2024
Standard-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 washoutEfficacy 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 reliefCardiac 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 peptide
2020
Study 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