2021
Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use
Wendt FR, Koller D, Pathak GA, Jacoby D, Miller EJ, Polimanti R. Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use. Clinical Pharmacology & Therapeutics 2021, 110: 777-785. PMID: 33837531, PMCID: PMC8376807, DOI: 10.1002/cpt.2260.Peer-Reviewed Original ResearchConceptsLDL-C concentrationsSimvastatin useLow-density lipoprotein cholesterol concentrationsLipoprotein cholesterol concentrationsDrug-metabolizing enzymesElectronic medical recordsStatin therapyStatin treatmentActivity scoreMedical recordsPilot cohortCholesterol concentrationsEuropean ancestry participantsMetabolizer phenotypeClinical decisionNAT2 allelesPolygenic riskNAT2Good responseUK BiobankBiological mechanismsPharmacogenesAssociationPotential benefitsPhenotypeGenetic 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 ResearchMeSH KeywordsAdultCardiomyopathiesFemaleHumansPeripartum PeriodPhenotypePregnancyRetrospective StudiesConceptsPeripartum 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 counseling
2020
Temporal 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 myocytesAssociation of Race With Disease Expression and Clinical Outcomes Among Patients With Hypertrophic Cardiomyopathy
Eberly LA, Day SM, Ashley EA, Jacoby DL, Jefferies JL, Colan SD, Rossano JW, Semsarian C, Pereira AC, Olivotto I, Ingles J, Seidman CE, Channaoui N, Cirino AL, Han L, Ho CY, Lakdawala NK. Association of Race With Disease Expression and Clinical Outcomes Among Patients With Hypertrophic Cardiomyopathy. JAMA Cardiology 2020, 5: 83-91. PMID: 31799990, PMCID: PMC6902181, DOI: 10.1001/jamacardio.2019.4638.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAtrial FibrillationBlack or African AmericanCardiomyopathy, HypertrophicCohort StudiesDeath, Sudden, CardiacDefibrillators, ImplantableFemaleGenetic TestingHealth Services AccessibilityHealthcare DisparitiesHeart FailureHeart SeptumHeart TransplantationHeart-Assist DevicesHumansMaleMiddle AgedMortalityPhenotypeQuality of Health CareStrokeUnited StatesWhite PeopleConceptsNYHA class IIIAssociation of raceVentricular assist device implantationOverall composite outcomeSeptal reduction therapyAssist device implantationHeart failureBlack patientsHypertrophic cardiomyopathyCause mortalityWhite patientsAtrial fibrillationClass IIICardiac transplantationGenetic testingComposite outcomeClinical outcomesDisease expressionDevice implantationReduction therapyNew York Heart Association functional class IIIMultivariable Cox proportional hazards regressionInvasive septal reduction therapySarcomeric Human Cardiomyopathy RegistryImplantable cardioverter-defibrillator therapy
2019
Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation
Ng R, Manring H, Papoutsidakis N, Albertelli T, Tsai N, See CJ, Li X, Park J, Stevens TL, Bobbili PJ, Riaz M, Ren Y, Stoddard CE, Janssen PM, Bunch TJ, Hall SP, Lo YC, Jacoby DL, Qyang Y, Wright N, Ackermann MA, Campbell SG. Patient mutations linked to arrhythmogenic cardiomyopathy enhance calpain-mediated desmoplakin degradation. JCI Insight 2019, 5 PMID: 31194698, PMCID: PMC6675562, DOI: 10.1172/jci.insight.128643.Peer-Reviewed Original Research