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
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 ResearchConceptsAcute heart failureCombination of diureticsDiuretic resistanceHeart failureDiureticsPreventionThe 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 fraction
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 literatureRenin-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
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 ResearchConceptsFGF-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 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 controlTherapyPatients
2020
Mechanisms 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 findingsPathophysiology 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 tubulesSodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series
Griffin M, Riello R, Rao VS, Ivey-Miranda J, Fleming J, Maulion C, McCallum W, Sarnak M, Collins S, Inzucchi SE, Testani JM. Sodium glucose cotransporter 2 inhibitors as diuretic adjuvants in acute decompensated heart failure: a case series. ESC Heart Failure 2020, 7: 1966-1971. PMID: 32476296, PMCID: PMC7373933, DOI: 10.1002/ehf2.12759.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureSodium-glucose cotransporter 2 inhibitorsGlucose cotransporter 2 inhibitorsDecompensated heart failureCotransporter 2 inhibitorsType 2 diabetesSGLT-2iBlood pressureHeart failureUrine outputYale-New Haven HospitalWeight lossIncidence of hypokalaemiaSGLT-2i initiationSGLT-2i therapyGlucose-lowering medicationsHeart failure outcomesCohort of patientsAverage weight lossDiuretic dosingDiuretic resistanceAdjunctive therapyWorsened survivalDiuretic efficiencyDiuretic monotherapyDiuretic 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 lossTherapyChlorothiazideMetolazoneTolvaptanDiureticsInfusionCohortLoop 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 StatementsConceptsLoop 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 reviewHospitalizationPatientsLoop Diuretic Resistance in a Patient with Acute Heart Failure
Cox Z, Testani J. Loop Diuretic Resistance in a Patient with Acute Heart Failure. 2019, 153-173. DOI: 10.1007/978-3-030-21033-5_11.ChaptersLoop diuretic resistanceDiuretic resistanceHeart failureAcute heart failure hospitalizationMechanism-based classification systemAcute heart failureHeart failure hospitalizationHeart failure cohortFailure hospitalizationDiuretic efficacyPatient populationTreatment optionsFailure cohortClassification systemPatientsUniversal definitionHospitalizationSerum 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 ResearchConceptsDiuretic 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 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
Early 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