CHAPTER XIX
CARDIOMYOPATHIES AND MYOCARDITIS
A. CARDIOMYOPATHIES
Definition: Diseases of the myocardium, which may be primary or secondary to disease elsewhere. This excludes diseases of the myocardium due to rheumatic fever, coronary artery disease, systemic hypertension, congenital heart diseases, valvulopathy, cor pulmonale or constrictive pericarditis.
Classifications (Goodwin 1984 – WHO):
I. Etiological criteria:
A) Primary cardiomyopathy (idiopathic):
1. Dilated cardiomyopathy.
2. Hypertrophic cardiomyopathy.
3. Restrictive cardiomyopathy
B) Secondary cardiomyopathy (secondary involvement of the myocardium due to a systemic disease)
1. Inflammatory:
a) Infective
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ð Viral.
ð Rickettsial.
ð Bacterial.
ð Mycobacterial.
ð Spirochetal.
ð Fungal.
ð Parasitic.
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b) Noninfective
ð Collagen diseases (PAN).
ð Granulomatous (Sarcoidosis).
2. Metabolic disorders:
a) Nutritional diseases:
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ð Thiamine avitaminosis (B1).
ð Pellagra.
ð Kwashiorkor.
ð Hypervitaminosis D.
ð Obesity.
ð Selenium deficiency.
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b) Endocrine diseases:
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ð Acromegaly.
ð Thyrotoxicosis.
ð Myxedema.
ð Uremia.
ð Cushing`s disease.
ð Pheocromocytoma.
ð Diabetes mellitus.
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c) Altered metabolism:
ð Gout.
ð Oxalosis.
ð Porphyria.
d) Electrolyte imbalance:
ð Hypophosphatemia.
ð Hypocalcemia.
3. Toxic aggression:
A. Alcohol.
B. Metals: cobalt, lead, antimony compounds, lithium, mercury.
C. Insect stings.
D. Snake bites.
E. Drug therapy (Bleomycin, Adriamycin, Phenothiazines, Tricyclic antidepressants, Chloroquine, Cyclophosphamide, Paracetamol, Reserpine, Corticosteroids, Cocaine, Methysergide, Doxorubicin).
4. Infiltrative diseases:
A. Amyloidosis.
B. Hemochromatosis.
C. Carcinoid syndrome (neoplastic).
D. Mucopolysaccharidosis.
5. Neuromuscular diseases: Myasthenia gravis.
6. Hemoglobinopathies (sickle cell anemia, thalassemia).
7. Physical agents:
1. Ionizing radiation.
2. Hypothermia.
8. Heart transplant rejection
II. Pathological criteria:
1. Dilated cardiomyopathy:
ð Large cavities having thin or normal walls.
ð SYSTOLIC failure.
2. Hypertrophic cardiomyopathy:
ð Obstructive – asymetrical hypertrophy of the interventricular septum.
ð Non-obstructive – small cavities having thick walls.
ð DIASTOLIC failure.
3. Restrictive cardiomyopathy:
ð Fibrosis of the endocardium and myocardium.
ð DIASTOLIC failure.
N.B.! (Braunwald 5th ed.)
1. “Most forms of secondary cardiomyopathy are characterized by the dilated cardiomyopathy pattern.”
2. “The distinction between these three functional categories is not absolute, and often there is overlap; in particular, patients with hypertrophic cardiomyopathy also have increased wall stiffness (as a consequence of the myocardial hypertrophy) and thus present some of the features of a restrictive cardiomyopathy.”
3. “It is difficult to fit a few conditions (such as arrhythmogenic right ventricular dysplasia, early or “latent” cardiomyopathy, and the entity of mildly dilated cardiomyopathy) neatly into the traditional functional classification scheme.”
Diagnosis:
1. Clinical, imagistical and electrocardiographical features of myocardial syndrome (heart failure, rhythm disturbances, gallop, lower limbs edemas, jugular veins distention, pulmonary congestive symptoms, cardiomegaly or cavity pressure disturbances).
2. Exclusion of other cardiovascular diseases (rheumatic fever, coronary artery disease, systemic hypertension, congenital heart diseases, valvulopathy, cor pulmonale or constrictive pericarditis).
3. Endomyocardial biopsy -- interpretation of biopsy specimens is using the Dallas criteria.
IDIOPATHIC DILATED CARDIOMYOPATHY
Definition: Dilated cardiomyopathy (DCM) is a syndrome characterized by cardiac enlargement and impaired systolic function (diminution in the contractile function) of one or both ventricles in the absence of external pressure overload, volume overload, or coronary artery disease. The loss of muscle function results in congestive heart failure. Synonym: congestive cardiomyopathy.
Incidence:
ð 5 to 8 cases per 100,000 population per year and appears to be increasing.
ð It occurs almost three times more frequently in blacks and males than in whites and females.
ð Average of age: 20 –40 years.
Etiology:
ð The cause of most cases of dilative cardiomyopathy is unknown.
ð More than 75 specific diseases of heart muscle can produce the clinical manifestations of DCM.
ð It is likely that this condition represents a final common pathway that is the end result of myocardial damage produced by a variety of cytotoxic, metabolic, immunological, familial, and infectious mechanisms (Fuster 1994).
ð The following features are mostly linked to IDCM:
1. Subclinical viral myocarditis (enteroviruses, coxsakie B, influenza) – 15%. Specific IgM viral antibodies occur in 1/3 of the patients.
2. Genetic predisposition -- 20-25%. Dominant autosomal transmission or X-linked.
3. Immunological disorders (HLA class II: DR4 and DQw4; antimyocardial antibodies to a variety of antigens: the myosin heavy chain, the beta-adrenoreceptor, the muscarinic receptor, laminin, and mitochondria; abnormalities of various T cells, including cytotoxic T cells, suppressor T lymphocytes, and natural killer cells)
ð The more important causes of secondary DCM include:
1. Prolonged ethanol abuse – the most reversible cause of DCM
2. Doxorubicin therapy, toxins (Co, Hg, Pb)– irreversible
3. Cocaine abuse
4. Human immunodeficiency virus,
5. Metabolic abnormalities
Pathology:
Macroscopy:
1. Enlargement and dilatation of all four chambers; the ventricles are more dilated than the atria.
2. Ventricular wall is normal or thin.
3. Intracavitary thrombi.
4. The cardiac valves are intrinsically normal, but the valvular rings are enlarged.
5. The coronary arteries usually are normal.
Microscopy:
1. Extensive areas of interstitial and perivascular fibrosis, particularly involving the left ventricular subendocardium.
2. Marked variation in myocyte size.
3. There is no or little cellular infiltration (in contrast to myocarditis).
Hemodynamic Considerations:
1. Decreased contractility (systolic failure) ® ventricular failure ® decreased systolic output. Compensatory mechanism: mild hypertrophy and increased heart rate. In time, this stage is overpass; dilatation and myocardium quality loss induce decreased cardiac output.
2. Increased residual volume. High end-diastolic ventricular pressure.
3. Marked ventricular dilatation ® enlargement of the atrioventricular rings (mitral and tricuspid regurgitation).
Clinical Features:
Onset:
1. Gradual development of both left and right-sided congestive heart failure symptoms and signs, or
2. Acute onset due to systemic or pulmonary embolism, acute viral infection, or severe arrhythmia.
Symptoms:
Left ventricular failure:
1. Dyspnea: exertional dyspnea ® orthopnea ® paroxysmal nocturnal dyspnea. The severity of dyspnea is diminishing after the appearance of right ventricular failure.
2. Fatigue and weakness due to diminished cardiac output.
3. Exercise intolerance (reduced skeletal muscle perfusion).
4. Systemic embolism.
5. Reduced cardiac output signs:
ð Cold, wet skin.
ð Oliguria (functional renal failure).
ð Syncope (reduced cerebral blood flow).
6. Chest pain (angina pectoris - like) occurs in about one-third of patients and may suggest:
ð Concomitant ischemic heart disease (subendocardial ischemia) due to reduction in the vasodilator reserve of the coronary microvasculature (despite angiographically normal coronary arteries). In the supply equation of the myocardium, there are excessive oxygen demands of the enlarged, thin-walled ventricle(s).
ð Pulmonary embolism.
ð Congestive hepatomegaly.
Physical examination:
1. Apical impulse is usually displaced laterally and powerless.
2. Tachycardia (usually sinus) + presystolic gallop sounds (S4) or ventricular gallops (S3) (summation gallop is heard when there is concomitant tachycardia).
3. Low audibility of heart sounds.
4. The second heart sound is paradoxical split in the presence of left bundle branch block.
5. Systolic murmurs of mitral or, less commonly, tricuspid valvular regurgitation (valvular annulus dilatation).
6. The systolic blood pressure is usually normal or low, and the pulse pressure is narrow, reflecting a diminished stroke volume (sometimes pulsus alternans).
Right ventricular failure (late occurrence; poor prognosis):
1. Lower limbs edema. Ascites.
2. Pulsatile hepatomegaly.
3. Jugular veins distention (visible a wave means tricuspid regurgitation).
N.B ! Important anamnestic features for IDCM:
A. Previous virus repeated infections – possible repeated myocarditis.
B. Unexpected resistance to classical treatment of heart failure.
C. Excessive sensibility to digitalic treatment: signs of digitalic intoxication (suggestive arrhythmias) after low doses of digoxin.
Paraclinical Investigations:
I. Biochemical tests (especially helpful for differential diagnosis):
ð serum phosphorus (hypophosphatemia);
ð serum calcium (hypocalcemia);
ð serum creatinine and urea nitrogen (uremia);
ð thyroid function studies (hypo- and hyperthyroidism);
ð iron studies (hemochromatosis).;
ð test for the human immunodeficiency virus (HIV) (this infection is an important and often unrecognized cause of congestive heart failure).
II. Chest roentgenogram:
ð generalized cardiomegaly (cardio-thoracic index > 0.60);
ð pulmonary interstitial and alveolar edema;
ð the azygos vein and superior vena cava are dilated.
III. Electrocardiography (+ Holter):
ð Sinus tachycardia.
ð Microvoltage or left ventricle hypertrophy aspect.
ð Atrial fibrillation (15-20%).
ð LBBB (30%).
ð RBBB.
ð ST and T wave abnormalities (ST depression and negative T).
ð Q waves or QS in V1-V4 or in V5-V6 (5-10%) due to fibrosis.
IV. Echocardiography (always necessary; assessing the heart function and excluding concomitant valvular or pericardial disease):
ð Dilated cavities (especially the ventricles).
ð Normal or thin ventricular walls and interventricular septum.
ð Cardiac thrombi.
ð Wall-motion abnormalities (usually global).
ð Increased end-diastolic ventricular volume.
ð Reduced ejection fractions < 30% (N = 50%)
ð Doppler studies are useful in assessing the severity of mitral (and tricuspid) regurgitation.
*Combining echocardiography with dobutamine infusion may identify patients with left ventricular dysfunction due to coronary artery disease by demonstrating provocable regional differences in wall motion and thus distinguish them from patients with idiopathic DCM.(Braunwald)
V. Cardiac catheterization and coronarography (usually are not necessary for positive diagnosis, but important in differentiation from ischemic heart disease or aortic stenosis):
ð left ventricular end-diastolic, left atrial, and pulmonary artery wedge pressures are usually elevated;
ð elevation of the right ventricular end-diastolic, right atrial, and central venous pressures;
ð normal aspect of coronary arteries (useful especially in the presence of Q waves);
VI. Thallium 201 scanning (helpful in distinguishing left ventricular enlargement caused by DCM from that caused by coronary artery disease): Normal image of left ventricle during rest.
VII. Endomyocardial biopsy (searching a secondary myocardial involvement).
Positive diagnosis:”per exclusionem:
1. Congestive heart failure having severe cardiomegaly, without an obvious cause.
2. Persistent ECG changes.
3. Effort gallop, usually released by rest.
Prognosis:
ð Poor long-term prognosis: 50% of hospitalized patients die in less than 3 years.
Differential diagnosis:
1. Ischemic cardiopathy (ischemic heart disease) – history, coronarography, +/- ECG.
2. Hypertensive cardiopathy – history, retinal examination, renal function evaluation.
3. Congenital cardiopathy – age, echocardiography.
4. Valvulopathy – possible history of rheumatic fever, characteristics of murmurs, echocardiography, chest X-ray.
5. Acute or chronic pericarditis – character of pain, chest X-ray, echocardiography +/- ECG.
6. Other cardiomyopathies (including alcoholic) – suggestive or specific laboratory tests.
ALCOHOLIC CARDIOMYOPATHY
The consumption of alcohol may result in myocardial damage by three basic mechanisms (Braunwald):
(1) a presumed direct toxic effect of alcohol or its metabolites;
(2) nutritional effects, most commonly in association with thiamine deficiency that leads to beriberi heart disease;
(3) rarely, toxic effects due to additives in the alcoholic drinks (e.g.: cobalt in beer).
Diagnosis of Alcoholic Cardiomyopathy needs some criteria, divided by Prof. C.I. Negoiţă into:
A) MAJOR CRITERIA:
1. Chronic (> 5 years) and excessive (80 g/day pure alcohol) abuse (80 g pure alcohol = 2 liters of beer = 1 liter wine = 200 ml whisky).
2. Congestive cardiopathy (heart failure). Diagnosis:
ð Clinical features: cardiomegaly, effort dyspnea, pulmonary stasis, lower limbs edema, jugular distension, various arrhythmias, etc.
ð Hemodynamic features: ventricular end-diastolic volumes are increased; reduced ejection fraction.
3. Clinical and paraclinical exclusion of other causes of heart failure and arrhythmias.
4. Total stop of alcohol consumption leads to improvements in clinical and hemodynamical features of the patient (N.B.!)
5. Laboratory features suggestive for chronic alcohol abuse: MCV > 93 m3, GGT > 40 U.I., de Rittis index > 2. These tests are non-specific (increased also in cholestatic syndromes, liver carcinoma, megaloblastic anemia), but suggestive.
B) MINOR CRITERIA:
1. Chronic alcoholism “marks”: psychical disorders, trembling of distal extremities, characteristic face.
2. Other organic diseases, induced by alcohol consumption: liver cirrhosis, acute/chronic pancreatitis, polinevritis, delirium tremens, Korsakov psychosis.
3. Age < 50 years.
4. Increased level of Ig A.
5. Normal coronary arteries. No cardiac pain.
6. Electrocardiographic abnormalities (ST, T) -- atrial fibrillation, atrial flutter, or ventricular premature contractions, particularly during the year-end holiday season (the “holiday heart syndrome”).
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA
Definition: Partial or total replacement of right ventricular muscle by adipose and fibrous tissue, leading to reentrant ventricular tachyarrhythmias of right ventricular origin (left bundle branch block configuration of the QRS complex). Synonym: right ventricular cardiomyopathy
Etiology: unclear; in 1/3 of the patients there is autosomal dominant inheritance of the disease
Clinical features
ð Male predominance
ð Normal physical examination
ð Inverted T waves in the right precordial electrocardiographic leads
ð Symptoms of palpitations and syncope
Echocardiography: dilated, poorly contractile right ventricle, usually with a quite normal left ventricle function.
Magnetic resonance imaging
ð fat in the right ventricular free wall
ð regional contractile abnormality
Endomyocardial biopsy: fatty or fibrous tissue in the right ventricle myocardium.
Diagnosis: The diagnosis of arrhythmogenic right ventricular myocardial is based on meeting two major, one major plus two minor, or four minor criteria as outlined in the table XIX-1. These criteria are based on the known structural and functional abnormalities of the right ventricle, family history, and repolarization/depolarization and electrical conduction disturbances.
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Category / Major criteria / Minor criteriaGlobal and/or regional dysfunction and structural alterations. / Severe dilatation and reduction of RV ejection.
Localized RV aneurysms (akinetic or dyskinetic areas with diastolic bulging).
Severe segmental dilatation of the RV. / Mild global dilatation and/or EF reduction with normal LV.
Mild segmental dilatation of the RV.
Regional RV hypokinesia.
Tissue characterization of walls. / Fibrofatty replacement of myocardium on endomyocardial biopsy.
Repolarization abnormalities. / Inverted T-waves in right precordial leads (V2 and V3)*
Depolarization/conduction abnormalities. / Epsilon waves or localized prolongation (>110 ms) of.the QRS complex in right precordial leads (V1–V3). / Late potentials on signal averaged ECG.
Arrhythmias. / LBBB type ventricular tachycardia (sustained and non-sustained).
Frequent ventricular extrasystoles (more than 1000/24h).
Family history. / Familial disease confirmed at autopsy or surgery. / Family history of premature sudden death (<35) due to.suspected RV dysplasia.
Family history (clinical diagnosis based on present criteria).
Table XIX-1: Criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy. (Reproduced from McKenna WJ, Thiene G, Nava A, et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Br Heart J 1994; 71:215–218.)
Note: RV, right ventricle; EF, ejection fraction; h, hours; LBBB, left bundle branch block. * Patient must be greater than twelve years old; in the absence of right bundle branch block.
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HYPERTROPHIC CARDIOMYOPATHY
Definition: Massive hypertrophy of the ventricle walls and of the interventricular septum, associated with reduction in ventricular cavities dimensions, in the absence of a cardiac or systemic cause. Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease and an important cause of morbidity and sudden cardiac death in young people, including competitive athletes (Maron 1995).