Clinical 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 washoutCardiac 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 peptideEfficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4
Masri A, Sherrid M, Abraham T, Choudhury L, Garcia-Pavia P, Kramer C, Barriales-Villa R, Owens A, Rader F, Nagueh S, Olivotto I, Saberi S, Tower-Rader A, Wong T, Coats C, Watkins H, Fifer M, Solomon S, Heitner S, Jacoby D, Kupfer S, Malik F, Meng L, Sohn R, Wohltman A, Maron M, Investigators R. Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4. Journal Of Cardiac Failure 2024, 30: 1439-1448. PMID: 38493832, DOI: 10.1016/j.cardfail.2024.02.020.Peer-Reviewed Original ResearchNonobstructive hypertrophic cardiomyopathyHypertrophic cardiomyopathyKansas City Cardiomyopathy Questionnaire Clinical Summary ScoreOpen-label phase 2 trialNew York Heart Association classHistory of aborted sudden cardiac deathNon-obstructive hypertrophic cardiomyopathyHigh-sensitivity cardiac troponin IAborted sudden cardiac deathBlood levels of biomarkersNT-proBNP levelsPhase 2 trialPlacebo-controlled studyHeart failure symptomsCardiac myosin inhibitorClinical summary scoreSudden cardiac deathClinically relevant improvementWeeks of washoutLevels of biomarkersCardiac troponin IHeart muscle cellsAsymptomatic reductionNT-proBNPAssociated with improvementsBaseline 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