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 withdrawalsQualitative 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 ResearchMeSH KeywordsAdultAgedCardiomyopathy, HypertrophicDyspneaFatigueFemaleHumansInterviews as TopicMaleMiddle AgedPatient Reported Outcome MeasuresQualitative ResearchQuality of LifeConceptsQualitative 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 for Obstructive Hypertrophic Cardiomyopathy. Reply.
Maron M, Coats C, Jacoby D. Aficamten for Obstructive Hypertrophic Cardiomyopathy. Reply. New England Journal Of Medicine 2024, 391: 665-666. PMID: 39141865, DOI: 10.1056/nejmc2408094.Peer-Reviewed Original ResearchBlack or African AmericanCardiomyopathy, HypertrophicClinical Trials as TopicHealthcare DisparitiesHumansPatient Selection
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 ResearchMeSH KeywordsAdultAgedAtrial FibrillationCardiomyopathy, HypertrophicCOVID-19FemaleHumansMaleMiddle AgedRegistriesSARS-CoV-2Ventricular Dysfunction, LeftConceptsSARS-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 classMuscle 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 ResearchMeSH KeywordsActomyosinCardiomyopathy, HypertrophicCardiomyopathy, Hypertrophic, FamilialHumansLIM Domain ProteinsMechanotransduction, CellularMuscle ProteinsMutationMyocytes, CardiacConceptsHypertrophic 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 ResearchMeSH KeywordsAgedBenzylaminesBiomarkersCardiac MyosinsCardiomyopathy, HypertrophicDouble-Blind MethodEchocardiographyExercise ToleranceFemaleHeartHumansMaleMiddle AgedUracilConceptsObstructive 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 ResearchMeSH KeywordsCardiomyopathy, HypertrophicDeath, Sudden, CardiacDefibrillators, ImplantableHumansPrimary PreventionRisk AssessmentRisk FactorsConceptsSudden 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 ResearchMeSH KeywordsCardiomyopathy, HypertrophicDeath, Sudden, CardiacDefibrillators, ImplantableHumansPrimary PreventionRisk AssessmentRisk FactorsConceptsSudden 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 outcomesMavacamten 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 ResearchMeSH KeywordsAdultAgedBenzylaminesCardiomyopathy, HypertrophicDouble-Blind MethodFemaleHealth StatusHumansMaleMiddle AgedQuality of LifeUracilConceptsKansas 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 optionsComputational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation
Thompson AD, Helms AS, Kannan A, Yob J, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Mazzarotto F, Olivotto I, Ho CY, Day SM. Computational prediction of protein subdomain stability in MYBPC3 enables clinical risk stratification in hypertrophic cardiomyopathy and enhances variant interpretation. Genetics In Medicine 2021, 23: 1281-1287. PMID: 33782553, PMCID: PMC8257482, DOI: 10.1038/s41436-021-01134-9.Peer-Reviewed Original ResearchMeSH KeywordsCardiomyopathiesCardiomyopathy, HypertrophicCarrier ProteinsHumansMutationMutation, MissenseRisk AssessmentConceptsHypertrophic cardiomyopathyClinical riskMissense variantsSarcomeric Human Cardiomyopathy RegistryHigh clinical riskClinical risk stratificationAdverse eventsComposite endpointRisk stratificationHCM patientsCommon causePatientsLoss of functionUncertain significanceMYBPC3Missense VUSCardiomyopathyHigh rateSubstantial numberSupportive evidenceVUSRiskVariant interpretationEvent analysisMethodsAmongClinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy
Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, Pereira AC, Ingles J, Semsarian C, Jacoby D, Colan SD, Rossano JW, Wittekind SG, Ware JS, Saberi S, Helms AS, Ho CY. Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy. European Heart Journal 2021, 42: 1988-1996. PMID: 33769460, PMCID: PMC8139852, DOI: 10.1093/eurheartj/ehab148.Peer-Reviewed Original ResearchMeSH KeywordsAdultAtrial FibrillationCardiomyopathy, HypertrophicHeart FailureHeart-Assist DevicesHumansRegistriesConceptsChildhood-onset hypertrophic cardiomyopathyLife-threatening ventricular arrhythmiasHeart failureHypertrophic cardiomyopathyAtrial fibrillationVentricular arrhythmiasComposite endpointHCM patientsRisk of HFSarcomeric Human Cardiomyopathy RegistryNatural historyAdvanced HF therapiesOverall composite outcomeObservational cohort studyClinical risk stratificationHypertrophic cardiomyopathy patientsAge of diagnosisVentricular assist deviceAdult-onset diseaseHF therapyClinical characteristicsCohort studyComposite outcomeBaseline visitRisk stratificationImpact of the new heart allocation policy on patients with restrictive, hypertrophic, or congenital cardiomyopathies
Chouairi F, Mullan CW, Sen S, Mori M, Fuery M, Elder RW, Lesse J, Norton K, Clark KA, Miller PE, Mulligan D, Formica R, Rogers JG, Jacoby D, Maulion C, Anwer M, Geirsson A, Desai NR, Ahmad T. Impact of the new heart allocation policy on patients with restrictive, hypertrophic, or congenital cardiomyopathies. PLOS ONE 2021, 16: e0247789. PMID: 33651802, PMCID: PMC7924739, DOI: 10.1371/journal.pone.0247789.Peer-Reviewed Original ResearchMeSH KeywordsAdultCardiomyopathy, HypertrophicCardiomyopathy, RestrictiveFemaleHeart Defects, CongenitalHeart TransplantationHumansMaleMiddle AgedPolicyRegistriesTissue and Organ ProcurementUnited StatesConceptsCongenital heart diseaseAllocation system changeHeart allocation systemNew heart allocation policyNew heart allocation systemTransplantation of patientsOrgan Sharing databasePost-transplantation outcomesPost-transplant survivalTime of transplantationMechanical circulatory supportRate of transplantationNumber of patientsHeart allocation policyNew allocation systemStatus 1ACardiac transplantAdult patientsSharing databaseWaitlist survivalCirculatory supportClinical benefitCongenital cardiomyopathyUnited NetworkCHD patientsMavacamten for hypertrophic obstructive cardiomyopathy – Authors' reply
Jacoby D, Ho CY, Lester SJ, Wang A, Olivotto I. Mavacamten for hypertrophic obstructive cardiomyopathy – Authors' reply. The Lancet 2021, 397: 369-370. PMID: 33516332, DOI: 10.1016/s0140-6736(20)32391-6.Peer-Reviewed Original Research
2020
Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy
Lakdawala NK, Olivotto I, Day SM, Han L, Ashley EA, Michels M, Ingles J, Semsarian C, Jacoby D, Jefferies JL, Colan SD, Pereira AC, Rossano JW, Wittekind S, Ware JS, Saberi S, Helms AS, Cirino AL, Leinwand LA, Seidman CE, Ho CY. Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy. Circulation Genomic And Precision Medicine 2020, 14: e003062. PMID: 33284039, DOI: 10.1161/circgen.120.003062.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyClinical outcomesNew York Heart Association IIIImplantable cardioverter-defibrillator utilizationSevere heart failure symptomsHeart failure symptomsReduced ejection fractionRetrospective cohort studyImpact of sexSex-based differencesHCM centersCause mortalityTract obstructionBaseline characteristicsCohort studyEjection fractionHeart failureVentricular arrhythmiasFemale sexHCM patientsMyocardial performanceFailure symptomsInternational registrySarcomere variantsHigh burdenMavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy
Saberi S, Cardim N, Yamani M, Schulz-Menger J, Li W, Florea V, Sehnert AJ, Kwong RY, Jerosch-Herold M, Masri A, Owens A, Lakdawala NK, Kramer CM, Sherrid M, Seidler T, Wang A, Sedaghat-Hamedani F, Meder B, Havakuk O, Jacoby D. Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy. Circulation 2020, 143: 606-608. PMID: 33190524, DOI: 10.1161/circulationaha.120.052359.Peer-Reviewed Original ResearchBenzylaminesCardiomyopathy, HypertrophicFemaleHumansMagnetic Resonance Imaging, CineMaleMiddle AgedUracilTemporal 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 groupSpatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy
Helms AS, Thompson AD, Glazier AA, Hafeez N, Kabani S, Rodriguez J, Yob JM, Woolcock H, Mazzarotto F, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Olivotto I, Ho CY, Day SM. Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients with Hypertrophic Cardiomyopathy. Circulation Genomic And Precision Medicine 2020, 13: 396-405. PMID: 32841044, PMCID: PMC7676622, DOI: 10.1161/circgen.120.002929.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathyPathogenic variantsClinical outcomesSarcomeric Human Cardiomyopathy RegistryTruncating variantsHypertrophic cardiomyopathy cohortAdverse event ratesSimilar clinical severityDetailed genotype-phenotype correlationRat ventricular myocytesC10 domainCardiomyopathy cohortGenotype-phenotype correlationMyofilament incorporationFamilial hypertrophic cardiomyopathyClinical severityGenotyped patientsCommon causeMorphological severityTime-event analysisCardiac morphologyPatientsLoss of functionCardiomyopathyVentricular myocytesStudy 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 therapyEvaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy
Ho CY, Mealiffe ME, Bach RG, Bhattacharya M, Choudhury L, Edelberg JM, Hegde SM, Jacoby D, Lakdawala NK, Lester SJ, Ma Y, Marian AJ, Nagueh SF, Owens A, Rader F, Saberi S, Sehnert AJ, Sherrid MV, Solomon SD, Wang A, Wever-Pinzon O, Wong TC, Heitner SB. Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy. Journal Of The American College Of Cardiology 2020, 75: 2649-2660. PMID: 32466879, DOI: 10.1016/j.jacc.2020.03.064.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBenzylaminesBiomarkersCardiomyopathy, HypertrophicDouble-Blind MethodEchocardiographyFemaleHumansMaleMiddle AgedUracilConceptsNonobstructive hypertrophic cardiomyopathyGeometric mean differencePlacebo groupHypertrophic cardiomyopathyN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptidePg/Mean differencePhase II studySerious adverse eventsVentricular ejection fractionMyocardial wall stressDose titrationNT-proBNPAdverse eventsII studySymptomatic patientsEjection fractionPharmacological therapyClinical parametersInitial doseNatriuretic peptideMean ageHigh burdenMavacamten