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
Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI
Aklilu A, Kumar S, Yamamoto Y, Moledina D, Sinha F, Testani J, Wilson F. Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI. Kidney360 2023, 4: 1371-1381. PMID: 37644648, PMCID: PMC10615381, DOI: 10.34067/kid.0000000000000250.Peer-Reviewed Original ResearchConceptsAcute kidney injuryHeart failure hospitalizationSodium-glucose cotransporter-2 inhibitor useSodium-glucose cotransporter 2 inhibitorsAcute heart failure hospitalizationCotransporter 2 inhibitorsCox regression analysisRenal recoveryFailure hospitalizationAKI diagnosisKidney injuryInhibitor useLower riskStage 5 chronic kidney diseaseTime-varying Cox regression analysisKidney Disease Improving Global OutcomesInverse probability-weighted analysisMulticenter retrospective cohort studyMultivariable Cox regression analysisStage 5 CKDAcute heart failureRetrospective cohort studyChronic kidney diseaseKidney function recoveryGlomerular filtration rateCritical 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 upregulationSodium restriction in patients with chronic heart failure and reduced ejection fraction: A randomized controlled trial
Ivey-Miranda J, Almeida-Gutierrez E, Herrera-Saucedo R, Posada-Martinez E, Chavez-Mendoza A, Mendoza-Zavala G, Cigarroa-Lopez J, Magaña-Serrano J, Rivera-Leaños R, Treviño-Mejia A, Revilla-Monsalve C, Flores-Umanzor E, Espinola-Zavaleta N, Orea-Tejeda A, Garduño-Espinosa J, Saturno-Chiu G, Rao VS, Testani J, Borrayo-Sanchez G. Sodium restriction in patients with chronic heart failure and reduced ejection fraction: A randomized controlled trial. Cardiology Journal 2023, 30: 411-421. PMID: 34490604, PMCID: PMC10287066, DOI: 10.5603/cj.a2021.0098.Peer-Reviewed Original ResearchConceptsQuality of lifeSodium restrictionAdverse safety eventsNT-proBNPHeart failureSodium intakeEjection fractionSafety eventsN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideStable HF patientsChronic heart failureNT-proBNP levelsReduced ejection fractionLow sodium intakeBeneficial cardiac effectsAdverse safety signalsSolid clinical evidenceGOV IDENTIFIERUrinary sodiumHF patientsSymptomatic hypotensionCardiac effectsSecondary outcomesBlood pressure“Pouring Salt in the Wound”: Sodium Restriction in Acute Heart Failure
Cox Z, Testani J. “Pouring Salt in the Wound”: Sodium Restriction in Acute Heart Failure. Journal Of Cardiac Failure 2023, 29: 997-999. PMID: 37236502, DOI: 10.1016/j.cardfail.2023.05.007.Commentaries, Editorials and Letters
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 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 volunteersSpot urine sodium in acute heart failure: differences in prognostic value on admission and discharge
Biegus J, Zymliński R, Fudim M, Testani J, Sokolski M, Marciniak D, Ponikowska B, Guzik M, Garus M, Urban S, Ponikowski P. Spot urine sodium in acute heart failure: differences in prognostic value on admission and discharge. ESC Heart Failure 2021, 8: 2597-2602. PMID: 33932273, PMCID: PMC8318409, DOI: 10.1002/ehf2.13372.Peer-Reviewed Original ResearchConceptsHazard ratioComposite endpointAHF rehospitalizationPrognostic significancePrognostic utilityAcute heart failure hospitalizationSpot urine sodiumAcute heart failureHeart failure hospitalizationMortality hazard ratioCourse of hospitalizationConfidence intervalsDifferent prognostic significanceEarly phaseAHF patientsOral furosemideCause mortalityFailure hospitalizationIndex hospitalizationUrine sodiumSodium excretionHeart failureStudy endpointClinical statusPrognostic valueNatriuretic 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
Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high‐risk acute heart failure patients
Biegus J, Zymliński R, Testani J, Marciniak D, Zdanowicz A, Jankowska EA, Banasiak W, Ponikowski P. Renal profiling based on estimated glomerular filtration rate and spot urine sodium identifies high‐risk acute heart failure patients. European Journal Of Heart Failure 2020, 23: 729-739. PMID: 33190378, DOI: 10.1002/ejhf.2053.Peer-Reviewed Original ResearchConceptsAcute heart failureGlomerular filtration rateHeart failureFiltration rateDay 1Acute heart failure patientsHospital heart failureSpot urine sodiumHeart failure patientsUrinary sodium concentrationAHF patientsInotrope useTherapeutic profilingUrine sodiumFailure patientsIndependent prognosticatorRenal functionDay 2PatientsEGFRConcomitant assessmentWater handlingSodium concentrationPrognosticatorExcretersEffect 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 changesFENaDiuresisFailureFirst-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution
Rao VS, Turner JM, Griffin M, Mahoney D, Asher J, Jeon S, Yoo PS, Boutagy N, Feher A, Sinusas A, Wilson FP, Finkelstein F, Testani JM. First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution. Circulation 2020, 141: 1043-1053. PMID: 31910658, PMCID: PMC7331276, DOI: 10.1161/circulationaha.119.043062.Peer-Reviewed Original ResearchConceptsStandard PD solutionExperimental heart failureHeart failurePD solutionsAdverse eventsPeritoneal dialysisSignificant discomfortSodium removalEnd-stage renal diseaseEnd pointElevated right atrial pressureMaintenance of euvolemiaPrimary end pointSecondary end pointsRight atrial pressureHuman proofLoss of responseSolute removalPorcine experimentsAtrial pressureRenal diseaseLoop diureticsSerum electrolytesHuman studiesPeritoneal membrane
2019
Natriuretic 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 ResearchConceptsAcute 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 abilityUrinary 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 interactionsDiuretic 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 studiesDR
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
2017
Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction
Ferreira JP, Girerd N, Duarte K, Coiro S, McMurray JJ, Dargie HJ, Pitt B, Dickstein K, Testani JM, Zannad F, Rossignol P. Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction. Circulation Heart Failure 2017, 10: e003500. PMID: 28159825, DOI: 10.1161/circheartfailure.116.003500.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedBiomarkersChloridesComorbidityDatabases, FactualFemaleHeart FailureHumansKaplan-Meier EstimateLinear ModelsMaleMiddle AgedMyocardial InfarctionNonlinear DynamicsPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicRetrospective StudiesRisk AssessmentRisk FactorsSodiumStroke VolumeVentricular Dysfunction, LeftVentricular Function, LeftConceptsHeart failureAcute myocardial infarctionSerum chlorideMyocardial infarctionPrognostic informationPrognostic variablesSodium levelsReduced left ventricular functionLow sodiumReduced ejection fractionLeft ventricular functionLower serum chlorideSignificant prognostic informationRelevant prognostic informationSerum chloride levelsPost-myocardial infarctionLow sodium levelsMore comorbiditiesCause mortalitySystolic dysfunctionCardiovascular mortalityEjection fractionVentricular functionClinical outcomesMortality rateRenal 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
Hypochloremia 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 sodium