Download Initial manifestation of DCM caused by a mutation in lamin A/C

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
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