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 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 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 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 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 predictionPatientsArrhythmiasSurvival Following Implantable Cardioverter‐Defibrillator Implantation in Patients With Amyloid Cardiomyopathy
Higgins AY, Annapureddy AR, Wang Y, Minges KE, Lampert R, Rosenfeld LE, Jacoby DL, Curtis JP, Miller EJ, Freeman JV. Survival Following Implantable Cardioverter‐Defibrillator Implantation in Patients With Amyloid Cardiomyopathy. Journal Of The American Heart Association 2020, 9: e016038. PMID: 32867553, PMCID: PMC7726970, DOI: 10.1161/jaha.120.016038.Peer-Reviewed Original ResearchConceptsImplantable cardioverter defibrillator implantationCardioverter-defibrillator implantationNonischemic cardiomyopathyCardiac amyloidosisDiabetes mellitusCerebrovascular diseaseVentricular tachycardiaMultivariable Cox proportional hazards regression modelsCox proportional hazards regression modelProportional hazards regression modelsKaplan-Meier survival curvesCox proportional hazards modelPropensity-matched cohortOutcomes of patientsHazards regression modelsProportional hazards modelCause mortalityICD implantationRenal functionMultivariable analysisConclusions MortalityRisk factorsRegistry dataAmyloid cardiomyopathyHigh riskDesmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy
Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, Mazzanti A, McCanta AC, Agarwal PP, Arscott P, Dellefave-Castillo LM, Vorovich EE, Nutakki K, Wilsbacher LD, Priori SG, Jacoby DL, McNally EM, Helms AS. Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy. Circulation 2020, 141: 1872-1884. PMID: 32372669, PMCID: PMC7286080, DOI: 10.1161/circulationaha.119.044934.Peer-Reviewed Original ResearchConceptsLV late gadolinium enhancementLate gadolinium enhancementSevere ventricular arrhythmiasAcute myocardial injuryMyocardial injuryRight ventricular cardiomyopathyVentricular arrhythmiasGadolinium enhancementVentricular cardiomyopathyEjection fractionSevere arrhythmiasFrequent premature ventricular contractionsPathogenic plakophilin-2 mutationNormal LV systolic functionLeft ventricle ejection fractionRight ventricular ejection fractionPositron emission tomography scanArrhythmogenic right ventricular cardiomyopathyNormal ventricular functionLV systolic functionVentricle ejection fractionVentricular ejection fractionEmission tomography scanSmall case seriesPlakophilin-2 mutations
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 ResearchAdvanced Cardiac Imaging and the Complexity of Diagnosing Cardiac Sarcoidosis
Miller EJ, Jacoby D. Advanced Cardiac Imaging and the Complexity of Diagnosing Cardiac Sarcoidosis. Circulation Cardiovascular Imaging 2019, 12: e009275. PMID: 31177819, DOI: 10.1161/circimaging.119.009275.Commentaries, Editorials and Letters