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 severityElectronic health record alerts for acute kidney injury: multicenter, randomized clinical trial
Wilson FP, Martin M, Yamamoto Y, Partridge C, Moreira E, Arora T, Biswas A, Feldman H, Garg AX, Greenberg JH, Hinchcliff M, Latham S, Li F, Lin H, Mansour SG, Moledina DG, Palevsky PM, Parikh CR, Simonov M, Testani J, Ugwuowo U. Electronic health record alerts for acute kidney injury: multicenter, randomized clinical trial. The BMJ 2021, 372: m4786. PMID: 33461986, PMCID: PMC8034420, DOI: 10.1136/bmj.m4786.Peer-Reviewed Original ResearchConceptsAcute kidney injuryElectronic health record alertsKidney injuryPrimary outcomeMedical recordsYale New Haven Health SystemCare practicesGlobal Outcomes creatinine criteriaLarge tertiary care centerComposite of progressionDays of randomizationReceipt of dialysisPrespecified secondary outcomesTertiary care centerPatients' medical recordsSmall community hospitalNon-teaching hospitalsElectronic health recordsCreatinine criteriaUsual careSecondary outcomesAdult inpatientsKidney diseaseClinical centersWorse outcomes
2020
Racial 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-proBNPReal-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept
Ugwuowo U, Yamamoto Y, Arora T, Saran I, Partridge C, Biswas A, Martin M, Moledina DG, Greenberg JH, Simonov M, Mansour SG, Vela R, Testani JM, Rao V, Rentfro K, Obeid W, Parikh CR, Wilson FP. Real-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept. American Journal Of Kidney Diseases 2020, 76: 806-814.e1. PMID: 32505812, PMCID: PMC8667815, DOI: 10.1053/j.ajkd.2020.05.003.Peer-Reviewed Original ResearchConceptsAKI alertsHospitalized adultsKidney injuryUrban tertiary care hospitalAcute kidney injurySerum creatinine levelsObservational cohort studyTertiary care hospitalSerum creatinine concentrationBeats/minElectronic health recordsAKI diagnosisCohort studyCreatinine levelsInpatient mortalitySystolic bloodFractional excretionCenter studyBlood biomarkersUnivariable associationsUrine microscopyCreatinine concentrationClinical careElevated riskUrea nitrogen
2019
Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction
Reddy YNV, Obokata M, Testani JM, Felker GM, Tang WHW, Abou-Ezzeddine OF, Sun JL, Chakrabothy H, McNulty S, Shah SJ, Lewis GD, Stevenson LW, Redfield MM, Borlaug BA. Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Journal Of Cardiac Failure 2019, 26: 101-107. PMID: 31618698, PMCID: PMC7036022, DOI: 10.1016/j.cardfail.2019.09.015.Peer-Reviewed Original ResearchConceptsRenal functionNonobese patientsHeart failureObese HFpEFObese patientsEjection fractionRenal responseAdverse renal responsesRight ventricular remodelingGlomerular filtration rateBody mass indexPlasma volume expansionSimilar weight lossCardiorenal hemodynamicsRenal dysfunctionPathophysiologic featuresMass indexAtrial fibrillationDecongestive therapyVentricular remodelingPericardial restraintFiltration rateHFpEFObese phenotypeSevere worseningA simple real-time model for predicting acute kidney injury in hospitalized patients in the US: A descriptive modeling study
Simonov M, Ugwuowo U, Moreira E, Yamamoto Y, Biswas A, Martin M, Testani J, Wilson FP. A simple real-time model for predicting acute kidney injury in hospitalized patients in the US: A descriptive modeling study. PLOS Medicine 2019, 16: e1002861. PMID: 31306408, PMCID: PMC6629054, DOI: 10.1371/journal.pmed.1002861.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAged, 80 and overConnecticutDecision Support TechniquesElectronic Health RecordsFemaleHospital MortalityHumansInpatientsMaleMiddle AgedPatient AdmissionPredictive Value of TestsPrognosisRenal DialysisRetrospective StudiesRisk AssessmentRisk FactorsSeverity of Illness IndexTime FactorsConceptsAcute kidney injuryImminent acute kidney injuryElectronic health recordsKidney injuryHospital 1Prediction of AKIRenal replacement therapyOptimal treatment strategyLaboratory dataReceiver operator characteristic curveInternal validation setAKI occurrenceAKI severityHospitalized adultsMedical comorbiditiesOverall cohortAdverse eventsHospitalized patientsSurgical wardsSignificant morbidityReplacement therapyExternal validation data setsHospital 2Hospital 3Study hospitalRenal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function
Rao VS, Ahmad T, Brisco-Bacik MA, Bonventre JV, Wilson FP, Siew ED, Felker GM, Anstrom KK, Mahoney DD, Bart BA, Tang WHW, Velazquez EJ, Testani JM. Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function. Circulation Heart Failure 2019, 12: e005552. PMID: 31163974, PMCID: PMC6585463, DOI: 10.1161/circheartfailure.118.005552.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overBiomarkersCreatinineFemaleHeart FailureHumansKidneyLipocalin-2MaleMiddle AgedProspective StudiesConceptsRenal tubular injury biomarkersTubular injury biomarkersHeart failure patientsAcute decompensated heart failure patientsDecompensated heart failure patientsTubular injury markersInjury biomarkersFailure patientsRenal functionInjury markersAcute decompensated heart failureVolume removalCARRESS-HF trialRenal function recoveryDecompensated heart failureRenal tubular injuryRenal effectsSerum creatinineTubular injuryBiomarker substudyHeart failurePharmacological therapyClinical outcomesFunction recoveryHigh incidenceAge associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients
Jain K, Tyagi T, Patell K, Xie Y, Kadado AJ, Lee SH, Yarovinsky T, Du J, Hwang J, Martin KA, Testani J, Ionescu CN, Hwa J. Age associated non-linear regulation of redox homeostasis in the anucleate platelet: Implications for CVD risk patients. EBioMedicine 2019, 44: 28-40. PMID: 31130473, PMCID: PMC6604369, DOI: 10.1016/j.ebiom.2019.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAge FactorsAgedAged, 80 and overAgingAnimalsAntioxidantsApoptosisBiomarkersBlood PlateletsCardiovascular DiseasesComorbidityDisease Models, AnimalFemaleHomeostasisHumansMaleMiceMiddle AgedOxidation-ReductionOxidative StressPlatelet ActivationPlatelet AdhesivenessReactive Oxygen SpeciesRisk AssessmentRisk FactorsConceptsRisk patientsMouse studiesPlatelet phenotypeMajor adverse cardiovascular eventsHigh cardiovascular risk patientsAdaptive increaseAdverse cardiovascular eventsCentral pathophysiological roleCVD risk patientsCardiovascular risk patientsAggressive antiplatelet therapyEffect of comorbidityAge group 40Young healthy subjectsAntiplatelet therapyCardiovascular eventsYear age cohortAdvanced ageCVD patientsGroup 40Healthy subjectsPathophysiological roleElderly populationCardiovascular pathologyPatientsNatriuretic 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 interactionsSerum 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 output
2018
The prognostic role of different renal function phenotypes in patients with acute heart failure
Palazzuoli A, Ruocco G, Pellicori P, Incampo E, Di Tommaso C, Favilli R, Evangelista I, Nuti R, Testani JM. The prognostic role of different renal function phenotypes in patients with acute heart failure. International Journal Of Cardiology 2018, 276: 198-203. PMID: 30503187, DOI: 10.1016/j.ijcard.2018.11.108.Peer-Reviewed Original ResearchConceptsAcute heart failureBUN increaseHeart failureIndependent predictorsPrognostic roleAdverse outcomesGlomerular filtration rate reductionBlood nitrogen ureaSigns of HFRenal function deteriorationBUN changeClinical congestionEffective decongestionFunction deteriorationRenal functionSerum creatininePoor outcomePrognostic relevanceComplete resolutionClinical signsPatientsNitrogen ureaHospitalizationBUNOutcomesPerturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT
Grodin JL, Testani JM, Pandey A, Sambandam K, Drazner MH, Fang JC, Tang WHW. Perturbations in serum chloride homeostasis in heart failure with preserved ejection fraction: insights from TOPCAT. European Journal Of Heart Failure 2018, 20: 1436-1443. PMID: 29893446, DOI: 10.1002/ejhf.1229.Peer-Reviewed Original ResearchConceptsSerum chloride levelsLoop diuretic useHeart failureSerum chlorideCause deathDiuretic useEjection fractionMultivariable Cox proportional hazards modelsCardiac Function Heart FailureCox proportional hazards modelAldosterone Antagonist TrialHeart failure hospitalizationPrimary composite endpointLower serum chlorideProportional hazards modelSerum chloride concentrationChloride levelsSpironolactone useCardiovascular deathFailure hospitalizationMultivariable adjustmentComposite endpointLoop diureticsClinical outcomesHazards modelWorsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury
Ahmad T, Jackson K, Rao VS, Tang WHW, Brisco-Bacik MA, Chen HH, Felker GM, Hernandez AF, O'Connor CM, Sabbisetti VS, Bonventre JV, Wilson FP, Coca SG, Testani JM. Worsening Renal Function in Patients With Acute Heart Failure Undergoing Aggressive Diuresis Is Not Associated With Tubular Injury. Circulation 2018, 137: 2016-2028. PMID: 29352071, PMCID: PMC6066176, DOI: 10.1161/circulationaha.117.030112.Peer-Reviewed Original ResearchMeSH KeywordsAcetylglucosaminidaseAcute DiseaseAcute Kidney InjuryAgedAged, 80 and overBiomarkersCreatinineCystatin CDiuresisFemaleGlomerular Filtration RateHeart FailureHepatitis A Virus Cellular Receptor 1HumansKidneyLipocalin-2MaleMiddle AgedSodium Potassium Chloride Symporter InhibitorsTime FactorsTreatment OutcomeUnited StatesConceptsKidney injury molecule-1Neutrophil gelatinase-associated lipocalinInjury molecule-1Acute heart failureGelatinase-associated lipocalinRenal tubular injuryTubular injury biomarkersAggressive diuresisROSE-AHF trialsTubular injuryInjury biomarkersRenal functionHeart failureMolecule-1D-glucosaminidaseHigh-dose loop diuretic therapyAcute heart failure treatmentKidney tubular injuryLoop diuretic therapyAcute kidney injuryGlomerular filtration rateHeart failure treatmentDiuretic therapyFurosemide equivalentsKidney injury
2017
An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial
Hanberg JS, Tang WH, Wilson FP, Coca SG, Ahmad T, Brisco MA, Testani JM. An exploratory analysis of the competing effects of aggressive decongestion and high-dose loop diuretic therapy in the DOSE trial. International Journal Of Cardiology 2017, 241: 277-282. PMID: 28392080, PMCID: PMC5471358, DOI: 10.1016/j.ijcard.2017.03.114.Peer-Reviewed Original ResearchConceptsHigh-dose loop diureticsDiuretic doseAggressive decongestionDose trialFluid outputLoop diureticsHigh-dose loop diuretic therapyDose-related adverse effectsAdverse effectsLoop diuretic doseLoop diuretic therapyHeart failure patientsNet fluid balanceNet fluid outputRate of deathEmergency department (ED) visitationPotential beneficial effectsHypothesis-generating observationsEffective decongestionDiuretic therapyFailure patientsAdverse outcomesDecongestive effectImproved outcomesFluid balance
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 implicationsDifferent diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance
Palazzuoli A, Testani JM, Ruocco G, Pellegrini M, Ronco C, Nuti R. Different diuretic dose and response in acute decompensated heart failure: Clinical characteristics and prognostic significance. International Journal Of Cardiology 2016, 224: 213-219. PMID: 27657476, DOI: 10.1016/j.ijcard.2016.09.005.Peer-Reviewed Original ResearchConceptsLower diuretic efficiencyChronic kidney diseaseDiuretic efficiencyAdverse eventsDose administrationAcute decompensated heart failureDecompensated heart failureAdverse event ratesDiuretic doseWRF occurrenceRenal dysfunctionClinical characteristicsRenal functionHeart failureHD patientsMultivariable analysisClinical statusPrognostic significanceAdverse outcomesContinuous administrationKidney diseaseDE patientsLD patientsBest modalityPatientsHypochloremia 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 sodiumHypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure
Ter Maaten JM, Damman K, Hanberg JS, Givertz MM, Metra M, O'Connor CM, Teerlink JR, Ponikowski P, Cotter G, Davison B, Cleland JG, Bloomfield DM, Hillege HL, van Veldhuisen DJ, Voors AA, Testani JM. Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart Failure. Circulation Heart Failure 2016, 9: e003109. PMID: 27507112, DOI: 10.1161/circheartfailure.116.003109.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAged, 80 and overBiomarkersChloridesDisease ProgressionDiureticsDown-RegulationDrug ResistanceFemaleHeart FailureHospitalizationHumansKaplan-Meier EstimateLinear ModelsMaleMiddle AgedMultivariate AnalysisProportional Hazards ModelsRisk FactorsTime FactorsTreatment OutcomeXanthinesConceptsAcute heart failureMEq/L.Heart failureDay 14Serum chloridePoor diuretic responseHours of admissionLower serum chlorideBlood urea nitrogenSerum chloride levelsAHF therapiesDiuretic resistancePROTECT trialNeurohormonal activationMultivariable adjustmentRenal functionHospital admissionMultivariable analysisDiuretic responseDiuretic responsivenessDiuretic targetChloride levelsUrea nitrogenHypochloremiaChloride homeostasis
2015
Perioperative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery
Schaub JA, Garg AX, Coca SG, Testani JM, Shlipak MG, Eikelboom J, Kavsak P, McArthur E, Shortt C, Whitlock R, Parikh CR. Perioperative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery. Kidney International 2015, 88: 576-583. PMID: 25830762, PMCID: PMC4556547, DOI: 10.1038/ki.2015.104.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAgedAged, 80 and overBiomarkersCardiac Surgical ProceduresChi-Square DistributionFatty Acid Binding Protein 3Fatty Acid-Binding ProteinsFemaleHumansLogistic ModelsMaleMiddle AgedMultivariate AnalysisNorth AmericaOdds RatioPerioperative PeriodProportional Hazards ModelsProspective StudiesRisk AssessmentRisk FactorsSeverity of Illness IndexUp-RegulationConceptsAcute kidney injurySevere acute kidney injuryCardiac surgeryKidney injuryKidney injury molecule-1Neutrophil gelatinase-associated lipocalinHeart-type fatty acid binding proteinAKI risk factorsInjury molecule-1Long-term mortalityBrain natriuretic peptideGelatinase-associated lipocalinH-FABP levelsMulti-center cohortTRIBE-AKI cohortFatty acid binding proteinLiver fatty acidHeart fatty acidCommon complicationSecondary outcomesSerum creatininePrimary outcomeInterleukin-18Risk stratificationCardiac injury