Cardiac Amyloidosis

Background

Cardiac amyloidosis is a clinical disorder caused by extracellular deposition of insoluble fibrils (approximately 7.5-10 nm wide) with beta-pleated sheet configuration.[1] The protein misfolding abnormalities result in amyloid fibrils and may manifest as primary, secondary, or familial amyloidosis. Amyloid deposition can occur in multiple organs (eg, heart, liver, kidney, skin, eyes, lungs, nervous system) resulting in a variety of clinical manifestations.[2] Cardiac involvement is a progressive disorder resulting in early death due to congestive heart failure (CHF) and arrhythmias. Cardiac involvement can occur as part of a systemic disease or as a localized phenomenon.[3, 4]

This article provides an overview of the primary systemic amyloidosis (AL) that predominantly affects the heart.

NextPathophysiology

The characteristic abnormality in amyloidosis is an abnormal folding of a protein, rendering it to be insoluble.[10] These abnormalities may be a result of genetic mutations or excess formation. Various proteins may form amyloid fibrils; light chain amyloidosis (AL) is the most common type of systemic amyloidosis that results from the proliferation of plasma cells in the bone marrow. The plasma cell burden in AL is about 5-10% and is a marker of poor prognosis.[8, 9] Lambda light chains are 3 times more likely involved than kappa chains.

Most cases of AL are associated with a benign monoclonal gammopathy. Only rarely is AL seen in patients with multiple myeloma, lymphoma, or macroglobulinemia. Amyloid deposition in the tissues causes disruption of architecture, induces oxidant stress, and results in organ dysfunction. Multiorgan involvement is common. Cardiac involvement is most common in the AL variety but is also seen in secondary, hereditary, and senile amyloidosis.

Cardiac amyloid deposition is most common in the myocardium but is also seen in the atria, pericardium, endocardium, and vasculature. The myocardium becomes thick (mean weight 500 g) with a rubbery consistency.[5] High-grade infiltration (>50%) of myocardium is most common in the AL variety, and 90% of cases have vascular involvement.[11] Epicardial vessels are typically spared, but microvascular involvement is common, resulting in tissue ischemia and infarction.[12, 13, 16] Resultant myocardial fibrosis adds to the myocardial dysfunction, causing heart failure and cardiac arrhythmias.

The ventricular cavities are typically normal in size, but the ventricles are stiff, which cause restrictive ventricular filling and biatrial enlargement. Pericardial involvement is common and leads to pericardial effusion.[6] Endocardial involvement may result in atrioventricular valve dysfunction. Intracardiac thrombosis is common and is seen in about 33% cases in autopsy specimens.[7]

Conduction system abnormalities (ie, bundle branch block and atrioventricular block) are frequent in amyloidosis. In a small series, severe sinoatrial node fibrosis was seen in 30% cases.[14]

PreviousNextEtiology

Primary amyloidosis (AL) is a type of plasma cell dyscrasia and is the most common type involving the heart.

Secondary systemic amyloidosis seen in chronic inflammatory conditions rarely involves the heart. Organ dysfunction is usually reversible with resolution of the underlying inflammatory disorder.

Senile amyloidosis is common in people over 80 years of age and has a better prognosis.

PreviousNextEpidemiologyUnited States statistics

Systemic amyloidosis (AL) is a rare disorder, and it is difficult to estimate the exact incidence due to changing diagnostic criteria. In Olmsted County, Minnesota, only 21 cases were diagnosed from Jan 1950 to Dec 1989. In this first population-based study, the incidence of AL was approximately 8.9 per million person years.[15] In the USA, 2000-2500 cases of AL are diagnosed annually.[17]

International statistics

Amyloidosis is reported as a cause of death in 1 in 1000 of the British population.

Racial differences in incidence

AL is uncommon in non-Caucasians and persons under 40 years of age.[21] Senile amyloidosis is 3 times more common in elderly African-Americans compared to Caucasians (8.2% vs 2.7%, respectively).[19] Hereditary cardiac amyloidosis resulting from a mutation in transthyretin (TTR) is more common in African Americans than Caucasians; 23% of the patients have this variant.[20]

Sexual differences in incidence

AL variety affects men and women equally.

Age-related differences in incidence

AL type is usually seen in persons over the age of 50 years. Although unusual, it can occur as early as the third decade. Late onset amyloidosis (senile) is seen in elderly patients and has a better prognosis than primary amyloidosis.

PreviousNextPrognosis

In general, cardiac involvement is a marker of poor prognosis. Therefore, any clinical, laboratory or imaging abnormality to suggest increased cardiac involvement will be indicative of a worse prognosis. No consensus has been reached about a single most important prognostic factor. The factors associated with a poor prognosis include the following:

Congestive heart failureSyncopeComplex arrhythmiaDegree of left ventricular hypertrophy (More=worse prognosis)Low left ventricular ejection fraction (LVEF)Restrictive hemodynamic.Right ventricular dilatationPulmonary hypertensionLow voltage on ECGHigh brain natriuretic peptide (BNP)High troponinT1 kinetics on gadolinium-enhanced MRI (to demonstrate extent of myocardial involvement)Complications

Complications include the following:

Atrial fibrillationCongestive heart failureEmbolism and strokeVentricular arrhythmiasHeart block requiring pacemaker implantationPericardial tamponadeDeathMortality/morbidity

Amyloidosis has a poor prognosis, and the median survival without treatment for AL is only 13 months. Cardiac involvement has the worst prognosis and results in death in about 6 months after onset of congestive heart failure. Only 5% of the patients with primary amyloidosis survive beyond 10 years.[18]

PreviousNextPatient Education

Educating patients about the dietary restrictions and medications is useful. Education about symptoms of heart failure and stroke would be helpful to seek early medical advice.

PreviousProceed to Clinical Presentation , Cardiac Amyloidosis