HCM is a condition of the heart in which a part of the myocardium or the muscle of the heart is enlarged without any obvious reasons. It is very common and affects people of all ages. HCM is a clinically heterogeneous but relatively common autosomal dominant genetic heart disease (1:500 of the general population for the disease phenotype recognized by echocardiography) that probably is the most frequently occurring cardiomyopathy (Maron, 2002). It is the most common cause of sudden cardiac death in the young (including trained athletes) and is an important substrate for heart failure disability at any age.
HCM is characterized morphologically and defined by a hypertrophied, nondilated left ventricle (LV) in the absence of another systemic or cardiac disease that is capable of producing the magnitude of wall thickening evident (e.g., systemic hypertension, aortic valve stenosis). Clinical diagnosis is customarily made with 2 dimensional echocardiography (or alternatively with cardiac magnetic resonance imaging) by detection of otherwise unexplained LV wall thickening, usually in the presence of a small LV cavity, after suspicion is raised by the clinical profile or as part of family screening (Maron et al., 2006).
When LV wall thickness is mild, differential diagnosis with physiological athlete’s heart may arise. Furthermore, individuals harboring a genetic defect for HCM do not necessarily express clinical markers of their disease such as LV hypertrophy on echocardiogram, ECG abnormalities, or symptoms at all times during life, and ECG alterations can precede the appearance of hypertrophy. Indeed, virtually any LV wall thickness, even when within normal limits, is consistent with the presence of an HCM-causing mutant gene, and diagnosis can be made by laboratory DNA analysis. Furthermore, recognition of LV hypertrophy may be age related with its initial appearance delayed well into adulthood (adult morphological conversion). Most HCM patients have the propensity to develop dynamic obstruction to LV outflow under resting or physiologically provocable conditions, produced by systolic anterior motion of the mitral valve with ventricular septal contact (Maron et al., 2006).
HCM is caused by a variety of mutations encoding contractile proteins of the cardiac sarcomere. Currently, 11 mutant genes are associated with HCM, most commonly |3-myosin heavy chain (the first identified) and myosin binding protein C (Barry et al., 2008; Lowey, 2002). The other 9 genes appear to account for far fewer cases of HCM and include troponin T and I, regulatory and essential myosin light chains, titin, a-tropomyosin, a-actin, a-myosin heavy chain, and muscle LIM protein (Barry et al., 2008; Selvetella & Lembo, 2005). This genetic diversity is compounded by considerable intragenic heterogeneity, with >400 individual mutations now identified. These most commonly are missense mutations but include insertions, deletions, and splice (split-site) mutations encoding truncated sarcomeric proteins (Maron et al., 2006). The characteristic diversity of the HCM phenotype is attributable to the disease causing mutations and probably to the influence of modifier genes and environmental factors.
In addition, nonsarcomeric protein mutations in 2 genes involved in cardiac metabolism have recently been reported to be responsible for primary cardiac glycogen storage diseases in older children and adults with a clinical presentation mimicking (or indistinguishable from) that of sarcomeric HCM. One of these conditions involves the gene encoding the y-2-regulatory subunit of the AMP-activated protein kinase (PRKAG2), associated with variable degrees of LV hypertrophy and ventricular pre-excitation. The other involves the gene encoding lysosome-associated membrane protein-2 (LAMP-2), resulting in Danon-type storage disease (Maron et al., 2006). Clinical manifestations are limited largely to the heart, usually with massive degrees of LV hypertrophy and ventricular pre-excitation. These disorders are now part of a subgroup of previously described infiltrative forms of LV hypertrophy such as Pompe disease, a glycogen storage disease caused by a-1,4 glycosidase (acid maltase deficiency) in infants, and Fabry’s disease, an X-linked recessive disorder of glycosphingolipid metabolism caused by a deficiency of the lysosomal enzyme a-galactosidase A, resulting in intracellular accumulation of glycosphingolipids. Undoubtedly, many other mutations causing cardiac hypertrophy by disrupting sarcomere, metabolic, and other genes remain to be identified (Elliott et al., 2008).
A number of other diseases associated with LV hypertrophy involve prominent thickening of the LV wall, occurring mostly in infants and children <4 years of age, which may resemble or mimic typical HCM caused by sarcomere protein mutations. These cardiomyopathies include secondary forms such as Noonan syndrome, an autosomal dominant cardiofacial condition associated with a variety of cardiac defects (most commonly, dysplastic pulmonary valve stenosis and atrial septal defect) resulting from mutations in PTPN11, a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2 genes. At present, the causes of most cases of pediatric cardiomyopathies are unknown (Maron et al., 2006).
Other diseases in this category are mitochondrial myopathies resulting from mutations encoding mitochondrial DNA (including Kearns-Sayre syndrome) or mitochondrial proteins associated with ATP electron transport chain enzyme defects that alter mitochondrial morphology. Also included in these considerations are metabolic myopathies representing ATP production and utilization defects involving abnormalities of fatty acid oxidation (acyl CoA dehydrogenase deficiencies) and carnitine deficiency, as well as infiltrative myopathies, i.e., glycogen storage diseases (type II; autosomal recessive Pompe disease), Hunter’s and Hurler’s diseases, and the transient and nonfamilial cardiomyopathy as part of generalized organomegaly, recognized in infants of insulin-dependent diabetic mothers. In older patients, a number of systemic diseases have been associated with hypertrophic forms of cardiomyopathy; these include Friedreich’s ataxia, pheochromocytoma, neurofibromatosis, lentiginosis, and tuberous sclerosis.
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
ARVC/D is predominantly a genetically determined heart muscle disorder that is characterized pathologically by fibrofatty replacement of the right ventricular (RV) myocardium (Basso et al., 2009). In the early stage of the disease, structural changes may be absent or subtle and confined to a localized region of the RV, typically the inflow tract, outflow tract, or apex of the RV, the "triangle of dysplasia." Progression to more diffuse RV disease and left ventricular (LV) involvement, typically affecting the posterior lateral wall, is common (Marcus et al., 2010).
ARVC/D is a familial disease in at least 50% of cases and is typically transmitted as an autosomal dominant trait with variable penetrance. On the basis of clinical studies and data obtained from pre-participation screening for sport activity, the estimated prevalence of the disease in the general population ranges from 1 in 1000 to 1 in 5000 (Nava et al., 2000).
ARVC/D has a broad clinical spectrum, usually presenting clinically with ventricular tachyarrhythmias (e.g., monomorphic ventricular tachycardia). Noninvasive clinical diagnosis may be confounding, without an easily obtained single test or finding that is definitively diagnostic, and generally requires an integrated assessment of electrical, functional, and anatomic abnormalities. Diagnosis often requires a high index of suspicion, frequently triggered by presentation with arrhythmias, syncope, or cardiac arrest, as well as global or segmental chamber dilatation or wall motion abnormalities (Marcus et al., 2010).
Noninvasive tests used to diagnose ARVC/D, in addition to personal and family history, include 12-lead ECG, echocardiography, right ventricular angiography, cardiac magnetic resonance imaging, and computerized tomography. Endomyocardial biopsy from the right ventricular free wall is a sensitive diagnostic marker when fibrofatty infiltration is associated with surviving strands of myocytes. ECGs most commonly show abnormal repolarization with T-wave inversion in leads V1 through V3 and small-amplitude potentials at the end of the QRS complex (epsilon wave); Brugada syndrome-like right bundle-branch block and right precordial ST-segment elevation accompanied by polymorphic ventricular tachycardia also have been reported in a small subpopulation of ARVC/D patients (Basso et al., 2009; Protonotarios et al., 2011).
ARVC/D shows autosomal dominant inheritance, albeit often with incomplete penetrance. Autosomal dominant ARVC/D has been mapped to 8 chromosomal loci, with mutations identified thus far in 4 genes: the cardiac ryanodine receptor RyR2, which is also responsible for familial catecholaminergic polymorphic ventricular tachycardia (CPVT); desmoplakin; plakophillin-2; and mutations altering regulatory sequences of the transforming growth factor-3 gene, which has a role in inflammation. Two recessive forms have been described in conjunction with palmoplantar keratoderma and woolly hair (Naxos disease) and with Carvajal syndrome, caused by mutations in junctional plakoglobin and desmoplakin, respectively. Although the function of desmosomal proteins to anchor intermediate filaments to desmosomes implicates ARVC/D as a primary structural abnormality, there is also a link to ion channel dysfunction (Maron et al., 2006).
Left ventricular noncompaction
Noncompaction of ventricular myocardium is a recently recognized congenital cardiomyopathy characterized by a distinctive ("spongy") morphological appearance of the LV myocardium. Noncompaction involves predominantly the distal (apical) portion of the LV chamber with deep intertrabecular recesses (sinusoids) in communication with the ventricular cavity, resulting from an arrest in the normal embryogenesis (Freedom et al., 2005). LV noncompaction (LVNC) may be an isolated finding or may be associated with other congenital heart anomalies such as complex cyanotic congenital heart disease. Diagnosis is made with 2-dimensional echocardiography, cardiac magnetic resonance imaging, or LV angiography (Chin et al., 1990). The natural history of LVNC is largely unresolved but includes LV systolic dysfunction and heart failure (and some cases of heart transplantation), thromboemboli, arrhythmias, sudden death, and diverse forms of remodeling. Both familial and nonfamilial cases have been described. In the isolated form of LVNC, ZASP (Z-line) and mitochondrial mutations, and X-linked inheritance resulting from mutations in the G4.5 gene encoding tafazzin (including association with Barth syndrome in neonates) have been reported. Noncompaction associated with congenital heart disease has been shown to result from mutations in the a-dystrobrevin gene and transcription factor NKX2.5 (Monserrat Iglesias, 2008).
Conduction system disease
Lenegre disease, also called as progressive cardiac conduction defect. It is characterized by primary progressive development of cardiac conduction defects in the His-Purkinje system, leading to widening of the QRS complex, long pauses, and bradycardia that may trigger syncope. Phenotypically sick sinus syndrome is similar to progressive cardiac conduction defect. Familial occurrence of both syndromes has been reported with an autosomal dominant pattern of inheritance. An ion channelopathy, in the form of SCN5A mutations, is thought to contribute to these conduction system defects. Wolff-Parkinson-White syndrome is familial in some cases, but information about the genetic causes is unavailable.
There is a growing list of uncommon inherited and congenital arrhythmia disorders caused by mutations in genes encoding defective ionic channel proteins, governing cell membrane transit of sodium and potassium ions (Aleong et al., 2007). These ion channel disorders include LQTS, short-QT syndrome (SQTS), Brugada syndrome, and CPVT. Nocturnal sudden unexplained death syndrome in young Southeast Asian males and Brugada syndrome are based on similar clinical and genetic profiles. A small proportion (5% to 10%) of sudden infant deaths also may be linked to ion channelopathies, including LQTS, SQTS, and Brugada syndrome (Modell & Lehmann, 2006). Clinical diagnosis of the ion channelopathies often can be made by identification of the disease phenotype on standard 12-lead ECG. Some of these cases had previously been classified as idiopathic ventricular fibrillation, a description that persists for a syndrome in which mechanistic understanding is lacking (Aleong et al., 2007; Kass, 2005).
This is the most common condition of the ion channelopathies. It is characterized by prolongation of ventricular repolarization and QT interval (corrected for heart rate) on the standard 12-lead ECG, a specific form of polymorphic ventricular tachycardia (torsade des pointes), and a risk for syncope and sudden cardiac death. Phenotypic expression (on the ECG) varies considerably, and ~25% to 50% of affected family members may show borderline or even normal QT intervals.
Two patterns of inheritance have been described in LQTS: a rare autosomal recessive disease associated with deafness (Jervell and Lange-Nielsen syndrome), which is caused by 2 genes that encode for the slowly activating delayed rectifier potassium channel (KCNQ1 and KCNE1 (minK)), and the much more common autosomal dominant disease unassociated with deafness (Romano-Ward syndrome), which is caused by mutations in 8 different genes. These include KCNQ1 (KvLQT1, LQT1), KCNH2 (HERG, LQT2), SCN5A (Na1.5, LQT3), ANKB (LQT4), KCNE1 (minK, LQT5), KCNE2 (MiRP1, LQT6), KCNJ2 (Kir2.1, LQT7, Andersen’s syndrome), and CACNA1C (Ca1.2, LQT8, Timothy syndrome). Of the 8 genes, 6 encode for cardiac potassium channels, 1 for the sodium channel (SCN5A, LQT3), and 1 for the protein ankyrin, which is involved in anchoring ion channels to the cellular membrane (ANKB) (Maron et al., 2006).
This syndrome is a relatively new clinical entity associated with sudden cardiac death in young people. First described in 1992, the syndrome is identified by a distinctive ECG pattern consisting of right bundle-branch block and coved ST-segment elevation in the anterior pre-cordial leads (V1 through V3). The characteristic ECG pattern is often concealed and may be unmasked with the administration of sodium channel blockers, including ajmaline, flecainide, procainamide, and pilsicainide. Familial autosomal dominant and sporadic forms have been linked to mutations in an a-subunit of the cardiac sodium channel gene SCN5A (the same gene responsible for LQT3) in 20% of patients. Another locus has been reported on the short arm of chromosome 3, but no gene has been identified. Sudden unexplained nocturnal death syndrome, found predominantly in young Southeast Asian males (i.e., those from Thailand, Japan, the Philippines, and Cambodia), is a disorder causing sudden death during sleep as a result of ventricular tachycardia/fibrillation. Some cases of sudden unexplained nocturnal death syndrome resulting from SCN5A gene mutations and Brugada syndrome have been shown to be phenotypically, genetically, and functionally the same disorder (Antzelevitch et al., 2005; Krittayaphong et al., 2003).
Catecholaminergic polymorphic ventricular tachycardia
CPVT is characterized by syncope, sudden death, polymorphic ventricular tachycardia triggered by vigorous physical exertion or acute emotion (usually in children and adolescents), a normal resting ECG, and the absence of structural cardiac disease. Family history of 1 or multiple sudden cardiac deaths are evident in 30% of cases. The resting ECG is unremarkable, except for sinus bradycardia and prominent U waves in some patients. The most typical arrhythmia of CPVT is bidirectional ventricular tachycardia presenting with an alternating QRS axis. The autosomal dominant form of the disease has been linked to the RyR2 gene encoding for the cardiac ryanodine receptor, a large protein that forms the Ca2+ release channel in the sarcoplasmic reticulum that is essential for regulation of excitation-contraction coupling and [Ca2+li levels. An autosomal recessive form has been linked to CASQ2, a gene that encodes for calsequestrin, a protein that serves as a major Ca2+-binding protein in the terminal cisternae of the sarcoplasmic reticulum. Calsequestrin is bound to the ryanodine receptor and participates in the control of excitation-contraction coupling (Wilde et al., 2008).
First described in 2000, the SQTS is characterized by a short QT interval (<330 ms) on an ECG and a high incidence of sudden cardiac death resulting from ventricular tachycardia/fibrillation. Another distinctive ECG feature of SQTS is the appearance of tall peaked T waves similar to those encountered with hyperkalemia. The syndrome has been linked to gain-of-function mutations in KCNH2 (HERG, SQT1), KCNQ1 (KvLQT1, SQT2), and KCNJ2 (Kir2.1, SQT3), causing an increase in the intensity of Ikr, Iks and Ikl, respectively (Gaita et al., 2003; Schimpf et al., 2005).
Idiopathic ventricular fibrillation
A subgroup of patients with sudden death appears in the literature with the designation of idiopathic ventricular fibrillation. However, it is likely that idiopathic ventricular fibrillation is not an independent disease entity but rather a conglomeration of conditions with normal gross and microscopic findings in which arrhythmic risk undoubtedly derives from molecular abnormalities, most likely ion channel mutations. At present, insufficient data are available to permit the classification of idiopathic ventricular fibrillation as a distinct cardiomyopathy (Chen et al., 1998).
Mixed (genetic and nongenetic)
DCM is the most common cardiomyopathy worldwide and has many causes. It is a heart muscle disorder defined by the presence of a dilated and poorly functioning left or both ventricles. It can be primary (genetic, mixed or predominantly familial non-genetic, or acquired) or secondary (e.g., infiltrative or autoimmune). This disease can be diagnosed in association with recognized cardiovascular disease; however, to qualify as DCM, the extent of myocardial dysfunction cannot be explained exclusively by abnormal loading conditions (hypertension, valve disease) or ischaemic heart disease (Elliott et al., 2008; Jefferies & Towbin, 2010). A large number of cardiac and systemic diseases can cause systolic impairment and left ventricular dilatation, but in the majority of patients no identifiable cause is found hence the term "idiopathic" dilated cardiomyopathy (IDC). There are experimental and clinical data in animals and humans suggesting that genetic, viral, and immune factors contribute to the pathophysiology of IDC (Elliott, 2000). DCM is associated with sudden cardiac death and heart failure, resulting in a large cost burden because of the very high rate of hospital admission and the potential need for heart transplantation. DCM is characterized mainly by left ventricular systolic (or diastolic in some case) dysfunction (abnormality of contraction), with an associated increase in mass and volume. Right ventricular dilation and dysfunction can also develop but are not needed for diagnosis. Prevalence in the general population remains undefined. This disorder develops at any age, in either sex, and in people of any ethnic origin (Rosamond et al., 2008; Towbin et al., 2006). In adults, DCM arises more commonly in men than in women. In children, the yearly incidence is 0.57 cases per 100000 per year overall, but is higher in boys than in girls (0.66 vs. 0.47 cases per 100000, P<0.006), in black people than in white people (0.98 vs. 0.46 cases per 100000, P<0.001), and in babies younger than 1 year than in children (4.40 vs. 0.34 cases per 100000, P<0.001). Two thirds of children are thought to have idiopathic disease (Towbin et al., 2006). In adults, the prevalence is 1 in 2500 individuals, with an incidence of 7 per 100000 per year (but it could be underdiagnosed). In many cases, the disease is inherited, and is called familial dilated cardiomyopathy (FDC). The familial type might account for 20-48% of all cases (Taylor et al., 2006). To achieve improved care and outcomes in children and adults, a broadened understanding of the causes of these disorders are needed.
In this disease, the left ventricle is dilated, and more spherical than usual with raised wall stress and depressed systolic function. Mitral regurgitation, thromboembolic events and ventricular arrhythmias can also develop. Occasionally, other rhythm disturbances such as atrioventricular block, supraventricular tachycardia with or without pre-excitation including Wolf-Parkinson-White syndrome and atrial fibrillation develop. In the most severe cases, affected individuals present with signs and symptoms of HF-diaphoresis, breathlessness at rest or with exertion, orthopnoea, exercise intolerance, early onset fatigue, abdominal pain, and pallor. Cachexia and peripheral oedema typically arise late in the course of the disease. Young children often have poor appetite and cachexia, similar to adults. Sinus tachycardia, gallop rhythm, jugular-venous distention, pallor, cool hands and feet, hepatomegaly, and a murmur that is consistent with mitral regurgitation are common findings at physical examination (Jefferies & Towbin, 2010; Luk et al., 2009). Additionally, peripheral oedema and ascites are late signs in children. DCM can occur in a number of X-linked diseases such as Becker’s and Duchenne’s muscular dystrophies. It may also occur in patients with mitochondrial DNA mutations and inherited metabolic disorders. Thus when taking a family history, specific attention should be given to a history of muscular dystrophy, features of mitochondrial disease (for example, familial diabetes, deafness, epilepsy, maternal inheritance), and signs and symptoms of other inherited metabolic diseases (Elliott, 2000) About 20-48% of DCM have been reported as familial, although with incomplete and age-dependent penetrance, and linked to a diverse group of >20 loci and genes ((Taylor et al., 2006)). Although genetically heterogeneous, the predominant mode of inheritance for DCM is autosomal dominant, with X-linked autosomal recessive and mitochondrial inheritance less frequent. Several of the mutant genes linked to autosomal dominant DCM encode the same contractile sarcomeric proteins that are responsible for HCM, including a-cardiac actin; a-tropomyosin; cardiac troponin T, I, and C; 3- and a-myosin heavy chain; and myosin binding protein C. Z-disc protein-encoding genes, including muscle LIM protein, a-actinin-2, ZASP, and titin, also have been identified.
DCM is also caused by a number of mutations in other genes encoding cytoskeletal/sarcolemmal, nuclear envelope, sarcomere, and transcriptional coactivator proteins. The most common of these probably is the lamin A/C gene, also associated with conduction system disease, which encodes a nuclear envelope intermediate filament protein. Mutations in this gene also cause Emery-Dreifuss muscular dystrophy. The X-linked gene responsible for Emery-Dreifuss muscular dystrophy, emerin (another nuclear lamin protein), also causes similar clinical features. Other DCM genes of this type include desmin, caveolin, and 3- and a-sarcoglycan, as well as the mitochondrial respiratory chain gene. X-linked DCM is caused by the Duchenne muscular dystrophy (dystrophin) gene, whereas G4.5 (tafazzin), a mitochondrial protein of unknown function, causes Barth syndrome, which is an X-linked cardioskeletal myopathy in infants (Maron et al., 2006).
RCM is defined as heart-muscle disease that results in impaired ventricular filling, with normal or decreased diastolic volume of either or both ventricles. Systolic function usually remains normal, at least early in the disease, and wall thickness may be normal or increased, depending on the underlying cause (Kushwaha et al., 1997).
The exact prevalence of RCM is unknown but it is probably the least common type of cardiomyopathy. RCM may be idiopathic, familial, or result from various systemic disorders, in particular, amyloidosis, sarcoidosis, carcinoid heart disease, scleroderma and anthracycline toxicity. Familial RCM is often characterized by autosomal dominant inheritance, which in some families is caused by mutations in the troponin I gene; in others, familial RCM is associated with conduction defects, caused by mutations in the desmin gene (usually associated with skeletal myopathy) (Fitzpatrick et al., 1990). Rarely, familial disease can be associated with autosomal recessive inheritance (such as haemochromatosis caused by mutations in the HFE gene, or glycogen storage disease), or with X-linked inheritance (such as Anderson-Fabry disease) (Elliott et al., 2008).
RCM can also be caused by endocardial pathology (fibrosis, fibroelastosis, and thrombosis) that impairs diastolic function. These disorders can be sub-classified according to the presence of eosinophilia into endomyocardial diseases with hypereosinophilia (e.g., hypereosinophilic syndromes (HES)) and endomyocardial disease without hypereosinophilia (e.g., endomyocardial fibrosis (EMF)) (Fauci et al., 1982). Parasitic infections, drugs such as methysergide, and inflammatory and nutritional factors have been implicated in acquired forms of EMF. Fibrous endocardial lesions of the right and/or left ventricular inflow tract cause incompetence of the atrioventricular valves (Kushwaha et al., 1997). Isolated left ventricular involvement results in pulmonary congestion and predominant right ventricular involvement leads to right heart failure.
Myocarditis (inflammatory cardiomyopathy)
Myocarditis is an acute or a chronic inflammatory process affecting the myocardium produced by a wide variety of toxins and drugs (e.g., cocaine, interleukin 2) or infectious agents, most commonly including viral (e.g., coxsackievirus, adenovirus, parvovirus, HIV), bacterial (e.g., diphtheria, meningococcus, psittacosis, streptococcus), rickettsial (e.g., typhus, Rocky Mountain spotted fever), fungal (e.g., aspergillosis, candidiasis), and parasitic (Chagas disease, toxoplasmosis), as well as Whipple disease (intestinal lipodystrophy), giant cell myocarditis, and hypersensitivity reactions to drugs such as antibiotics, sulfonamides, anticonvulsants, and anti-inflammatories. Endocardial fibroelastosis is a DCM in infants and children that is a consequence of viral myocarditis in utero (mumps) (Maron et al., 2006).
Myocarditis typically evolves through active, healing, and healed stages. It is characterized progressively by inflammatory cell infiltrates leading to interstitial edema and focal myocyte necrosis and ultimately replacement fibrosis (Calabrese & Thiene, 2003). These pathological processes create an electrically unstable substrate predisposing to the development of ventricular tachyarrhythmias. In some instances, an episode of viral myocarditis (frequently subclinical) can trigger an autoimmune reaction that causes immunologic damage to the myocardium or cytoskeletal disruption, culminating in DCM with LV dysfunction. Evidence for the evolution of myocarditis to DCM comes from several sources, including animal models, the finding of inflammatory infiltrates and persistence of viral RNA in endomyocardial biopsies from patients with DCM, and the natural history of patients with selected conditions such as Chagas disease. The list of agents responsible for inflammatory myocarditis overlaps with that of the infectious origin of DCM, thereby underscoring the potential interrelationship between the 2 conditions (Cooper, 2009).
Myocarditis can be diagnosed by established histopathological, histochemical, or molecular criteria, but it is challenging to identify clinically. Suspicion may be raised by chest pain, exertional dyspnea, fatigue, syncope, palpitations, ventricular tachyarrhythmias, and conduction abnormalities or by acute congestive heart failure or cardiogenic shock associated with LV dilatation and/or segmental wall motion abnormalities and ST-T changes on ECG. When myocarditis is suspected from the clinical profile, an endomyocardial biopsy may resolve an otherwise ambiguous situation by virtue of diagnostic inflammatory (leukocyte) infiltrate and necrosis (i.e., the Dallas criteria) but also is limited by insensitivity and false-negative histological results. The diagnostic yield of myocardial biopsies can be enhanced substantially by molecular analysis with DNA-RNA extraction and polymerase chain reaction amplification of the viral genome. In addition to the inflammatory process, viral genome encoded proteases appear to disrupt the cytoskeletal sarcomeric linkages of cardiomyocytes (Calabrese & Thiene, 2003; Parrillo, 2001).
Stress ("Tako-Tsubo") cardiomyopathy
Stress cardiomyopathy, first reported in Japan as "takotsubo," is a recently described clinical entity characterized by acute but rapidly reversible LV systolic dysfunction in the absence of atherosclerotic coronary artery disease, triggered by profound psychological stress (Sealove et al., 2008; Sharkey et al., 2005). This distinctive form of ventricular stunning typically affects older women and preferentially involves the distal portion of the LV chamber ("apical ballooning"), with the basal LV hypercontractile. Although presentation often mimics ST-segment-elevation myocardial infarction, outcome is favorable with appropriate medical therapy.
The most important secondary cardiomyopathies are provided in the Table 1. This list, however, is not intended to represent an exhaustive and complete tabulation of the vast number of systemic conditions reported to involve the myocardium. Rather, it is limited to the most common of these diseases most consistently associated with a cardiomyopathy.