Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias
Haghighi K, Gardner G, Vafiadaki E, Kumar M, Green LC, Ma J, Crocker JS, Koch S, Arvanitis DA, Bidwell P, Rubinstein J, van de Leur R, Doevendans PA, Akar FG, Tranter M, Wang HS, Sadayappan S, DeMazumder D, Sanoudou D, Hajjar RJ, Stillitano F, Kranias EG. Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias. Journal Of Personalized Medicine 2021, 11: 502. PMID: 34204946, PMCID: PMC8226909, DOI: 10.3390/jpm11060502.Peer-Reviewed Original ResearchRight ventricleMalignant ventricular arrhythmiasEarly risk factorsAction potential durationCaMKII inhibitor KN93Stress-induced impairmentCellular pathogenic mechanismsProarrhythmic parametersSR Ca loadPrognostic factorsRisk stratificationVentricular arrhythmiasHumanized micePoor prognosisVentricular tachyarrhythmiasFatal arrhythmiasAsymptomatic carriersElectrocardiographic featuresRisk factorsAtrioventricular conductionContractile parametersPotential durationCardiomyopathy onsetPathogenic mechanismsHuman wild typeArrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Raad N, Bittihn P, Cacheux M, Jeong D, Ilkan Z, Ceholski D, Kohlbrenner E, Zhang L, Cai CL, Kranias EG, Hajjar RJ, Stillitano F, Akar FG. Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation. Circulation 2021, 144: 441-454. PMID: 34024116, PMCID: PMC8456417, DOI: 10.1161/circulationaha.119.043502.Peer-Reviewed Original ResearchConceptsHuman PLNRapid pacingInterventricular activation delayHumanized mouse modelAction potential prolongationLocal conduction blockSteep repolarization gradientsArrhythmogenic featuresMacroreentrant circuitHemodynamic changesElectric remodelingElectrophysiological remodelingRight ventricleVentricular tachycardiaPotential prolongationSudden deathConduction blockMouse modelAdult knockArrhythmia susceptibilityAdrenergic stimulationStructural remodelingArrhythmogenic phenotypeArrhythmia mechanismsRegulatory protein phospholamban