The Cardiomyopathies

April 2007 Esayas K.G Jimma University 1

Dilated cardiomyopathy It is characterized by unexplained dilatation and impaired contractile performance of one or both ventricles. DCM causes about third of cases of CHF. Left &/or right ventricular systolic pumping function is impaired, leading to progressive cardiac enlargement and hypertrophy by remodeling. Symptoms of CHF typically appear only after remodeling has been ongoing for months or even years. There is however, no correlation between the degree of contractile dysfunction & severity of the symptoms.
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Etiology: No cause is apparently known.  Thought to be the end result of myocardial damage produced by a variety of toxic, metabolic, or infectious agents.  It may be the late sequellae of acute viral myocarditis, possibly mediated by an autoimmune mechanism.  Reversible forms of DCM occur in:  Alcohol abuse  Pregnancy  Thyroid disease  Cocaine abuse  Chronic uncontrolled tachycardial  20-40% of patients have familial forms of disease with mutations of genes encoding cytoskeletal, contractile, and nuclear membrane proteins.  It is typically heterogeneous but most commonly autosomal dominant transmission;autosomal recesive, mitochondrial, and x-linked inheritance may also be seen.  Right ventricular dyplasia is a unique familial cardiomyopathy marked by progressive replacement of the right ventricular wall with adipose tissue. It is often associated with ventricular arrhythmias & sudden death.
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Epidemiology:-occurs worldwide
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Is commonly a disease of middle age men Prevalence is increasing currently

Clinical features: Sxs. of biventricular failure develop gradually in most patients.  Some pts have LV dilatation for months or even years before becoming symptomatic. ۞
 Syncope due to arrhythmia  Thromboembolism(ventricular thrombus)  Non-specific chest pain

 Note:-presence of typical angina pectoris is unusual &

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suggests the presence of concomitant ischemic heart disease.
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Physical examination: Shifted PMI→ cardiac enlargement  Signs of CHF  Third and 4th heart sounds are commonly found  MR/TR may occur  In advanced disease
 Narrow pulse pressure  Raised JVP

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Jimma University

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Investigations

CXR:- cardiomegaly, significantly LV  ↑ed vascular markings  Signs of interstial or alveolar edema ECG:-sinus tachycardia
AF  Ventricular arrhythmia  LA abnormalities  Diffuse non-specific ST-T wave abnormalities  Sometimes interventricular conduction defects & low voltage.

Echo.:-LV dilatation with normal, minimally thickened, or thinned wall. Systolic dysfunction (↓ed EF)  Cardiac catheterization & coronary angiography are often performed to exclude IHD.  Angiography shows dilated, diffusely hypokinetic LV with some degree of MR. April 2007 Esayas K.G Jimma University 6

Management  Standard therapy of heart failure with:
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Salt restriction ACEi/ARB Diuretics produce symptomatic improvement digitalis β-blockers spironolactone for patients with recent or current advanced HF

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Avoid: - alcohol Calcium channel blockers NSADs Systemic embolization is a concern→consider chronic anticoagulation Antiarrhythmic are best avoided for fear of proarrhythmia, unless they are needed to treat symptomatic or serious arrhythmias. ICD- is useful for patients with symptomatic ventricular arrhythmias cardiac transplantation!-In patients with advanced disease who are refractory to medical therapy.
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Prognosis  Most patients have a downhill course  Majority particularly those > 55 yrs die within 3 yrs of Sx.  Death is usually due to either CHF or ventricular tachy−or bradyarrhythmiacardia.  Sudden death is a constant threat.  Spontaneous improvement or stabilization occurs in about a quarter of patients.

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Restrictive cardiomyopathy It is the rarest of the three types of CMP. It is more common in countries such as equatorial Africa where it is acquired 2o to endomyocardial disease. RCMs arise from loss of ventricular distensibility as a result of either myocardial or endomyocardial disease. The pathologic hallmark is myocardial fibrosis, hypertrophy, or inflammation due to variety of causes. The most common cause is endomyocardial fibrosis (EMF), which often occurs in association with eosinophilia ( hypereosinophilic syndrome). Other causes are:
Amyloidosis Hemochromatosis Glycogen deposition Sarcoidosis Fabry’s disease Scleroderma Mediastinal radiation Neoplastic infiltration Esayas K.G

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…continued  The hemodynamic hallmark of RCM is abnormal diastolic function; the ventricular walls are excessively rigid and impede ventricular filling.  There is partial obliteration of the ventricular cavity by fibrous tissue and thrombus:  

Abnormally ↑ed resistance to ventricular filling Thromboembolic complications in 1/3rd of patients

 The inability of ventricles to fill limits cardiac

output and raises filling pressure.

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Jimma University

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Clinical features  Exercise intolerance & dyspnea are usually the most prominent symptoms.  Dependent edema, ascites, & hepatomegaly  Raised JVP with Kussmaul’s sign  Heart sounds may be distant & 3rd & 4th heart sounds are common  RCM resembles constrictive Pericarditis in most cases, in RCM apical impulse is usually easily palpable, & MR is more common.
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Investigation:  ECG: - low voltage, non-specific ST-T wave changes & various arrhythmias.  ECHO:  symmetrically thickened left ventricular walls & normal or

slightly reduced ventricular volume & systolic function
 Doppler recordings demonstrate accentuated early diastolic filling.

 Cardiac cathetherizatiion: -

↓ed cardiac output  Elevation of the right and left ventricular end-diastolic pressure & plateau configuration of the diastolic portion of the ventricular pressure pulse

 Endomyocardial Bx

CT/MRI
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differentiate RCM from constrictive pericarditis
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Treatment:  The treatment is as for any cardiac failure-but usually disappointing.  Chronic anticoagulation is often recommended  Cardiac transplantation

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Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is a complex but a common form of genetic heart disease typically inherited in an autosomal dominant fashion with variable penetrance and expressivity. HCM is the leading cause of sudden cardiac death in people under 30 years and responsible for exercise disability at almost any age. It is characterized by a hypertrophied and non dilated left and/or right ventricles in the absence of obvious causes like AS or HTN.

Prevalence: is 0.2% of the general population: Sex:  HCM is identified slightly more commonly in males than in females. However, the genetic inheritance pattern is autosomal dominant, without gender predilection.  HCM usually presents at an earlier age in females than in males. Females with HCM tend to be more symptomatic and are more likely to be disabled by their symptoms. Age:  HCM may occur at any age from newborn to elderly.  HCM is a progressive condition that worsens over time if left untreated.  Its most common presentation is in the third decade of life. April 2007 Esayas K.G Jimma University 14

Causes:
 The actual cause of HCM is defects in the genes encoding for several of the

sarcomeric proteins.

Genetic causes: -

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About 50% of all patients with HCM have positive family history compatible with autosomal dominant transmission.. Familial HCM is a genetically heterogeneous disease because it is caused by defects at multiple genetic loci. At least 12 different genes on at least 6 chromosomes are associated with HCM, and more than 200 different mutations have been discovered.  40% of these are associated with mutations of the cardiac βmyocin heavy chain gene on chromosome-1  15%-mutation of cardiac troponin T gene on chromosome-1  20%-mutations of myosin binding protein c (chromosome 11)  5%-mutation of α-tropomyosin gene
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 Echocardiographic studies have confirmed that

about 1/3rd of the 1st degree relatives of patients with HCM have evidence of the disease. Other suggested causes of HCM are: Abnormal calcium kinetics:

 ↑ed intracellular calcium concentration as a result of ↑ed

no. of calcium channels→ myocardial hypertrophy & disarray.

Abnormal sympathetic stimulation
 ↑ed responsiveness of heart to catecholamines  Excessive production of cathecholamines  ↓ed neuronal uptake of catecholamines

Cardiac structural abnormalities
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Pathology:  The right, the left, or both ventricles may be involved.  RVH is :
 usually symmetric  Seen in over 30% of patients  Isolated RVH is rare

• Hypertrophy on the left is usually asymmetric, involving the interventricular septum & the free wall than the posterior wall.
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LVH Over 60% of patients will have structural abnormalities of MV(↑leaflet area, elongation of leaflets, or anomalous papillary muscle insertion into the anterior MV).
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The two important features of LVH: 2. Heterogeneous hypertrophy, often with preferential hypertrophy of the interventricular septum resulting in asymmetric septal hypertrophy (ASH). 3. A dynamic left ventricular outflow tract pressure gradient, related to a narrowing of the subaortic areas as a consequence of SAM of the MV. The pathophysiologic abnormality is diastolic dysfunction characterized by increased stiffness of the hypertrophied muscle →↑diastolic filling pressure & is present despite a hyperdynamic LV.
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Hemodynamics:  

Many individuals with HCM demonstrate left ventricular dynamic out flow obstruction. The degree of obstruction is variable and is dependent on the amount of blood in the ventricles immediately before ventricular systole. Dynamic outflow obstruction is always due to SAM of MV against the hypertrophied septum.

The three basic mechanisms of dynamic changes resulting in pressure gradient are:1. 2. 3.

Increased left ventricular contractility Decreased ventricular volume (Preload) Decreased aortic impedance & pressure (After load)

♣ Conditions that increase myocardial contractility (exercise, sympathomimetics, & digitalis glycosides) and those that decrease ventricular volume (valsalva maneuver, nitroglycerine, amyl nitrates & tachycardia) aggravate it.
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C/F  Clinical feature is highly variable:  Many are asymptomatic or mildly symptomatic & may be relatives of patients with known disease.  The first manifestation of the disease may be sudden cardiac death, in childhood or adolescents, often during or after physical exertion.  The arrhythmia that causes sudden death is ventricular fibrillation in more than 80% of individuals with HCM.
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In symptomatic patients, common symptoms are:  Dyspnea
 It is the most common presenting symptom of HCM occuring in

as many as 90% of symptomatic patients.

 Syncope
 Syncope is a common symptom of HCM, resulting from

inadequate cardiac output on exertion or from cardiac arrhythmia.

 Presyncope( near syncope= "graying out" spells)  Angina  Palpitations  Orthopnea and paroxysmal nocturnal dyspnea

Symptoms of Congestive heart failure  Dizziness  Note:-symptoms are not closely related to the presence or severity of an outflow pressure gradient.

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Physical Examination:  Most patients with gradients demonstrate a double or triple apical precordial impulse, a rapidly rising carotid arterial pulse, & 4th heart sound.  The hallmark of obstructive HCM is a systolic crescendodecrescendo murmur is heard best between the apex and left sternal border; it radiates to the suprasternal notch but not to the carotid arteries or neck.
 The murmur and the gradient across the LV outflow tract diminish

with any increase in preload or increase in afterload and increase with any decrease in preload or afterload
 Holosystolic murmur of mitral regurgitation is heard in

patients with SAM of the MV and significant LV outflow gradients.
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Investigations  CXR- usually normal ( occasionally increased cardiac silhouette)  Electrocardiography
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ECG is normal in 5% of symptomatic & 25% of asymptomatic patients. At the time of diagnosis, 10% are in AF Majority of them have an interventricular conduction delay.
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ST segment depression and T-wave changes are the most common abnormalities associated with voltage changes of LVH. Wide speared, deep , broad Q waves in the inferior leads that suggest an old MI Left axis deviation Arrhythmia-SVT, AF, VT conduction abnormalities (i.e., PR prolongation, bundle branch block, Wolff-Parkinson-White syndrome ), P-wave abnormalities of left &/or right atrial overload (atrial enlargement). . Esayas K.G Jimma University 24

Echocardiography- mainstay of diagnosis for HCM.  LVH > 13 mm (usually >15mm),septum often 1-3 or more times thicker than the high posterior free wall and at least 4-6 mm thicker than normal for each age group.  Echocardiography also typically reveals diastolic dysfunction with reduced LV compliance.

The hallmarks of the obstructive type of HCM consist of SAM of the anterior MV and ASH, with a septal wall thickness-toposterior wall thickness ratio greater than 1.4:1.

Other echocardiographic findings in individuals with HCM may include the following:
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Small LV cavity. Reduced septal motion and thickening during systole, Normal or increased motion of the posterior wall Left atrial enlargement mitral regurgitation K.G Jimma University Esayas

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Exercise testing:
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About third of pts. Will have an abnormal BP response ST segment changes associated with symptoms of angina, are found in 25% of pts.

Radionuclide imaging with thallium or technetium may demonstrate reversible defects. Cardiac catheterization Histologic Findings: bizarre and disorganized arrangements of cardiac muscle cells ( cell-to-cell disarray) and myocardial fibrosis of the septum.
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Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis Aortic stenosis Echocardiography Aortic valve calcification Dilated ascending aorta Ventricular hypertrophy Physical examination Murmur of AI Pulse pressure after PVC Valsalva maneuver Carotid pulsation April 2007 Common Increased Decreased intensity of murmur Normal No Decreased Increased intensity of murmur Brisk, jerky, or bisferiens pulse (a collapse of Jimma University the pulse followed by a secondary rise) 27 Common Common Concentric No Rare Asymmetric, often involving the septum Hypertrophic cardiomyopathy

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Criteria to differentiate b/n HCM and Athlete’s heart
HCM
Athlete’s Heart ( Physiologic LVH)
Substantially symmetrical <16 Normal or ↑ed (≥55) Normal Present uncommon

Distribution of hypertrophy Max. LV wall thickness (mm) LV cavity dimension(mm) LV filling and relaxation Regression of LVH with detraining Marked ECG abnormalities
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Mostly asymmetrical >16 Normal or ↓ed (< 45) Usually abnormal Absent or marginal common

Familial evidence of usually present Absent HCM Esayas K.G Jimma University Peak O2 consumption Normal or ↓ed >5o ml/kg/min

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Management  Treatment of HCM is directed towards decreasing the LV outflow tract gradient and symptoms of dyspnea, chest pain & syncope.  Treatment options for pts with HCM depend upon the heart condition & severity of symptoms, and are intended to decrease the stress on the heart and relieve symptoms.

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Medical Therapy:
It is successful in majority of pts. Medications help relax the heart & reduce the degree of obstruction.

b. c.

β-blockers (metoprolol, atenolol, bisoprolol, propranolol)

↓outflow obstruction & ↑ventricular compliance

Calcium channel blockers (verapamil, deltiazem)
Are alternative to β-blockers  Improve diastolic filling by improving diastolic relaxation & decreasing outflow gradient due to depression of cardiac contractility. Note:-Nifedipine should be avoided!

β-blockers + calcium channel blockers should used cautiously.

d.

Amiodarone (class III antiarrhythmic agent)
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Its use is generally reserved for potentially life-threatening ventricular arrhythmias Reduces risk of SCD

e.

Disopyramide (class-I antiarrrhytmic agent)

Pharmacologic therapy is primarily intended to alleviate the symptoms associated with HCM, no drug has been shown to alter the natural history of the disease in either symptomatic or asymptomatic patients. Esayas K.G Jimma University April 2007 30

1. Transvenous dual-chamber permanent pacing
↓ LV outflow obstruction by altering the pattern of ventricular depolarization and contraction. Doesn’t reduce risk of ventricular arrhythmias & sudden death Used as adjunct with medical therapy

1. Septal Alcohol ablation
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Implantable cardioverter defibrillator (ICD)

Indicated in patients:
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Who survive cardiac arrest With high risk ventricular arrhythmias

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↓SCD Superior to antiarrhytmiac drug therapy

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Surgical Mgt.( Myectomy):

Indications:
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Severe symptoms refractory to medical therapy Outflow gradient of >50mmHg either provocation or at rest

Cardiac transplantation!

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GENERAL MANGEMENT OF PATIENTS WITH HCM  Advise individuals with HCM to avoid strenuous activity, anaerobic exercise such as weight lifting. Don’t permit competitive level sports if any of the following are present:
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Significant outflow gradient Significant ventricular or supraventricular arrhythmia Marked LVH Hx. of sudden death in relatives with HCM Confirmed malignant genotype

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Avoid administration of inotropic agents Avoid nitrates & sympathomimetic amines except in pts. with HCM & concomitant coronary artery disease. Cardiac glycosides are contraindicated except in pts. with uncontrolled AF. ACEi and ARB are better avoided. Avoid diuretics because of their effect on Left ventricular volume. Alcohol ingestion should be avoided; even social alcohol ingestion may induce sufficient VD to exacerbate an outflow pressure gradient. First degree relatives of patients with HCM should be screened by April 2007 Esayas K.G Jimma University 34 echocardiography.

2.

Complications of HCM: Congestive heart failure
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observed in individuals with severe cases of HCM. It may occur as a result of a combination of impaired diastolic function and subendocardial ischemia. Patients with CHF have a high likelihood of recurrent heart failure due to both mitral regurgitation and profound diastolic dysfunction.
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3.

Atrial fibrillation with mural thrombosis formation
Common late in the course of the disease Anticoagulation is necessary in patients with chronic AF

4.

5.

Other types of arrhythmia (ventricular fibrillation, supraventricular tachycardia associated with WolffParkinson-White syndrome, ventricular tachycardia), Infective endocarditis-occurs in 10% of patients →Prophylaxis is indicated in patients with resting obstruction and MR
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Myocardial ischemia:-despite normal epicardial coronary arteries,myocardial ischemia is common in HCM. Potential causes of the ischemia are:

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Increased muscle mass Elevated diastolic filling pressures Enhanced myocardial O2 demand (increased wall stress) Systolic compression of arteries Impaired vasodilator reserve

3.

Sudden death

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Prognosis:  Natural history is variable  HCM frequently causes no or only mild disability over a life time, and many patients achieve normal life expectance.  In symptomatic ones it is a chronic illness with lifestyle restrictions.  Mortality rate in individuals with HCM is 4% per year.  The major cause of death in HCM is sudden cardiac death that may occur in asymptomatic patients.
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Predictors of SCD are: 2. Age < 30yrs. 3. Patients with prior cardiac arrest 4. Patients with family Hx of sudden death due to HCM 5. Recurrent syncope or any Hx of syncope during childhood 6. Marked ventricular hypertrophy ( >30mm) 7. Sustained supraventricular or ventricular tachycardia 8. Hypotensive response to exercise testing 9. Specific mutations in genes encoding for troponin T & myosin.
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Identifiable & treatable mechanisms of SCD in HCM
 Paroxysmal AF-amiodaron  Sustained monomorphic VT- amiodaron + ICD  Ischemia-high dose verapamil  Conduction disease-pacemaker  Accessory pathway -ablation

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There is no correlation between the risk of sudden death & the severity of symptoms or the presence or severity of the outflow tract pressure gradient!

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References Harrison’s principles of Internal Medicine, 16th edition, 2005.USA Concise Oxford Text Book of Medicine, 2000. UK European Journal of Cardiovascular prevention and Rehabilitation UpToDate online, 15.1, Feb.2007 Online References

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