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-controlledAficamtenStandard-of-Care Medication Withdrawal in Patients With Obstructive Hypertrophic Cardiomyopathy Receiving Aficamten in FOREST-HCM
Masri A, Choudhury L, Barriales-Villa R, Elliott P, Maron M, Nassif M, Oreziak A, Owens A, Saberi S, Tower-Rader A, Rader F, Garcia-Pavia P, Olivotto I, Nagueh S, Wang A, Heitner S, Jacoby D, Kupfer S, Malik F, Melloni C, Meng L, Wei J, Sherrid M, Abraham T, Investigators F. Standard-of-Care Medication Withdrawal in Patients With Obstructive Hypertrophic Cardiomyopathy Receiving Aficamten in FOREST-HCM. Journal Of The American College Of Cardiology 2024, 84: 1839-1849. PMID: 39477631, DOI: 10.1016/j.jacc.2024.09.002.Peer-Reviewed Original ResearchConceptsObstructive hypertrophic cardiomyopathyKansas City Cardiomyopathy Questionnaire-Clinical Summary ScoreStandard-of-careSOC therapyAdverse eventsDose reductionTherapy withdrawalHypertrophic cardiomyopathyTreatment of obstructive hypertrophic cardiomyopathyPro-B-type natriuretic peptide levelsN-terminal pro-B-type natriuretic peptide levelsTreatment-emergent adverse eventsHigh-sensitivity troponin IOutflow tract gradientEmergent adverse eventsNYHA functional classFirst-line therapyNatriuretic peptide levelsOff-target side effectsSummary scoreControlled clinical trialsMeasures of efficacyClinical measures of efficacyStable doseNo withdrawalsClinical application of biomarkers in obstructive hypertrophic cardiomyopathy: insights from SEQUOIA-HCM
Coats C, Masri A, Barriales-Villa R, Abraham T, Claggett B, Hagege A, Ho C, Lee M, Maron M, Owens A, Tfelt-Hansen J, Watkins H, Jacoby D, Wohltman A, Januuzi J. Clinical application of biomarkers in obstructive hypertrophic cardiomyopathy: insights from SEQUOIA-HCM. European Heart Journal 2024, 45: ehae666.2033. DOI: 10.1093/eurheartj/ehae666.2033.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathyLeft ventricular ejection fractionNT-proBNPCardiac biomarkersHypertrophic cardiomyopathyN-terminal pro B-type natriuretic peptidePro B-type natriuretic peptideSensitive cardiac troponin INYHA class II-IIICirculating cardiac biomarkersOutflow tract gradientVentricular ejection fractionBaseline NT-proBNPPre-specified analysisBaseline biomarker valuesBiomarker valuesCardiopulmonary exercise testingClass II-IIIPeak oxygen consumptionMultivariate regression analysisCardiac troponin IHs-cTnI.Dose titrationEjection fractionDrug washoutImpact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy Results From SEQUOIA-HCM
Maron M, Masri A, Nassif M, Barriales-Villa R, Abraham T, Arad M, Cardim N, Choudhury L, Claggett B, Coats C, Düngen H, Garcia-Pavia P, Hagège A, Januzzi J, Kulac I, Lee M, Lewis G, Ma C, Michels M, Oreziak A, Owens A, Spertus J, Solomon S, Tfelt-Hansen J, van Sinttruije M, Veselka J, Watkins H, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Wohltman A, Olivotto I, Investigators S. Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy Results From SEQUOIA-HCM. Journal Of The American College Of Cardiology 2024, 84: 1821-1831. PMID: 39352339, DOI: 10.1016/j.jacc.2024.09.003.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathyN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideSeptal reduction therapyHypertrophic cardiomyopathyNatriuretic peptideReduction therapySymptomatic obstructive hypertrophic cardiomyopathyExercise capacityCardiac myosin inhibitorProportion of patientsTreatment of patientsHemodynamic responseAssociated with substantial improvementsOutflow gradientPlacebo groupAficamtenEnhanced exercise capacityClinical efficacyEfficacy measuresClinical impactPlaceboResponder analysisPatientsCardiomyopathyQualitative interview study of patient-reported symptoms, impacts and treatment goals of patients with obstructive hypertrophic cardiomyopathy
Shore S, Ervin C, Kosa K, Fehnel S, Salberg L, Butzner M, Heitner S, Jacoby D, Saberi S. Qualitative interview study of patient-reported symptoms, impacts and treatment goals of patients with obstructive hypertrophic cardiomyopathy. BMJ Open 2024, 14: e081323. PMID: 39289016, PMCID: PMC11409399, DOI: 10.1136/bmjopen-2023-081323.Peer-Reviewed Original ResearchConceptsQualitative interview studyTreatment goalsShortness of breathTreatment goals of patientsInterview studyAffecting health statusGoals of patientsHypertrophic Cardiomyopathy AssociationPatient-reported symptomsSemi-structured interviewsPhysical functionPatient experiencePatient perspectiveSymptom burdenUS adultsObstructive HCMObstructive hypertrophic cardiomyopathyHealth statusTelephone interviewsPsychosocial impactChest pain/pressureLifestyle-limiting symptomsHypertrophic cardiomyopathyImproving shortness of breathDizziness/light-headednessEffect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy SEQUOIA-HCM CMR Substudy
Masri A, Cardoso R, Abraham T, Claggett B, Coats C, Hegde S, Kulac I, Lee M, Maron M, Merkely B, Michels M, Olivotto I, Oreziak A, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Solomon S, Wohltman A, Kwong R, Kramer C, Investigators S. Effect of Aficamten on Cardiac Structure and Function in Obstructive Hypertrophic Cardiomyopathy SEQUOIA-HCM CMR Substudy. Journal Of The American College Of Cardiology 2024, 84: 1806-1817. PMID: 39217563, DOI: 10.1016/j.jacc.2024.08.015.Peer-Reviewed Original ResearchCardiovascular magnetic resonanceObstructive hypertrophic cardiomyopathyOutflow tract obstructionReduce cardiovascular eventsCardiac remodelingAtrial fibrillationHeart failureCardiovascular eventsAssociated with progressive heart failureLeft ventricular (LV) hypertrophyPhase 3 double-blindSymptomatic obstructive hypertrophic cardiomyopathyLV outflow tract obstructionMaximal LV wall thicknessLeft atrial volume indexAtrial volume indexLV mass indexLV) hypertrophyPlacebo-controlled trialProgressive heart failureFavorable cardiac remodelingLeft atrial dilatationCardiac myosin inhibitorLeft atrial sizeLV wall thicknessImpact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy
Hegde S, Claggett B, Wang X, Jering K, Prasad N, Roshanali F, Masri A, Nassif M, Barriales-Villa R, Abraham T, Cardim N, Coats C, Kramer C, Maron M, Michels M, Olivotto I, Saberi S, Jacoby D, Heitner S, Kupfer S, Meng L, Wohltman A, Malik F, Solomon S, Investigators S. Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy. Journal Of The American College Of Cardiology 2024, 84: 1789-1802. PMID: 39217556, DOI: 10.1016/j.jacc.2024.08.002.Peer-Reviewed Original ResearchLeft ventricular ejection fractionObstructive hypertrophic cardiomyopathySymptomatic obstructive hypertrophic cardiomyopathyLVOT gradientKCCQ-CSSNT-proBNPAssociated with improvementsHypertrophic cardiomyopathyKansas City Cardiomyopathy Questionnaire Clinical Summary ScoreCardiac structureMeasures of LV diastolic functionLV global circumferential strainN-terminal pro-B-type natriuretic peptideLV global longitudinal strainLV end-systolic volumePro-B-type natriuretic peptideEchocardiographic measures of cardiac structureMeasures of cardiac structureLateral e' velocityLV diastolic functionAtrial volume indexGlobal longitudinal strainLV systolic functionPlacebo-controlled studyGlobal circumferential strainCardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial
Coats C, Masri A, Barriales-Villa R, Abraham T, Brinkley D, Claggett B, Hagege A, Hegde S, Ho C, Kulac I, Lee M, Maron M, Olivotto I, Owens A, Solomon S, Tfelt-Hansen J, Watkins H, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Wohltman A, Januzzi J, Zhang Y, Yang H, Shao C, Yuan Z, Zeng Q, Li X, Ma C, Wang Y, Shu Y, Chen M, Tao L, Li X, Wang J, Yu Z, Cheng X, Hong K, Zemanek D, Bundgaard H, Thune J, Jensen M, Mogensen J, Hagege A, Habib G, Charron P, Lhermusier T, Trochu J, Reant P, Logeart D, Mitrovic V, Bekfani T, Edelmann F, Seidler T, Meder B, Christian Schulze P, Stoerk S, Rassaf T, Merkely B, Zfat-Zwas D, Arad M, Halabi M, Paz O, Piltz X, Olivotto I, Targetti M, Metra M, Canepa M, Musumeci B, Emdin M, Michels M, Amin A, Knackstedt C, Oreziak A, Wojakowski W, Dudek D, Toste A, Mesquita Bastos J, Barriales-Villa R, Garcia Pavia P, Ramón Gimeno Blanes J, Jesus Hidalgo Urbano R, Garcia Alvarez A, Miguel Rincón Diaz L, Vicente Ripoll Vera T, Elliott P, Coats C, Cooper R, Mahmod M, Bradlow W, Pantazis A, Teresa Tome Esteban M, Masri A, Nassif M, Marian A, Owens D, Wheeler M, McGrew F, Bach R, Wever-Pinzon O, Collado E, Turer A, Hannawi B, Geske J, Owens A, Symanski J, Kramer C, Sarswat N, Ahmad F, Abraham T, Markowitz J, Lakdawala N, Choudhury L, Jani S, Brinkley M, Bilen O, Asher C, Emani S, Sharma A, Fermin D, Lyle M, Raymer D, Darlington A, Maron M, Nielsen C, Wang A, Nagueh S, Martinez M, Desai M, Tower-Rader A, Kelly J, Rader F, Sen S, Bering P, Maurer M, Mitter S, Sherrid M, Wong T, Hussain Z, Saberi S, Naidu S, Silva Enciso J. Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial. European Heart Journal 2024, 45: 4464-4478. PMID: 39217447, PMCID: PMC11544315, DOI: 10.1093/eurheartj/ehae590.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathyNT-proBNPHs-cTnI concentrationsHs-cTnIHypertrophic cardiomyopathyCardiac biomarkersLeft ventricular outflow tract gradientConcentrations of N-terminal pro-B-type natriuretic peptideN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideConcentrations of NT-proBNPHigh-sensitivity cardiac troponin IMeasurement of NT-proBNPMeasures of diastolic functionOutflow tract gradientNT-proBNP reductionWeeks of treatmentBaseline NT-proBNPLeft ventricular thicknessPre-specified analysisBaseline concentrationsCardiac troponin IPeak oxygen uptakeDiastolic functionNatriuretic peptideEffect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy Results From SEQUOIA-HCM
Sherrod C, Saberi S, Nassif M, Claggett B, Coats C, Garcia-Pavia P, Januzzi J, Lewis G, Ma C, Maron M, Miao Z, Olivotto I, Veselka J, Butzner M, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Wohltman A, Spertus J. Effect of Aficamten on Health Status Outcomes in Obstructive Hypertrophic Cardiomyopathy Results From SEQUOIA-HCM. Journal Of The American College Of Cardiology 2024, 84: 1773-1785. PMID: 39217569, DOI: 10.1016/j.jacc.2024.08.014.Peer-Reviewed Original ResearchKCCQ overall summary scoresKansas City Cardiomyopathy QuestionnaireObstructive hypertrophic cardiomyopathyHealth statusQuality of lifePatient-reported health statusParticipants' health statusHealth status outcomesHypertrophic cardiomyopathyHealth status benefitsHealth status improvementPatients' health statusClinically important changeProportion of participantsSymptoms of fatigueSymptomatic obstructive hypertrophic cardiomyopathyStatus outcomesSummary scoreImprove healthCardiac myosin inhibitorProportion of patientsBaseline scoresImportant changesShortness of breathStatus improvementEfficacy and Safety of Aficamten in Patients with Obstructive Hypertrophic Cardiomyopathy and Very High Left Ventricular Outflow Tract Gradients
Veselka J, Abraham T, Barriales-Villa R, Claggett B, Coats C, Hegde S, Januzzi J, Maron M, Masri A, Miao Z, Nassif M, Olivotto I, Jacoby D, Heitner S, Kupfer S, Malik F, Meng L, Wohltman A, Gimeno J. Efficacy and Safety of Aficamten in Patients with Obstructive Hypertrophic Cardiomyopathy and Very High Left Ventricular Outflow Tract Gradients. Journal Of Cardiac Failure 2024, 30: s9. DOI: 10.1016/j.cardfail.2024.08.014.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathyOutflow tract gradientSecondary endpointsHypertrophic cardiomyopathyCardiac biomarkersPhase 3 placebo-controlled trialsLeft ventricular outflow tract gradientGroup 2Group 1Symptomatic obstructive hypertrophic cardiomyopathyTreatment-emergent adverse eventsExercise capacityEmergent adverse eventsBaseline to weekEffective treatment optionInhibitor therapyNT-proBNPPrimary endpointEchocardiographic dataBetween-group differencesBaseline characteristicsAficamtenAdverse eventsTreatment optionsSymptom reliefCardiovascular Hospitalizationspost Septal Myectomy For Obstructive Hypertrophic Cardiomyopathy: A 3-year Analysis Of 5,101 Patients
Altibi A, Elman M, Zhao Y, Chehab J, Butzner M, Heitner S, Jacoby D, Sohn R, Masri A. Cardiovascular Hospitalizationspost Septal Myectomy For Obstructive Hypertrophic Cardiomyopathy: A 3-year Analysis Of 5,101 Patients. Journal Of Cardiac Failure 2024, 30: 199-200. DOI: 10.1016/j.cardfail.2023.10.201.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathyIncidence of cardiovascular hospitalizationsSeptal myectomyCardiovascular hospitalizationChronic kidney diseaseChronic obstructive pulmonary diseaseHypertrophic cardiomyopathyPost-SMVentricular arrhythmiasHeart failureCumulative incidence of cardiovascular hospitalizationsFollow-upYears median follow-upMedian follow-upAdvanced HF therapiesHealth claims databaseAdvanced heart failureEmergency department visitsPacemaker/implantable cardioverter defibrillatorObstructive pulmonary diseaseHF therapyAtrial fibrillation/flutterCumulative incidenceCardiac arrestMultivariate regression modelCharacteristics And Procedural Complications Of Septal Myectomy For Obstructive Hypertrophic Cardiomyopathy In The United States
Altibi A, Elman M, Zhao Y, Chehab J, Butzner M, Heitner S, Jacoby D, Sohn R, Masri A. Characteristics And Procedural Complications Of Septal Myectomy For Obstructive Hypertrophic Cardiomyopathy In The United States. Journal Of Cardiac Failure 2024, 30: 177-178. DOI: 10.1016/j.cardfail.2023.10.149.Peer-Reviewed Original ResearchObstructive hypertrophic cardiomyopathySeptal myectomyBaseline characteristicsHypertrophic cardiomyopathyInpatient complicationsConcomitant mitral valve repairVentricular septal defectMitral valve repairMitral valve replacementPredictor of inpatient complicationsCohort of patientsOutcomes of SMValve repairSeptal defectValve replacementAtrial fibrillation/flutterAnoxic brain damagePacemaker implantationAdult patientsHeart blockCardiac arrestEmergency intubationProcedural outcomesContinuous enrollmentMyectomyBaseline 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
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 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
Temporal Trend of Age at Diagnosis in Hypertrophic Cardiomyopathy
Canepa M, Fumagalli C, Tini G, Vincent-Tompkins J, Day SM, Ashley EA, Mazzarotto F, Ware JS, Michels M, Jacoby D, Ho CY, Olivotto I, Investigators T. Temporal Trend of Age at Diagnosis in Hypertrophic Cardiomyopathy. Circulation Heart Failure 2020, 13: e007230-e007230. PMID: 32894986, PMCID: PMC7497482, DOI: 10.1161/circheartfailure.120.007230.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyHCM diagnosisSarcomeric Human Cardiomyopathy RegistryGenetic testingHeart failure symptomsObstructive hypertrophic cardiomyopathyNon-US sitesEra of diagnosisLikely pathogenic variantsClinical characteristicsOlder patientsFamilial hypertrophic cardiomyopathyHCM populationVentricular hypertrophyFemale ratioFailure symptomsSporadic diseasePathogenic variantsAdvanced diagnostic toolsDiagnosisTemporal trendsStable maleMild phenotypeAgePatientsMavacamten 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
2019
Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial.
Heitner SB, Jacoby D, Lester SJ, Owens A, Wang A, Zhang D, Lambing J, Lee J, Semigran M, Sehnert AJ. Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: A Clinical Trial. Annals Of Internal Medicine 2019, 170: 741-748. PMID: 31035291, DOI: 10.7326/m18-3016.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdrenergic beta-AntagonistsAdultAgedBenzylaminesCardiomyopathy, HypertrophicCardiovascular AgentsDose-Response Relationship, DrugDrug Therapy, CombinationExercise ToleranceFemaleHumansMaleMiddle AgedOxygen ConsumptionProspective StudiesStroke VolumeUracilVentricular Function, LeftYoung AdultConceptsObstructive hypertrophic cardiomyopathyLVOT gradientDyspnea scoreAdverse eventsCohort BPeak VO2Hypertrophic cardiomyopathyLeft ventricular outflow tract gradientVentricular outflow tract gradientEnd pointCommon adverse eventsOutflow tract gradientUnrelated adverse eventsOpen-label designPrimary end pointSecondary end pointsPhase 2 trialVentricular ejection fractionML/Peak oxygen consumptionEffect of mavacamtenHigher plasma concentrationsMavacamten treatmentLVOT obstructionTract gradient