2024
Aficamten and Cardiopulmonary Exercise Test Performance
Lee M, Masri A, Nassif M, Barriales-Villa R, Abraham T, Claggett B, Coats C, Gimeno J, Kulac I, Landsteiner I, Ma C, Maron M, Olivotto I, Owens A, Solomon S, Veselka J, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Wohltman A, Lewis G, Wang A, Sherrid M, Kelly J, Marian A, Owens A, Wever-Pinzon O, Owens D, Wheeler M, Nagueh S, Rader F, McGrew F, Wong T, O'Neill T, Bach R, Martinez M, Lakdawala N, Collado E, Turer A, Desai Y M, Hussain Z, Tower-Rader A, Hannawi B, Geske J, Saberi S, Phelan D, Kramer C, Sarswat N, Ahmad F, Choudhury L, Markowitz J, Sen S, Bering P, Maron M, Jani S, Brinkley D, Naidu S, Maurer M, Moss N, Bilen O, Silva Enciso J, Fraser R, Akinboboye O, Asher C, Emani S, Sharma A, Fermin D, Lyle M, Raymer D, Darlington A, Resnic F, Nielsen C, Metra M, Musumeci B, Emdin M, Targetti M, Canepa M, Michels M, Knackstedt C, Amin A, Barriales Villa R, Garcia Pavia P, Gimeno Blanes J, Hidalgo Urbano R, Rincon Diaz L, Ripoll Vera T, Garcia Alvarez A, Zemanek D, Jensen M, Mogensen J, Thune J, Bundgaard H, Charron P, Trochu J, Habib G, Lhermusier T, Reant P, Hagege A, Logeart D, Mitrovic V, Edelmann F, Seidler T, Meder B, Schulze P, Stoerk S, Bekfani T, Rassaf T, Merkely B, Arad M, Halabi M, Zwas D, Piltz X, Paz O, Habib M, Dudek D, Oreziak A, Wojakowski W, Toste Batista A, Mesquita Bastos J, Elliott P, Mahmod M, Coats C, Cooper R, Bradlow W, Pantazis A, Tome Esteban M, McGinnis S, Campain J, Cocca-Spofford D, Giverts I, Griskowitz C, Newlands C, Moreno F. Aficamten and Cardiopulmonary Exercise Test Performance. JAMA Cardiology 2024, 9: 990-1000. PMID: 39230885, PMCID: PMC11375526, DOI: 10.1001/jamacardio.2024.2781.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathySymptomatic obstructive hypertrophic cardiomyopathyBaseline to weekHypertrophic cardiomyopathyRandomized clinical trialsExercise performanceVentilatory efficiencyClinical trialsPrimary outcomeExercise testPlacebo-corrected improvementCardiac myosin inhibitorPhase 3 trialClinical measuresImpaired exercise capacityCardiopulmonary exercise testingExercise performance measuresHeart rate reserveSubmaximal exercise performancePeak heart rateClinically meaningful thresholdsPlacebo groupDouble-blindPlacebo-controlledAficamtenBaseline Characteristics of Patients in SEQUOIA-HCM: A Phase 3 Trial of Aficamten in Obstructive Hypertrophic Cardiomyopathy
Maron M, Abraham T, Coats C, Olivotto I, Lee M, Arad M, Cardim N, Ma C, Choudhury L, Düngen H, Garcia-Pavia P, Hagege A, Lewis G, Michels M, Oreziak A, Owens A, Tfelt-Hansen J, Veselka J, Watkins H, Heitner S, Jacoby D, Kupfer S, Malik F, Meng L, Wohltman A, Masri A. Baseline Characteristics of Patients in SEQUOIA-HCM: A Phase 3 Trial of Aficamten in Obstructive Hypertrophic Cardiomyopathy. Journal Of Cardiac Failure 2024, 30: s3. DOI: 10.1016/j.cardfail.2023.11.006.Peer-Reviewed Original ResearchLeft ventricular outflow tract obstructionObstructive hypertrophic cardiomyopathySymptomatic obstructive hypertrophic cardiomyopathyBaseline characteristics of patientsCardiac myosin inhibitorPhase 3 trialCharacteristics of patientsBaseline characteristicsHypertrophic cardiomyopathyNew York Heart Association functional classVentricular outflow tract obstructionN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideTreated with beta-blockersHigh-sensitivity cardiac troponin IBaseline New York Heart Association functional classOutflow tract obstructionPlacebo-controlled trialBaseline to weekHeart failure symptomsIndividual daily doseReduced exercise capacityCardiac troponin IMyocardial hypercontractilityOral placebo
2021
Mavacamten 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 ResearchConceptsKansas 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 therapy