2025
Phenotypic Selectivity of Artificial Intelligence-enhanced Electrocardiography in Cardiovascular Diagnosis and Risk Prediction.
Croon P, Dhingra L, Biswas D, Oikonomou E, Khera R. Phenotypic Selectivity of Artificial Intelligence-enhanced Electrocardiography in Cardiovascular Diagnosis and Risk Prediction. Circulation 2025 PMID: 40888124, DOI: 10.1161/circulationaha.125.076279.Peer-Reviewed Original ResearchElectronic health recordsNon-cardiovascular conditionsPhenome-wide association studyCross-sectional phenotypingNew-onset cardiovascular diseaseCardiovascular diseaseProspective cohort studyPhenotypic associationsHealth recordsLeft ventricular hypertrophyStructural heart diseaseAI-ECGAssociated with cardiovascular phenotypesPearson correlation coefficientDiagnosis codesCohort studyCardiovascular risk markersLogistic regressionAssociation studiesCardiovascular diagnosisMitral regurgitationAortic stenosisCardiovascular conditionsStudy populationDetection of LVSDChanges in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide
Lu Y, Liu Y, Totojani T, Kim C, Khera R, Xu H, Brush J, Krumholz H, Abaluck J. Changes in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide. JAMA Network Open 2025, 8: e2526013. PMID: 40779264, PMCID: PMC12334959, DOI: 10.1001/jamanetworkopen.2025.26013.Peer-Reviewed Original ResearchConceptsHealth care expendituresCardiovascular risk factorsCare expendituresCohort studyRisk factorsYale New Haven Health SystemCohort study of adultsType 2 diabetes statusLong-term impactStudy of adultsHealth systemRetrospective cohort studyBlood pressureHemoglobin A1c reductionMain OutcomesTotal cholesterolSentara HealthcareInpatient staySecondary outcomesGlucagon-like peptide-1 receptor agonistsPrimary outcomeHealthPeptide-1 receptor agonistsAssociated with clinical outcomesAssociated with reductionsRisk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study
Morales D, Bu F, Viernes B, DuVall S, Matheny M, Simon K, Falconer T, Richter L, Ostropolets A, Lau W, Man K, Chattopadhyay S, Mathioudakis N, Minty E, Nishimura A, Sun F, Yin C, Seager S, Chai Y, Zhou J, Lu Y, Reyes C, Pistillo A, Duarte-Salles T, Blacketer C, Schuemie M, Ryan P, Krumholz H, Hripcsak G, Khera R, Suchard M. Risk of Thyroid Tumors With GLP-1 Receptor Agonists: A Retrospective Cohort Study. Diabetes Care 2025, 48: 1386-1394. PMID: 40465422, PMCID: PMC12281980, DOI: 10.2337/dc25-0154.Peer-Reviewed Original ResearchRisk of thyroid tumorThyroid tumorsGLP-1RADPP-4isHazard ratioThyroid malignancyCohort studyIncreased riskSodium-glucose cotransporter 2 inhibitorsElectronic health record databaseGlucagon-like peptide 1 receptor agonistsEstimate hazard ratiosRandom-effects meta-analysisGLP-1 receptor agonistsPeptide 1 receptor agonistsDipeptidyl peptidase 4 inhibitorsThyroid tumor incidenceUsers of SGLT2isHealth record databaseSecond-line treatmentType 2 diabetes mellitusNew-user cohort studyRetrospective cohort studyUsers of sulfonylureasIntention-to-treatArtificial Intelligence–Enabled Prediction of Heart Failure Risk From Single-Lead Electrocardiograms
Dhingra L, Aminorroaya A, Pedroso A, Khunte A, Sangha V, McIntyre D, Chow C, Asselbergs F, Brant L, Barreto S, Ribeiro A, Krumholz H, Oikonomou E, Khera R. Artificial Intelligence–Enabled Prediction of Heart Failure Risk From Single-Lead Electrocardiograms. JAMA Cardiology 2025, 10: 574-584. PMID: 40238120, PMCID: PMC12004248, DOI: 10.1001/jamacardio.2025.0492.Peer-Reviewed Original ResearchYale New Haven Health SystemELSA-BrasilPCP-HFNew-onset HFHarrell's C-statisticProspective population-based cohortUK Biobank (UKBBrazilian Longitudinal StudyELSA-Brasil participantsC-statisticPopulation-based cohortIntegrated discrimination improvementReclassification improvementRisk of deathUKB participantsHealth systemRetrospective cohort studyDiscrimination improvementMain OutcomesLeft ventricular systolic dysfunctionHF riskUKBCohort studySingle-lead ECGIndependent of ageRisk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort study
Janetzki J, Kim J, Minty E, Lee J, Morales D, Khera R, Kim C, Alshammari T, DuVall S, Matheny M, Falconer T, Kim S, Phan T, Nguyen P, Hsu M, Hsu J, Park R, Man K, Seager S, Van Zandt M, Gilbert J, Ryan P, Schuemie M, Suchard M, Hripcsak G, Pratt N, You S. Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort study. EClinicalMedicine 2025, 81: 103096. PMID: 39975698, PMCID: PMC11836508, DOI: 10.1016/j.eclinm.2025.103096.Peer-Reviewed Original ResearchUrinary tract infectionRisk of aortic aneurysmTreat urinary tract infectionsOutpatient settingAortic aneurysmIndex dateCohort studyHazard ratioUrinary tract infection treatmentYonsei University College of MedicineRetrospective cohort studyPropensity scoreCox proportional hazards modelsPropensity-matched pairsRandom-effects meta-analysisProportional hazards modelNational Health and Medical Research Council (NHMRCUniversity College of MedicineSystemic fluoroquinolonesTract infectionsNo significant differenceBayesian random-effects meta-analysisFollow-upPrimary outcomeIncreased risk
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 dataPerformance 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 discriminationA Multimodal Video-Based AI Biomarker for Aortic Stenosis Development and Progression
Oikonomou E, Holste G, Yuan N, Coppi A, McNamara R, Haynes N, Vora A, Velazquez E, Li F, Menon V, Kapadia S, Gill T, Nadkarni G, Krumholz H, Wang Z, Ouyang D, Khera R. A Multimodal Video-Based AI Biomarker for Aortic Stenosis Development and Progression. JAMA Cardiology 2024, 9: 534-544. PMID: 38581644, PMCID: PMC10999005, DOI: 10.1001/jamacardio.2024.0595.Peer-Reviewed Original ResearchCardiac magnetic resonanceAortic valve replacementCardiac magnetic resonance imagingAV VmaxSevere ASAortic stenosisCohort studyPeak aortic valve velocityCohort study of patientsAortic valve velocityCohort of patientsTraditional cardiovascular risk factorsAssociated with faster progressionStudy of patientsCedars-Sinai Medical CenterAssociated with AS developmentCardiovascular risk factorsCardiovascular imaging modalitiesIndependent of ageModerate ASEjection fractionEchocardiographic studiesValve replacementRisk stratificationCardiac structureDevelopment and multinational validation of an algorithmic strategy for high Lp(a) screening
Aminorroaya A, Dhingra L, Oikonomou E, Saadatagah S, Thangaraj P, Vasisht Shankar S, Spatz E, Khera R. Development and multinational validation of an algorithmic strategy for high Lp(a) screening. Nature Cardiovascular Research 2024, 3: 558-566. PMID: 39195936, PMCID: PMC12190734, DOI: 10.1038/s44161-024-00469-1.Peer-Reviewed Original ResearchElectronic health recordsAssociated with premature atherosclerotic cardiovascular diseaseElevated Lp(aHealth recordsUK BiobankPremature atherosclerotic cardiovascular diseaseMachine learning modelsAtherosclerotic cardiovascular diseaseCohort studyReal-world settingsTargeted screeningCardiovascular diseaseLearning modelsNovel targeted therapeuticsAlgorithmic strategiesCohortProbability thresholdScreeningClinical featuresValidation cohortElevated lipoproteinRisk inspectionARICLp(a
2023
Predicting aortic stenosis progression using a video-based deep learning model of aortic stenosis built for single-view two-dimensional echocardiography
Oikonomou E, Holste G, Mcnamara R, Velazquez E, Nadkarni G, Ouyang D, Krumholz H, Wang Z, Khera R. Predicting aortic stenosis progression using a video-based deep learning model of aortic stenosis built for single-view two-dimensional echocardiography. European Heart Journal 2023, 44: ehad655.040. DOI: 10.1093/eurheartj/ehad655.040.Peer-Reviewed Original ResearchLeft ventricular ejection fractionSevere aortic stenosisAortic stenosisAS progressionAV VmaxTransthoracic echocardiographyYale New Haven Health SystemBaseline left ventricular ejection fractionAortic stenosis progressionModerate aortic stenosisRetrospective cohort studyVentricular ejection fractionTwo-dimensional echocardiographyMean rateModerate ASAS severityCohort studyEjection fractionPatient sexStenosis progressionTTE studiesEligible participantsSerial monitoringSpecialized centersTimely diagnosisLifetime healthcare expenses across demographic and cardiovascular risk groups: The application of a novel modeling strategy in a large multiethnic cohort study
Khera R, Kondamudi N, Liu M, Ayers C, Spatz E, Rao S, Essien U, Powell-Wiley T, Nasir K, Das S, Capers Q, Pandey A. Lifetime healthcare expenses across demographic and cardiovascular risk groups: The application of a novel modeling strategy in a large multiethnic cohort study. American Journal Of Preventive Cardiology 2023, 14: 100493. PMID: 37397263, PMCID: PMC10314135, DOI: 10.1016/j.ajpc.2023.100493.Peer-Reviewed Original ResearchOverweight/obesityRisk factorsRace/ethnicityHealthcare expensesCardiovascular risk factorsCardiovascular risk groupsNon-black individualsMultiethnic Cohort StudySignificant independent associationYears of ageBlack individualsDallas Heart StudyCohort studyCohort enrollmentOutpatient claimsIndependent associationRisk groupsHigh prevalenceHeart StudyOlder ageHealthcare spendingHypertensionObesitySmokingDiabetesQuantifying Blood Pressure Visit-to-Visit Variability in the Real-World Setting: A Retrospective Cohort Study
Lu Y, Linderman G, Mahajan S, Liu Y, Huang C, Khera R, Mortazavi B, Spatz E, Krumholz H. Quantifying Blood Pressure Visit-to-Visit Variability in the Real-World Setting: A Retrospective Cohort Study. Circulation Cardiovascular Quality And Outcomes 2023, 16: e009258. PMID: 36883456, DOI: 10.1161/circoutcomes.122.009258.Peer-Reviewed Original ResearchConceptsRetrospective cohort studyBlood pressure valuesPatient characteristicsReal-world settingCohort studyPatient subgroupsYale New Haven Health SystemMean body mass indexSystolic blood pressure valuesBlood pressure visitHistory of hypertensionCoronary artery diseaseManagement of patientsMultivariable linear regression modelsBlood pressure readingsBody mass indexPatient-level measuresBlood pressure variationAbsolute standardized differencesNon-Hispanic whitesAntihypertensive medicationsReal-world practiceVisit variabilityArtery diseaseRegression models
2022
Time in therapeutic range for targeted temperature management and outcomes following out-of-hospital cardiac arrest
Wheelock K, Chan P, Chen L, de Lemos J, Miller P, Nallamothu B, Girotra S, Khera R. Time in therapeutic range for targeted temperature management and outcomes following out-of-hospital cardiac arrest. Resuscitation 2022, 182: 109650. PMID: 36442596, PMCID: PMC9885789, DOI: 10.1016/j.resuscitation.2022.11.016.Peer-Reviewed Original ResearchConceptsFavorable neurologic outcomeHospital cardiac arrestTherapeutic rangeNeurologic outcomeOverall survivalTemperature managementCardiac arrestFavorable neurologic survivalFavorable neurological outcomeRetrospective cohort studyTargeted temperature managementHigh therapeutic rangeRisk-adjusted analysisComatose survivorsNeurologic survivalNeurological outcomeCohort studyHospital dischargeMedian durationMedian timeCurrent guidelinesCompression trialTreatment targetsSignificant associationGoal temperature
2021
Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries
Wheelock KM, Ross JS, Murugiah K, Lin Z, Krumholz HM, Khera R. Clinician Trends in Prescribing Direct Oral Anticoagulants for US Medicare Beneficiaries. JAMA Network Open 2021, 4: e2137288. PMID: 34870678, PMCID: PMC8649845, DOI: 10.1001/jamanetworkopen.2021.37288.Peer-Reviewed Original ResearchConceptsDOAC useAnticoagulant prescriptionOral anticoagulantsUS cliniciansMedicare beneficiariesNational clinical practice guidelinesElevated bleeding riskOral anticoagulant prescriptionsRetrospective cohort studyDirect oral anticoagulantsClinical practice guidelinesUS Medicare beneficiariesInternal medicine physiciansNumber of cliniciansAnticoagulant prescribingDOAC prescriptionsUnique cliniciansBleeding riskCohort studyAnticoagulant strategiesPrescription claimsPractice guidelinesMAIN OUTCOMEMost indicationsMedicare populationNonalcoholic 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 patientsUse of Machine Learning Models to Predict Death After Acute Myocardial Infarction
Khera R, Haimovich J, Hurley NC, McNamara R, Spertus JA, Desai N, Rumsfeld JS, Masoudi FA, Huang C, Normand SL, Mortazavi BJ, Krumholz HM. Use of Machine Learning Models to Predict Death After Acute Myocardial Infarction. JAMA Cardiology 2021, 6: 633-641. PMID: 33688915, PMCID: PMC7948114, DOI: 10.1001/jamacardio.2021.0122.Peer-Reviewed Original ResearchConceptsMachine learning modelsMeta-classifier modelLearning modelNeural networkGradient descent boostingAcute myocardial infarctionContemporary machineGradient descentXGBoost modelXGBoostHospital mortalityCohort studyLogistic regressionMyocardial infarctionNetworkChest Pain-MI RegistryPrecise classificationIndependent validation dataInitial laboratory valuesNovel methodLarge national registryHigh-risk individualsData analysisValidation dataResolution of riskPrevalence of Missing Data in the National Cancer Database and Association With Overall Survival
Yang DX, Khera R, Miccio JA, Jairam V, Chang E, Yu JB, Park HS, Krumholz HM, Aneja S. Prevalence of Missing Data in the National Cancer Database and Association With Overall Survival. JAMA Network Open 2021, 4: e211793. PMID: 33755165, PMCID: PMC7988369, DOI: 10.1001/jamanetworkopen.2021.1793.Peer-Reviewed Original ResearchConceptsNational Cancer DatabaseNon-small cell lung cancerOverall survivalCell lung cancerCancer DatabaseMedical recordsLung cancerProstate cancerBreast cancerPatient recordsComplete dataRetrospective cohort studyCohort studyCancer RegistryCommon cancerVariables of interestHigh prevalenceMAIN OUTCOMEPatientsClinical advancementReal-world data sourcesCancerPrevalenceSurvivalHeterogeneous differences
2020
Temporal Trends in Heart Failure Incidence Among Medicare Beneficiaries Across Risk Factor Strata, 2011 to 2016
Khera R, Kondamudi N, Zhong L, Vaduganathan M, Parker J, Das SR, Grodin JL, Halm EA, Berry JD, Pandey A. Temporal Trends in Heart Failure Incidence Among Medicare Beneficiaries Across Risk Factor Strata, 2011 to 2016. JAMA Network Open 2020, 3: e2022190. PMID: 33095250, PMCID: PMC7584929, DOI: 10.1001/jamanetworkopen.2020.22190.Peer-Reviewed Original ResearchConceptsHeart failure incidenceHF risk factorsHF incidenceClinical Modification codesRisk factorsAcute MIMedicare beneficiariesFailure incidenceHF prevention strategiesRisk factor strataNational cohort studyService Medicare beneficiariesUnique Medicare beneficiariesInternational Statistical ClassificationRace/ethnicityPrior HFPrevalent hypertensionCohort studyIncident HFNinth RevisionPrevious diagnosisCardiovascular conditionsTenth RevisionMAIN OUTCOMEInternational ClassificationPerformance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index
Khera R, Pandey A, Ayers CR, Carnethon MR, Greenland P, Ndumele CE, Nambi V, Seliger SL, Chaves PHM, Safford MM, Cushman M, Xanthakis V, Ramachandran V, Mentz RJ, Correa A, Lloyd-Jones DM, Berry JD, de Lemos JA, Neeland IJ. Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index. JAMA Network Open 2020, 3: e2023242. PMID: 33119108, PMCID: PMC7596579, DOI: 10.1001/jamanetworkopen.2020.23242.Peer-Reviewed Original ResearchConceptsHigh-sensitivity C-reactive proteinPooled Cohort EquationsASCVD riskAtherosclerotic cardiovascular diseaseBody mass indexBMI categoriesCohort EquationsObesity categoriesCohort studySevere obesityWaist circumferenceBMI groupsMass indexUnderweight categoryAtherosclerotic cardiovascular disease riskMean baseline BMIRisk of ASCVDUsual clinical measuresCardiovascular disease riskC-reactive proteinPooled individual-level dataSevere obesity groupLongitudinal cohort studyNormal weight categoryAdults ages 40Revascularization Practices and Outcomes in Patients With Multivessel Coronary Artery Disease Who Presented With Acute Myocardial Infarction and Cardiogenic Shock in the US, 2009-2018
Khera R, Secemsky EA, Wang Y, Desai NR, Krumholz HM, Maddox TM, Shunk KA, Virani SS, Bhatt DL, Curtis J, Yeh RW. Revascularization Practices and Outcomes in Patients With Multivessel Coronary Artery Disease Who Presented With Acute Myocardial Infarction and Cardiogenic Shock in the US, 2009-2018. JAMA Internal Medicine 2020, 180: 1317-1327. PMID: 32833024, PMCID: PMC9377424, DOI: 10.1001/jamainternmed.2020.3276.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCohort StudiesCoronary VesselsFemaleFollow-Up StudiesHospital MortalityHumansMaleMiddle AgedMyocardial InfarctionPatient DischargePercutaneous Coronary InterventionRisk AssessmentRisk FactorsShock, CardiogenicST Elevation Myocardial InfarctionTime FactorsTreatment OutcomeUnited StatesConceptsST-segment elevation myocardial infarctionMultivessel percutaneous coronary interventionMultivessel coronary artery diseasePercutaneous coronary interventionAcute myocardial infarctionCoronary artery diseaseCulprit vessel percutaneous coronary interventionCardiogenic shockHospital mortalityArtery diseaseMyocardial infarctionCohort studyPrimary outcomeHospital variationPCI strategyMedicare beneficiariesUnderwent multivessel PCISignificant hospital variationElevation myocardial infarctionSubset of patientsHigh-risk populationRecent evidenceHospital complicationsPCI useRevascularization practice
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