2023
Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design
Cox Z, Siddiqi H, Stevenson L, Bales B, Han J, Hart K, Imhoff B, Ivey-Miranda J, Jenkins C, Lindenfeld J, Shotwell M, Miller K, Ooi H, Rao V, Schlendorf K, Self W, Siew E, Storrow A, Walsh R, Wrenn J, Testani J, Collins S. Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design. American Heart Journal 2023, 265: 121-131. PMID: 37544492, PMCID: PMC10592235, DOI: 10.1016/j.ahj.2023.07.014.Peer-Reviewed Original ResearchAcute decompensated heart failureUrine chemistryDiuretic strategyIntravenous diuresisUsual careAcute heartHeart failureClinical trialsGlobal clinical statusKey exclusion criteriaUsual care strategyAcute heart failureDecompensated heart failureRandomized clinical trialsKey inclusion criteriaMultiple clinical trialsPaucity of evidenceDiuretic dosingDiuretic therapyPrimary outcomePatient's symptomsClinical statusTreatment trialsValvular stenosisClinical state
2022
Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome
Cox ZL, Rao VS, Testani JM. Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome. Kidney360 2022, 3: 954-967. PMID: 36128483, PMCID: PMC9438407, DOI: 10.34067/kid.0006372021.Commentaries, Editorials and LettersConceptsCardiorenal syndromeDiuretic resistanceSodium avidityAcute decompensated heart failureDecompensated heart failureRenal sodium avidityHeart failure phenotypeResistance mechanismsDiuretic therapyHeart failureFailure populationNovel mechanismMultiple etiologiesGlomerular filtrationTherapeutic strategiesFailure phenotypeSyndromeTranslate findingsAviditySpecific transportersTherapyEtiologyPopulationRecent literature
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 volunteersThe 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 congestionMultinephron 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 controlTherapyPatientsNatriuretic 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 findingsDiuretic 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 physiologyTherapy
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 lossTherapyChlorothiazideMetolazoneTolvaptanDiureticsInfusionCohortControlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET‐1 and TARGET‐2 studies
Biegus J, Zymlinski R, Siwolowski P, Testani J, Szachniewicz J, Tycińska A, Banasiak W, Halpert A, Levin H, Ponikowski P. Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET‐1 and TARGET‐2 studies. European Journal Of Heart Failure 2019, 21: 1079-1087. PMID: 31127666, DOI: 10.1002/ejhf.1533.Peer-Reviewed Original ResearchConceptsAcute heart failureEnd of therapyHeart failureDiuretic-based regimenStandard diuretic therapyPatient global assessmentPrimary efficacy endpointCentral venous pressureSystolic blood pressureDiuretic therapyEffective decongestionMean diuresisEfficacy endpointRenal injuryBlood pressureVenous pressureMean creatinineOwn controlPatientsTherapyGlobal assessmentFluid lossSodium lossTherapy supportDecongestionNatriuretic Response Is Highly Variable and Associated With 6-Month Survival Insights From the ROSE-AHF Trial
Hodson DZ, Griffin M, Mahoney D, Raghavendra P, Ahmad T, Turner J, Wilson FP, Tang WHW, Rao VS, Collins SP, Mullens W, Testani JM. Natriuretic Response Is Highly Variable and Associated With 6-Month Survival Insights From the ROSE-AHF Trial. JACC Heart Failure 2019, 7: 383-391. PMID: 31047017, PMCID: PMC6501816, DOI: 10.1016/j.jchf.2019.01.007.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureROSE-AHF trialsSodium excretionNet fluid balanceWorse prognosisFluid balanceHigh-dose loop diuretic therapyNegative net fluid balanceGreater sodium excretionLoop diuretic agentsLoop diuretic therapyDecompensated heart failureDietary sodium intakeDiuretic therapyUrinary sodiumNatriuretic responseHeart failureSodium intakeUrine outputSodium retentionVolume overloadFluid retentionSodium balanceDiuretic agentsPrognostic abilityThe 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
Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury
Ahmad T, Jackson K, Rao VS, Tang WHW, Brisco-Bacik MA, Chen HH, Felker GM, Hernandez AF, O'Connor CM, Sabbisetti VS, Bonventre JV, Wilson FP, Coca SG, Testani JM. Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury. Circulation 2018, 137: 2016-2028. PMID: 29352071, PMCID: PMC6066176, DOI: 10.1161/circulationaha.117.030112.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosaminidaseAcute DiseaseAcute Kidney InjuryAgedAged, 80 and overBiomarkersCreatinineCystatin CDiuresisFemaleGlomerular Filtration RateHeart FailureHepatitis A Virus Cellular Receptor 1HumansKidneyLipocalin-2MaleMiddle AgedSodium Potassium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsKidney injury molecule-1Neutrophil gelatinase-associated lipocalinInjury molecule-1Acute heart failureGelatinase-associated lipocalinRenal tubular injuryTubular injury biomarkersAggressive diuresisROSE-AHF trialsTubular injuryInjury biomarkersRenal functionHeart failureMolecule-1D-glucosaminidaseHigh-dose loop diuretic therapyAcute heart failure treatmentKidney tubular injuryLoop diuretic therapyAcute kidney injuryGlomerular filtration rateHeart failure treatmentDiuretic therapyFurosemide equivalentsKidney injury
2017
An 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 balance
2013
Loop Diuretic Efficiency
Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, Tang WH. Loop Diuretic Efficiency. Circulation Heart Failure 2013, 7: 261-270. PMID: 24379278, PMCID: PMC4386906, DOI: 10.1161/circheartfailure.113.000895.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseCause of DeathDiuresisDose-Response Relationship, DrugFemaleFollow-Up StudiesGlomerular Filtration RateHeart FailureHospital MortalityHumansInjections, IntravenousMaleMiddle AgedPatient DischargePennsylvaniaPrognosisProspective StudiesSodium Potassium Chloride Symporter InhibitorsSurvival RateTreatment OutcomeConceptsLower diuretic efficiencyDiuretic efficiencyNet fluid outputDiuretic doseHeart failureFluid outputBaseline characteristicsPoor long-term outcomesDecompensated heart failureDistinct prognostic informationDose of diureticsPrimary discharge diagnosisCongestive heart failureTraditional prognostic factorsLong-term outcomesCatheterization variablesFurosemide equivalentsDiuretic therapyRenal functionWorsened survivalPrognostic factorsUrine outputDecongestive therapyDischarge diagnosisConsecutive admissions