2025
Computational Phenomapping of Randomized Clinical Trial Participants to Enable Assessment of Their Real-World Representativeness and Personalized Inference
Thangaraj P, Oikonomou E, Dhingra L, Aminorroaya A, Jayaram R, Suchard M, Khera R. Computational Phenomapping of Randomized Clinical Trial Participants to Enable Assessment of Their Real-World Representativeness and Personalized Inference. Circulation Cardiovascular Quality And Outcomes 2025, 18: e011306. PMID: 40261065, PMCID: PMC12203226, DOI: 10.1161/circoutcomes.124.011306.Peer-Reviewed Original ResearchConceptsElectronic health record patientElectronic health recordsDistance metricRandomized clinical trialsElectronic health record dataMachine learning methodsYale New Haven Health SystemElectronic health record cohortRandomized clinical trial participantsLearning methodsHeart failureClinical trial participationTOPCAT participantsReal worldMultidimensional metricRCT participantsHealth recordsTreatment effectsHealth systemCharacteristics of patientsRandomized clinical trial cohortsTrial participantsMetricsUnited StatesNovel statisticEnsemble Deep Learning Algorithm for Structural Heart Disease Screening Using Electrocardiographic Images PRESENT SHD
Dhingra L, Aminorroaya A, Sangha V, Pedroso A, Shankar S, Coppi A, Foppa M, Brant L, Barreto S, Ribeiro A, Krumholz H, Oikonomou E, Khera R. Ensemble Deep Learning Algorithm for Structural Heart Disease Screening Using Electrocardiographic Images PRESENT SHD. Journal Of The American College Of Cardiology 2025, 85: 1302-1313. PMID: 40139886, PMCID: PMC12199746, DOI: 10.1016/j.jacc.2025.01.030.Peer-Reviewed Original ResearchConceptsStructural heart diseaseYale-New Haven HospitalTransthoracic echocardiogramRisk stratificationHeart failureLeft-sided valvular diseaseSevere left ventricular hypertrophyLeft ventricular ejection fractionReceiver-operating characteristic curveVentricular ejection fractionLeft ventricular hypertrophyHeart disease screeningELSA-BrasilEnsemble deep learning algorithmRisk of deathConvolutional neural network modelEjection fractionEnsemble deep learning approachVentricular hypertrophyDeep learning algorithmsNew Haven HospitalDeep learning approachValvular diseaseNeural network modelClinical cohortUso da Inteligência Artificial Aplicada ao Eletrocardiograma para Diagnóstico de Disfunção Sistólica Ventricular Esquerda
de Santana W, Pinto M, Barreto S, Foppa M, Giatti L, Khera R, Ribeiro A. Uso da Inteligência Artificial Aplicada ao Eletrocardiograma para Diagnóstico de Disfunção Sistólica Ventricular Esquerda. Arquivos Brasileiros De Cardiologia 2025, 122: e20240740. PMID: 40396866, PMCID: PMC12108124, DOI: 10.36660/abc.20240740.Peer-Reviewed Original ResearchConceptsLeft ventricular systolic dysfunctionLeft ventricular ejection fractionNegative predictive valueDiagnostic odds ratioPositive predictive valueHeart failureDetect left-ventricular systolic dysfunctionPredictive valueVentricular systolic dysfunctionVentricular ejection fractionNegative likelihood ratioPositive likelihood ratioDiagnostic accuracy cross-sectional studyLikelihood ratioCross-sectional studySystolic dysfunctionEjection fractionEvaluating HFAUC-ROCElectrocardiographic alterationsOdds ratioEchocardiogramROC curveScreening toolElectrocardiogramEffects of Tirzepatide in Type 2 Diabetes Individual Variation and Relationship to Cardiometabolic Outcomes
Aminorroaya A, Oikonomou E, Biswas D, Jastreboff A, Khera R. Effects of Tirzepatide in Type 2 Diabetes Individual Variation and Relationship to Cardiometabolic Outcomes. Journal Of The American College Of Cardiology 2025, 85: 1858-1872. PMID: 40368575, PMCID: PMC12186526, DOI: 10.1016/j.jacc.2025.03.516.Peer-Reviewed Original ResearchConceptsElevated body mass indexCardiometabolic abnormalitiesBody mass indexOdds of elevated body mass indexType 2 diabetesIndividual participant data meta-analysisMass indexParticipant data meta-analysisOdds of MetSCardiometabolic risk factorsComponents of metabolic syndromeData meta-analysisHigh-density lipoprotein cholesterolCardiometabolic healthStudy design differencesMixed-effects modelsBaseline usePhase 3 randomized clinical trialSodium-glucose cotransporter 2 inhibitorsOddsStudy outcomesEffects of tirzepatideMeta-analysisRisk factorsClinical subpopulationsArtificial intelligence-guided detection of under-recognised cardiomyopathies on point-of-care cardiac ultrasonography: a multicentre study
Oikonomou E, Vaid A, Holste G, Coppi A, McNamara R, Baloescu C, Krumholz H, Wang Z, Apakama D, Nadkarni G, Khera R. Artificial intelligence-guided detection of under-recognised cardiomyopathies on point-of-care cardiac ultrasonography: a multicentre study. The Lancet Digital Health 2025, 7: e113-e123. PMID: 39890242, PMCID: PMC12084816, DOI: 10.1016/s2589-7500(24)00249-8.Peer-Reviewed Original ResearchConceptsYale New Haven Health SystemPoint-of-care ultrasonographyMount Sinai Health SystemTransthyretin amyloid cardiomyopathyArtificial intelligenceHealth systemAmyloid cardiomyopathyHypertrophic cardiomyopathyRetrospective cohort of individualsCardiomyopathy casesTesting artificial intelligenceConvolutional neural networkSinai Health SystemCohort of individualsOpportunistic screeningHypertrophic cardiomyopathy casesMulti-labelPositive screenAI frameworkEmergency departmentMortality riskNeural networkLoss functionCardiac ultrasonographyAugmentation approachEvaluation of a Machine Learning-Guided Strategy for Elevated Lipoprotein(a) Screening in Health Systems
Aminorroaya A, Dhingra L, Oikonomou E, Khera R. Evaluation of a Machine Learning-Guided Strategy for Elevated Lipoprotein(a) Screening in Health Systems. Circulation Genomic And Precision Medicine 2025, 18: e004632. PMID: 39846171, PMCID: PMC11835527, DOI: 10.1161/circgen.124.004632.Peer-Reviewed Original ResearchConceptsYale New Haven Health SystemHealth systemVanderbilt University Medical CenterHealth system electronic health recordUniversity Medical CenterCoronary Artery Risk DevelopmentMulti-Ethnic Study of AtherosclerosisElectronic health recordsMedical CenterUS health systemHealth system patientsAssociated with significantly higher oddsMulti-Ethnic StudyUS-based cohortStudy of AtherosclerosisSignificantly higher oddsHealth recordsUK BiobankAtherosclerosis RiskRisk DevelopmentHigher oddsElevated Lp(aUniversal screeningSystem patientsStudy cohort
2024
Impact of the COVID-19 pandemic on hospital-based heart failure care in New South Wales, Australia: a linked data cohort study
McIntyre D, Quintans D, Kazi S, Min H, He W, Marschner S, Khera R, Nassar N, Chow C. Impact of the COVID-19 pandemic on hospital-based heart failure care in New South Wales, Australia: a linked data cohort study. BMC Health Services Research 2024, 24: 1364. PMID: 39516863, PMCID: PMC11545568, DOI: 10.1186/s12913-024-11840-0.Peer-Reviewed Original ResearchConceptsHeart failure careNew South WalesHospital admissionHealth service utilisationAdministrative health recordsPrimary diagnosis of heart failureData cohort studyRate of admissionPre-pandemicHealth of patientsSouth WalesCOVID-19 pandemicHospital utilisationService utilisationHealth recordsED presentationsMortality dataDiagnosis of heart failureCOVID-19 burdenEmergency departmentCohort studyPrimary diagnosisData collectionCareAustralian dataNatural Language Processing of Clinical Documentation to Assess Functional Status in Patients With Heart Failure
Adejumo P, Thangaraj P, Dhingra L, Aminorroaya A, Zhou X, Brandt C, Xu H, Krumholz H, Khera R. Natural Language Processing of Clinical Documentation to Assess Functional Status in Patients With Heart Failure. JAMA Network Open 2024, 7: e2443925. PMID: 39509128, PMCID: PMC11544492, DOI: 10.1001/jamanetworkopen.2024.43925.Peer-Reviewed Original ResearchConceptsFunctional status assessmentArea under the receiver operating characteristic curveClinical documentationElectronic health record dataHF symptomsOptimal care deliveryHealth record dataAssess functional statusStatus assessmentClinical trial participationProcessing of clinical documentsFunctional status groupCare deliveryOutpatient careMain OutcomesMedical notesTrial participantsNew York Heart AssociationFunctional statusQuality improvementRecord dataHeart failureClinical notesDiagnostic studiesStatus groupsRacial and Ethnic Disparities in Age-Specific All-Cause Mortality During the COVID-19 Pandemic
Faust J, Renton B, Bongiovanni T, Chen A, Sheares K, Du C, Essien U, Fuentes-Afflick E, Haywood T, Khera R, King T, Li S, Lin Z, Lu Y, Marshall A, Ndumele C, Opara I, Loarte-Rodriguez T, Sawano M, Taparra K, Taylor H, Watson K, Yancy C, Krumholz H. Racial and Ethnic Disparities in Age-Specific All-Cause Mortality During the COVID-19 Pandemic. JAMA Network Open 2024, 7: e2438918. PMID: 39392630, PMCID: PMC11581672, DOI: 10.1001/jamanetworkopen.2024.38918.Peer-Reviewed Original ResearchConceptsCOVID-19 public health emergencyNon-HispanicPublic health emergencyOther Pacific IslanderExcess mortalityAlaska NativesUS populationExcess deathsRates of excess mortalityCross-sectional study analyzed dataYears of potential lifeMortality relative riskNon-Hispanic whitesCross-sectional studyPacific IslandersStudy analyzed dataAll-cause mortalityEthnic groupsMortality disparitiesMortality ratioTotal populationDeath certificatesEthnic disparitiesMain OutcomesDecedent ageCause-Specific Mortality Rates Among the US Black Population
Arun A, Caraballo C, Sawano M, Lu Y, Khera R, Yancy C, Krumholz H. Cause-Specific Mortality Rates Among the US Black Population. JAMA Network Open 2024, 7: e2436402. PMID: 39348122, PMCID: PMC11443349, DOI: 10.1001/jamanetworkopen.2024.36402.Commentaries, Editorials and LettersComparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes A Multinational, Federated Analysis of LEGEND-T2DM
Khera R, Aminorroaya A, Dhingra L, Thangaraj P, Pedroso Camargos A, Bu F, Ding X, Nishimura A, Anand T, Arshad F, Blacketer C, Chai Y, Chattopadhyay S, Cook M, Dorr D, Duarte-Salles T, DuVall S, Falconer T, French T, Hanchrow E, Kaur G, Lau W, Li J, Li K, Liu Y, Lu Y, Man K, Matheny M, Mathioudakis N, McLeggon J, McLemore M, Minty E, Morales D, Nagy P, Ostropolets A, Pistillo A, Phan T, Pratt N, Reyes C, Richter L, Ross J, Ruan E, Seager S, Simon K, Viernes B, Yang J, Yin C, You S, Zhou J, Ryan P, Schuemie M, Krumholz H, Hripcsak G, Suchard M. Comparative Effectiveness of Second-Line Antihyperglycemic Agents for Cardiovascular Outcomes A Multinational, Federated Analysis of LEGEND-T2DM. Journal Of The American College Of Cardiology 2024, 84: 904-917. PMID: 39197980, PMCID: PMC12045554, DOI: 10.1016/j.jacc.2024.05.069.Peer-Reviewed Original ResearchConceptsGLP-1 RAsSecond-line agentsGLP-1Antihyperglycemic agentsCardiovascular diseaseMACE riskGlucagon-like peptide-1 receptor agonistsSodium-glucose cotransporter 2 inhibitorsPeptide-1 receptor agonistsDipeptidyl peptidase-4 inhibitorsEffects of SGLT2isType 2 diabetes mellitusPeptidase-4 inhibitorsAdverse cardiovascular eventsCox proportional hazards modelsRandom-effects meta-analysisCardiovascular risk reductionTarget trial emulationProportional hazards modelPerformance of contemporary cardiovascular risk stratification scores in Brazil: an evaluation in the ELSA-Brasil study
Camargos A, Barreto S, Brant L, Ribeiro A, Dhingra L, Aminorroaya A, Bittencourt M, Figueiredo R, Khera R. Performance of contemporary cardiovascular risk stratification scores in Brazil: an evaluation in the ELSA-Brasil study. Open Heart 2024, 11: e002762. PMID: 38862252, PMCID: PMC11168182, DOI: 10.1136/openhrt-2024-002762.Peer-Reviewed Original ResearchConceptsPooled Cohort EquationsELSA-BrasilRisk scoreCardiovascular diseaseCVD eventsCommunity-based cohort studyArea under the receiver operating characteristic curveCVD risk scoreELSA-Brasil studyIncident CVD eventsMiddle-income countriesAdjudicated CVD eventsCardiovascular disease riskCVD scoreCohort EquationsNational guidelinesRisk stratification scoresWhite womenAge/sex groupsCohort studyProspective cohortLMICsSex/race groupsHigher incomeRisk discrimination
2023
Persistence on Novel Cardioprotective Antihyperglycemic Therapies in the United States
Nargesi A, Clark C, Aminorroaya A, Chen L, Liu M, Reddy A, Amodeo S, Oikonomou E, Suchard M, McGuire D, Lin Z, Inzucchi S, Khera R. Persistence on Novel Cardioprotective Antihyperglycemic Therapies in the United States. The American Journal Of Cardiology 2023, 196: 89-98. PMID: 37012183, PMCID: PMC11007258, DOI: 10.1016/j.amjcard.2023.03.002.Peer-Reviewed Original ResearchConceptsSGLT-2iGLP-1RAsGlucagon-like peptide-1 receptor agonistsUnited States administrative claims databasesSodium-glucose cotransporter 2 inhibitorsCommercial insurancePeptide-1 receptor agonistsType 2 diabetes mellitusSodium-glucose cotransporter-2 inhibitorsConsistent medication useHealth outcome benefitsCotransporter 2 inhibitorsElevated cardiovascular riskInitiation of therapyAdministrative claims databaseProportion of daysCotransporter-2 inhibitorsRate of prescriptionAntihyperglycemic therapyCardiovascular riskDiabetes mellitusMedication useCardioprotective effectsPrescription practicesClaims databaseVariation in hospital use of cardiac resynchronization therapy-defibrillator among eligible patients and association with clinical outcomes
Chui P, Lan Z, Freeman J, Enriquez A, Khera R, Akar J, Masoudi F, Ong E, Curtis J. Variation in hospital use of cardiac resynchronization therapy-defibrillator among eligible patients and association with clinical outcomes. Heart Rhythm 2023, 20: 1000-1008. PMID: 36963741, DOI: 10.1016/j.hrthm.2023.03.022.Peer-Reviewed Original ResearchConceptsEligible patientsICD RegistryCardiac resynchronizationNational Cardiovascular Data Registry ICD RegistryCRT-D implantationCRT-D useHospital-level outcomesStrong guideline recommendationsHospital-level variationPatient-level outcomesIntraclass correlation coefficientQuality improvement effortsHospital mortalityGuideline indicationsReadmission ratesSelect patientsClinical outcomesGuideline recommendationsHospital variationHospital ratesUse of CRTHospital levelHospital usePatientsCase mix
2022
Individualising intensive systolic blood pressure reduction in hypertension using computational trial phenomaps and machine learning: a post-hoc analysis of randomised clinical trials
Oikonomou EK, Spatz ES, Suchard MA, Khera R. Individualising intensive systolic blood pressure reduction in hypertension using computational trial phenomaps and machine learning: a post-hoc analysis of randomised clinical trials. The Lancet Digital Health 2022, 4: e796-e805. PMID: 36307193, PMCID: PMC9768739, DOI: 10.1016/s2589-7500(22)00170-4.Peer-Reviewed Original ResearchConceptsSystolic blood pressure controlBlood pressure controlIntensive systolic blood pressure controlType 2 diabetesPressure controlCardiovascular benefitsClinical trialsMajor adverse cardiovascular eventsFirst major adverse cardiovascular eventLarge randomised clinical trialsACCORD-BP trialAdverse cardiovascular eventsRandomised clinical trialsSystolic blood pressureCox regression analysisTreatment effectsHazard ratio estimatesACCORD-BPBP trialCardiovascular eventsBlood pressurePrimary outcomeStandard treatmentBaseline variablesIndex patientsSubjective Financial Hardship due to Medical Bills Among Patients With Heart Failure in the United States: The 2014–2018 Medical Expenditure Panel Survey
Ali HR, Valero-Elizondo J, Wang SY, Cainzos-Achirica M, Bhimaraj A, Khan SU, Khan MS, Mossialos E, Khera R, Nasir K. Subjective Financial Hardship due to Medical Bills Among Patients With Heart Failure in the United States: The 2014–2018 Medical Expenditure Panel Survey. Journal Of Cardiac Failure 2022, 28: 1424-1433. PMID: 35839928, DOI: 10.1016/j.cardfail.2022.06.009.Peer-Reviewed Original ResearchMeasures of Financial Hardship From Health Care Expenses Among Families With a Member With Atherosclerotic Cardiovascular Disease in the US
Wang SY, Valero-Elizondo J, Cainzos-Achirica M, Desai NR, Nasir K, Khera R. Measures of Financial Hardship From Health Care Expenses Among Families With a Member With Atherosclerotic Cardiovascular Disease in the US. JAMA Health Forum 2022, 3: e221962. PMID: 35977226, PMCID: PMC9308060, DOI: 10.1001/jamahealthforum.2022.1962.Peer-Reviewed Original ResearchConceptsFinancial hardshipFinancial burdenPocket medical expensesMedical Expenditure Panel SurveyHealth care expensesHigher incomePanel SurveyHealth careCare expensesFinancial consequencesHealth care costsForgone carePublic insuranceMedical billsSubstantial financial burdenMedical expensesIncomeDisparate measuresHardshipCare costsRepresentative surveySubjective measuresComprehensive frameworkExpenseInsuranceCost-Related Medication Nonadherence in Adults With Diabetes in the United States: The National Health Interview Survey 2013-2018.
Taha MB, Valero-Elizondo J, Yahya T, Caraballo C, Khera R, Patel KV, Ali HJR, Sharma G, Mossialos E, Cainzos-Achirica M, Nasir K. Cost-Related Medication Nonadherence in Adults With Diabetes in the United States: The National Health Interview Survey 2013-2018. Diabetes Care 2022, 45: 594-603. PMID: 35015860, DOI: 10.2337/dc21-1757.Peer-Reviewed Original ResearchConceptsCost-related medication nonadherenceNational Health Interview SurveyLack of insuranceMedication nonadherenceNational Health Interview Survey 2013Duration of diabetesHigher comorbidity burdenSelf-reported diabetesHealth Interview SurveyWorse health outcomesHealth-related expendituresComorbidity burdenInsulin useCurrent smokingLess medicationMedication adherenceFemale sexWeighted prevalenceHigher oddsAge subgroupsSkipping dosesDiabetesHealth outcomesElderly adultsNHIS participants
2021
Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States
Sangha V, Lipska K, Lin Z, Inzucchi SE, McGuire DK, Krumholz HM, Khera R. Patterns of Prescribing Sodium-Glucose Cotransporter-2 Inhibitors for Medicare Beneficiaries in the United States. Circulation Cardiovascular Quality And Outcomes 2021, 14: e008381. PMID: 34779654, PMCID: PMC9022137, DOI: 10.1161/circoutcomes.121.008381.Peer-Reviewed Original ResearchConceptsType 2 diabetesMedicare beneficiariesSodium-glucose cotransporter 2 inhibitorsLarge randomized clinical trialsMedicare Part D prescriber dataChronic kidney diseaseCotransporter 2 inhibitorsAtherosclerotic cardiovascular diseasePercent of cliniciansRandomized clinical trialsUS Medicare beneficiariesAdvanced practice providersCross-sectional studyKidney outcomesSGLT2i useSulfonylurea prescriptionUnique cliniciansCardiovascular deathMedication classesKidney diseaseLabel indicationsClinical trialsSGLT2iCardiovascular diseasePractice providersNonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries
Fudim M, Zhong L, Patel KV, Khera R, Abdelmalek MF, Diehl AM, McGarrah RW, Molinger J, Moylan CA, Rao VN, Wegermann K, Neeland IJ, Halm EA, Das SR, Pandey A. Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries. Journal Of The American Heart Association 2021, 10: e021654. PMID: 34755544, PMCID: PMC8751938, DOI: 10.1161/jaha.121.021654.Peer-Reviewed Original ResearchConceptsNonalcoholic fatty liver diseaseIncident heart failureReduced ejection fractionFatty liver diseaseHeart failureEjection fractionMedicare beneficiariesHF subtypesLiver diseaseHigh riskBackground Nonalcoholic fatty liver diseaseBaseline NAFLDAssociation of NAFLDNew-onset heart failureConclusions PatientsCohort studyPrior diagnosisBlack patientsNinth RevisionKidney diseaseOutpatient claimsRisk factorsIndependent associationHigh burdenMedicare patients
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