Cardiomyopathies

Denisa Jindrová Cardiomyopathies

Definition Cardio– (heart) Myo – (muscle) Pathy (disease) Heterogeneousgroupofdiseasesassosiatedwith a mechanicalorelectricaldysfunctionwith a different etiology, clinicalcourseandtherapy

Myocardial disorder, in which heart muscle is structurally and functionally abnormal • In the primary absence of • coronary artery disease • hypertension • valvular and congenital heart diseases • ………sufficient to explain the observed abnormality Definition

Classification (CMP) • Hypertrophic CMP (HCM) • Dilated CMP (DCM) • Restrictive CMP (RCM) • Arrhythmogenic CMP (ARVC) • UnclassifiedCMPs • Leftventricularnoncompaction (LVNC) • Stress-induced CMP • Tachycardia-induced CMP

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

Etiology Primary dysfunction of cardiomyocytes (by genetic or exogenous insult) Insult leads to disorder of contraction or relaxation Long-standing activation of compensatory neurohumoral mechanisms (eventually accentuates heart failure) Oxidative stress, hypertrophy, fibrosis, apoptosis

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

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

Hypertrophic cardiomyopathy (HCM) • Most common genetically determined cardiovascular disease • Prevalence 0,2% ( in Czech Republic cca 20 000 patients) • Left vetricular thickness and/or mass in the absence of loading conditions capable of causing such an extent hypertrophy • valvular disease (aortic stenosis) • arterial hypertension • Genotypically and phenotypically heterogeneous

Hypertrophic cardiomyopathy Most often (60 to 70percent) caused by mutations in one of several sarcomere genes which encode components of the contractile apparatus of the heart β myozin heavy chain Myosin binding protein C Metabolic and storage disorders (Fabry disease)

Patology and patophysiology 1. Hypertrophied myocytes 2. „Disarray“ - myocytes arranged in a chaotic and disorganized fashion 3. Intersticial fibrosis Diastolic dysfunction (deterioration of compliance) → systolic dysfunction → risk of malignant arrhyrhmia → ischemia

Hypertrophy of left ventricle Septum, anterior wall Septal thickness more than 15 mm

LVOT obstruction Pressure gradient due to intracavitary obstruction during systole Mechanism of LVOT obstruction Narrowed diameter of the LVOT due to increased septal wall thickness Apically positioned papillary muscles that tether the mitral valve plane toward the ventricular septum Elongated anterior leaflet of the mitral valve ↓ LVOT obstruction

LVOT obstruction • „Rule of one third“ • 1/3 none • 1/3 present at rest • 1/3 present after provocative maneuvers • Valsalva maneuver, nitrate • Depends on haemodynamic conditions • Preload, afterload, hydratation, blood pressure Why it is important to know about it? - higher risk of heart failure progression, higher mortality - curative therapy

Symptoms • Many patients with HCM have no or only minor symptoms • Dyspnea • Diastolic dysfunction • LVOT obstruction • Chest pain • Myocardial hypertrophy • Microvascular dysfunction • Palpitation • Diastolic dysfunction → high pressure in atria → atrial dilatation → atrial fibrillation • Syncope • Malignant arrhytmia • Sudden death • Malignant arrhytmia • Myocardial heterogenity • Higher risk in childhood (5% per year) x 7th decade

Family history • Phisical examination • systolic murmur at the apex and lower left sternal border • ECG • heterogenous • LVH, patol. Q , QS, …. • ECHO – golden standard • septal thickness more than 15 mm, papillary muscles hypertrophy, mitral anterior leaflet elongation, pressure gradient • MRI • regions of myocarrdial fibrosis • regions of late gadolinium enhancement (LGE) • Stress test • blood pressure responce • ECG monitoring • ventriculararrhythmia • Selective coronarography Diagnosis

Therapy • 1. Sudden death prevention • - Based on the presence of risk factors SCD • - ACCF/AHA x ESC guidelines • - ICD implantation • Age • Family History of SCD • Syncope • LV thickness • LVOT gradient • LA diamether • Nonsustain VT • Abnormal blood pressure response

Medical therapy • Heart failure therapy • BB • Diuretics • ACEi, sartans (systolic dysfunction) • Aldosterone receptors blockers (systolic dysfunction) • Obstruction • BB • Verapamil • Prevention of thromboembolic complications of atrial fibrillation • amiodaron, dronedaron, sotalol • warfarin, NOACs

Septal reduction therapy (for ventricular obstruction) • Surgical myectomy • Septal ablation • Symptomatic patients despite the optimal medical therapy • A small amount of alcohol is induced into a septal branch • Myocardial scar and subsequent reductionin the diameter of the basal septum

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). Prevalence 1/2 500

Dilated cardiomyopathy • Specific causes • Inflammatory • History of myocarditis • Viral aetiology+ predisposition • Toxic • Alhohol induced • 90g alcolol/day 5 years + predisposition • Cocain induced • Drug induced • Peripartal • 1/2000 birth, unknown patophysiology • Muscular dystrophias • Duchen and Becker • Familiar DCM • 1/3 predisposition • sarcomeric, cytoskeletal , nuclear membrane genes • DCM of unknownetilogy

Patology and patophysiology Myocytal malfunction (atrophy/hypertrophy) Instersticial fibrosis → impaired systolic and diastolic function → compensatory mechanisms Dilatation (escpecially LV) - diffuse, RV (x CAD) Low CO, congestion Mitral regurgitation, secondary

Signs, symptoms and diagnostics • Heart failure- low CO, congestion • Arrhythmias • Sudden death • SVT, AF- mitral regurgitation- atrial dilatation • Thrombiin left ventricle/ left atrial appendage – CMP • ECG • ECHO – ventricular dilatation and dysfunction • Lab– NT-proBNP • Selective coronarography- CAD exclusion • Stress test- prognosis • MRI • EMB– inflammatory CMP

Therapy • Sudden death prevention • Based on symptoms and severe systolic dysfunction (EF lessthan 35% + symtomatologie NYHA II-IV) • Heart failure therapy • Drug therapy • CRT • Mechanical assist devices • Heart transplant • Prevention of thromboembolic complications of atrial fibrillation • - NOAC, Warfarin

Arrhytmogenic cardiomyopathy Replacement of myocardium by adipose and fibrous tissue RV, LV Prevalence 1:2000 – 1:5000 Genetic disorder- desmosomal protein genes

Work up • ECG • – typical • epsilon, neg. T v V1-V3 • LBBB morphology VES • ECHO • MRI • EMB

Symptoms Therapy Heart failure (of both ventricles) Arrhythmias Sudden death • Sudden death prevention • ICD implantation • primary\secondary prevention • Heart failure therapy • Treatment of ventricular tachycardias

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

Histology a patophysiology

Work- up Symptoms Heart failure Symptoms of underlying disease 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

Left ventricular non-compaction • Rare (cca 1:7000) • Primary genetic disease • - Sarcomeric and mitochondrial genes • ECHO • Non-compacted myocardium • especially in the apical part of the left ventricle

Cardiomyopathies