2024
Impact 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 analysisPatientsCardiomyopathy
2021
Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy
Goli R, Li J, Brandimarto J, Levine LD, Riis V, McAfee Q, DePalma S, Haghighi A, Seidman JG, Seidman CE, Jacoby D, Macones G, Judge DP, Rana S, Margulies KB, Cappola TP, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Alexis JD, Boehmer J, Kamiya C, Gustafsson F, Damm P, Ersbøll AS, Goland S, Hilfiker-Kleiner D, McNamara DM, Investigators T, Arany Z. Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy. Circulation 2021, 143: 1852-1862. PMID: 33874732, PMCID: PMC8113098, DOI: 10.1161/circulationaha.120.052395.Peer-Reviewed Original ResearchConceptsPeripartum cardiomyopathyClinical presentationRisk factorsPrevalence of preeclampsiaVentricular ejection fractionStrong risk factorImportant risk factorTiming of presentationInternational academic centersPrevalence of TTNtvClinical recoveryHeart failureClinical outcomesEjection fractionInclusion criteriaTherapeutic approachesClinical informationGenotype/phenotype associationsAcademic centersTTNtvCardiomyopathyTruncating variantsGenetic testingWomenGenetic counselingComputational 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 ResearchConceptsHypertrophic cardiomyopathyClinical riskMissense variantsSarcomeric Human Cardiomyopathy RegistryHigh clinical riskClinical risk stratificationAdverse eventsComposite endpointRisk stratificationHCM patientsCommon causePatientsLoss of functionUncertain significanceMYBPC3Missense VUSCardiomyopathyHigh rateSubstantial numberSupportive evidenceVUSRiskVariant interpretationEvent analysisMethodsAmong
2020
Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions
Zhang X, Walsh R, Whiffin N, Buchan R, Midwinter W, Wilk A, Govind R, Li N, Ahmad M, Mazzarotto F, Roberts A, Theotokis PI, Mazaika E, Allouba M, de Marvao A, Pua CJ, Day SM, Ashley E, Colan SD, Michels M, Pereira AC, Jacoby D, Ho CY, Olivotto I, Gunnarsson GT, Jefferies JL, Semsarian C, Ingles J, O’Regan D, Aguib Y, Yacoub MH, Cook SA, Barton PJR, Bottolo L, Ware JS. Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions. Genetics In Medicine 2020, 23: 69-79. PMID: 33046849, PMCID: PMC7790749, DOI: 10.1038/s41436-020-00972-3.Peer-Reviewed Original ResearchConceptsRare missense variantsCardiac conditionsSevere adverse outcomesMissense variantsDisease-specific informationAdverse outcomesClinical severityPatient outcomesHypertrophic cardiomyopathyAge 60Disease statusDisease specificityFunction variantsBenign variantsCardiomyopathyRare variationProportion of variantsDisease-associated variantsOutcomesVariant interpretationProbability of pathogenicityGene-disease relationshipsVariant pathogenicity predictionPatientsArrhythmiasSpatial 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 myocytes
2019
Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes
Sewanan LR, Schwan J, Kluger J, Park J, Jacoby DL, Qyang Y, Campbell SG. Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes. JACC Basic To Translational Science 2019, 4: 495-505. PMID: 31468004, PMCID: PMC6712054, DOI: 10.1016/j.jacbts.2019.03.004.Peer-Reviewed Original ResearchHypertrophic cardiomyopathySarcomeric gene mutationsMiniature swine modelPluripotent stem cell-derived cardiomyocytesExtracellular matrix abnormalitiesStem cell-derived cardiomyocytesPoor relaxationCell-derived cardiomyocytesHealthy cardiomyocytesExtracellular matrixMouse modelPharmacological correctionProlonged contractionSwine modelHealthy extracellular matrixMuscle contractionGene mutationsMatrix abnormalitiesTwitch dynamicsCardiomyocytesContractionCardiomyopathyTherapyMyocardiumAbnormalitiesPrediction of ventricular arrhythmia and sudden death in arrhythmogenic right ventricular cardiomyopathy
McKenna WJ, Asaad NA, Jacoby DL. Prediction of ventricular arrhythmia and sudden death in arrhythmogenic right ventricular cardiomyopathy. European Heart Journal 2019, 40: 1859-1861. PMID: 30977786, DOI: 10.1093/eurheartj/ehz195.Commentaries, Editorials and LettersParticipation in thrill-seeking activities by patients with hypertrophic cardiomyopathy: Individual preferences, adverse events and physician attitude
Papoutsidakis N, Heitner S, Ingles J, Semsarian C, Mannello M, Salberg L, Waldman C, Vaccaro B, Maurizi N, Olivotto I, Jacoby D. Participation in thrill-seeking activities by patients with hypertrophic cardiomyopathy: Individual preferences, adverse events and physician attitude. American Heart Journal 2019, 214: 28-35. PMID: 31152873, DOI: 10.1016/j.ahj.2019.04.001.Peer-Reviewed Original ResearchConceptsMinor adverse eventsMajor adverse eventsAdverse eventsHCM patientsHypertrophic cardiomyopathyThrill-seeking activitiesPhysician adviceSudden cardiac deathAdult HCM patientsShared-decision makingTime of surveyCardiac deathDefinitive recommendationsRisk factorsHCM diagnosisSafety dataPhysicians' attitudesPatientsAnonymous online surveyReporting participationSame dayCardiomyopathySpecific adviceParticipantsAdviceResponse by Ho et al to Letter Regarding Article, “Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)”
Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Lakdawala NK, Ware JS, Helms AS, Colan SD, Seidman CE, Olivotto I, Investigators F. Response by Ho et al to Letter Regarding Article, “Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)”. Circulation 2019, 139: 1559-1560. PMID: 30883221, PMCID: PMC6445361, DOI: 10.1161/circulationaha.118.039069.Peer-Reviewed Case Reports and Technical Notes