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
2023
SGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint?
Borlaug B, Testani J. SGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint? European Heart Journal 2023, 44: 2944-2946. PMID: 37220086, DOI: 10.1093/eurheartj/ehad345.Commentaries, Editorials and LettersIn-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility
Ivey-Miranda J, Rao V, Cox Z, Moreno-Villagomez J, Mahoney D, Maulion C, Bellumkonda L, Turner J, Collins S, Wilson F, Krumholz H, Testani J. In-Hospital Observation on Oral Diuretics After Treatment for Acute Decompensated Heart Failure: Evaluating the Utility. Circulation Heart Failure 2023, 16: e010206. PMID: 36896716, PMCID: PMC10186250, DOI: 10.1161/circheartfailure.122.010206.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureDecompensated heart failureDiuretic responseDiuretic dosingOral diureticsHeart failureMulticenter cohortHospital observationLower readmission ratesNet fluid balanceDays postdischargeReadmission ratesHospital readmissionUrine outputReadmission riskFluid statusFluid balanceHospital measuresDose selectionCohortProvider decisionsWeight changeReadmissionDiureticsPatients
2021
The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology
Mullens W, Damman K, Harjola V, Mebazaa A, Rocca H, Martens P, Testani J, Tang W, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic P, Ruschitzka F, Coats A. The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology. Kidneys 2021, 8: 43-61. DOI: 10.22141/2307-1257.8.1.2019.157796.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsUse of diureticsHeart failureElectrolyte disturbancesAcute heart failure episodeAcute heart failureHeart Failure AssociationCommon electrolyte disturbanceHeart failure episodesGoal of therapyResponse/resistanceRelief of congestionSigns of congestionDiuretic resistanceDiuretic strategyDiuretic therapyRenal functionVolume overloadDiuretic responseAvailable guidelinesDiureticsEuropean SocietyFailure episodesPosition statementEuvolaemiaEvaluation of congestionUse 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, 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 rateOutcomesMellitusT2DMDiureticsSymptomsMortalityBaselineTrials
2020
Pathophysiology 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 changesFENaDiuresisFailure
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 lossTherapyChlorothiazideMetolazoneTolvaptanDiureticsInfusionCohortDiuretic 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 studiesDRThe use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology
Mullens W, Damman K, Harjola V, Mebazaa A, Rocca H, Martens P, Testani JM, Tang WHW, Orso F, Rossignol P, Metra M, Filippatos G, Seferovic PM, Ruschitzka F, Coats AJ. The use of diuretics in heart failure with congestion — a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal Of Heart Failure 2019, 21: 137-155. PMID: 30600580, DOI: 10.1002/ejhf.1369.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsUse of diureticsHeart failureElectrolyte disturbancesAcute heart failure episodeAcute heart failureHeart Failure AssociationCommon electrolyte disturbanceHeart failure episodesGoal of therapyResponse/resistanceRelief of congestionSigns of congestionDiuretic resistanceDiuretic strategyDiuretic therapyRenal functionVolume overloadDiuretic responseAvailable guidelinesDiureticsEuropean SocietyFailure episodesPosition statementEuvolaemiaEvaluation of congestion
2018
Outcomes 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
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 locationRenal 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
2011
Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure
Testani JM, Cappola TP, Brensinger CM, Shannon RP, Kimmel SE. Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure. Journal Of The American College Of Cardiology 2011, 58: 375-382. PMID: 21757114, PMCID: PMC3980479, DOI: 10.1016/j.jacc.2011.01.052.Peer-Reviewed Original ResearchConceptsHigh-dose loop diureticsBlood urea nitrogenLoop diureticsBUN levelsNeurohormonal activationBaseline characteristicsHeart failureNormal BUN levelChronic heart failureRisk of deathBlood urea nitrogen concentrationElevated BUN levelsCongestive symptomsOverall cohortWorsened survivalImproved survivalPrimary outcomeAdverse outcomesUrea nitrogen concentrationDiureticsUrea nitrogenBUN concentrationPatientsMortalitySurvival