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 ResearchMeSH KeywordsAgedCardio-Renal SyndromeDiureticsDrug ResistanceFemaleFurosemideHeart FailureHumansMaleMiddle AgedProspective StudiesSodiumSodium Potassium Chloride Symporter InhibitorsConceptsDiuretic 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
Prevention and treatment of diuretic resistance in acute heart failure: when to use which combination of diuretics?
Martens P, Testani J, Damman K. Prevention and treatment of diuretic resistance in acute heart failure: when to use which combination of diuretics? European Heart Journal 2023, 44: 2978-2981. PMID: 37572039, DOI: 10.1093/eurheartj/ehad463.Peer-Reviewed Original ResearchThe 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 weightThe importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial
Eder M, Griffin M, Moreno-Villagomez J, Bellumkonda L, Maulion C, Asher J, Wilson F, Cox Z, Ivey-Miranda J, Rao V, Butler J, Borlaug B, McCallum W, Ramos-Mastache D, Testani J. The importance of forward flow and venous congestion in diuretic response in acute heart failure: Insights from the ESCAPE trial. International Journal Of Cardiology 2023, 381: 57-61. PMID: 37023862, DOI: 10.1016/j.ijcard.2023.04.002.Peer-Reviewed Original ResearchMeSH KeywordsHeart FailureHumansHyperemiaSodium Potassium Chloride Symporter InhibitorsStroke VolumeVentricular Function, LeftConceptsRight atrial pressureDiuretic efficiencyRight atrial areaDiuretic responseVenous congestionHeart failureCardio-renal interactionsLoop diuretic doseAcute heart failureRenal perfusion pressureLow cardiac outputMean arterial pressureRight ventricular systolicCongestive heart failureVentricular ejection fractionNet fluid outputForward flowDiuretic doseDiuretic resistanceTTE parametersCardiac indexVentricular systolicArterial pressureAtrial pressureEjection fractionEffect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure
Mentz R, Anstrom K, Eisenstein E, Sapp S, Greene S, Morgan S, Testani J, Harrington A, Sachdev V, Ketema F, Kim D, Desvigne-Nickens P, Pitt B, Velazquez E, Adams K, Bhatt K, DeWald T, Axsom K, Murthy S, Rich J, Testani J, Smith B, Vader J, McCulloch M, Skopicki H, Psotka M, Heroux A, Lala-Trindade A, Stevens G, Tang W, Lev Y, William P, Eberly A, Gottleib S, Haught W, Grafton G, Larned J, Tejwani L, Mody F, Krim S, Robinson M, Fang J, Adler A, Bell A, Banerjee D, Ruiz Duque E, Mizyed A, Rommel J, Arhinful J, Goyal P, Hall M, Hummel S, Shetty S, Haas D, Vilaro J, Alexy T, Herre J, Clark J, Ambrosy A, Gaglianello N, Ramasubbu K, Meadows J, Tabtabai S, Sherwood M, Hasni S, D'Urso M, Muneer B, Dunlap S, Davis W, Friedman D, Guglin M, Ferguson A, Abbate A, Smart F. Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure. JAMA 2023, 329: 214-223. PMID: 36648467, PMCID: PMC9857435, DOI: 10.1001/jama.2022.23924.Peer-Reviewed Original ResearchMeSH KeywordsAgedFemaleFurosemideHeart FailureHospitalizationHumansMaleMiddle AgedPatient DischargeSodium Potassium Chloride Symporter InhibitorsTorsemideTreatment OutcomeConceptsCause mortalityHeart failureTorsemide groupFurosemide groupTotal hospitalizationsCause hospitalizationEffects of torsemideDiuretic strategyPrespecified subgroupsSecondary outcomesEjection fractionMedian agePrimary outcomeHospitalizationMAIN OUTCOMEPatientsFurosemideMortalityMonthsTorsemidePrimary hypothesisSignificant differencesFinal dateOutcomesTrials
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 LettersMeSH KeywordsCardio-Renal SyndromeDiureticsHeart FailureHumansSodiumSodium Potassium Chloride Symporter InhibitorsConceptsCardiorenal 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
FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions
Ivey-Miranda JB, Stewart B, Cox ZL, McCallum W, Maulion C, Gleason O, Meegan G, Amatruda JG, Moreno-Villagomez J, Mahoney D, Turner JM, Wilson FP, Estrella MM, Shlipak MG, Rao VS, Testani JM. FGF-23 (Fibroblast Growth Factor-23) and Cardiorenal Interactions. Circulation Heart Failure 2021, 14: e008385. PMID: 34689571, PMCID: PMC8782627, DOI: 10.1161/circheartfailure.121.008385.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overDiuresisDiureticsFemaleFibroblast Growth Factor-23Heart FailureHumansMaleMiddle AgedReninSodiumSodium Potassium Chloride Symporter InhibitorsConceptsFGF-23Cardiorenal interactionsHeart failureDiuretic resistanceSodium avidityNeurohormonal activationMultivariable analysisDistal tubular sodium reabsorptionLoop diuretic doseTubular sodium reabsorptionGlomerular filtration rateCardiorenal dysfunctionDiuretic doseDiuretic treatmentNT-proBNPFractional excretionDiuretic administrationSodium reabsorptionPeak diuresisFiltration rateCare centerUrine samplingAnimal modelsSerum chlorideDisease severityCompensatory 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 ResearchMeSH KeywordsDiureticsHeart FailureHumansNatriuresisSodiumSodium Potassium Chloride Symporter InhibitorsConceptsAcute 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 volunteersRenal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction
Rao VS, Maulion C, Asher JL, Ivey-Miranda J, Cox ZL, Moreno-Villagomez J, Mahoney D, Turner JM, Wilson FP, Wilcox CS, Testani J. Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction. AJP Regulatory Integrative And Comparative Physiology 2021, 321: r588-r594. PMID: 34405731, DOI: 10.1152/ajpregu.00115.2021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCardio-Renal SyndromeDisease Models, AnimalDiuresisFemaleFluid TherapyFurosemideGlomerular Filtration RateHeart FailureHemodynamicsInfusions, IntravenousKidneyNatriuresisRenal Plasma FlowSodium Potassium Chloride Symporter InhibitorsSus scrofaConceptsRenal plasma flowGlomerular filtration rateCongestive HFTubular pressureHeart failure hospitalizationPara-aminohippurate clearanceCentral venous pressureHigh fractional excretionNegative pressure therapyUrinary collecting systemNegative pressure treatmentSimilar diuresisFailure hospitalizationRenal dysfunctionCardiac tamponadeIothalamate clearanceFractional excretionRenal parametersKidney functionRenal congestionRenal responseRight kidneyVenous pressurePressure therapyControl kidneysMultinephron 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 ResearchMeSH KeywordsAcute DiseaseDiureticsHeart FailureHumansMineralocorticoid Receptor AntagonistsProspective StudiesRetrospective StudiesSodium Potassium Chloride Symporter InhibitorsConceptsAcute 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 ResearchMeSH KeywordsAgedBiomarkersCohort StudiesDrug MonitoringFemaleHeart FailureHumansMaleMiddle AgedModels, BiologicalNatriuresisProof of Concept StudySodiumSodium Potassium Chloride Symporter InhibitorsUrinalysisConceptsLoop 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 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 outputDiuretic 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 StatementsMeSH KeywordsDiureticsGastrointestinal AbsorptionHeart FailureHumansKidneyReview Literature as TopicSodium Potassium Chloride Symporter InhibitorsConceptsHeart 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 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
Loop diuretic resistance complicating acute heart failure
Cox ZL, Testani JM. Loop diuretic resistance complicating acute heart failure. Heart Failure Reviews 2019, 25: 133-145. PMID: 31520280, DOI: 10.1007/s10741-019-09851-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAcute DiseaseDiureticsDrug ResistanceHeart FailureHumansInfusions, IntravenousPractice Guidelines as TopicSodium Potassium Chloride Symporter InhibitorsConceptsLoop diuretic resistanceDiuretic resistanceHeart failureAcute heart failure hospitalizationMechanism-based classification systemAcute heart failureHeart failure hospitalizationOngoing clinical trialsUniversal clinical applicationDiuretic strategyFailure hospitalizationDiuretic efficacyClinical trialsWorse outcomesTreatment pathwaysAnatomical locationClinical applicationCurrent literatureResistance mechanismsCurrent best practiceOutcomesClassification systemLiterature reviewHospitalizationPatientsNatriuretic 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 ResearchMeSH KeywordsAcute DiseaseAgedAged, 80 and overFemaleHeart FailureHumansMaleMiddle AgedMortalityNatriuresisPrognosisProportional Hazards ModelsSodiumSodium Potassium Chloride Symporter InhibitorsSurvival RateWater-Electrolyte BalanceWater-Electrolyte ImbalanceConceptsAcute 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 abilitySerum 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 ResearchMeSH KeywordsAgedAged, 80 and overAlbuminuriaCohort StudiesFemaleHeart FailureHumansInterleukin-6MaleMiddle AgedSerum AlbuminSodium Potassium Chloride Symporter InhibitorsConceptsDiuretic 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 StatementsMeSH KeywordsDiureticsDrug ResistanceHeart FailureHumansNephronsPrognosisSodiumSodium Potassium Chloride Symporter InhibitorsConceptsAcute 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
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 recordsDiureticsOlder drugs with infantile evidence: the illustrative example of loop diuretics
Bikdeli B, Testani JM, Ross JS, Krumholz HM. Older drugs with infantile evidence: the illustrative example of loop diuretics. European Heart Journal - Quality Of Care And Clinical Outcomes 2018, 4: 232-234. PMID: 29617967, PMCID: PMC6030914, DOI: 10.1093/ehjqcco/qcy012.Peer-Reviewed Case Reports and Technical NotesDose-Response Relationship, DrugHeart FailureHumansSodium Potassium Chloride Symporter InhibitorsTreatment Outcome