2021
Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy
Hegde SM, Lester SJ, Solomon SD, Michels M, Elliott PM, Nagueh SF, Choudhury L, Zemanek D, Zwas DR, Jacoby D, Wang A, Ho CY, Li W, Sehnert AJ, Olivotto I, Abraham TP. Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. Journal Of The American College Of Cardiology 2021, 78: 2518-2532. PMID: 34915982, DOI: 10.1016/j.jacc.2021.09.1381.Peer-Reviewed Original ResearchConceptsObstructive hypertrophic cardiomyopathySystolic anterior motionAnterior motionDiastolic functionHypertrophic cardiomyopathyN-terminal pro-B-type natriuretic peptideMitral valve systolic anterior motionPro-B-type natriuretic peptidePeak exercise oxygen consumptionLeft ventricular diastolic functionVentricular outflow tract obstructionKey echocardiographic parametersAtrial volume indexOutflow tract obstructionVentricular diastolic functionExercise oxygen consumptionEffect of mavacamtenMyocardial wall stressEXPLORER-HCMLVOT gradientEchocardiographic featuresEchocardiographic parametersLVOT obstructionTract obstructionExercise capacityMavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial
Spertus JA, Fine JT, Elliott P, Ho CY, Olivotto I, Saberi S, Li W, Dolan C, Reaney M, Sehnert AJ, Jacoby D. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2021, 397: 2467-2475. PMID: 34004177, DOI: 10.1016/s0140-6736(21)00763-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBenzylaminesCardiomyopathy, HypertrophicDouble-Blind MethodFemaleHealth StatusHumansMaleMiddle AgedQuality of LifeUracilConceptsKansas City Cardiomyopathy QuestionnaireSymptomatic obstructive hypertrophic cardiomyopathyObstructive hypertrophic cardiomyopathyHypertrophic cardiomyopathyPatients' health statusQuality of lifeHealth statusWeek 30KCCQ overall summary scoreAvailable pharmacological optionsKCCQ-OS scorePlacebo-controlled trialPhase 3 trialProportion of patientsPrimary treatment goalOverall summary scoreDisease-specific measuresEffect of mavacamtenHealth status analysisNew potential strategyEXPLORER-HCMPlacebo groupAdult patientsBristol-Myers Squibb CompanyPharmacological options
2020
Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial
Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D, investigators E, Bartunek J, Bondue A, Van Craenenbroeck E, Kubanek M, Zemanek D, Jensen M, Mogensen J, Thune J, Charron P, Hagege A, Lairez O, Trochu J, Axthelm C, Duengen H, Frey N, Mitrovic V, Preusch M, Schulz-Menger J, Seidler T, Arad M, Halabi M, Katz A, Monakier D, Paz O, Viskin S, Zwas D, Olivotto I, Rocca H, Michels M, Dudek D, Oko-Sarnowska Z, Oreziak A, Wojakowski W, Cardim N, Pereira H, Barriales-Villa R, Pavia P, Blanes J, Urbano R, Diaz L, Elliott P, Yousef Z, Abraham T, Afshar K, Alvarez P, Bach R, Becker R, Choudhury L, Fermin D, Jacoby D, Jefferies J, Kramer C, Lakdawala N, Lester S, Marian A, Masri A, Maurer M, Nagueh S, Owens A, Owens D, Rader F, Saberi S, Sherrid M, Shirani J, Symanski J, Turer A, Wang A, Wever-Pinzon O, Wheeler M, Wong T, Yamani M. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2020, 396: 759-769. PMID: 32871100, DOI: 10.1016/s0140-6736(20)31792-x.Peer-Reviewed Original ResearchConceptsObstructive hypertrophic cardiomyopathyKansas City Cardiomyopathy Questionnaire clinical summary scoreSymptomatic obstructive hypertrophic cardiomyopathyHypertrophic cardiomyopathyLVOT gradientNYHA classPrimary endpointDynamic left ventricular outflow tract obstructionNew York Heart Association class IILeft ventricular outflow tract obstructionTreatment-emergent adverse eventsVentricular outflow tract obstructionAvailable pharmacological optionsKey pathophysiological abnormalityNYHA class reductionNYHA functional classOutflow tract obstructionPlacebo-controlled trialPhase 3 trialML/Disease-specific treatmentPeak oxygen consumptionGreater increaseLVOT obstructionPlacebo groupStudy Design and Rationale of EXPLORER-HCM
Ho CY, Olivotto I, Jacoby D, Lester SJ, Roe M, Wang A, Waldman CB, Zhang D, Sehnert AJ, Heitner SB. Study Design and Rationale of EXPLORER-HCM. Circulation Heart Failure 2020, 13: e006853. PMID: 32498620, DOI: 10.1161/circheartfailure.120.006853.Peer-Reviewed Original ResearchConceptsNew York Heart Association classLV outflow tract obstructionObstructive hypertrophic cardiomyopathyOutflow tract obstructionPeak oxygen consumptionEXPLORER-HCMTract obstructionAssociation classEnd pointExercise capacityNew York Heart Association functional class IIDynamic LV outflow tract obstructionKansas City Cardiomyopathy QuestionnaireLV outflow tract gradientSymptomatic obstructive hypertrophic cardiomyopathyUnexplained left ventricular hypertrophyOxygen consumptionExploratory end pointsFunctional class IIOutflow tract gradientPlacebo-controlled trialSecondary end pointsPhase 2 studyPhase 3 trialCurrent medical therapyEvaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy
Ho CY, Mealiffe ME, Bach RG, Bhattacharya M, Choudhury L, Edelberg JM, Hegde SM, Jacoby D, Lakdawala NK, Lester SJ, Ma Y, Marian AJ, Nagueh SF, Owens A, Rader F, Saberi S, Sehnert AJ, Sherrid MV, Solomon SD, Wang A, Wever-Pinzon O, Wong TC, Heitner SB. Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy. Journal Of The American College Of Cardiology 2020, 75: 2649-2660. PMID: 32466879, DOI: 10.1016/j.jacc.2020.03.064.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBenzylaminesBiomarkersCardiomyopathy, HypertrophicDouble-Blind MethodEchocardiographyFemaleHumansMaleMiddle AgedUracilConceptsNonobstructive hypertrophic cardiomyopathyGeometric mean differencePlacebo groupHypertrophic cardiomyopathyN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptidePg/Mean differencePhase II studySerious adverse eventsVentricular ejection fractionMyocardial wall stressDose titrationNT-proBNPAdverse eventsII studySymptomatic patientsEjection fractionPharmacological therapyClinical parametersInitial doseNatriuretic peptideMean ageHigh burdenMavacamtenEmpagliflozin in Heart Failure
Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, Suda N, Siwakoti K, Ahmad T, Jacoby D, Riello R, Bellumkonda L, Cox Z, Collins S, Jeon S, Turner JM, Wilson FP, Butler J, Inzucchi SE, Testani JM. Empagliflozin in Heart Failure. Circulation 2020, 142: 1028-1039. PMID: 32410463, PMCID: PMC7521417, DOI: 10.1161/circulationaha.120.045691.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsCotransporter 2 inhibitorsNeurohormonal activationHeart failureRenal dysfunctionBlood volumeHeart failure-related outcomesPlacebo-controlled crossover studyType 2 diabetes mellitusProximal tubular siteHeart failure outcomesStable heart failureUrinary glucose excretionUric acid levelsElectrolyte wastingEmpagliflozin monotherapyOral empagliflozinPlacebo periodStudy drugGlucose excretionNatriuretic effectPotassium wastingTubular sitesDiabetes mellitusFractional excretion
2019
Machine Learning Prediction of Mortality and Hospitalization in Heart Failure With Preserved Ejection Fraction
Angraal S, Mortazavi BJ, Gupta A, Khera R, Ahmad T, Desai NR, Jacoby DL, Masoudi FA, Spertus JA, Krumholz HM. Machine Learning Prediction of Mortality and Hospitalization in Heart Failure With Preserved Ejection Fraction. JACC Heart Failure 2019, 8: 12-21. PMID: 31606361, DOI: 10.1016/j.jchf.2019.06.013.Peer-Reviewed Original ResearchConceptsHF hospitalizationRisk of mortalityEjection fractionBlood urea nitrogen levelsLogistic regressionPrevious HF hospitalizationHeart failure hospitalizationReduced ejection fractionReceiver-operating characteristic curveRisk of deathBody mass indexBlood urea nitrogenUrea nitrogen levelsHealth status dataMean c-statisticKCCQ scoresTOPCAT trialFailure hospitalizationHeart failureHemoglobin levelsMass indexC-statisticHospitalizationUrea nitrogenMortality