Cardiomyopathies Pavol Tomašov

European Society of Cardiology (ESC): Definition European Society of Cardiology (ESC): Diseases with abnormal myocardial structure or function in the absence of ischemic insult or loading conditions capable of causing such disorder (CAD, hypertension, valvular disease, congenital heart disease).

Classification Cardiomyopathies HCM DCM ARVC RCM Unclassified Familial/Genetic Non-familial/Non.genetic Unidentified gene defect Disease sub-type Idiopathic

Restrictive cardiomyopathy Left ventricular non-compaction Normal heart DCM ARVC Restrictive cardiomyopathy HCM

ACC/AHA classification

Pathophysiology Mutation Exogenous insult Contraction and relaxation disorder Ineffective energy utilization Altered Ca ions handling Activation of compensatory neurohumoral mechanisms Apoptosis Fibrosis Hypertrophy Heart failure Arrhythmia, sudden death Thromboembolic complication

Therapy Exogenous insult prevention Sudden death prevention Primary Secondary Heart failure therapy Symptomatic Life prolonging Prevention of thromboembolic complications

Genetics Some cardiomyopathies are monogenic disorders Primary genetic – HCM, ARVC, LVNC Mixed etiology – DCM (20-40 %), RCM (rare) Great variability of genotype and phenotype Hundreds and thousands of mutations Many genes Various types of inheritence Different phenotypes in identical mutations

Hypertrophic cardiomyopathy Increased left ventricular thickness and/or mass in the absence of loading conditions capable of causing such extent of hypertrophy (hypertension, valvular disease, congenital heart disease).

Hypertrophic cardiomyopathy Most common monogenic disorder of the heart with a prevalance of 1:500 Mutations in sarcomeric genes (20 genes, 2000 mutations) β myosin heavy chain Myosin binding protein C Metabolic disorders (Fabry disease)

Pathology

Ventricular obstruction Pressure gradient due to intracavitary obstruction during systole Left ventricular outflow tract – anterior mitral leaflet and hypertrophic interventricular septum. Midventricular – papillary muscles Right ventricular obstruction

Symptoms Majority of patients are asymptomatic Dyspnoe Chest pain Palpitation Syncope Symptoms of stroke Sudden death

Work up ECG ECHO MRI Stress test Ambulatory ECG monitoring Selective coronary angiography

Therapy Sudden death prevention Based on the presence of risk factors Heart failure therapy Septal reduction therapy (for ventricular obstruction) Prevention of thromboembolic complications of atrial fibrillation

Drug therapy Obstruction Betablockers Verapamil Heart failure Diuretics ACE inhibitors, sartans (systolic dysfunction) Aldosterone receptors blockers (systolic dysfunction)

Septal reduction therapy Surgical myectomy Alcohol septal ablation

Dilated cardiomyopathy Dilated left ventricle with systolic dysfunction in the absence of coronary ischemia or loading conditions capable of causing such dysfunction (CAD, hypertension, valvular disease, congenital heart disease).

Dilated cardiomyopathy Prevalence app. 1:2500 Mixed etiology Familial DCM – sarcomeric, cytoskeletal , nuclear membrane genes Toxic Inflammatory Peripartal

Pathology

Outcomes Heart failure Arrhytmias Sudden death

Work up ECG ECHO Selective coronary angiography MRI Endomyocardial biopsy

Therapy Sudden death prevention Based on symptoms and severe systolic dysfunction Heart failure therapy Drug therapy Mechanical assist devices Heart transplant Prevention of thromboembolic complications of atrial fibrillation

Arrhytmogenic cardiomyopathy Prevalence app. 1:2000 – 1:5000 Primary genetic disease Desmosomal protein genes Replacement of myocardium by adipose and fibrous tissue

Outcomes Heart failure (of both ventricles) Arrhytmias Sudden death

Work up ECG MRI ECHO Endomyocardial biopsy

Therapy Sudden death prevention Heart failure therapy Treatment of ventricular tachycardias

Left ventricular non-compaction Rare Primary genetic disease Sarcomeric and mitochondrial genes Non-compacted myocardium, especially in the apical part of the left ventricle

Restrictive cardiomyopathy Rare Mixed etiology Sarcomeric genes Restrictive physiology of diastolic filling Non-dilated ventricles, dilated atria

Cardiac amyloidosis

Work-up ECG MRI ECHO Laboratory diagnosis of amyloid protein – free light chains, paraprotein Endomyocardial biopsy Scintigraphy – tnasthyretin amyloidosis

Therapy Heart failure therapy (including heart transplant) Liver transplant Hematology Specific therapy against amyloid protein

Case report Woman, 75 years Comes to ED for new-onset chest pain and weakness History: hyperthyreosis Drugs: Thyrozol Family history: no cardiovascular diseases Physical: BP 105/70, HR 92/min, RR 20 breaths/min, sat O2 94%

ECHO – anterior wall akinesis, LV EF 35%, mild mitral regurgitation, no dilation of right-sided chambers, no pericardial effusion

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