collins SP, Jenkins CA, Baughman A, Miller KF, Storrow AB, Han JH, Brown NJ, Liu D, Luther JM, McNaughton CD, Self WH, Peng D, Testani JM, Lindenfeld J. Early urine electrolyte patterns in patients with acute heart failure. ESC Heart Failure 2018, 6: 80-88. PMID: 30295437, PMCID: PMC6351901, DOI: 10.1002/ehf2.12368.Peer-Reviewed Original ResearchConceptsAcute heart failureDiuretic administrationDiuretic resistanceHeart failureLoop diureticsLow urinary sodiumEscalation of therapyUrine sodium excretionSubset of patientsSystolic blood pressureEmergency department patientsUrine sodium concentrationAHF diagnosisAHF patientsIntravenous diureticsUrinary sodiumED staySodium excretionUrinary electrolytesUrine sodiumNatriuretic responseStandard therapyBlood pressureDepartment patientsUrine outputOutcomes 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 recordsDiureticsPerturbations 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 model
2017
Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure
Rao VS, Planavsky N, Hanberg JS, Ahmad T, Brisco-Bacik MA, Wilson FP, Jacoby D, Chen M, Tang WHW, Cherney DZI, Ellison DH, Testani JM. Compensatory Distal Reabsorption Drives Diuretic Resistance in Human Heart Failure. Journal Of The American Society Of Nephrology 2017, 28: 3414-3424. PMID: 28739647, PMCID: PMC5661276, DOI: 10.1681/asn.2016111178.Peer-Reviewed Original ResearchConceptsDiuretic resistanceHeart failureLoop diureticsSodium reabsorptionHigh-dose loop diureticsDistal tubular sodium reabsorptionSodium exitLoop diuretic administrationTubular sodium reabsorptionHuman heart failureFurosemide equivalentsDistal reabsorptionConsecutive patientsFractional excretionSodium handlingDiuretic administrationProximal tubularControl cohortCare centerTreatment strategiesAnimal modelsDiureticsNet sodiumFENaTubular locationAn exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial
Hanberg JS, Tang WH, Wilson FP, Coca SG, Ahmad T, Brisco MA, Testani JM. An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial. International Journal Of Cardiology 2017, 241: 277-282. PMID: 28392080, PMCID: PMC5471358, DOI: 10.1016/j.ijcard.2017.03.114.Peer-Reviewed Original ResearchConceptsHigh-dose loop diureticsDiuretic doseAggressive decongestionDose trialFluid outputLoop diureticsHigh-dose loop diuretic therapyDose-related adverse effectsAdverse effectsLoop diuretic doseLoop diuretic therapyHeart failure patientsNet fluid balanceNet fluid outputRate of deathEmergency department (ED) visitationPotential beneficial effectsHypothesis-generating observationsEffective decongestionDiuretic therapyFailure patientsAdverse outcomesDecongestive effectImproved outcomesFluid balanceRenal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure
Maaten J, Rao VS, Hanberg JS, Wilson F, Bellumkonda L, Assefa M, Broughton J, D'Ambrosi J, Tang W, Damman K, Voors AA, Ellison DH, Testani JM. Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure. European Journal Of Heart Failure 2017, 19: 1014-1022. PMID: 28105769, PMCID: PMC6231236, DOI: 10.1002/ejhf.757.Peer-Reviewed Original ResearchConceptsAcute heart failureLoop diuretic resistanceRenal tubular responseDiuretic resistanceDiuretic responseRenal tubulesAHF patientsHeart failureLoop diureticsTubular responseRenal tubular resistanceBumetanide doseEffective decongestionIntravenous bumetanidePoor outcomeUrine collectionTubular resistanceSum of defectsPatient variabilityUrea clearancePatientsCommon barriersDoseClearanceDiuretics
2016
Hypochloremia 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 sodium