Amyloid deposits can be found commonly in hearts during autopsy examination. The incidence increases with advanced age (mostly in patients over 60 years of age).      

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Myeloma -associated (primary) amyloidosis :  Cardiac involvement occurs in approximately 90% of cases of myeloma-associated (primary) amyloidosis.

This form of amyloidosis occurs in association with multiple myeloma but may also occur in the absence associated disease.

Amyloid deposits are most likely to involve the spleen, kidneys, liver, and adrenal glands.

Secondary amyloidosis :  Cardiac involvement also occurs in about 55% patients with amyloidosis associated with chronic illness (secondary amyloidosis) such as rheumatoid arthritis, tuberculosis, osteomyelitis, bronchiectasis, or lymphoma.

In this type of amyloidosis the major deposits occur in the tongue, gastrointestinal tract, lungs, skeletal muscles, skin and other mesodermal tissues and organs in addition to the heart.

Amyloidosis restricted to the heart:  A distinctive type of amyloidosis has been described in which amyloid is restricted largely to the heart. Deposits either do not appear in other organs or are present in  insignificant amounts.

This is in contrast to the systemic forms of amyloidosis in which involvement of other organs is extensive.

 It is of considerable interest that the average age of persons with amyloid deposits confined to the heart is higher than that of those with primary systemic amyloidosis or amyloid disease complicating multiple myeloma.

Senile cardiac amyloidosis: The disease affects elderly persons, usually in the seventh to ninth decades, and thus seems to be a manifestation of senescence. It is sometimes referred to as senile cardiac amyloidosis.

Hereditary types: In addition to the foregoing forms of amyloidosis, certain hereditary types have been reported in which heart may become involved, and in one type it is the organ predominantly affected.

Although cardiac deposits of amyloid can be found, commonly in most instances the deposits are relatively slight and produce no gross morphologic change and are clinically insignificant.

Less commonly, cardiac amyloidosis may be sufficiently severe to cause cardiac symptoms, and in only rare instances can death from congestive cardiac failure be attributed to cardiac amyloidosis.

When the heart is severely involved, amyloid deposits may occur throughout the interstitium of ventricular and atrial myocardium.

Subendocardial deposits are especially common in the atria. The wall of the coronary arteries and arterioles and conduction pathways also may be involved.

These deposits may be readily detectable macroscopically; the ventricles may be enlarged, firm and rubbery in consistency, and tan in colour.

Discrete nodular deposits of amylod may be evident on cross sections of the ventricles or under the atrial endocardium.

There are multiple subendocardial deposits of glistening, partially translucent amyloid deposits in the atrium.

Similar nodules may occur on the epicardial surface or the parietal pericardium. Involvement of the valvular endocardium also may occur.

Microscopically, amyloid occurs in extracellular, eosinophilic, amorphous hyaline deposits. These deposits may form rings completely surrounding and compressing individual myocytes.

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In severe cases atrophy vacuolization, or even complete loss of muscle fibers may occur.

Deposits may occur in the wall of small and medium-sized arteries and veins and in the interstitium of the endocardium or epicardium.

Amyloid may be suspected from evaluation of hematoxylin and eosin-stained microscopic sections because of the ring-like encircling of myofibers and the lack of the wavy fibrillar character of collagen.

However, amyloid can be more easily distinguished from collagen by staining with Congo Red or crystal violet. With the Congo Red stain, amyloid is red orange, the protein is birefringent so that when Congo Red- stained tissue is viewed under polarized light it transmits an apple-green color. With the crystal violet stain, amyloid has a metachromatic reddish-purple cast.

Amyloidosis and the heart: a comprehensive review.Arch Intern Med. 2006 Sep 25;166(17):1805-13

Infiltration of the heart from insoluble protein deposits in amyloidosis often results in restrictive cardiomyopathy that manifests late in its course with heart failure and conduction abnormalities. While the rare primary amyloidosis-related heart disease has been well characterized, senile amyloidosis occurring in the seventh decade of life most frequently affects the heart. Early diagnosis of cardiac amyloidosis may improve outcomes but requires heightened suspicion and a systematic clinical approach to evaluation. Demonstration of tissue infiltration of biopsy specimens using special stains, followed by immunohistochemical studies and genetic testing, is essential in defining the specific protein involved. The therapeutic strategy depends on the characterization of the type of amyloid protein and extent of disease and may include chemotherapy, stem cell transplantation, and liver transplantation. Heart transplantation is controversial and is generally performed only at isolated centers.

Patterns of isolated atrial amyloid: a study of 100 hearts on autopsy.Cardiovasc Pathol. 2006 Sep-Oct;15(5):287-90.

Isolated atrial amyloid (IAA), one of the most common members of the family of age-related ("senile") amyloids, seems to play a role in the pathogenesis of atrial fibrillation. Patterns of IAA deposition were histologically studied in the hearts of 100 elderly patients. The incidence (%) and severity (grade 0-3) of atrial IAA deposits increase with age, from 75% incidence and 0.50 average grade in patients aged 51-60 years, to 86% incidence and 1.49 average grade in those aged 81-90 years. Deposits are more pronounced in females (88% incidence, 1.45 average grade) than in males (68% incidence, 0.79 average grade). Left atrial deposits are more pronounced (78% incidence, 1.25 average grade) than right atrial deposits (67% incidence, 1.09 average grade). The distribution of IAA in the walls of the left atrium is uneven, with deposits being more pronounced in the anterior wall than in both the posterior wall and the left appendage. IAA deposits are heavier (1.34 average grade) in patients with chronic atrial fibrillation than in those with sinus rhythm (1.01 average grade); the difference, however, lacks statistical significance. Hypertension, diabetes mellitus, hypertrophy of the heart, coronary atherosclerosis, and dilatation of the atria show no significant relationship to the incidence or severity of atrial amyloidosis.

Cardiac pathology of extracardiac origin (II). The cardiac repercussion of amyloidosis and hemochromatosis.Rev Esp Cardiol. 1997 Nov;50(11):790-801

Although rare, amyloidosis and hemochromatosis are the infiltrative diseases in which the heart is more frequently involved. The most common clinical presentation is heart failure with hemodynamic features of restrictive heart disease in cardiac amyloidosis. The diagnosis is often made because of symptoms of other organ involvement, although sometimes cardiac symptoms may be the initial manifestation. The non-specific clinical presentation and the low prevalence of these cardiomyopathies make the diagnosis difficult if the clinician does not suspect it. Once symptoms develop, the evolution is fast. Usually, the unsatisfactory and ineffective treatment of amyloidosis and hemochromatosis contribute to the poor prognosis. The indication of cardiac transplantation in advanced cases is questionable because of the high recurrence of the illness.

Histopathological study of valvular deposits of amyloid protein in cardiac amyloidosis.J Cardiol. 1996;27 Suppl 2:31-7; discussion 38.

Cardiac amyloidosis is associated with amyloid deposits in cardiac valves which also show the thickening of leaflets and cusps. This study examined amyloid deposits on cardiac valves to investigate the possible involvement in echocardiographic valvular abnormalities in 17 patients with systemic amyloidosis (12 males and 5 females aged 44 to 82, mean 66.4 years) in the autopsy files of the National Cardiovascular Center between 1980 and 1993. All four cardiac valves were examined histologically using hematoxylin-eosin and Congo red stains with polarization. All cusps and leaflets were divided into six segments and all segments of each cusp and leaflet were scored for the proportional area of amyloid deposit (from 0 to 3). The immunohistochemical types of amyloid proteins were immunoglobulin light chain-related (AL) amyloidosis in 16 cases, and amyloid A-related (AA) amyloidosis in one case. Twelve of 16 cases with AL amyloidosis were subclassified as AL lambda type and 4 were subclassified as AL kappa type. In the atrioventricular valve leaflets, the atrial side of basal portion showed the most remarkable amyloid deposits among the six segments. In the semilunar valves, amyloid deposits were mild in the tip and middle portions. Among the patients with AL amyloidosis, those with AL lambda type amyloid appeared to have greater deposits than those with AL kappa type amyloid. Mitral valves appearing abnormal by echocardiography had greater amyloid deposits. However, considering other factors affecting valvular function, the relationship between the localization or the degree of amyloid deposition and endocardiographic valvular abnormalities was unclear.

Pathology of amyloidosis and amyloid heart disease.Appl Pathol. 1984;2(6):341-56

Amyloidosis is a family of disorders of the immune system. Each member of the family is characterized clinically by a unique syndrome and chemically by a specific amyloid fibril protein. The diagnosis of amyloidosis requires histopathologic identification of amyloid deposits in the affected tissues. Since none of the commonly used histochemical stains is specific for amyloid and their sensitivity is variable, application of a battery of staining methods (two or more) is essential for the histologic diagnosis of amyloidosis. The heart may be affected in any form of systemic amyloidosis and in senile amyloidosis. Cardiac amyloidosis is an important cause of progressive heart failure and refractory arrhythmia of obscure origin, especially in elderly persons. The average survival time of amyloid heart disease after the onset of symptoms is less than 3 years. Clinically, amyloid heart disease may mimic constrictive pericarditis, coronary artery disease, valvular heart disease, and idiopathic hypertrophic or congestive cardiomyopathy. A confirmatory biopsy is needed for diagnosis since cardiac amyloidosis has no pathognomonic symptoms and signs, nor diagnostic electrocardiographic, radiologic, cardioangiographic and echocardiographic findings.

Amyloid deposits in bioprosthetic cardiac valves after long-term implantation in man. A new localization of amyloidosis.Am J Pathol. 1984 Mar;114(3):431-42

Congo red staining with microscopic examination under polarized light was performed in 30 porcine bioprosthetic cardiac valves and one autologous fascia lata valve explanted from 31 patients in order to detect the presence of amyloid. Microdeposits of amyloid were present in the sewing ring of the fascia lata valve and in 10 porcine bioprostheses, and this finding was confirmed by transmission electron microscopy in 3 porcine bioprostheses. All amyloid-laden porcine valves had been implanted for at least 33 months before removal, and all except two showed dysfunction and/or severe degeneration of cuspal tissue. Statistical analyses failed to establish any correlation between the presence of amyloid and patient-related factors. In a majority of porcine bioprostheses amyloid was permanganate-sensitive and tryptophan-positive. The pathogenesis of this new form of heart valve amyloidosis might consist in penetration of human macrophages in deteriorated bioprosthetic cusps and their interaction with blood-borne amyloid precursors.

Clinical significance of histopathologic patterns of cardiac amyloidosis.Mayo Clin Proc. 1984 Aug;59(8):547-55.

Cardiac amyloidosis may be asymptomatic or an important cause of progressive heart failure and refractory arrhythmia. To identify the morphologic markers of clinically significant cardiac amyloidosis, we analyzed the hearts of 47 patients with autopsy-proven cardiac amyloidosis (21 with primary amyloidosis [AL] and 26 with senile cardiac amyloidosis [SCA]) histologically for the extent and pattern of amyloid deposits. The extent of amyloid deposition was graded 1 through 4, corresponding with less than 10%, 10 to 25%, 26 to 50%, and more than 50% histologic involvement of the myocardium, respectively. The pattern of deposits was classified as nodular, perifiber, or mixed type, and the presence or absence of vascular involvement was determined. The hearts with primary amyloidosis showed predominantly high-grade deposits (76% grades 3 and 4), a perifiber (65%) or mixed (30%) pattern of deposits, and frequent (90%) vascular involvement. The hearts with senile cardiac amyloidosis tended to have low-grade deposits (62% grades 1 and 2), a nodular pattern (92%) of deposits, and infrequent (4%) vascular involvement. Clinically significant cardiac amyloidosis was associated with grade 2 or greater amyloid deposits in the heart and with involvement of intramyocardial arterioles.

Cardiac amyloidosis causing ventricular tachycardia. Diagnosis made by endomyocardial biopsy.Chest. 1989 Dec;96(6):1431-3

In patients with malignant ventricular arrhythmias, endomyocardial biopsy may be helpful when all other findings from the workup are negative. A case of nonsustained polymorphic ventricular tachycardia is presented. The findings from an echocardiogram, coronary angiogram, and cardiac catheterization were negative. An electrophysiologic study showed inducible nonsustained ventricular tachycardia. A right ventricular endomyocardial biopsy was diagnostic of cardiac amyloid. The findings from a workup for systemic amyloidosis were negative. Primary cardiac amyloidosis should be considered in patients with malignant arrhythmias and no documented heart disease, and endomyocardial biopsy is helpful in making this diagnosis.

Senile amyloidosis of the heart.Kardiologiia. 1986 Feb;26(2):25-9.

A morphologic study of 376 hearts from individuals who died between 75 and 98 years of age demonstrated senile amyloidosis of the heart in 307 (82%) of the cases, using the Congo red stains for polarized light studies and the thiosine red for luminescent microscopy. The frequency of cardiac amyloidosis detection increased with age, and reached 100% in those above 90. Clinico-anatomical correlations showed repolarization changes to be the most common findings (80%), followed by arrhythmia (over 50%), conductivity disorders and reduced voltage of electrocardiographic waves. Chronic heart failure was less common (about 10%). In most cases, moderately marked coronary atherosclerosis was also found at autopsy. Amyloidosis was thought to be making a more significant contribution towards myocardial lesions, as compared to atherosclerosis, in elderly people above 85 years of age.

FUNCTIONAL ANATOMY OF THE HEART

ANATOMY OF THE ATRIUM