2024
Volenrelaxin (LY3540378) increases Renal Plasma Flow: A Randomized Phase 1 Trial
San Tham L, Heerspink H, Wang X, Verdino P, Saifan C, Benson E, Goldsmith P, Wang Z, Testani J, Haupt A, Sam F, Cherney D. Volenrelaxin (LY3540378) increases Renal Plasma Flow: A Randomized Phase 1 Trial. Nephrology Dialysis Transplantation 2024, gfae112. PMID: 38782726, DOI: 10.1093/ndt/gfae112.Peer-Reviewed Original ResearchMeasured glomerular filtration rateEffective renal plasma flowRenal plasma flowKidney perfusionIncreased renal plasma flowPlacebo-adjusted changeMultiple-ascending dosePhase 1 trialGlomerular filtration rateChronic heart failureChronic kidney diseaseDiastolic blood pressureRenal arteriolar resistanceExtended half-lifeCardiorenal functionDouble-blindPlacebo SCRelaxin proteinSC doseAdverse eventsMeasured GFRArteriolar resistanceClinical developmentHeart failureOrthostatic hypotension
2023
Sodium 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
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 useRenal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology
Mullens W, Martens P, Testani JM, Tang WHW, Skouri H, Verbrugge FH, Fudim M, Iacoviello M, Franke J, Flammer AJ, Palazzuoli A, Barragan PM, Thum T, Marcos MC, Miró Ò, Rossignol P, Metra M, Lassus J, Orso F, Jankowska EA, Chioncel O, Milicic D, Hill L, Seferovic P, Rosano G, Coats A, Damman K. Renal effects of guideline‐directed medical therapies in heart failure: a consensus document from the Heart Failure Association of the European Society of Cardiology. European Journal Of Heart Failure 2022, 24: 603-619. PMID: 35239201, DOI: 10.1002/ejhf.2471.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsChronic heart failureHeart failureRenal functionEjection fractionClinical practiceConsensus documentSodium-glucose cotransporter 2 inhibitorsGuideline-directed medical therapyReduced ejection fraction patientsEjection fraction patientsHeart Failure AssociationCotransporter 2 inhibitorsEuropean SocietyPharmacologic treatment optionsPoor renal functionDisease-modifying therapiesGood clinical practiceTreatment-induced changesDrug implementationHF drugsCardiology guidelinesESC guidelinesRenal effectsMedical therapyLifesaving therapy
2020
Pathophysiology 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 tubulesEvaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology
Mullens W, Damman K, Testani JM, Martens P, Mueller C, Lassus J, Tang WHW, Skouri H, Verbrugge FH, Orso F, Hill L, Ural D, Lainscak M, Rossignol P, Metra M, Mebazaa A, Seferovic P, Ruschitzka F, Coats A. Evaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology. European Journal Of Heart Failure 2020, 22: 584-603. PMID: 31908120, DOI: 10.1002/ejhf.1697.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGlomerular filtration rateHeart failureKidney functionFiltration rateRenal functionSerum creatinineAcute heart failure episodeGuideline-directed medical therapyImproved long-term outcomesCardio-renal dysfunctionCardio-renal interactionsAcute heart failureChronic heart failureHeart Failure AssociationHeart failure careHeart failure stateHeart failure episodesAppropriate clinical contextLong-term outcomesRenal function assessmentFurther treatment strategiesNeurohumoral blockersLoop diureticsMedical therapyWorse outcomes
2019
Chronic Heart Failure Is Infrequently Associated With Renal Dysfunction in Hypertrophic Cardiomyopathy
Rowin EJ, Romashko M, Testani JM, Koethe BC, Saxena D, Udelson JE, Maron BJ, Maron MS. Chronic Heart Failure Is Infrequently Associated With Renal Dysfunction in Hypertrophic Cardiomyopathy. Journal Of Cardiac Failure 2019, 25: 690-692. PMID: 31158468, DOI: 10.1016/j.cardfail.2019.05.012.Peer-Reviewed Original ResearchUrinary 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
Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure
Grodin JL, Mullens W, Dupont M, Taylor DO, McKie PM, Starling RC, Testani JM, Tang WHW. Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure. International Journal Of Cardiology 2018, 252: 112-116. PMID: 29249420, DOI: 10.1016/j.ijcard.2017.11.024.Peer-Reviewed Original ResearchConceptsPulmonary capillary wedge pressureAdvanced chronic heart failureFick cardiac indexPulmonary artery systolic pressureRight atrial pressureVentricular assist device placementHeart transplantHeart rateHeart failureSerum chlorideHigher cardiac filling pressuresPoor long-term outcomesSerum Cl levelsCapillary wedge pressureCardiac filling pressuresChronic heart failureAdvanced heart failureInvasive hemodynamic assessmentHeart failure patientsRisk of deathLong-term outcomesLower serum chlorideConventional clinical parametersBackward regression modelAssociation of hemodynamics
2016
Hypochloraemia is strongly and independently associated with mortality in patients with chronic heart failure
Testani JM, Hanberg JS, Arroyo JP, Brisco MA, Ter Maaten JM, Wilson FP, Bellumkonda L, Jacoby D, Tang WH, Parikh CR. Hypochloraemia is strongly and independently associated with mortality in patients with chronic heart failure. European Journal Of Heart Failure 2016, 18: 660-668. PMID: 26763893, PMCID: PMC5471359, DOI: 10.1002/ejhf.477.Peer-Reviewed Original ResearchConceptsChronic heart failureHeart failureSerum chlorideSerum sodiumLow serum sodiumHeart failure pathophysiologyGreater disease severityBEST trialDiuretic dosesSerum chloride valuesRenal functionWorsened survivalPrognostic importanceAdverse outcomesUnivariate analysisHyponatraemiaHypochloraemiaPatientsDisease severityMortalityAdditional researchFailureChloride valuesCritical roleSodiumImportance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure
Grodin JL, Verbrugge FH, Ellis SG, Mullens W, Testani JM, Tang WH. Importance of Abnormal Chloride Homeostasis in Stable Chronic Heart Failure. Circulation Heart Failure 2016, 9: e002453. PMID: 26721916, PMCID: PMC4702267, DOI: 10.1161/circheartfailure.115.002453.Peer-Reviewed Original ResearchMeSH KeywordsAgedBiomarkersChloridesChronic DiseaseCoronary AngiographyDown-RegulationFemaleHeart FailureHumansKaplan-Meier EstimateMaleMiddle AgedMultivariate AnalysisPrognosisProportional Hazards ModelsProspective StudiesRisk AssessmentRisk FactorsTime FactorsWater-Electrolyte BalanceWater-Electrolyte ImbalanceConceptsChronic heart failureStable chronic heart failureHeart failureLower serum chlorideSerum chlorideMortality riskElective diagnostic coronary angiographyLow serum chloride levelLong-term prognostic valueAdjusted mortality riskDiagnostic coronary angiographySerum chloride levelsAdjusted riskCause mortalityElectrolyte abnormalitiesCoronary angiographyStable patientsPrognostic implicationsPrognostic valueMultivariable modelChloride levelsSodium levelsPatientsChloride homeostasisMortality
2015
Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure
Grodin JL, Simon J, Hachamovitch R, Wu Y, Jackson G, Halkar M, Starling RC, Testani JM, Tang WH. Prognostic Role of Serum Chloride Levels in Acute Decompensated Heart Failure. Journal Of The American College Of Cardiology 2015, 66: 659-666. PMID: 26248993, DOI: 10.1016/j.jacc.2015.06.007.Peer-Reviewed Original ResearchConceptsAcute decompensated heart failureSerum chloride levelsDecompensated heart failureSerum sodium levelsHeart failureSodium levelsADHF cohortMultivariable risk-adjusted analysisMultivariable risk adjustmentChronic heart failureLong-term mortalityRisk-adjusted analysisChloride levelsElectrolyte abnormalitiesConsecutive patientsPrognostic roleSerum sodiumPrognostic significancePrognostic valueValidation cohortCleveland ClinicClinical significanceRisk adjustmentCohortMortality
2013
Potential Effects of Digoxin on Long-Term Renal and Clinical Outcomes in Chronic Heart Failure
Testani JM, Brisco MA, Tang WH, Kimmel SE, Tiku-Owens A, Forfia PR, Coca SG. Potential Effects of Digoxin on Long-Term Renal and Clinical Outcomes in Chronic Heart Failure. Journal Of Cardiac Failure 2013, 19: 295-302. PMID: 23663810, PMCID: PMC3694335, DOI: 10.1016/j.cardfail.2013.03.002.Peer-Reviewed Original ResearchConceptsDigitalis Investigation GroupRenal dysfunctionHeart failureClinical outcomesFavorable renal responseHospitalization-free survivalLong-Term RenalChronic heart failureSerum creatinine levelsGlomerular filtration rateHypothesis-generating findingsLong-term improvementDIG trialCreatinine levelsRenal functionKidney functionRenal responseFiltration rateDigitalis glycosidesPatientsDigoxinHospitalizationDeathAdditional researchInvestigation group
2011
Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure
Testani JM, Cappola TP, Brensinger CM, Shannon RP, Kimmel SE. Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure. Journal Of The American College Of Cardiology 2011, 58: 375-382. PMID: 21757114, PMCID: PMC3980479, DOI: 10.1016/j.jacc.2011.01.052.Peer-Reviewed Original ResearchConceptsHigh-dose loop diureticsBlood urea nitrogenLoop diureticsBUN levelsNeurohormonal activationBaseline characteristicsHeart failureNormal BUN levelChronic heart failureRisk of deathBlood urea nitrogen concentrationElevated BUN levelsCongestive symptomsOverall cohortWorsened survivalImproved survivalPrimary outcomeAdverse outcomesUrea nitrogen concentrationDiureticsUrea nitrogenBUN concentrationPatientsMortalitySurvival