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Initial manifestation of DCM caused by a mutation in lamin A/C-gene in early pregnancy Dr. Anna Neugebauer Medizinische Klinik 1 CCP Venice 2014 DCM Characterized by left ventricular dilatation and impaired systolic function Leading cause of heart failure Genetic inheritance is increasingly elucidated with variants baring prognostic significance for SCD Leopoldina Krankenhaus Schweinfurt history 26 – year old actress 9.12.06: cardiac arrest on stage: CPR and defibrillation Hospital: exclusion of neurological complications Transfer to Cardiology department 15th week of gestation: no harm to fetus suspected to all-or- none law of early gestation Leopoldina Krankenhaus Schweinfurt Cardiologic examinations ECG: Sinus rhythm, f 103/min, incomplete right bundle branch block, no ST-Elevation Echo: nondilated left ventricle with slight septal hypertrophy and moderate systolic dysfunction Holter recording: several non-sustained ventricular tachycardia →invasive examinations were avoided due to pregnancy Leopoldina Krankenhaus Schweinfurt Gynecological examination: First one at day of admission: No vaginal bleeding, positive heart beating, crown-rump length 21 mm, amniotic cavity intact In course of gravidity: No gynecological problems Detailed family history Father AICD because of ventricular tachycardia Father´s sister: died of sudden cardiac death at the age of 50 Paternal grandfather died suddenly at the age of 37 Family heart disease assumed Leopoldina Krankenhaus Schweinfurt Therapy and clinical course Metoprolol 47,5 mg ½-0-½ life-vest (wearable automatic defibrillator) before discharge Close cardiological and obstetrical surveillance Spent last three weeks of gestation in hospital due to nsvts Gave birth to a healthy boy by cesarean section at 18.06.06 (surgery without complications) Leopoldina Krankenhaus Schweinfurt Further course after delivery After delivery implantation of an ICD for secondary prophylaxis Coronary angiography: no coronary heart disease endomyocardial biopsy: no active myocarditis, no storage disease Genetic testing: proof of DCM, non-described mutation in lamin A/C-gene (stop mutation: 1400G>A , pTrp467Stop heterozygote) Leopoldina Krankenhaus Schweinfurt Further course until now Several effective AICD- shocks because of ventricular tachycardia 8/11 bradycardia and AV-bloc II Mobitz because of lymeborreliosis 10/11 bivent system Now listed for heart transplantation Boy healthy – so far not tested for DCM Leopoldina Krankenhaus Schweinfurt conclusion Cause of familial DCM – 50% of all cases of idiopathic cardiomyopathies- are mutations in the cytoskeletal/sarcomeric protein-encoding genes, especially including lamin A/C Hints for lamin A/C-mutation: ventricular tachycardia, conduction defects, mild dilatation with severe dysfunction, elevated CK-levels and perhaps skeletal muscle involvement. Identification of mutation carriers may lead to early prevention of SCD. Leopoldina Krankenhaus Schweinfurt Conclusion- Prognosis : Significantly worse for people with LMNA-mutation Higher cardiac mortality because of SCD (because of arrhythmias) or heart failure Leopoldina Krankenhaus Schweinfurt DCM due to lamin-A/C gene mutation Figure 5 Kaplan-Meier cumulative survival curves for (A) cardiovascular death, (B) cardiovascular death or transplant, and (C) cardiovascular death, transplant, or major cardiac events in 105 patients with dilated cardiomyopathy, carriers of lamin A/C gene mutations (dashed lines), and non-carriers (solid lines). P values are derived by Cox regression. Matthew R.G. Taylor, Pamela R. Fain et al. Natural history Of dilated cardiomyopathy due to lamin A/C gene mutations JACC 2003;41; 771-780 Medizinische Klinik I, Leopoldina Krankenhaus Schweinfurt Thank you for your attention