Cardiac amyloidosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]; Raviteja Guddeti, M.B.B.S. [3]
Overview
Cardiac amyloidosis is a well-known progressive condition, which has been reported with varying incidence rates. It refers to extracellular deposition of light chains of some serum proteins, that assume a beta pleated structure.
Myocardial involvement results in congestive heart failure and fatal arrhythmias and is the leading cause of death in patients with amyloidosis. Systemic amyloidosis of AL and TTR type is often associated with amyloid deposition in heart valves, in addition to blood vessels and myocardium [1] [2] In this classical type of valvular amyloidosis are the deposits occur in previously unaltered valves.
There is also another type of cardiac amyloidosis restricted entirely to the heart valves (surgically removed for chronic valvular disease) or only the atria (also called isolated atrial amyloidosis). The deposits are small and restricted to the areas of scarring and calcification.[3] The amyloid protein has not been identified but it has been demonstrated not to be AL or AA [4] [5]
This condition is heavily underdiagnosed because the thickening of ventricles from extracellular deposition of amyloid material in the heart is mostly attributed to chronic hypertension, which is also a feature of cardiac amyloidosis.
Cardiac amyloidosis should be suspected in the following scenarios:
Congestive heart failure and an increase in left ventricular wall thickness (>12 mm) in the absence of hypertension or other causes of increased LV mass
Congestive heart failure and an Increase in left ventricular wall thickness (>12 mm) in the absence of hypertension or other causes of increased LV mass in an African-American > 60 years old
Congestive heart failure with preserved left ventricular ejection fraction fraction (HFPEF) in an individual > 60 years old
Congestive heart failure in individuals with unexplained neuropathy, bilateral carpal tunnel syndrome without risk factors, atrial fibrillation, particularly in elderly males
Signs or symptoms in an indvidual with a family history of amyloidosis.
Diagnosis of cardiac ATTR in individuals with CMR or echocardiography consistent with cardiac amyloidosis.
Patients with suspected cardiac ATTR amyloidosis and contraindications to CMR such as renal insufficiency or an implantable cardiac device .
Pathophysiology
The characteristic feature of cardiac amyloidosis is abnormal deposition of abnormally folded light chains of several serum proteins, making them insoluble and accumulate in various organs. This abnormal folding of proteins is most commonly a result of genetic mutations or excessive formation. Involvement of cardiac muscle can lead to heart failure, arrhythmias and advanced conduction disorders.[6]
Differentiating Cardiac Amyloidosis from Other Diseases
Cardiomyopathy with congestive heart failure is the most common amyloidosis syndrome, especially in patients with no history of ischemia such as the presence of prior documented myocardial infarction or presence of coronary artery disease risk factors.[7] Cardiac amyloidosis should be included in the differential diagnoses in patients with unexplained congestive heart failure and no history of valvular disease, long-standing hypertension or ischemia.[7]
Natural History, Complications and Prognosis
The presence or absence of cardiac involvement with amyloid is the most important prognostic factor.[7] Untreated CA is associated with a very high mortality rate. The most common complications include heart failure, sudden cardiac death due to electromechanical dissociation and pericardial effusion.
Diagnosis
History and Symptoms
Amyloidosis is a multi-system disease involving many organs simultaneously. Approximately more than 50% of the patients with amyloidosis present with right heart failure symptoms. The most common symptoms observed in patients with cardiac amyloidosis include fatigue, weight loss, and periorbital purpura.[8]
Physical Examination
Cardiac amyloidosis is difficult to diagnose. More than 50% of the patients with cardiac amyloidosis present with signs and symptoms suggestive of right heart failure. Common physical exam findings include elevated jugular venous pressure, third heart sound and pedal edema.
Laboratory Findings
There is no specific diagnostic blood test, radiograph, or scan that can be used to diagnose amyloidosis; hence, awareness of the disease is necessary to identify patients with amyloidosis.[9]
Electrocardiogram
The combination of low voltage electrocardiographic pattern and increased thickness of the left ventricular posterior wall and interventricular septum on echocardiogram is highly specific for cardiac amyloidosis. Conduction and rhythm disturbances are common in cardiac amyloidosis, however direct infiltration of the specialized conduction tissue of the heart by the amyloid does not account for the majority of these disturbances.
Imaging
Cardiac MRI
Amyloidosis is an infiltrative disease resulting in deposition of amyloid in the extracellular spaces of the tissues. Amyloid infiltration of the heart leads to expansion of these extracellular spaces resulting in retainment of gadolinium dye during cardiac magnetic resonance imaging. This retainment of gadolinium leads to signal enhancement in the late washout phase during delayed enhanced cardiac imaging.
Echocardiography
Transthoracic echocardiography is most commonly used in the initial evaluation of cardiac amyloidosis. The most common echocardiographic finding is thickening of the left ventricle. Echocardiographic findings strongly correlate with the degree of cardiac dysfunction and disease progression with mildly or moderately increased wall thickness in the early asymptomatic phase and severe thickening and hypokinesia of the left ventricular posterior wall and interventricular septum in clinically apparent cardiac dysfunction. Echocardiographic findings have both diagnostic and prognostic importance.
Other Imaging Findings
Nuclear cardiac scans like MUGA and radionuclide ventriculography (RNV) are not used routinely early in the diagnosis of cardiac amyloidosis. However, when performed, these scans show increased uptake of technetium by the myocardium correlating well with the degree of involvement.
Cardiac Biopsy
A cardiac biopsy that reveals amyloid confirms the diagnosis. Biopsy of other tissues may also confirm the diagnosis. Amyloidosis is frequently confirmed by biopsy of abdominal fat, rectal submucosa, kidney, or bone marrow.
Treatment
Medical Therapy
Major cardiac manifestations of systemic amyloidosis include heart failure and fatal arrhythmias. Therefore treatment of cardiac amyloidosis includes treatment of heart failure and arrhythmias and treatment of the underlying disease. Treatment of heart failure associated with cardiac amyloidosis differs from therapy usually attempted in patients with systolic or diastolic dysfunction.
Surgery
When heart function is very poor, a heart transplant may be considered for some patients, but not those with AL type amyloidosis since their disease compromises many organs. In one type of secondary amyloidosis, liver transplantation is also required.
Future or Investigational Therapies
New therapies targeting the serum amyloid protein (SAP), which is an excellent immunogen and a universal component of all amyloid deposits, using monoclonal antibodies are currently being investigated.
References
- ↑ Pomerance, A. The pathology of senile cardiac amyloidosis. J. Pathol. Bacteriol. 91, 357. 1966
- ↑ Buja, L. M., Khoi, N. B., and Roberts W. C. Clinically significant cardiac amyloidosis. Clinicopathologic findings in 15 patients. Am. J. Cardiol., 26, 394. 1970
- ↑ Goffin, Y. A. Microscopic amyloid deposits in the heart valves: a common local complication of chronic damage and scarring. J. Clin. Pathol., 33, 262. 1980
- ↑ Goffin, Y. A., Murdoch, W., Cornwell, G. G. III, and Sorenson, G. D. Microdeposits of amyloid in sclerocalcific heart valves: a histochemical and immunoflourescence study. J. Clin. Pathol., 36, 1342. 1983
- ↑ Amyloid and amyloidosis. Gilles Grateau, Robert A. Kyle, Martha Skinner, 2005 ISBN 0-8493-3534-5
- ↑ Dharmarajan K, Maurer MS (2012). "Transthyretin cardiac amyloidoses in older North Americans". Journal of the American Geriatrics Society. 60 (4): 765–74. doi:10.1111/j.1532-5415.2011.03868.x. PMC 3325376. PMID 22329529. Unknown parameter
|month=ignored (help) - ↑ 7.0 7.1 7.2 Gertz MA, Lacy MQ, Dispenzieri A (1999). "Amyloidosis: recognition, confirmation, prognosis, and therapy". Mayo Clinic Proceedings. Mayo Clinic. 74 (5): 490–4. doi:10.4065/74.5.490. PMID 10319082. Retrieved 2012-02-13. Unknown parameter
|month=ignored (help) - ↑ Kyle RA, Gertz MA (1995). "Primary systemic amyloidosis: clinical and laboratory features in 474 cases". Seminars in Hematology. 32 (1): 45–59. PMID 7878478. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Hawkins PN (1997). "The diagnosis, natural history and treatment of amyloidosis. The Goulstonian Lecture 1995". Journal of the Royal College of Physicians of London. 31 (5): 552–60. PMID 9429195.
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