il ruolo del cardiologo nelle miopatie
DESCRIPTION
Presentazione realizzata dalla dott.ssa Daniela Miani, Unità Scompenso e Trapianto Cardiaco, AOU S. Maria della Misericordia di Udine, nell'ambito del corso "Le malattie neuromuscolari", Udine, 16 dicembre 2013. Per maggiori informazioni: http://malattierare.aou.udine.it/TRANSCRIPT
Il ruolo del cardiologo nelle miopatie
Daniela Miani
AZIENDA OSPEDALIERO-UNIVERSITARIA
“S. MARIA DELLA MISERICORDIA”
UDINE
Dipartimento di Scienze Cardiotoraciche
malattie neuromuscolari dell’adulto: dalla diagnosi al follow-up e gestione
delle complicanze. Creazione di un percorso assistenziale coordinato per le
malattie neuromuscolari
UDINE 16 dicembre 2013
Background
• Heart and skeletal muscle share similar
molecular, anatomical and clinical features.
• Cardiomyocytes and skeletal myofibers have
the same sarcomeric structure
• General architecture of the cell, calcium
handling, regenerative capacity is different
Background
• Structural and funcional gene abnormalities
producing degeneration of the heart muscle can
similarly produce degeneration of the skeletal
muscle and viceversa.
• 26% of paediatric cardiomyopathies have
associated neuromuscolar disorders disease (Towbin
JA et al al Jama 2006)
• 25% of genes associated with cardiomyopathies
are also causative of neuromuscolar disorders
as allelic forms.(Kostareva A et al Front Biosci 2013)
Case Report - 1
� DE female (born 10/1/1955)
� Age 35 years: first episode of sustained VT with Left Bundle Branch morphology and inferior axis. Treated with DC shock
� ECG : SR, 1°AVB, RBBB + LAH� Echocardiogram: DV 72 ml SV 54 ml. EF 30% Hypokinesiaof inferior basal segments. PAP32 mmHg.
� Coronarography: normal coronary arteries
� EMB: non sufficient.
� EPS : negative for arrhythmias induction.
� Discharged in therapy with : Amiodaron ->Sotalol, Ramipril, Tapazole
ECG
Case Report 1
Case Report - 1
� EF 45%-> 25%
� 8/4/2000 ICD implanted
� 2005: Multiple sustained VT treated with DC shock
� NYHA III Class.
� Echo: EF 16% diastolic dysfunction III°.
� Therapy: Digitalis, Aldacton , Tiroxin , Bisoprolol, Furosemide, Metolazon, Amiodaron
� Right Heart Cardiac Cat: CI 1,69, CO 2,5 WP 19, VP 20, PAP 34/19-25 SVR 1605 DS/cm5
� Cardiac transplantation 11/2/2006
Ventricular tachycardia LBB inferior axis
(150 bpm)
Case Report 1
Case Report 1
ECG
Neurological examination (2006)
� Suspected limb girdle myopathy. CK and LDH mild elevated.
� EMG confirms hypotesys of protopathic myopathy
�NE confirms proximal strenght deficiency at girdlelevel with winged scapula and hyperlordosis, ambulation anserina deficiency of neck flexormuscles, abduce arms for 75°(F=3+)
�Deficiency muscle gluteus medius and ileopsoas.
� EMG: primitive myopathic suffering of biceps brachiiand tibialis anterior
Case Report 1
Pathology: gross examination
Case Report 1
Dystrophin A
Case Report 1
Dystrophin B
Case Report 1
Case Report - 2
PL, female 59y proband
�Hystory of Atrial fibrillation and flutter since 25 yrs
� ECG: WPW, LV hypertrophy ->LBBB
� ECHO: mild hypertrophy, FE 56%-> DCM (46yrs)
�Myopathy, normal CK, hypoacusia
�Heart transplant at 51yrs (2002) for cardiac arrestdue to VF
�Genetic mutation: LAMP2+ (249 G>A)
Case Report 2
Case Report 2
ECG
Case Report 2
ECG
Neurological examination
�Age 54, she reported muscolar weakness and myalgia. She had mild proximal and flexormuscle weakness, facial hypomimia. CK levelswere normal
�Cognitive records were normal (IQ=82 by WAIS R scale). Quadriceps femori muscle biopsyshowed mild myopathic changes without fibervacuolization
Case Report 2
Pathology: gross examination
Case Report 2
Case Report 2
H&E
Collections of infiltrating macrophages and focal PAS-positive accumulation were also present. Microscope magnification, 400
Vacuolization and autophagic degeneration of cardiomyocytesand extensive replacement fibrosis in cardiac muscle
Case Report 2
MD, male 30y son
� Symptomatic since 28 yrs: palpitations, presyncopal episode
� ECG: WPW, LVH
� ICD on 2005
� Echo: left ventricle enlarged with septal hypertrophy (basal12 mm medium 15 mm with apical trabecole); normal EF (60%); biatrial enlargement.
� Heart failure
� Heart transplant at 34 yrs (2007)
� Cognitive impairment; myopathy; obesity
� Genetic mutation: LAMP2+ (249 G>A)
Case Report 3
Neurological investigation
� Age 28 muscle weakness and CK 1094U/l skeletal musclebiopsy: vacuolar myopathy with PAS positive material. Muscle CT scan: moderate proximal and distal atrophy oflower limbs
� Age 30 mild difficulty in climbing stairs and lifting weights
� NE: mild waddling gait with hyperlordosis. Gower’s sign, distal leg muscle hypotrophy, mild weakness of proximaland distal girdles, neck flexor and facial muscles.
� PE: IQ 77 (WAIS R) delayed psychomotor development. EEG: Diffuse slow dys-arrhythmia.
Case Report 3
Case Report 3
ECG
Pathology: gross examination
Case Report 3
Case Report 3
H&E
Case Report 3
Different degrees of skeletal muscle fibers involvementmilder degree of vacuolization and many fibers with apparently normal features
mild myopathic changes but no fiber vacuolization or degeneration.
Case Report 2-3
CM, female 42y niece
� Symptomatic since 34 years for palpitations
� Physical examination: normal
� ECG: normal
� Echo: normal
� RMN: normal
� Holter monitoring: BEV >30/h, > 50/h, couplets, NSVT max 6 beats
� Genetic screening in 2005: LAMP2 +
Case Report 4
Case Report 4
ECG
Case Report 5
ECG
Case Report 5
Dystrophin A
Case Report 5
Dystrophin B
Case Report 5
Masson's Trichrome
Case Report 5
Case Report 6
� FC born 5/24/1975
�Diagnosis of Becker Disease at 13 year
� Biopsy Muscle triceps: evolutive myopathy
� 14 years: EF 35%, 19 years EF 40%
� 22 years advanced heart failure: ICD
�Vo2 max 23,9 ml/kg/min
� Teraphy: Furosemide, Bisoprolol, Enalapril, Spironolactone, Digitalis
Case Report 6
ECG
Case Report 6
Case Report 6
Case Report 6
Case Report 7
� TE born 4/27/1975
�History of familial dilated cardiomyopathy
�Age 23 BAV II degree -> PM
�Coronary angiography: normal. EF 65%
� EMB not significant
�Age 35 atrial flutter RF ablation
�Age 38 paroxismal atrial fibrillation
� Echo: Normal EF
Case Report 7
ECG
Case Report 7
ECG
� TE age 38 symptoms: weakness
� EMG : deficit myopathic primitive
�NE : Deficiency of neck flexor, deficiency ofthe flexion of the tight compatible withdiagnosis of myofibrillar myopathy
Case Report 7
Case Report 7
Case Report 7
Case Report 8
� SL born 3/22/1947
� Age 33 familial dilated cardiomyopathy
� Age 47 Heart Transplant
� Age 63 weakness, gait difficulty, deficit of the shoulder girdle and pelvic.
� CK normal
� MB: hystology and hystochimic compatible withmyopathy: focal accumulation of Alpha B crystallina, desmin and myotillin
� Compatible with myofibrillar myopathy
Dystrophin A
Case Report 8
Dystrophin B
Case Report 8
Plakoglobin 40x
Case Report 8
Circulation. 2006; 113: 1807-1816
Circulation. 2006; 113: 1807-1816
Cardiomyopathies
Primaryconfined to heart
Secondary
Part of NMDPredominant
manifestation of NMD
Conclusions
Patients with CMP require special attention bythe cardiologist and neurologist
Baseline evaluation include:
�Cardiological clinical evaluation
�12 lead ECG
�Echocardiography
� In selected cases more sophisticated cardiovascular evaluations are required.
Conclusions�NMD may be accompanied by all types of CMP
�Diagnosis relies on both the cardiologist and neurologist having hight index of suspicionevaluating minor cardiac or neuromuscolarcomplains
�Underlying etiology can be molecularlydetermined through genetic testing
�Genetic etiology is informative for diagnosis, genetic counseling and increasingly to guide therapy
Clinical historyA 19-year-old man presented to our hospital for a self-limiting loss of consciousness while playing a soccer match. After an extensive clinical evaluation and radiological examination with cardiac magnetic resonance, the diagnosis of isolated left ventricular non compaction (LVNC) was established. Two years later, at the age of 21, the patient underwent successful heart transplantation for a dilated cardiomyopathy with a severe left ventricular disfunction.
Pathology: gross examination
The explanted heart weighted 450 g with a transverse diameter of 11 cm and a vertical diameter of 13.5 cm; the thickness of the left and right ventricle was 1,8 and 0,8 cm respectively. Grossly, on cut sections, the left ventricular wall demonstrated deep recesses and trabeculationsinvolving two thirds of the thickness of the wall (see figures in the next slides).
Pathology: gross examination
Pathology: gross examination
Pathology: gross examination
Pathology: gross examination
Whole-mount transversal section of the left ventricle: H&E and Azan-Mallory Trichrome stain showing miocardial
trabeculations, deep recesses involving 2/3 of the wall, interstitial and replacement fibrosis.
Section of the left ventricle: Gomori Trichrome stain showing interstitial and replacement fibrosis (5x)