Il ruolo del cardiologo nelle miopatie

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)