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 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-headednessAficamten 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 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-controlledAficamtenEfficacy 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 reliefImpact 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 Symptomatic Non-Obstructive 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 Non-Obstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4. Journal Of Cardiac Failure 2024 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 improvementsCardiovascular 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
2022
Impact of SARS‐Cov‐2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry
Gimeno JR, Olivotto I, Rodríguez AI, Ho CY, Fernández A, Quiroga A, Espinosa MA, Gómez‐González C, Robledo M, Tojal‐Sierra L, Day SM, Owens A, Barriales‐Villa R, Larrañaga JM, Rodríguez‐Palomares J, González‐del‐Hoyo M, Piqueras‐Flores J, Reza N, Chumakova O, Ashley EA, Parikh V, Wheeler M, Jacoby D, Pereira AC, Saberi S, Helms AS, Villacorta E, Gallego‐Delgado M, de Castro D, Domínguez F, Ripoll‐Vera T, Zorio‐Grima E, Sánchez‐Martínez J, García‐Álvarez A, Arbelo E, Mogollón MV, Fuentes‐Cañamero M, Grande E, Peña C, Monserrat L, Lakdawala NK, Muñoz‐Esparza C, García‐Pinilla J, Robles‐Mezcua A, Moreno‐Flores M, Peña M, Merlo M, Cubillo D, Climent‐Payá V, Dankovtseva E, Vilela A, García‐Pavía P, Casas G. Impact of SARS‐Cov‐2 infection in patients with hypertrophic cardiomyopathy: results of an international multicentre registry. ESC Heart Failure 2022, 9: 2189-2198. PMID: 36255281, PMCID: PMC9288745, DOI: 10.1002/ehf2.13964.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionVentricular outflow tract obstructionOutflow tract obstructionRisk of mortalityHypertrophic cardiomyopathySARS-CoV-2HCM patientsSystolic impairmentTract obstructionOdds ratioBaseline New York Heart Association classNew York Heart Association classLeft ventricular outflow tract obstructionControl groupPresence of HCMBaseline functional classInternational multicentre registryVentricular systolic impairmentSevere clinical courseMulticentre registryNew onsetRespiratory failureAdverse eventsICU careAssociation classSarcomere protein modulation: The new frontier in cardiovascular medicine and beyond
Morelli C, Ingrasciotta G, Jacoby D, Masri A, Olivotto I. Sarcomere protein modulation: The new frontier in cardiovascular medicine and beyond. European Journal Of Internal Medicine 2022, 102: 1-7. PMID: 35534374, DOI: 10.1016/j.ejim.2022.04.020.Peer-Reviewed Original ResearchConceptsHeart failureCardiovascular medicineVentricular outflow obstructionHeart muscle diseaseDegenerative neuromuscular diseaseSpecific disease mechanismsCardiovascular deathOutflow obstructionSystolic functionRandomized trialsUnderlying pathophysiologyCardiac patientsOmecamtiv mecarbilHypertrophic cardiomyopathyFunctional capacityNeuromuscular diseaseMuscle diseaseAvailable evidenceContractile proteinsSkeletal muscleTranslational researchPromising targetDiseaseDisease mechanismsFailureMuscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxation
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 capacityWorldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy.
Nauffal V, Marstrand P, Han L, Parikh VN, Helms AS, Ingles J, Jacoby D, Lakdawala NK, Kapur S, Michels M, Owens AT, Ashley EA, Pereira AC, Rossano JW, Saberi S, Semsarian C, Ware JS, Wittekind SG, Day S, Olivotto I, Ho CY. Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy. European Heart Journal 2021, 42: 3932-3944. PMID: 36282238, DOI: 10.1093/eurheartj/ehab598.Peer-Reviewed Original ResearchConceptsSudden cardiac deathAppropriate ICD therapyNon-US sitesHypertrophic cardiomyopathyUS sitesICD therapySCD riskICD recipientsImplantation rateImplantable cardioverter-defibrillator (ICD) implantation ratesMultivariable Cox proportional hazards modelsImplantable cardioverter-defibrillator utilizationSarcomeric Human Cardiomyopathy RegistryCox proportional hazards modelHCM Risk-SCD scoreICD implantation ratesPrimary prevention ICDsSCD risk factorsRisk stratification algorithmLong-term outcomesLow-risk populationSignificant differencesSCD/Cardiac deathClinical outcomesWorldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy
Nauffal V, Marstrand P, Han L, Parikh VN, Helms AS, Ingles J, Jacoby D, Lakdawala NK, Kapur S, Michels M, Owens AT, Ashley EA, Pereira AC, Rossano JW, Saberi S, Semsarian C, Ware JS, Wittekind SG, Day S, Olivotto I, Ho CY. Worldwide differences in primary prevention implantable cardioverter defibrillator utilization and outcomes in hypertrophic cardiomyopathy. European Heart Journal 2021, 42: 3932-3944. PMID: 34491319, PMCID: PMC8497072, DOI: 10.1093/eurheartj/ehab598.Peer-Reviewed Original ResearchConceptsSudden cardiac deathAppropriate ICD therapyNon-US sitesHypertrophic cardiomyopathyUS sitesICD therapySCD riskICD recipientsImplantation rateImplantable cardioverter-defibrillator (ICD) implantation ratesMultivariable Cox proportional hazards modelsImplantable cardioverter-defibrillator utilizationSarcomeric Human Cardiomyopathy RegistryCox proportional hazards modelHCM Risk-SCD scoreICD implantation ratesPrimary prevention ICDsSCD risk factorsRisk stratification algorithmLong-term outcomesLow-risk populationSignificant differencesSCD/Cardiac deathClinical outcomesLoss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation
Sewanan LR, Park J, Rynkiewicz MJ, Racca AW, Papoutsidakis N, Schwan J, Jacoby DL, Moore JR, Lehman W, Qyang Y, Campbell SG. Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation. The Journal Of General Physiology 2021, 153: e202012640. PMID: 34319370, PMCID: PMC8321830, DOI: 10.1085/jgp.202012640.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyHeart tissueCellular hypertrophyEngineered Heart TissuePathological cardiac hypertrophyThin filament mutationsMavacamten treatmentDiastolic dysfunctionDisease featuresHypertrophic effectCardiac hypertrophyContractile differencesHypertrophyFundamental disease mechanismsCrossbridge activityInherited disorderOverall Ca2Uncertain significancePatient phenotypesDisease mechanismsLow Ca2PatientsK mutationMavacamtenTissue