cardiomyopathy

PowerPoint Presentation: 

Presentation of some haert disease Prepared by Mohammed A Q

Chapet 1 : 

Chapet 1 CARDIOMYOPATHIES

PowerPoint Presentation: 

Most cardiac disease is secondary to some other condition (e.g., coronary atherosclerosis, hypertension, or valvular heart disease). However, there are some that are attributable to intrinsic myocardial dysfunction. Such myocardial diseases are termed cardiomyopathies (literally, heart muscle diseases ). They are a diverse group that includes inflammatory disorders ( myocarditis ), immunologic diseases (e.g., sarcoidosis ), systemic metabolic disorders (e.g., hemochromatosis ), muscular dystrophies, and genetic disorders of cardiac muscle cells. In many cases, cardiomyopathies are of unknown etiology (termed idiopathic ); however, several previously "idiopathic" cardiomyopathies have been shown to be caused by specific genetic abnormalities in cardiac energy metabolism or structural and contractile proteins. CARDIOMYOPATHIES

PowerPoint Presentation: 

classification divides cardiomyopathies into three groups : Dilated cardiomyopathy Hypertrophic cardiomyopathy Restrictive cardiomyopathy CARDIOMYOPATHIES

PowerPoint Presentation: 

Among these, dilated cardiomyopathy is most common (90% of cases), and restrictive cardiomyopathy is the least frequent. Within each pattern there is a spectrum of clinical severity, and each of these three patterns can be caused by a specific identifiable cause or can be idiopathic (Table 11-5). While the recent A merican H eart A ssociation classification is intellectually more satisfying, we follow here the time-honored clinicopathologic classification since, at present, it is more useful for patient management. CARDIOMYOPATHIES

PowerPoint Presentation: 

Before we go into further details, some comments are in order about myocarditis . They are included here under the umbrella of cardiomyopathies since there is clinical overlap between some cases of myocarditis and dilated cardiomyopathy and in a proportion of cases, dilated cardiomyopathy can be shown to evolve from acute myocarditis . Indeed, since experts at the American Heart Association also include myocarditis among cardiomyopathies , we seem to be in good company

PowerPoint Presentation: 

Dilated Cardiomyopathy

PowerPoint Presentation: 

Dilated cardiomyopathy (DCM) is characterized by progressive cardiac dilation and contractile (systolic) dysfunction , usually with concurrent hypertrophy . It is sometimes called congestive cardiomyopathy . Approximately 25% to 35% of DCM cases have a familial (genetic) basis . Others result from a variety of acquired myocardial insults including toxic exposures (e.g., chronic alcoholism), myocarditis , and pregnancy-associated changes (see later). In some patients, the cause of DCM is unknown . Such cases are appropriately called idiopathic dilated cardiomyopathy . Many in this category are likely to be of genetic origin. Regardless of the cause, all share a similar clinicopathologic picture . Dilated Cardiomyopathy

PowerPoint Presentation: 

The heart in DCM is characteristically enlarged (two to three times its normal weight) and flabby , with dilation of all chambers . Because of the wall thinning that accompanies dilation, the ventricular thickness may be less than, equal to, or greater than normal. Mural thrombi are common and may be a source of thromboemboli . By definition there is no primary valve pathology ; consequently, any valvular insufficiency is a secondary consequence of ventricular chamber dilation. The coronary arteries are usually free of significant atherosclerotic stenosis . Morphology

PowerPoint Presentation: 

The histologic abnormalities in DCM are nonspecific . Microscopically most myocytes are hypertrophied with enlarged nuclei , but many are attenuated, stretched, and irregular. There is variable interstitial and endocardial fibrosis ; scattered scars are also often present, probably marking previous myocyte ischemic necrosis caused by reduced perfusion (due to poor contractile function) and increased demand (due to myocyte hypertrophy). The extent of the changes frequently does not reflect the degree of dysfunction or the patient's prognosis.

PowerPoint Presentation: 

Pathogenesis When discovered clinically, DCM is frequently at its end stage, and many hearts show only the nonspecific findings described above. As a result the etiology can often only be inferred by the patient's medical history, or it is based on epidemiologic evidence. The causes of DCM can be grouped into four broad categories: Viral. The nucleic acid "footprints" from coxsackievirus B and other enteroviruses can occasionally be detected in the myocardium. Moreover, sequential endomyocardial biopsies have documented cases where there is progression from myocarditis to DCM. Consequently, some cases of DCM are attributed to myocarditis ; even without direct evidence of inflammation, simply finding viral transcripts may be sufficient to invoke a myocarditis that was "missed" in its early stages .

PowerPoint Presentation: 

Alcohol or other toxic exposure . Alcohol abuse is strongly associated with development of DCM. Alcohol and its metabolites, especially acetaldehyde, have a direct toxic effect on myocardium. Moreover, chronic alcoholism can be associated with thiamine deficiency, introducing an element of beriberi heart disease .Nevertheless, the cause-and-effect relationship with alcohol alone is debated, and no morphologic features serve to distinguish alcoholic cardiomyopathy from DCM of any other cause . Nonalcoholic toxic insults include certain chemotherapeutic agents, particularly doxorubicin ( Adriamycin ), and cobalt

PowerPoint Presentation: 

Genetic influences . Familial forms of DCM account for 25% to 35% of cases; autosomal dominant inheritance is the predominant pattern; X-linked, autosomal recessive, and mitochondrial inheritances are less common. Most of the genetic abnormalities seem to involve the myocyte cytoskeleton . Although not the most common form, X-linked DCM caused by mutation in the dystrophin gene is the best understood. Dystrophin is an intracellular structural protein that plays a critical role in linking the cytoskeleton of striated muscle with the extracellular matrix ; indeed, dystrophin is mutated in the most common muscular dystrophies .Interestingly, some patients with dystrophin gene mutations have DCM as the primary clinical feature. Other cytoskeletal proteins involved in DCM include α-cardiac actin (links the sarcomere with dystrophin ), desmin (the principal intermediate-filament protein in cardiac myocytes ), and the nuclear lamins A and C . Mitochondrial gene deletions and mutations in genes encoding enzymes involved in fatty acid beta-oxidation can presumably cause DCM by altering myocardial ATP generation

PowerPoint Presentation: 

Peripartum cardiomyopathy occurs late in gestation or several weeks to months postpartum. The etiology is multifactorial , including pregnancy-associated hyper-tension , volume overload , nutritional deficiency , other metabolic derangement , and/or an immunologic response ( e.g., abnormal cytokine production ). Fortunately, approximately half of these patients spontaneously recover normal function

PowerPoint Presentation: 

DCM can occur at any age, including in childhood, but it most commonly occurs between ages 20 and 50 years. It typically presents with slowly progressing (e.g., shortness of breath and poor exertional capacity ), but patients can slip precipitously from a compensated to a decompensated state. The fundamental defect in DCM is ineffective contraction . Hence in end-stage DCM, the cardiac ejection fraction is typically less than 25% . Secondary mitral regurgitation and abnormal cardiac rhythms are common, and embolism from intracardiac thrombi can occur. Fifty percent of patients die within 2 years , and only 25% survive longer than 5 years ; Death is usually due to progressive cardiac failure or arrhythmia. In most cases cardiac transplantation is the only definitive treatment. Clinical Features

PowerPoint Presentation: 

Hypertrophic Cardiomyopathy

PowerPoint Presentation: 

Hypertrophic cardiomyopathy (HCM) (also known as idiopathic hypertrophic subaortic stenosis ) is characterized by myocardial hypertrophy , abnormal diastolic filling , and-in a third of cases- ventricular outflow obstruction . As discussed below, the obstruction, in some cases, is dynamic, caused by the anterior leaflet of the mitral valve . The heart is thick-walled, heavy, and hyper contracting, in striking contrast to the flabby, poorly contractile heart in DCM. Systolic function is usually preserved in HCM, but the myocardium does not relax and therefore shows primary diastolic dysfunction.

PowerPoint Presentation: 

Morphology The essential gross feature of HCM is massive myocardial hypertrophy without ventricular dilation .The classic pattern of HCM involves disproportionate thickening of the ventricular septum relative to the left ventricle free wall (so-called asymmetrical septal hypertrophy ); nevertheless, in about 10% of cases there is concentric hypertrophy. On longitudinal sectioning, the ventricular cavity loses its usual round-to-ovoid shape and is compressed into a "banana-like " configuration .Often present is an endocardial plaque in the left ventricular outflow tract, as well as a thickening of the anterior mitral leaflet . Both findings reflect contact of the anterior mitral leaflet with the septum during ventricular systole and correlate with functional left ventricular outflow tract obstruction.

PowerPoint Presentation: 

The characteristic histologic features in HCM are severe myocyte hypertrophy, myocyte (and myofiber ) disarray, and interstitial and replacement fibrosis

PowerPoint Presentation: 

Pathogenesis Almost all cases of HCM are caused by missense point mutations in one of several genes encoding the sarcomeric proteins that form the contractile apparatus of striated muscle .In most cases, the pattern of transmission is autosomal dominant with variable expression. Greater than 100 causal mutations have been identified in at least 12 sarcomeric genes , with the β-myosin heavy chain being most frequently affected, followed by myosin-binding protein C and troponin T . These three genes account for 70% to 80% of all cases of HCM. Although it is clear that these genetic defects underlie HCM, the sequence of events leading from mutations to disease is still poorly understood. A current proposal suggests that HCM represents a compensatory change in response to impaired contractility. In this model, ineffective myocyte contraction triggers exuberant growth factor release with subsequent intense compensatory hypertrophy ( causing myofiber disarray ) and fibroblast proliferation (causing interstitial fibrosis).

PowerPoint Presentation: 

Clinical Features HCM is characterized by a massively hypertrophied left ventricle that paradoxically provides a markedly reduced stroke volume . This pathophysiologic effect is a direct consequence of impaired diastolic filling and overall smaller chamber size. In addition, roughly 25% of patients have dynamic obstruction to the left ventricular outflow by the anterior leaflet of the mitral valve . Reduced cardiac output and a secondary increase in pulmonary venous pressure cause exertional dyspnea , and there is a harsh systolic ejection murmur . A combination of massive hypertrophy , high left ventricular pressures, and compromised intramural coronary arteries frequently leads to myocardial ischemia (with angina) , even in the absence of concomitant coronary artery disease. Major clinical problems include atrial fibrillation with mural thrombus formation, IE of the mitral valve, CHF, arrhythmias, and sudden death. Most patients are improved by therapy that promotes ventricular relaxation; occasionally, partial surgical excision of septal muscle is necessary to relieve the outflow tract obstruction.

PowerPoint Presentation: 

Restrictive Cardiomyopathy

PowerPoint Presentation: 

Restrictive cardiomyopathy is characterized by a primary decrease in ventricular compliance , resulting in impaired ventricular filling during diastole (simply put, the wall is stiffer ). The contractile (systolic) function of the left ventricle is usually unaffected. Thus, the functional state can be confused with that of constrictive pericarditis or hypertrophic cardiomyopathy . Restrictive cardiomyopathy can be idiopathic or associated with systemic diseases that also happen to affect the myocardium-for example, radiation fibrosis, amyloidosis , hemochromatosis , sarcoidosis , or products of inborn errors of metabolism. For each of these causes, the curious reader is referred to the more complete discussion in the relevant chapters. Genetic factors are less clearly defined in restrictive cardiomyopathy .

PowerPoint Presentation: 

Morphology In idiopathic restrictive cardiomyopathy the ventricles are of approximately normal size or slightly enlarged, the cavities are not dilated , and the myocardium is firm. Biatrial dilation is commonly observed. Microscopically there is interstitial fibrosis , varying from minimal and patchy to extensive and diffuse. Restrictive cardiomyopathy of disparate causes may have similar gross morphology. However, endomyocardial biopsy can reveal disease-specific features (e.g., amyloid , iron overload, sarcoid granulomas ).

PowerPoint Presentation: 

Myocarditis

PowerPoint Presentation: 

In myocarditis there is inflammation of the myocardium with resulting injury. It is important, however, to emphasize that the presence of inflammation alone is not diagnostic of myocarditis ; for example, inflammatory infiltrates can also occur as a secondary response to ischemic injury. In myocarditis , the inflammatory process is the cause of-rather than a response to-myocardial injury.

PowerPoint Presentation: 

Morphology During active myocarditis the heart may appear normal or dilated . The ventricular myocardium is typically flabby and often mottled by patchy or diffuse foci of pallor and/or hemorrhage . Mural thrombi can be present. Microscopically, active myocarditis shows an interstitial inflammatory infiltrate, with focal necrosis of myocytes adjacent to the inflammatory cells

PowerPoint Presentation: 

Lymphocytic myocarditis is most common .If the patient survives the acute phase of myocarditis , the inflammatory lesions either resolve, leaving no residual changes, or heal by progressive fibrosis. Lymphocytic myocarditis

PowerPoint Presentation: 

Hypersensitivity myocarditis has interstitial and perivascular infiltrates composed of lymphocytes, macrophages, and a high proportion of eosinophils Hypersensitivity myocarditis

PowerPoint Presentation: 

Giant-cell myocarditis is a morphologically distinctive entity characterized by widespread inflammatory cellular infiltrates containing multinucleate giant cells (formed by macrophage fusion) interspersed with lymphocytes, eosinophils , and plasma cells. Giant-cell myocarditis probably represents the aggressive end of the spectrum of lymphocytic myocarditis , and there is at least focal-and frequently extensive-necrosis .This variant carries a poor prognosis Giant-cell myocarditis

PowerPoint Presentation: 

Chagas myocarditis is distinctive by virtue of the parasitization of scattered myofibers by trypanosomes accompanied by an inflammatory infiltrate of neutrophils , lymphocytes, macrophages, and occasional eosinophils Chagas myocarditis

PowerPoint Presentation: 

Pathogenesis

PowerPoint Presentation: 

The clinical spectrum of myocarditis is broad. At one end, the disease is asymptomatic and patients recover without sequelae , and at the other end is the precipitous onset of heart failure or arrhythmias , occasionally with sudden death. Between these extremes are the many forms of presentation, associated with a variety of symptoms (e.g., fatigue , dyspnea , palpitations , pain , and fever ). The clinical features of myocarditis can even mimic those of acute MI. Occasionally, over many years, patients can progress from myocarditis to DCM . Clinical Features

PowerPoint Presentation: 

Chapet 2 Cardiac Tumer

PowerPoint Presentation: 

The most common tumor of the heart is a metastatic tumor; tumor metastases to the heart occur in about 5% of patients dying of cancer. Although any malignancy can secondarily involve the heart, certain tumors have a higher predilection to spread to the heart. In descending order these tumors are carcinoma of the lung, lymphoma, breast cancer, leukemia, melanoma, carcinomas of the liver, and colon. Metastatic Neoplasms

PowerPoint Presentation: 

Primary Neoplasms Primary cardiac tumors are uncommon; in addition, most primary cardiac tumors are also (thankfully) benign. The five most common have no malignant potential and account for 80% to 90% of all primary heart tumors. In descending order of frequency (adults) the primary cardiac tumors are: myxomas , fibromas , lipomas , papillary fibroelastomas , rhabdomyomas , and angiosarcomas (this last one is malignant). Only the myxomas and rhabdomyomas will receive any significant attention here.

PowerPoint Presentation: 

Myxomas Myxomas are the most common primary tumor of the adult heart .Roughly 90% are located in the atria, with the left atrium accounting for 80% of those. Myxomas are almost always single and are most commonly located at the fossa ovalis ( atrial septum). They range from small (<1 cm) to impressive (≤10 cm), sessile or pedunculated masses .and can vary from globular hard masses to soft , translucent, villous lesions with a gelatinous appearance. Pedunculated forms are often sufficiently mobile to swing into the mitral or tricuspid valves during systole, causing intermittent obstruction. Sometimes such mobility exerts a "wrecking-ball" effect, causing damage to the valve leaflets .

PowerPoint Presentation: 

Histologically myxomas are composed of stellate , multinucleated myxoma cells with hyperchromatic nuclei, admixed with cells showing endothelial, smooth muscle, and/or fibroblastic differentiation, all embedded in an abundant acid mucopolysaccharide ground substance .Hemorrhage , poorly organizing thrombus , and mononuclear inflammation are also usually present.

PowerPoint Presentation: 

Clinical Features The major clinical manifestations are due to valvular "ball-valve" obstruction , embolization , or a syndrome of constitutional symptoms, such as fever and malaise . Constitutional symptoms are probably due to the elaboration of interleukin-6, a major mediator of the acute-phase response. Echocardiography is the diagnostic modality of choice, and surgical resection is almost uniformly curative.

PowerPoint Presentation: 

Rhabdomyomas Rhabdomyomas are the most frequent primary tumor of the heart in infants and children ; they are frequently discovered because of an obstruction of a valvular orifice or cardiac chamber . Cardiac rhabdomyomas occur with high frequency in patients with tuberous sclerosis . Rhabdomyomas are probably better classified as hamartomas or malformations rather than true neoplasms ; recent work suggests that these lesions may be caused by defective apoptosis during developmental remodeling.

PowerPoint Presentation: 

Rhabdomyomas are generally small, gray-white myocardial masses up to several centimeters in diameter that protrude into the ventricular chambers. Histologically they have a mixed population of cells; the most characteristic of which are large, rounded, or polygonal cells containing numerous glycogen-laden vacuoles separated by strands of cytoplasm running from the plasma membrane to the more or less centrally located nucleus . These are the so-called spider cells. Morphology

PowerPoint Presentation: 

Chapet 3 Cardiac Transplantaion

PowerPoint Presentation: 

An estimated five million people in the United States have heart failure, and 300,000 die each year as a direct consequence. Cardiac transplantation is increasingly an option for these patients (mostly for IHD and dilated cardiomyopathy ), with roughly 2000 performed annually in the U.S. (3000 a year worldwide). A brief look at the numbers suggests that many more patients die while on a waiting list (estimated at 50,000 per year) than are successfully transplanted. Indeed, even though the demand for hearts has doubled in the last decade, largely as a result of better ways to support patients in severe failure, the actual supply has dropped Beyond the issues of supply and demand , the major complications of cardiac transplantation are acute cardiac rejection and graft coronary arteriosclerosis

PowerPoint Presentation: 

Rejection is typically diagnosed by endomyocardial biopsy of the transplanted heart; it is characterized by an interstitial lymphocytic inflammation with associated myocyte damage .The histology is similar to that seen in viral myocarditis .In both instances, T-cell-mediated killing and local cytokine production can materially compromise cardiac function. When myocardial injury is not extensive , the "rejection episode" can be reversed by immunosuppressive therapy. Advanced rejection can be irreversible and fatal.

PowerPoint Presentation: 

Cardiac allograft rejection typified by lymphocytic infiltrate, with associated damage to cardiac myocytes . Note the similarity between rejection and typical viral myocarditis

PowerPoint Presentation: 

Graft coronary arteriosclerosis, demonstrating severe diffuse concentric intimal thickening producing critical stenosis . The internal elastic lamina (arrow) and media are intact .

PowerPoint Presentation: 

Graft coronary arteriosclerosis (GCA) is the single most important long-term limitation for cardiac transplantation. It is a late, progressive, diffusely stenosing intimal proliferation in the coronary arteries, leading to ischemic injury. Within 5 years of transplantation, 50% of patients have significant GCA, and virtually all patients have lesions within 10 years. The pathogenesis of GCA involves immunologic responses that induce local production of growth factors that promote intimal smooth muscle cell recruitment and proliferation with extracellular matrix synthesis. GCA is a particularly vexing problem, because it can lead to silent MI (transplant patients have denervated hearts and do not experience angina), progressive CHF, or SCD. Despite these problems, the outlook for transplanted patients is generally good, with a 1-year survival of 80% and 5-year survivals of more than 60% (compared with 50% and <10%, respectively, in medically managed end-stage heart failure).