2021
Loss 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
2020
Evaluation 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 ResearchConceptsNonobstructive 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