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
The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure
Biegus J, Zymliński R, Testani J, Fudim M, Cox Z, Guzik M, Iwanek G, Hurkacz M, Raj D, Marciniak D, Ponikowska B, Ponikowski P. The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure. European Journal Of Heart Failure 2023, 25: 1323-1333. PMID: 37042083, DOI: 10.1002/ejhf.2852.Peer-Reviewed Original ResearchMeSH KeywordsDiureticsFurosemideHeart FailureHumansObservational Studies as TopicProspective StudiesSodium Potassium Chloride Symporter InhibitorsConceptsAcute heart failureDiuretic responseHeart failureChronic usersTubular deliveryUrine volumeAcute heart failure patientsGlomerular filtration rateHeart failure patientsHigher urine volumeDiuretic exposureFurosemide deliveryFurosemide usersGood diuresisFurosemide doseFailure patientsNatriuretic responseFurosemide useTubular responseFiltration rateObservational studyUrine excretionNaïve groupHealthy individualsBody weight
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 controlTherapyPatients
2020
Prediction and measurement of diuretic responsiveness after oral administration of furosemide to healthy dogs and dogs with congestive heart failure
Loughran KA, Larouche‐Lebel É, Huh T, Testani JM, Rao VS, Oyama MA. Prediction and measurement of diuretic responsiveness after oral administration of furosemide to healthy dogs and dogs with congestive heart failure. Journal Of Veterinary Internal Medicine 2020, 34: 2253-2264. PMID: 33125814, PMCID: PMC7694836, DOI: 10.1111/jvim.15952.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsDiureticsDog DiseasesDogsFurosemideHeart FailureHumansProspective StudiesConceptsCongestive heart failureSpot urine samplesDiuretic responsivenessHeart failureHealthy dogsOral administrationUrine samplesCumulative urine volumeUrinary Na excretionProspective interventional studyUrine sodiumNa excretionUrine volumeInterventional studyUvolClinical importanceHuman patientsClinical settingDogsFurosemideCharacteristic curveResponsivenessAdministrationMinutesPatientsReal-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept
Ugwuowo U, Yamamoto Y, Arora T, Saran I, Partridge C, Biswas A, Martin M, Moledina DG, Greenberg JH, Simonov M, Mansour SG, Vela R, Testani JM, Rao V, Rentfro K, Obeid W, Parikh CR, Wilson FP. Real-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept. American Journal Of Kidney Diseases 2020, 76: 806-814.e1. PMID: 32505812, PMCID: PMC8667815, DOI: 10.1053/j.ajkd.2020.05.003.Peer-Reviewed Original ResearchConceptsAKI alertsHospitalized adultsKidney injuryUrban tertiary care hospitalAcute kidney injurySerum creatinine levelsObservational cohort studyTertiary care hospitalSerum creatinine concentrationBeats/minElectronic health recordsAKI diagnosisCohort studyCreatinine levelsInpatient mortalitySystolic bloodFractional excretionCenter studyBlood biomarkersUnivariable associationsUrine microscopyCreatinine concentrationClinical careElevated riskUrea nitrogenEffect 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 ResearchMeSH KeywordsDiureticsFurosemideHeart FailureHumansProspective StudiesSodiumSodium Potassium Chloride Symporter InhibitorsUreaConceptsAcute 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 lossTherapyChlorothiazideMetolazoneTolvaptanDiureticsInfusionCohortAdverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction
Reddy YNV, Obokata M, Testani JM, Felker GM, Tang WHW, Abou-Ezzeddine OF, Sun JL, Chakrabothy H, McNulty S, Shah SJ, Lewis GD, Stevenson LW, Redfield MM, Borlaug BA. Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Journal Of Cardiac Failure 2019, 26: 101-107. PMID: 31618698, PMCID: PMC7036022, DOI: 10.1016/j.cardfail.2019.09.015.Peer-Reviewed Original ResearchConceptsRenal functionNonobese patientsHeart failureObese HFpEFObese patientsEjection fractionRenal responseAdverse renal responsesRight ventricular remodelingGlomerular filtration rateBody mass indexPlasma volume expansionSimilar weight lossCardiorenal hemodynamicsRenal dysfunctionPathophysiologic featuresMass indexAtrial fibrillationDecongestive therapyVentricular remodelingPericardial restraintFiltration rateHFpEFObese phenotypeSevere worseningRenal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function
Rao VS, Ahmad T, Brisco-Bacik MA, Bonventre JV, Wilson FP, Siew ED, Felker GM, Anstrom KK, Mahoney DD, Bart BA, Tang WHW, Velazquez EJ, Testani JM. Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function. Circulation Heart Failure 2019, 12: e005552. PMID: 31163974, PMCID: PMC6585463, DOI: 10.1161/circheartfailure.118.005552.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersCreatinineFemaleHeart FailureHumansKidneyLipocalin-2MaleMiddle AgedProspective StudiesConceptsRenal tubular injury biomarkersTubular injury biomarkersHeart failure patientsAcute decompensated heart failure patientsDecompensated heart failure patientsTubular injury markersInjury biomarkersFailure patientsRenal functionInjury markersAcute decompensated heart failureVolume removalCARRESS-HF trialRenal function recoveryDecompensated heart failureRenal tubular injuryRenal effectsSerum creatinineTubular injuryBiomarker substudyHeart failurePharmacological therapyClinical outcomesFunction recoveryHigh incidenceUrinary Sodium Profiling in Chronic Heart Failure to Detect Development of Acute Decompensated Heart Failure
Martens P, Dupont M, Verbrugge FH, Damman K, Degryse N, Nijst P, Reynders C, Penders J, Tang WHW, Testani J, Mullens W. Urinary Sodium Profiling in Chronic Heart Failure to Detect Development of Acute Decompensated Heart Failure. JACC Heart Failure 2019, 7: 404-414. PMID: 31047021, DOI: 10.1016/j.jchf.2019.02.011.Peer-Reviewed Original ResearchConceptsChronic HF patientsHF patientsHeart failureSodium excretionAcute decompensated heart failureAcute heart failure hospitalizationLongitudinal changesChronic heart failureDecompensated heart failureHeart failure hospitalizationHigher sodium excretionUrinary sodium concentrationGlomerular filtration rate measurementInterindividual differencesLarge interindividual differencesFiltration rate measurementAHF hospitalizationDyspnea scoreFailure hospitalizationNT-proBNPChronic heartEjection fractionIndependent predictorsClinical endpointsPathophysiologic interactions
2018
The 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 ureaHospitalizationBUNOutcomesEarly 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 output
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 location
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 modalityPatientsHypochloremia 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 sodiumImportance 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 homeostasisMortalityRapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure
Testani JM, Hanberg JS, Cheng S, Rao V, Onyebeke C, Laur O, Kula A, Chen M, Wilson FP, Darlington A, Bellumkonda L, Jacoby D, Tang WH, Parikh CR. Rapid and Highly Accurate Prediction of Poor Loop Diuretic Natriuretic Response in Patients With Heart Failure. Circulation Heart Failure 2016, 9: e002370. PMID: 26721915, PMCID: PMC4741370, DOI: 10.1161/circheartfailure.115.002370.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAdministration, IntravenousAgedBiomarkersBumetanideDrug MonitoringDrug ResistanceFemaleHeart FailureHumansMaleMiddle AgedModels, BiologicalNatriuresisPredictive Value of TestsProspective StudiesReproducibility of ResultsSodiumSodium Potassium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeUrinalysisConceptsAcute decompensated heart failureDecompensated heart failureNatriuretic responseSpot urine samplesSodium outputHeart failureDiuretic administrationAcute decompensated heart failure patientsDecompensated heart failure patientsLoop diuretic administrationPrimary therapeutic objectiveUrine samplesHeart failure patientsPositive sodium balanceNet fluid outputDiuretic dosingIntravenous bumetanideMedian doseFailure patientsDiuretic responseSodium balanceUrine collectionFluid balanceTherapeutic objectivesFluid output
2015
False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria
Lin J, Fernandez H, Shashaty MG, Negoianu D, Testani JM, Berns JS, Parikh CR, Wilson FP. False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria. Clinical Journal Of The American Society Of Nephrology 2015, 10: 1723-1731. PMID: 26336912, PMCID: PMC4594067, DOI: 10.2215/cjn.02430315.Peer-Reviewed Original ResearchConceptsSerum creatinine valuesGlobal Outcomes creatinine criteriaSerum creatinineCreatinine valuesCreatinine criteriaClinical cohortBiologic variabilityProportion of patientsSerum creatinine changesHigher baseline valuesFalse positive rateAKI diagnosisAKI studiesAdult patientsCreatinine changesBlood drawReference cohortOverall false-positive rateBaseline valuesCreatinine measurementsPatientsCreatinineHypothetical patientsDiagnosis rateSimulation cohortPerioperative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery
Schaub JA, Garg AX, Coca SG, Testani JM, Shlipak MG, Eikelboom J, Kavsak P, McArthur E, Shortt C, Whitlock R, Parikh CR. Perioperative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery. Kidney International 2015, 88: 576-583. PMID: 25830762, PMCID: PMC4556547, DOI: 10.1038/ki.2015.104.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAged, 80 and overBiomarkersCardiac Surgical ProceduresChi-Square DistributionFatty Acid Binding Protein 3Fatty Acid-Binding ProteinsFemaleHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisNorth AmericaOdds RatioPerioperative PeriodProportional Hazards ModelsProspective StudiesRisk AssessmentRisk FactorsSeverity of Illness IndexUp-RegulationConceptsAcute kidney injurySevere acute kidney injuryCardiac surgeryKidney injuryKidney injury molecule-1Neutrophil gelatinase-associated lipocalinHeart-type fatty acid binding proteinAKI risk factorsInjury molecule-1Long-term mortalityBrain natriuretic peptideGelatinase-associated lipocalinH-FABP levelsMulti-center cohortTRIBE-AKI cohortFatty acid binding proteinLiver fatty acidHeart fatty acidCommon complicationSecondary outcomesSerum creatininePrimary outcomeInterleukin-18Risk stratificationCardiac injury
2014
Insufficient Natriuretic Response to Continuous Intravenous Furosemide Is Associated With Poor Long-Term Outcomes in Acute Decompensated Heart Failure
Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, Tang WH. Insufficient Natriuretic Response to Continuous Intravenous Furosemide Is Associated With Poor Long-Term Outcomes in Acute Decompensated Heart Failure. Journal Of Cardiac Failure 2014, 20: 392-399. PMID: 24704538, PMCID: PMC4067259, DOI: 10.1016/j.cardfail.2014.03.006.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureContinuous intravenous furosemideDecompensated heart failureLong-term outcomesIntravenous furosemideNatriuretic responseRenal functionUrine sodiumHeart failureClinical outcomesUrine creatinineAdverse long-term clinical outcomesAdverse long-term outcomesLong-term clinical outcomesPoor long-term outcomesAdverse long-term eventsWeight lossContinuous furosemide infusionNet urine outputUrine sodium excretionAdverse clinical outcomesGlomerular filtration rateNet fluid outputGreater likelihoodLow urine sodium