2025
Proteins associated with rehospitalization, mortality and diuretic resistance in acutely decompensated heart failure
Hubbell K, Rao V, Scherzer R, Shlipak M, Ivery‐Miranda J, Bansal N, Cox Z, Testani J, Estrella M. Proteins associated with rehospitalization, mortality and diuretic resistance in acutely decompensated heart failure. ESC Heart Failure 2025 PMID: 40504107, DOI: 10.1002/ehf2.15342.Peer-Reviewed Original ResearchAcute decompensated heart failureDecompensated heart failureDiuretic responseHeart failureHF rehospitalizationRisk of HF rehospitalizationBiomarker modelAssociated with poor outcomesAssociated with decreased riskAssociated with increased riskAssociated with cardiometabolic diseasesAssociated with mortalityAssociated with rehospitalizationDiuretic resistanceMedian ageResistance cohortClinical factorsPoor outcomeSociodemographic/lifestyle factorsPrognostic toolCombined biomarkersCardiometabolic diseasesPatientsAmbulatory settingMortality riskSerum chloride and the response to combining loop and thiazide diuretics for acute heart failure: the ALCALOTIC study
Núñez J, Miñana G, Villalonga M, Asenjo M, Carrera M, Epelde F, Gil M, Chivite D, Contra A, Pla X, Casado J, Miró Ò, de la Espriella R, Testani J, Trullàs J. Serum chloride and the response to combining loop and thiazide diuretics for acute heart failure: the ALCALOTIC study. Internal And Emergency Medicine 2025, 1-11. PMID: 40379935, DOI: 10.1007/s11739-025-03961-z.Peer-Reviewed Original ResearchAcute heart failureHeart failureDiuretic responseSerum chlorideThiazide diureticsWeight lossAssociated with smaller weight lossPatients admitted with acute heart failurePathophysiology of heart failureIn-hospital weight lossAssociated with higher weight lossObservational cohort studyDiuretic resistanceHF prognosisThiazideCohort studyDiureticsPatientsHyperchloraemiaOverall populationHypochloraemiaClinical sitesSerumSmall weight lossFailureNatriuretic response prediction equation for use with oral diuretics in heart failure
Ivey-Miranda J, Rao V, Cox Z, Moreno-Villagomez J, Mastache D, Collins S, Testani J. Natriuretic response prediction equation for use with oral diuretics in heart failure. European Heart Journal 2025, 46: 2410-2418. PMID: 40272149, PMCID: PMC12208776, DOI: 10.1093/eurheartj/ehaf268.Peer-Reviewed Original ResearchConceptsMechanisms of diuretic resistanceArea under the curvePoor diuretic responseDiuretic responseHeart failureDiuretic doseOral diureticsNatriuretic responseHF patient cohortsLoop diuretic doseOral loop diureticsUrine samplesTimed urine collectionsOral loopDiuretic resistanceLoop diureticsDiuretic administrationUrine volumePatient cohortUrine collectionStudy visitsDiureticsPatientsUrineDoseSalt repletion and diuretic response: The role of serum chloride. A post‐hoc analysis of the SALT‐HF trial on furosemide and hypertonic saline solution administration in ambulatory patients with worsening heart failure
Núñez J, Miñana G, de la Espriella R, Zegrí‐Reiriz I, Comín‐Colet J, Gracia J, Morales‐Rull J, Llàcer P, Diez‐Villanueva P, de Juan Bagudá J, Cortés C, Goirigolzarri‐Artaza J, García‐Pinilla J, Barrios E, del Prado Díaz S, Jiménez‐Marrero S, Restrepo‐Córdoba M, Testani J, Marcos M. Salt repletion and diuretic response: The role of serum chloride. A post‐hoc analysis of the SALT‐HF trial on furosemide and hypertonic saline solution administration in ambulatory patients with worsening heart failure. European Journal Of Heart Failure 2025 PMID: 39933832, DOI: 10.1002/ejhf.3597.Peer-Reviewed Original ResearchWorsening Heart FailureHypertonic saline solutionPost Hoc AnalysisAmbulatory patientsIV furosemideNatriuretic responseCongestion scoreDiuretic responseHeart failureBaseline serum chloride levelsSerum chlorideClinical congestion scoreOvercome diuretic resistanceUrinary sodium excretionHeart failure eventsSerum chloride levelsPost-hocBetween-treatment effectsDiuretic resistanceChloride levelsDouble-blindLoop diureticsDiuretic efficacyNatriuretic effectSodium excretion
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 ResearchConceptsAcute 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 ResearchConceptsRight 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 fractionIn-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
2022
Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure
Amatruda JG, Scherzer R, Rao VS, Ivey-Miranda JB, Shlipak MG, Estrella MM, Testani JM. Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Patients With Heart Failure. Kidney Medicine 2022, 4: 100465. PMID: 35620081, PMCID: PMC9127684, DOI: 10.1016/j.xkme.2022.100465.Peer-Reviewed Original ResearchDiuretic doseTotal reninDiuretic responseDiuretic resistanceFractional excretionHeart failureActive reninSystem activationRenin-angiotensin-aldosterone system activationHigher plasmaActive renin levelsAldosterone system activationLower diuretic efficiencyPlasma total reninRAAS inhibitor useChronic heart failureMultivariable-adjusted modelsHigh-quality trialsLow fractional excretionFurosemide equivalentsRAAS blockadeAldosterone levelsRAAS activationRenin levelsInhibitor use
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 congestionNatriuretic 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
Venous Congestion, Not Cardiac Index is Associated with Diuretic Resistance
Eder M, Griffin M, Fleming J, Gleason O, Meegan G, Ivey-Miranda J, Cox Z, Rao V, Testani J. Venous Congestion, Not Cardiac Index is Associated with Diuretic Resistance. Journal Of Cardiac Failure 2020, 26: s30-s31. DOI: 10.1016/j.cardfail.2020.09.095.Peer-Reviewed Original ResearchRight atrial pressureBaseline right atrial pressureAcute decompensated heart failureCardiac indexLow cardiac indexDiuretic efficiencyMin/m2Daily urine outputDiuretic resistanceUrine outputDiuretic responseVenous congestionDiuretic doseHeart failureDE groupHigher baseline right atrial pressureHigher right atrial pressureElevated right atrial pressureBaseline cardiac indexLoop diuretic doseDecompensated heart failureCongestive heart failureSubset of patientsGreater diuretic responseCardiorenal interactionsMechanisms 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 findingsEffect 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
Rapid and Accurate Assessment of Diuretic Response: Validation of an Equation to Predict Diuretic Induced Sodium Output Using a Spot Urine Sample
Griffin M, Struyk G, Fleming J, Shamlian P, Wycallis E, Pattoli M, Thomas A, Stewart B, Barnett J, Gomez N, Ivey-Miranda J, Rao V, Testani J. Rapid and Accurate Assessment of Diuretic Response: Validation of an Equation to Predict Diuretic Induced Sodium Output Using a Spot Urine Sample. Journal Of Cardiac Failure 2019, 25: s52-s53. DOI: 10.1016/j.cardfail.2019.07.148.Peer-Reviewed Original ResearchPoor diuretic responseSpot urine samplesNet fluid balanceDiuretic responseSodium excretionUrine collectionDiuretic administrationSodium outputValidation cohortWeight lossUrine samplesFluid balanceCumulative sodium excretionTypes of diureticsRoutine clinical practiceNet fluid lossAssessment of responseDiuretic doseDiuretic periodDiuretic therapyBladder dysfunctionLoop diureticsSpot urineMedical recordsClinical trialsThe 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
2017
Renal 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
Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF)
Grodin JL, Sun JL, Anstrom KJ, Chen HH, Starling RC, Testani JM, Tang WH. Implications of Serum Chloride Homeostasis in Acute Heart Failure (from ROSE-AHF). The American Journal Of Cardiology 2016, 119: 78-83. PMID: 27816115, PMCID: PMC5161696, DOI: 10.1016/j.amjcard.2016.09.014.Peer-Reviewed Original ResearchConceptsAcute heart failureSerum Cl levelsHeart failureClinical outcomesDiuretic responseAcute heart failure trialsRenal Optimization Strategies EvaluationShort-term clinical responseCumulative sodium excretionLoop diuretic doseHeart Failure TrialLong-term mortalitySerum chloride levelsCystatin C changesDiuretic dosePostdischarge outcomesSodium excretionCl levelsClinical responseRenal functionDiuretic efficiencyFailure TrialAdditional adjustmentCystatin CTherapeutic implications041 Influence of Local Renal Versus Systemic RAAS Activation on Loop Diuretic Response and Clinical Outcomes in Heart Failure
Rao V, Hanberg J, Broughton J, Assefa M, Testani J. 041 Influence of Local Renal Versus Systemic RAAS Activation on Loop Diuretic Response and Clinical Outcomes in Heart Failure. Journal Of Cardiac Failure 2016, 22: s17. DOI: 10.1016/j.cardfail.2016.06.058.Peer-Reviewed Original Research090 Aspirin Does Not Have a Significant Impact on Loop Diuretic Response or Renin Release in Heart Failure Patients
Broughton J, Hanberg J, Assefa M, Rao V, Testani J. 090 Aspirin Does Not Have a Significant Impact on Loop Diuretic Response or Renin Release in Heart Failure Patients. Journal Of Cardiac Failure 2016, 22: s34-s35. DOI: 10.1016/j.cardfail.2016.06.108.Peer-Reviewed Original Research
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