CARDIOMYOPATHY A heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction, which usually (but

not invariably) exhibit inappropriate ventricular hypertrophy or dilatation, and are due to a variety of etiologies that frequently are genetic. Cardiomyopathies are either confined to the heart or are part of generalized systemic disorders, often leading to cardiovascular death or progressive heart failure- related disability. (Maron BJ, 2006)

CLASSIFICATION OF CARDIOMYOPATHIES As new data emerges, this requires further review and revision in the future. Recently, under the auspices of the American Heart Association, A contemporary classification of cardiomyopathies has been presented, relying substantially on recent advances in the characterization of diseases affecting the myocardium. In particular, the popular hypertrophic-diated-restrictive cardiomyopathies classification has major limitations by virtue of mixing anatomic designations. (i.e., hypertrophic and dilated) with a functional one (i.e., restrictive). Consequently, confusion frequently arises when the same disease could legitimately appear in two or even three categories. OVERVIEW I. I.A GENETIC I.A.1. HYPERTROPHIC CARDIOMYOPATHY -genetic disease transmitted as an autosomal dominant trait - most frequently occurring cardiomyopathy -Characteristics: Unexplained hypertrophied and nondilated LV When LV wall thickness is mild, differential diagnosis with physiologic athletes -Diagnostics: ECG alterations 2D- echo: hypertrophy Lab DNA analysis: + HCM-causing mutant gene -Clinical Manifestations: Largely limited to the , with massive degrees of LV hypertrophy Ventricular pre- excitation PRIMARY CARDIOMYOPATHIES

I.A.1. HYPERTROPHIC CARDIOMYOPATHY (ASSYMETRIC SEPTAL HYPERTROPHY/ IDIOPATHIC HYPERTROPHIC SUBAORTIC STENOSIS) -massive hypertrophy of the ventricular septum -primary muscle hypertrophy which may exist with or without a dynamic LV outflow tract gradient- WHO -PATHOLOGY: Defects or mutation that alter the actin-myosin crossbridge formation affects movement and force generation of the thick and thin filaments asymmetric hypertrophy of septum with a small left ventricular cavity Coronary arterioles in the septum gets smaller because of intimal hyperplasia MI Large and bizarre fibrosis present with degenerating muscle fibers whorling Endocardium thickened by fibrous tissue Mitral valve is intrinsically normal however there is a displacement of the hypertrophied papillary muscles alteration in load and contractility of the LV arrythmias, LVO obstruction, diastolic dysfunction, mitral regurgitation Either rhythm abnormality or activation of LV baroreceptors results in a reflex vasodilation decrease both pre and afterload syncope Left atrium is dilated by autopsy -MANIFESTATIONS: murmurs Dyspnea Angina Syncope -DIAGNOSTICS: Echocardiogram: stiff, noncompliant, hypertrophied ventricle and abnormal relaxation of the elevated LV filling pressure LVO tract obstruction & mitral regurgitation diastolic filling abnormalities :primary tool for defining presence of LVO :diffuse hypertrophy of entire septum with convex septal contour ECG:LV hypertrophy T wave inversion Abnormal Q waves: stimulating MI Normal sinus rhythm Increased wall thickness: consider infiltrative disorder or athlete;s

Ambulatory monitor setting: supraventricular tachycardia, PVCs, nonsustained VTach, Afib CXR: mild to moderate enlargement of cardiac silhouette LV: round contour Enlarged left atrium and right-sided chambers Doppler: dagger shaped signal on continuous wave

-TREATMENT/ THERAPY GUIDELINES Screening all first-degree relatives is recommended. Low to moderate aerobic exercise- permitted as part of healthy lifestyle A. MEDICAL THERAPY Beta-adrenergic blocking agents -initial drug of choice -decreased rate response to exercise -decreased outflow tract gradient with exercise -relief of angina by a decrease in myocardial oxygen demand -improvement in diastolic filling -no proven reduction in the incidence of sudden cardiac death -should be titrated to obtain 60bpm resting up to 400mEq of metoprolol Calcium channel blockers -decreases inotropy and chronotropy -may improve angina better than beta blockers -resting heart rate: 60 bpm; titrate up to 480 mg /d -CAUTION! No Dihydropidine-class calcium channel blockers: pure vasodilators that reduces afterload

NURSING CONSIDERATIONS HISTORY TAKING Obtain comprehensive heredofamilial cardiovascular diseases to establish genetic ties. Establish the past medical history of the patient. Because many patients have a history of HCM, thus medicating with diuretics and vasodilators aggravates the symptoms. HCM is asymptomatic to some patients, but upon chest auscultation, murmurs could be heard. Conduct thorough PA and extensive history taking.

PHYSICAL EXAMINATION Assess also for carotid pulsations. Spike and dome pattern is a classic physical finding for HCM. Spike and dome pattern-(briskly) a rapid rise followed by a midsystolic drop that is in turn followed by a secondary wave. The midsystolic drop in amplitude of the carotid pulse contour is caused by premature closure of the aortic valve and coincides with systolic anterior motion of the mitral valve. The late peak is caused by relief of the outflow tract gradient as the mitral valve leaflet returns to its original position. JVP: normal in most HCM patients :decrease in the compliance of ventricle. Assess apical impulse. This is always abnormal in patients with HCM reflects myocardial hypertrophy. Apical impulse is a sustained systolic thrust. Systolic thrill may be palpable at apex from severe mitral regurgitation LVO tract obstruction: ascertain crescendo-decrescendo murmur located at left sterrnal border Aortic valve disease: diastolic decrescendo As a nurse, dynamic ausculatation should be performed to differentiate the murmur. Most reliable method for diagnosing LVO tract obstruction is the response of the murmur to stand-squat-stand position. From stand-squat: increase afterload and pre load murmur decrease in intensity From squat-stand: reduced afterload increase in murmur intensity Educate patient. Patients with HCM often describe increase in symptoms during hot, humid weather, because of fluid loss and vasodilation decrease preload and afterload.

I.A.2. ARRHYTMOGENIC RIGHT VENTRIICULAR CARDIOMYOPATHY/ ARRYHTMOGENIC RIGHT VENTRICULAR DYSPLASIA -Uncommon inheritable heart muscle disease -Autosomal dominant inheritance -Predominantly involves RV with progressive loss of myocytes and fibrofatty tissue replacement

-Specific feature: Aneurysms of RV in the triangle of dysplasia (inflow, apex, outflow) -Most common cause of death among athletes -Sudden death: may be the first manifestation -Life threatening tachyarrythmias, palpitations -CHF; Right or Biventricular pump failure -Diagnostics: 12- lead ECG: abnormal repolarization and T wave inversion Echocardiography RV angiography CT/MRI Endomyocardial biopsy from RV wall -Treatment: Lifestyle alterations: avoid intense physical activities Anti-arrythmic drugs ICD transplant: final option

I.A.3.

LEFT VENTRICULAR NONCOMPACTION - Non compaction of ventricular myocardium: congenital cardiomyopathy -Natural Hx of LVNC is largely unresolved but includes: LV systolic dysfunction HF Thromboemboli Arrhythmias Sudden death Diverse remodeling -Characteristics: Spongy morphologic appearance of LV myocardium: distal (apical portion of the LV chamber) -Diagnosis: 2D-echo LV angiography

I.A.4 I.A. 5

GLYCOGEN STORAGE (will be discussed at I.B.2.a3) CONDUCTION SYSTEM DISEASE

-Lenegre disease, also known as progressive cardiac conduction defect (PCCD) -Characterized as: Primary progressive development of cardiac conduction defects in the Purkinje fibers system leading to widening QRS complex and AV block with long pauses and bradycardia= may trigger syncope Sick sinus syndrome: typically similar to PCCD Familial occurrence of both syndromes has been reported with an autosomal dominant pattern of inheritance I.A.6. MITOCHONDRIAL MYOPATHIES (spontaneous discussion with the succeeding myopathies) -caused by mutations encoding mitochondrial DNA -ATP electron transport chain enzyme defects which alter mitochondrial morphology -considered also in metaboloic myopathies involving production and use defects abnormalities (deficiencies and glycogen storage diseases) I.A.7. ION CHANNELOPATHIES -Inherited arrhythmia disorders caused by mutations in genes encoding defective ionic channel proteins governing transit of Sodium, Potassium and Calcium ions Includes: I.A.7a. LQTS -most common of the ion channelopathies -Characterized as: Prolonged ventricular repolarization and QT interval on standard 12lead ECG A specific form of polymorphic VTach (Torsade de Pointes) Risk of syncope Sudden cardiac death

I.A.7b. Brugada Syndrome -Characteristics: Identified by a distinct ECG pattern consisting right bundle-branch block and coved ST segment elevation in the anterior precordial leads. The pattern is often concealed and may be unmasked with administration of Sodium channel blockers (Procainamide)

 Mutation in cardiac sodium channel gene

I.A.7c. Sudden Unexplained Nocturnal Death Syndrome -Predominantly found in young Asian males (Thailand, Japan, Philippines, Cambodia) -disorder causing death during sleep because of VTach/VFib -this gene mutation and Brugada syndrome have been shown to phenotypically, genetically and functionally the same disorder.

I.A.7d. Catecholaminergic Polymorphic Ventricular Tachycardia (Cpvt) -Characterized by: Syncope Sudden death PVT Normal resting ECG: unremarkable with the exception of sinus bradycardia and prominent u waves in some patients Absence of structural cardiac disease Most typical arrythmia: bidirectional VTach presenting with an alternating QRS axis -Triggered by vigorous physical exertion or acute emotion; CR exceeds 120-125 bpm threshold -mutation in the gene essential for regulation of excitation-contraction coupling and intracellular calcium levels

I.A.7e. Short QT Syndrome -Char. As: Short QT interval on ECG High incidence of Sudden cardiac death caused by VTach/VFib Appearance of tall peaked T waves on ECG, similar to hyperkalemia

I.B MIXED GENETIC AND NONGENETIC I.B.1 DILATED CARDIOMYOPATHY -Char. As:

 Ventricular chamber enlargement Systolic dysfunction Normal LV wall thickness -leads to progressive HF and decline in LV contractile function, conduction system abnormalities, ventricular and supraventricular arrhythmias, thromboembolism and sudden or heart failure related death -irreversible form of muscle disease

-autosomal dominant with X-linked -3rd most common cause of HF -most common indication of -Etiologies: Virus (cardiotropic: coxsackievirus, HIV, parvosirus) Bacteria Rickettsiae Fungal Mycobacterial Parasite (Chagas dse., T. cruzii) Other causes: chemotherapeutic agents, metals, autoimmune and systemic disorders, pheochromocytoma, neuromuscular disorders, muscular dystrophies and mitochondrial, metabolic, endocrine and nutritional disorders, idiopathic causes transplant

-Diagnostics: 2D-echo I.B.2 PRIMARY RESTRICTIVE (NONHYPERTROPHIED) CARDIOMYOPATHY -rare form of nonhypertrophied, non dilated -Char. by: Normal or decreased volume of both ventricles Associated with biatrial enlargement Normal LV wall thickness and AV valves Impaired ventricular filling with restrictive physiology And normal or near normal systolic function muscles disease and a cause of HF

I.C.

ACQUIRED

I. C. 1. INFLAMMATORY CARDIOMYOPATHY I.C.1.a MYOCARDITIS -acute/ chronic inflammatory process affecting the myocardium (frequently subclinical) -can trigger autoimmune reaction that causes immunologic damage to the myocardium -typically evolves through active healing and healed stages characterized progressively by inflammatory cell infiltrates leading to interstitial edema and focal myocyte necrosis and replacement of fibrosis. - electrically unstable substrate - potential predisposition to VTach/ sudden death -Causes: Toxins and drugs Infectious agents Viral: most common (coxsackie, HIV, parvovirus) Rickettsial Fungal Parasitic Immune (giant cell myocarditis) and Hypersensitivity reactions

-Diagnostics: Histopathology/ histochemically Endomyocardial biopsy: inflammatory (leukocyte) infiltrate and necrosis ECG: ST-T changes; LV dilatation Challenging to id clinically -Manifestations: Chest pain, exertional dyspnea, fatigue, syncope, palpitations, VTachyarrythmias, conduction abnormalities, acute CHF/ cardiogenic shock

I.C.2

STRESS CARDIOMYOPATHY I.C.2.a TAKO- TSUBO -Char. By: Acute but rapidly reversible LV systolic dysfunction in the absence of atherosclerotic CAD

 Triggered by profound stress Distinction: involves the distal portion of LV chamber apicl ballooning with the basal LV hypercontractile -Presentation: Mimics ST segment elevation MI

II.

SECONDARY CARDIOMYOPATHIES (see reproduced copy)