At that time, it was decided not to repeat endomyocardial biopsy because of normal results on molecular expression testing (a noninvasive technique called AlloMap®7-9), which is performed to assess for heart transplant rejection. The patient’s lipid panel remained within normal limits. CBC indicated persistent anemia and leukopenia. Urine protein and BNP test results were not available.
Since undergoing cardiac transplantation, the patient has resumed his normal routine activities, including some type of exercise five days per week. He said his diet is maintained in moderation. He denied shortness of breath, chest pain, dizziness, or edema. He has returned to full-time employment and has vacationed in Croatia, Italy, and Central America.
DISCUSSION
Familial amyloidosis is an autosomal dominant disease characterized by the production of mutated proteins, most commonly ATTR. Presence of the ATTR Val 122Ile allele has been reported in 3.9% of all black Americans, and in one study, 23% of black Americans diagnosed with cardiac amyloidosis at autopsy were heterozygous for this variant allele.10-12 ATTR Val122Ile usually manifests in the fifth
or sixth decade of life with its characteristic presentation of infiltrative/restrictive cardiomyopathy,13 resulting in heart failure and sometimes peripheral neuropathy.10,11,14
Pathophysiology
In patients with ATTR Val122Ile, cardiomyopathy results from the deposition of mutant protein fibrils in the cardiac muscle, leading to restricted heart wall motion10,15 and stiffening of the cardiac ventricles, with subsequent disruption of the diastolic filling properties of the cardiac muscle.16 Fluid overload and heart failure follow.3,10,17 The atrium of the heart dilates, and the walls of the ventricles become thickened and fibrous.18 Liepnieks and Benson6 reported that the cadaver heart of one Val122Ile patient infiltrated with amyloid protein fibrils weighed 725 g—more than double the weight of an average adult heart.
In patients with cardiac amyloidosis, ECG can detect arrhythmia, and echocardiography shows cardiac enlargement; however, as in the case patient, cardiac catheterization shows normal coronary arteries.15,16,19,20 Thus, previously healthy patients who present with heart failure and negative results on cardiac catheterization should undergo further work-up for cardiac amyloidosis.19
Amyloidosis affects all populations globally.10 In systemic amyloidosis, amyloid releases into the plasma, infiltrating and impairing multiple organs. Poor survival has been reported in patients with heart failure symptoms resulting from amyloid deposition.20,21
Types of Amyloidosis
Primary amyloidosis, the most common of the three amyloidosis types, can be systemic or localized.22 It occurs when protein fibrils, developed from immunoglobin light chains or monoclonal plasma cells and measuring 7 to 10 nm in diameter, adhere to the heart, kidneys, peripheral nerves, eyes, and other organs.5,11,20,23,24 Known for its relation to multiple myeloma,19 primary amyloidosis is associated with a poor prognosis.3,10
Secondary amyloidosis results from a chronic inflammatory disorder, such as rheumatoid arthritis or ankylosing spondylitis—conditions that trigger the production of amyloid proteins.3,10 This type has also been associated with substance abuse and AIDS.23
Familial or hereditary amyloidosis, according to Benson,10 is a group of diseases, each resulting from mutation in a specific protein. In the United States, the most common type of familial amyloidosis is ATTR.11 More than 100 mutant types of ATTR proteins have been identified, each involving a specific nationality or group of nationalities.10,11,23
Mutant ATTR amyloid, when deposited in specific organs, leads to their dysfunction and ultimate failure.6 ATTR may affect the cardiac, gastric, renal, ophthalmic, or nervous system. Depending on the ATTR variant, the resulting clinical features are age- and time-dependent, with onset most common between the third and fifth decade of life.10
Prevalence
The prevalence of ATTR Val 122Ile amyloidosis is reportedly high in West Africa, and in the US African-American population (3.9%).4,11,14,25,26 In a study conducted at a county hospital in Indianapolis, 3% of black newborns were found positive for ATTR Val122Ile through DNA sampling of umbilical cord blood.25 These statistics are of concern, as ATTR amyloidosis could be a significant health concern in a patient population that is already medically underserved.
Yamashita et al25 estimate that 1.35 million Americans of African-American descent may be affected by ATTR Val122Ile and vulnerable to restrictive cardiomyopathy–related heart failure and death. At the very least, this disorder can impair quality of life, especially in the presence of other comorbid conditions.
Clinical Presentation
The presence of exertional syncope at presentation is ominous, as it may be a marker of severe restrictive cardiomyopathy, postural hypotension due to excessive diuresis or autonomic neuropathy, ventricular arrhythmias from localized hypoperfusion, and rarely from cardiac tamponade due to pericardial involvement.27 Despite widespread involvement of the conduction system in specimens at autopsy, high-grade IV block is unusual.3
Diagnostic Studies
ECG. Both ECG and Holter monitoring can detect the arrhythmias and conduction disturbances (eg, first-degree AV block, low voltage patterns) associated with cardiac amyloidosis. Patients often experience syncopal and near-syncopal episodes as a result of conduction disturbances.28 Patients with conditions such as cardiac amyloidosis who present with severe heart failure are at high risk for sudden death secondary to conduction disturbances. Many have benefited from implanted defibrillators.29