ΜΥΟΚΑΡΔΙΟΠΑΘΕΙΕΣ. Ανεξήγητη βραδυκαρδία µε ή χωρίς διαταραχές κολποκοιλιακής αγωγής: τι µπορεί να κρύβει? ΕΦΗ Ι. ΠΡΑΠΠΑ Καρδιολόγος

Transcription

1 ΜΥΟΚΑΡΔΙΟΠΑΘΕΙΕΣ Ανεξήγητη βραδυκαρδία µε ή χωρίς διαταραχές κολποκοιλιακής αγωγής: τι µπορεί να κρύβει? ΕΦΗ Ι. ΠΡΑΠΠΑ Καρδιολόγος Β Καρδιολογική Κλινική, ΠΓΝΑ «Ο ΕΥΑΓΓΕΛΙΣΜΟΣ»

2 CONFLICT of INTEREST : none declared

3 CLASSIFICATION OF THE CARDIOMYOPATHIES: a position statement from the ESC Working Group on myocardial and pericardial diseases Eur Heart Journal we define a cardiomyopathy as: A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of CAD, hypertension, valvular disease and CHD sufficient to cause the observed myocardial abnormality phenotype RED FLAGS genotype unexplained bradycardia ± AVD = RED FLAG

4 Cardiomyopathies and Cardiac Conduction Disturbances HCM FABRY (GLA) DANON (LAMP2) AMPK (PRKAG2) DCM RCM Other phenotypes LMNA EMD SCN5A DES SCN5A

5 HCM phenotype

6 FABRY DISEASE familial storage disease (metabolic cardiomyopathy) caused by a deficiency of the lysosomal enzyme A-galactosidase A (a- Gal) substrate accumulation Stroke, ear, eye, CNS heart angiokeratoma renal ANS vacuolization in lysosomes acroparesthesia

7 Θολερότης φακού και κερατοειδούς, µε φυσιολογική όραση «Fabry cataract» Split-lamp Life expectancy: 40yrs Prevalence : 6-8% of concentric LVH Delay in diagnosis : 14 years!!

8 Pacemaker in 10-20% Prevalence : 8% of concentric LVH - Sinus bradycardia - Short PR - Later AVB DIAGNOSIS - αgal activity - biopsy - Genetic analysis MRI Concentric LVH LGE basal-mid posterolateral

9 crusial! Distinguish FABRY from HCM is

10 X-linked dominant lysosomal disease, due to a primary deficiency of lysosome-associated membrane protein 2 caused by several mutations in the LAMP2 gene DANON DISEASE Pathological hallmark: intracytoplasmic vacuoles containing autophagic material and glycogen in cardiac and skeletal muscle cells. Prevalence : 6-8% of concentric LVH

11 Phenotype: cardiomyopathy (88%, HCM), skeletal myopathy (muscle weakness, CPK), liver, retina, lungs, mental retardation (70%). Early onset (mean age 17yrs), women later (mild disease, HCM + DCM). ECG: - very high voltage of LV - inverted T waves - WPW (35%) Echo: - massive LVH, mostly concentric

12 There is no specific treatment for Danon disease, except heart transplantation! ICD fails to terminate lethal ventricular tachyarrhythmias in most Cheng at al. EHJ 2012 Marron editorial. EHJ 2012 crusial! Distinguish HCM from DANON is Danon is characterized by early morbidity and limited life expectancy, with survival beyond 25yrs uncommon! 65mm The DANON REGISTRY reports the following disease landmarks on average: First symptoms 12yrs, rapid deterioration (6mo), transplant 18yrs, death without transplant 19yrs boy, 12 27yrs old

13 (AMP kinase) 19yo, PR PRKG2 mutation The AMP kinase is enzyme system that appears to act as a fuel gauge in cells, as a modulator of ATP sensitivity to cellular energy requirements. PRKG2 mutations may cause LVH mimicking HCM + (WPW and AVB) + skeletal myopathy ECG: gradual changes, unrelated to LVH progression. 28yo, rsr + LAH LVH slowly progressive Myopathy : 15%, severe myalgia during/ after short burst of aerobic exercise. Proximal skeletal myopathy. EMG may be normal. Biopsy: mitochondrial proliferation with minimal excess glycogen

14 DCM phenotype

15 LAMINOPATHIES The LMNA gene encodes nuclear lamin A and C, intermediate filament proteins that are components of the nuclear lamina. LMNA = 5-8% of DCM pts Lu. LMNA. Disease Models and Mechanisms 2011

16 CARDIAC INVOLVEMENT : DCM ± ARRHYTHMIC DISORDERS Progression of age-related phenotypes in LMNA Patients with LMNA may present a wide range of arrhythmic disturbances, either bradyarrhytmias (conduction disturbances and AV-blocks, sinus node dysfunction, atrial standstill) or tachyarrhythmias (AF, VT, VF), in variable combinations, and with frequent association with LV dysfunction and HF. Severity of arrhythmias is usually not related to the presence and degree of neuromuscular impairment. Emery Dreifuss muscular dystrophy: wasting of humeral muscle + elbow contracture AVB, later DCM

17 Index case AF with complete AVB, LBBB Male, 64yrs old, aborted SD LBBB, AF from 40y EF~48% MRI : IVS mid-wall LGE (fibrosis) LMNA mutation ICD. 6 months later: VT from basal IVS - ablation Wenckebach Son, asymptomatic ECG EF normal No MRI LMNA mutation ICD for primary prevention

18 JACC 2012

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20 LAMINOPATHIES are a functional continuum of related disorders rather than separate diseases. In this setting, each phenotype may be mistakenly considered as a specific diagnosis by physicians working without a pedigree or long-term follow-up. Cardiology 2011 H. Boudoulas et al.

21 Ion channel SCN5A mutation DCM Male 47yo. LBBB when 30yo. DCM+AF Most genes associated with DCM encode for structural proteins involved with contractile function and the cytoskeletal matrix. Discovery of mutation in gene SCN5A associated with DCM suggests that dysfunction in electrical excitability, caused by disruption of sodium channel function, Male 41yo. AF/RBBB when 22. Normal EF also leads to dilation remodeling. Common phenotype: Early AVB, SN dysfunction, AF, years later DCM

22 Desminopathies are heterogeneous group of severe, dominantly inherited myopathies, often accompanied by cardiomyopathy, with syncope or sudden death due to conduction defects. (DCM, IVNC, RCM). Onset and progression are variable. DESMIN myopathy/cardiomyopathy

23 Health [in] Code

24 Cardiologists don t think in cardiac conduction disturbances like an important entity 4 requests in the last 2 years! Health [in] Code

25 Cardiology 2011 H. Boudoulas et al.

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