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
Improved Decongestion With Devices in Decompensated Heart Failure Does the End Justify the Means? ∗
Testani J, Butler J, Packer M. Improved Decongestion With Devices in Decompensated Heart Failure Does the End Justify the Means? ∗. JACC Heart Failure 2023, 11: 1576-1578. PMID: 37940218, DOI: 10.1016/j.jchf.2023.07.006.Peer-Reviewed Original ResearchPrevention 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 ResearchCritical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes
Packer M, Wilcox C, Testani J. Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes. Circulation 2023, 148: 354-372. PMID: 37486998, PMCID: PMC10358443, DOI: 10.1161/circulationaha.123.064346.Peer-Reviewed Original ResearchConceptsSGLT2 inhibitorsProximal renal tubulesRenal tubulesProximal tubular effectHeart failure outcomesHeart failure eventsSodium-hydrogen exchanger 3Renal tubular sodiumProgressive volume lossLong-term treatmentReabsorption of glucoseTreatment-related changesChronic diuresisPharmacological toleranceTubular effectsClinical courseFractional excretionHeart failureTubular sodiumCardioprotective effectsRenal compensationDiuretic effectIndividual patientsDurable improvementDegree of upregulationSGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint?
Borlaug B, Testani J. SGLT2 inhibitors and diuretics in heart failure: clicking reset on the renal volume setpoint? European Heart Journal 2023, 44: 2944-2946. PMID: 37220086, DOI: 10.1093/eurheartj/ehad345.Commentaries, Editorials and LettersMeSH KeywordsBenzhydryl CompoundsDiureticsHeart FailureHumansSodium-Glucose Transporter 2 InhibitorsThe 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 weightIn-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
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
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 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 volunteersMultinephron 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 controlTherapyPatientsUse of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA‐REG OUTCOME trial
Pellicori P, Fitchett D, Kosiborod MN, Ofstad AP, Seman L, Zinman B, Zwiener I, Wanner C, George J, Inzucchi SE, Testani JM, Cleland JGF. Use of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA‐REG OUTCOME trial. European Journal Of Heart Failure 2021, 23: 1085-1093. PMID: 34031968, PMCID: PMC11497224, DOI: 10.1002/ejhf.2220.Peer-Reviewed Original ResearchConceptsUse of LDDiagnosis of HFHeart failureLoop diureticsHF diagnosisEMPA-REG OUTCOME trialType 2 diabetes mellitusSigns of congestionCardiovascular eventsCardiovascular mortalityOutcome trialsDiabetes mellitusPatient subgroupsPatientsDiagnosisHigh rateOutcomesMellitusT2DMDiureticsSymptomsMortalityBaselineTrialsReply Protocolized Diuretic Approach Using the Natriuretic Equation: Careful Patient Selection Is Needed
Rao VS, Ivey-Miranda JB, Cox ZL, Testani JM. Reply Protocolized Diuretic Approach Using the Natriuretic Equation: Careful Patient Selection Is Needed. Journal Of The American College Of Cardiology 2021, 77: 2758-2759. PMID: 34045035, DOI: 10.1016/j.jacc.2021.03.322.Commentaries, Editorials and LettersEarly diuretic strategies and the association with In-hospital and Post-discharge outcomes in acute heart failure
Fudim M, Spates T, Sun JL, Kittipibul V, Testani JM, Starling RC, Tang WHW, Hernandez AF, Felker GM, O'Connor CM, Mentz RJ. Early diuretic strategies and the association with In-hospital and Post-discharge outcomes in acute heart failure. American Heart Journal 2021, 239: 110-119. PMID: 34052212, DOI: 10.1016/j.ahj.2021.05.011.Peer-Reviewed Original ResearchMeSH KeywordsCreatinineDiureticsDrug MonitoringFemaleFurosemideHeart FailureHospitalizationHumansInfusions, IntravenousInjections, IntravenousMaleMiddle AgedMortalityNatriuretic Peptide, BrainOutcome and Process Assessment, Health CarePatient ReadmissionPeptide FragmentsTime-to-TreatmentUnited StatesConceptsIntermittent bolus administrationAcute heart failureDecompensated heart failureHeart failurePost-discharge outcomesDiuretic strategyDay mortalityBolus administrationDays/dischargeHigher baseline creatinineIntermittent bolus groupTotal urine outputBaseline creatinineDiuretic regimenHigh NTproBNPCause mortalityHF readmissionHF rehospitalizationHospital outcomesBaseline characteristicsCardiovascular mortalityIn-HospitalRenal functionBolus groupContinuous therapyThe Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study
Moledina DG, Simonov M, Yamamoto Y, Alausa J, Arora T, Biswas A, Cantley LG, Ghazi L, Greenberg JH, Hinchcliff M, Huang C, Mansour SG, Martin M, Peixoto A, Schulz W, Subair L, Testani JM, Ugwuowo U, Young P, Wilson FP. The Association of COVID-19 With Acute Kidney Injury Independent of Severity of Illness: A Multicenter Cohort Study. American Journal Of Kidney Diseases 2021, 77: 490-499.e1. PMID: 33422598, PMCID: PMC7791318, DOI: 10.1053/j.ajkd.2020.12.007.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedC-Reactive ProteinCohort StudiesCOVID-19CreatinineDiureticsFemaleHospital MortalityHumansIntensive Care UnitsLength of StayMaleMiddle AgedProportional Hazards ModelsRenal DialysisRenal Insufficiency, ChronicRespiration, ArtificialRisk FactorsSARS-CoV-2Severity of Illness IndexUnited StatesVasoconstrictor AgentsConceptsAcute kidney injurySARS-CoV-2Cohort studyRisk factorsCOVID-19Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testingTime-updated Cox proportional hazards modelsDialysis-requiring acute kidney injuryYale New Haven Health SystemHigher inflammatory marker levelsMore acute kidney injuryCox proportional hazards modelMulticenter cohort studyHigh rateInflammatory marker levelsTraditional risk factorsProportional hazards modelCoronavirus disease 2019KDIGO criteriaNephrotoxin exposureKidney injuryInjury independentUnivariable analysisNasopharyngeal samplesMarker levels
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 ResearchConceptsCongestive heart failureSpot urine samplesDiuretic responsivenessHeart failureHealthy dogsOral administrationUrine samplesCumulative urine volumeUrinary Na excretionProspective interventional studyUrine sodiumNa excretionUrine volumeInterventional studyUvolClinical importanceHuman patientsClinical settingDogsFurosemideCharacteristic curveResponsivenessAdministrationMinutesPatientsPathophysiology 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 tubulesRacial Differences in Diuretic Efficiency, Plasma Renin, and Rehospitalization in Subjects With Acute Heart Failure
Morris AA, Nayak A, Ko YA, D’Souza M, Felker GM, Redfield MM, Tang WHW, Testani JM, Butler J. Racial Differences in Diuretic Efficiency, Plasma Renin, and Rehospitalization in Subjects With Acute Heart Failure. Circulation Heart Failure 2020, 13: e006827. PMID: 32635768, PMCID: PMC7474850, DOI: 10.1161/circheartfailure.119.006827.Peer-Reviewed Original ResearchConceptsPlasma renin activityAcute heart failureLevels of PRADiuretic efficiencyHeart failureBlack patientsNonblack patientsAcute heart failure clinical trialsRacial differencesBaseline plasma renin activityHeart failure clinical trialsHigher diuretic efficiencyMeasures of decongestionRisk of rehospitalizationNonischemic heart failureNet fluid balanceSubset of subjectsGreater fluid lossRace/ethnic groupsCARRESS-HFDOSE-AHFFurosemide equivalentsROSE-AHFAldosterone systemNT-proBNPSodium 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 monotherapyEmpagliflozin in Heart Failure
Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure. Circulation 2020, 142: 1028-1039. PMID: 32410463, PMCID: PMC7521417, DOI: 10.1161/circulationaha.120.045691.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsCotransporter 2 inhibitorsNeurohormonal activationHeart failureRenal dysfunctionBlood volumeHeart failure-related outcomesPlacebo-controlled crossover studyType 2 diabetes mellitusProximal tubular siteHeart failure outcomesStable heart failureUrinary glucose excretionUric acid levelsElectrolyte wastingEmpagliflozin monotherapyOral empagliflozinPlacebo periodStudy drugGlucose excretionNatriuretic effectPotassium wastingTubular sitesDiabetes mellitusFractional excretion