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
2022
Pragmatic randomized trial assessing the impact of digital health technology on quality of life in patients with heart failure: Design, rationale and implementation
Victoria‐Castro A, Martin M, Yamamoto Y, Ahmad T, Arora T, Calderon F, Desai N, Gerber B, Lee KA, Jacoby D, Melchinger H, Nguyen A, Shaw M, Simonov M, Williams A, Weinstein J, Wilson FP. Pragmatic randomized trial assessing the impact of digital health technology on quality of life in patients with heart failure: Design, rationale and implementation. Clinical Cardiology 2022, 45: 839-849. PMID: 35822275, PMCID: PMC9346973, DOI: 10.1002/clc.23848.Peer-Reviewed Original ResearchConceptsQuality of lifeHF patientsYale New Haven Health SystemKansas City Cardiomyopathy QuestionnaireDigital health technologiesHeart failure careHealth technologiesDigital health interventionsDisease exacerbationHF clinicUsual carePrimary outcomeClinical outcomesHeart failurePatient engagementPatientsHealth interventionsDigital health toolsPatient empowermentHealth systemPatient usabilityHealth toolsEarly detectionFirst enrollmentHealthcare system
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 mutationMavacamtenTissueVariability in Blood Pressure Assessment in Patients Supported with the HeartMate 3TM
Cowger JA, Estep JD, Rinde-Hoffman DA, Givertz MM, Anderson AS, Jacoby D, Chen L, Brieke A, Mahr C, Hall S, Ewald GA, Dirckx N, Baker AT, Pinney SP. Variability in Blood Pressure Assessment in Patients Supported with the HeartMate 3TM. ASAIO Journal 2021, 68: 374-383. PMID: 34172641, DOI: 10.1097/mat.0000000000001497.Peer-Reviewed Original ResearchConceptsDoppler opening pressureSystolic blood pressureRadial pulsePalpable radial pulseBlood pressure controlBlood pressure assessmentHeartMate 3 patientsCuff measuresMedication titrationPalpable pulseBlood pressureMean arterialMedical managementPulse pressureBP valuesPressure assessmentPressure controlPatientsOpening pressureMmHgModerate correlationNoninvasive measurementNoninvasive instrumentPearson correlationOutpatientsComputational 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
Psychological stress in heart failure: a potentially actionable disease modifier
Harris KM, Jacoby DL, Lampert R, Soucier RJ, Burg MM. Psychological stress in heart failure: a potentially actionable disease modifier. Heart Failure Reviews 2020, 26: 561-575. PMID: 33215323, PMCID: PMC8026548, DOI: 10.1007/s10741-020-10056-8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHeart failurePsychological stressHeart failure symptomsHeart failure patientsLife stressorsDisease-related consequencesQuality of lifePatterns of exposureAdverse eventsFailure patientsDisease courseEjection fractionPatients' qualityModifiable factorsPatient subgroupsSymptom exacerbationDaily life stressorsFailure symptomsPathophysiological pathwaysEffective diseaseFunctional limitationsDiminished qualityPatientsActionable pathwaysStress exposureEvaluating Recruitment Strategies for a Randomized Clinical Trial with Heart Failure Patients
Conley S, O’Connell M, Linsky S, Moemeka L, Darden JW, Gaiser EC, Jacoby D, Yaggi H, Redeker NS. Evaluating Recruitment Strategies for a Randomized Clinical Trial with Heart Failure Patients. Western Journal Of Nursing Research 2020, 43: 785-790. PMID: 33158412, PMCID: PMC8099934, DOI: 10.1177/0193945920970229.Peer-Reviewed Original ResearchConceptsClinic-based recruitmentMultiple recruitment strategiesPatient portalsClinical trialsElectronic databasesChronic stable heart failureElectronic medical record databaseRecruitment strategiesStable heart failureHeart failure patientsChronic medical conditionsRandomized clinical trialsMedical record databaseBaseline data collectionCognitive behavioral therapyFailure patientsHeart failureMedical recordsMedical conditionsPatientsRecruitment goalsRecord databaseBehavioral therapySupport groupsTrialsDisease-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 predictionPatientsArrhythmiasTemporal 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 phenotypeAgePatientsSpatial 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 myocytesDifferential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes
Ivey-Miranda JB, Kunnirickal S, Bow L, Maulion C, Testani JM, Jacoby D, Kransdorf EP, Bellumkonda L. Differential Impact of Class I and Class II Panel Reactive Antibodies on Post-Heart Transplant Outcomes. Journal Of Cardiac Failure 2020, 27: 40-47. PMID: 32750489, DOI: 10.1016/j.cardfail.2020.07.012.Peer-Reviewed Original ResearchConceptsPanel reactive antibodyCause mortalityReactive antibodiesClass IClass II panel reactive antibodiesAdult heart transplant patientsPost-heart transplant outcomesClass IIRejection-related mortalityHeart transplant patientsOrgan Sharing dataHeart transplantationTransplant outcomesTransplant patientsSensitized patientsUnited NetworkIsolated elevationHigh riskGroup 2Group 1High mortalityCombined elevationGroup 4MortalityPatientsZinc Deficiency as a Reversible Cause of Heart Failure.
Rosenblum H, Bikdeli B, Wessler J, Gupta A, Jacoby DL. Zinc Deficiency as a Reversible Cause of Heart Failure. Texas Heart Institute Journal 2020, 47: 152-154. PMID: 32603465, PMCID: PMC7328074, DOI: 10.14503/thij-17-6586.Peer-Reviewed Case Reports and Technical NotesConceptsHeart failureZinc supplementationDepressed left ventricular systolic functionNew-onset heart failureLeft ventricular systolic functionZinc levelsLow plasma zinc levelsZinc deficiencyVentricular systolic functionPlasma zinc levelsCross-sectional studyCardiomyocyte oxidative stressOngoing pathogenesisReversible causesSystolic functionLower plasmaMyocardial structureNutritional deficienciesAnorexia nervosaOxidative stressPatientsSupplementationChief causeDeficiencyFailureHypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry
Marstrand P, Han L, Day SM, Olivotto I, Ashley EA, Michels M, Pereira AC, Wittekind SG, Helms A, Saberi S, Jacoby D, Ware JS, Colan SD, Semsarian C, Ingles J, Lakdawala NK, Ho CY. Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Insights from the SHaRe Registry. Circulation 2020, 141: 1371-1383. PMID: 32228044, PMCID: PMC7182243, DOI: 10.1161/circulationaha.119.044366.Peer-Reviewed Original ResearchConceptsLeft ventricular systolic dysfunctionVentricular ejection fractionComposite outcomeHypertrophic cardiomyopathyNatural historyEjection fractionLeft ventricular cavity sizeVentricular systolic dysfunctionPredictor of prognosisVentricular cavity sizeProportional hazards modelSignificant predictorsSystolic dysfunctionMedian timeAtrial fibrillationSpecialty centersSarcomeric variantsHazards modelIncident developmentPatientsEnd stageRelative rarityPrognosisOutcomesPredictorsMyosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy
Toepfer CN, Garfinkel AC, Venturini G, Wakimoto H, Repetti G, Alamo L, Sharma A, Agarwal R, Ewoldt JF, Cloonan P, Letendre J, Lun M, Olivotto I, Colan S, Ashley E, Jacoby D, Michels M, Redwood CS, Watkins HC, Day SM, Staples JF, Padrón R, Chopra A, Ho CY, Chen CS, Pereira AC, Seidman JG, Seidman CE. Myosin Sequestration Regulates Sarcomere Function, Cardiomyocyte Energetics, and Metabolism, Informing the Pathogenesis of Hypertrophic Cardiomyopathy. Circulation 2020, 141: 828-842. PMID: 31983222, PMCID: PMC7077965, DOI: 10.1161/circulationaha.119.042339.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsCardiac MyosinsCardiomyopathy, HypertrophicCells, CulturedEnergy MetabolismHumansInduced Pluripotent Stem CellsMiceMolecular Dynamics SimulationMuscle RelaxationMutation, MissenseMyocardial ContractionMyocytes, CardiacMyosin Heavy ChainsProtein ConformationSarcomeresConceptsProportion of myosinAdverse clinical outcomesHypertrophic cardiomyopathyHeart failureUnknown clinical significanceClinical outcomesClinical significancePathogenic variantsSarcomere functionSarcomere protein genesPathogenic missense variantsMyosin missense mutationsHemodynamic requirementsImpaired relaxationContractile abnormalitiesHealthy rodentsHypertrophic remodelingHemodynamic demandsPatient riskPoor relaxationCardiomyocyte contractilityHeart functionMyosin ATPase activityPatientsAllosteric modulators
2019
Participation 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 adviceParticipantsAdvice