Amyloid Heart Disease
Section snippets
Amyloid heart disease: general overview
Amyloidosis most commonly involves more than one organ system. When a diagnosis of extracardiac amyloidosis has already been made, symptoms arising from the heart are readily attributable to cardiac amyloidosis. Unfortunately, when cardiac amyloidosis is an isolated disorder, or even when the cardiac manifestations of undiagnosed multiorgan amyloidosis predominate, the diagnosis is often not entertained until late in the course of the disease. The various types of systemic amyloidoses tend to
Clinical findings
The common clinical feature among the various forms of cardiac amyloidosis is the presence of congestive heart failure associated with a nondilated left ventricle with thickened walls and a normal or mildly reduced left ventricular ejection fraction. Because the disease affects all parts of the heart, biventricular heart failure is usually present, although the presenting feature is often that of severe right-sided heart failure. Peripheral edema may be profound and ascites is often present in
Echocardiography
Echocardiography is almost universally available and is usually one of the earliest tests employed in the investigation of suspected heart disease. Cardiac amyloidosis can be suspected by its typical appearance on the echocardiogram (Fig 5). The disease is characterized by ventricular wall thickening, due to amyloid infiltration of the myocardium, in the absence of left ventricular dilation. Unfortunately, even advanced cases of amyloidosis are sometimes misdiagnosed by cardiologists who are
AL amyloidosis
AL amyloidosis is probably the most commonly recognized form of amyloid heart disease. The disease is a plasma cell dyscrasia, in which circulating amyloidogenic light chains interact in the heart with cell membrane constituents and glycosaminoglycosides and other local matrix components.34 Deposition of amyloid occurs in the extracellular space, causing myocardial damage, and it has been postulated that there is also direct cell toxicity mediated by the formation of light chain oligomers.34
Treatment of AL cardiac amyloidosis
The approach to management of AL cardiac amyloidosis is twofold: treatment of the heart failure and treatment of the underlying plasma cell dyscrasia. Patients with AL amyloidosis of the heart tend to respond poorly to conventional heart failure therapies. Careful titration of diuretics and salt restriction remains the mainstay of management. Calcium-channel blockers have no role in the management and their use is often associated with significant worsening of heart failure.50 Despite the
Hereditary amyloidosis
Hereditary forms of cardiac amyloidosis are usually associated with mutation in the gene for the plasma protein transthyretin (TTR), and are referred to as ATTR. About 100 different amyloidogenic missense point mutations have been described80 and the heart is a frequent target for deposition in ATTR amyloidosis. The male to female ratio is around 50:50, in contrast to a slight male preponderance in AL amyloid with cardiac involvement.15 The amyloid deposits are composed of a combination of
Senile systemic amyloid
Wild-type TTR amyloid deposition (SSA) is found at autopsy in about 25% of individuals older than 80 years,81 although in most cases, the deposits are generally found in small quantities and there is no clinical significance or abnormality during life. The clinical picture of SSA occurs only when the amyloid deposits are extensive enough to produce an increase in left ventricular wall thickness. There is some evidence that, in SSA, the TTR is more likely to be composed of fragments of the TTR
Potential new therapies
Elucidation of aspects of the molecular pathogenesis of amyloid and amyloidosis is generating a variety of novel approaches to therapy.115, 116, 117, 118 Small molecule ligands that stabilize the native tetrameric structure of TTR and prevent its fibrillogenesis are being actively investigated for prophylaxis and therapy in TTR amyloidosis.119, 120, 121, 122, 123 The non steroidal anti-inflammatory diflusinal has been found to stabilize the tetrameric structure of TTR. This action reduces
Secondary (AA) amyloidosis
AA amyloidosis, previously termed secondary amyloidosis, is a rare complication of chronic inflammatory disorders. The fibrils are derived from the acute phase reactant SAA. Although cardiac deposits are often present on histology, echocardiographic abnormalities and clinical symptoms of cardiac AA amyloidosis are rare, occurring in only about 2% of cases. The prognosis is thought to be substantially better than in cases of AL amyloid.129 Treatment involves suppressing the underlying disease.
Isolated atrial amyloid
Atrial natriuretic peptide (ANP) is synthesized locally by atrial myocytes,130 and can be deposited locally within the atria as amyloid. Isolated atrial amyloid (IAA) is a disease of the elderly, with a female preponderance that contrasts with senile TTR amyloid.93 The incidence of IAA in elderly hearts is high, with one autopsy study describing IAA in 91 of 100 hearts.131 Isolated atrial amyloid first appears in the fourth decade, and its prevalence increases by approximately 15% to 20% per
Summary
Early detection of cardiac amyloidosis is the best method to obtain the best possible outcome, as it allows for a broader range of therapeutic options. Clinical awareness of the disease and a high index of clinical suspicion are critical to early diagnosis, but unfortunately, many cases are diagnosed late in the disease. In AL amyloidosis, severe cardiac involvement precludes high dose chemotherapy, but in the uncommon cases where infiltration is limited to the heart, combined heart
Statement of Conflict of Interest
The authors declare that there are no conflicts of interest.
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Statement of Conflict of Interest: see page 358.