normal">Echocardiography. In patients with ATTR Val122Ile cardiac amyloidosis, echocardiography reveals thickened ventricular walls (ie, measuring ≥ 15 mm; normal, ≤ 11 mm).19 Amyloid-restrictive cardiomyopathy is associated with a marked dissociation between short- and long-axis systolic function, in cases in which left ventricular ejection fraction is normal.30
Echocardiography may demonstrate the characteristic specular or granular sparkling appearance that signifies advanced disease.15,21 Only a minority have this pattern in the myocardium, however, and changes in echocardiographic technology have made this finding less noticeable.30
normal">MRI. Among more recently used diagnostic studies, cardiac magnetic resonance (CMR) has been reported to demonstrate late gadolinium enhancement (LGE) in perhaps 80% of patients with familial amyloidosis and cardiac involvement (as determined through biopsy and Congo Red stain). LGE-CMR shows darkening of the cardiac tissue, a common occurrence in amyloidosis.31
LGE is associated with increased thickness of both left and right ventricles, lower ECG voltage patterns, elevated BNP, and elevated troponin T.31,32 Globally, LGE is associated with the worst prognosis in patients with cardiac amyloidosis. Use of LGE-CMR testing can help facilitate early detection of cardiac amyloidosis in patients who may be vulnerable to cardiac damage.31
Cardiac catheterization. In patients with cardiac amyloidosis, cardiac catheterization usually shows normal coronary arteries.3
Diagnosis
Early diagnosis of ATTR cardiac amyloidosis is crucial to the patient’s survival; it should be ruled out in any African-American patient with unexplained heart failure and echocardiography showing increased wall thickness with a nondilated left ventricular cavity. Additional clues include significant proteinuria, hepatomegaly disproportionate to the degree of heart failure, or corresponding neuropathy. Known family history of the disease, along with variant type, allows for a prompt and correct diagnosis.10
It has been reported that most clinicians who encounter heart failure, particularly in black patients, do not consider amyloidosis in the differential diagnosis, because of the high prevalence of hypertension and congestive heart failure in this population.10,15,19 As a result, amyloidosis often goes undiagnosed.19
Findings of enlarged and thickened cardiac walls on echocardiography but normal coronary arteries on cardiac catheterization should alert the treating clinician to further work-up for cardiac amyloidosis.19 In such a patient, according to Kristen et al,21 endomyocardial biopsy with Congo Red staining is the gold standard for diagnosis of amyloidosis.
In ATTR Val122Ile familial amyloidosis, it is unclear whether patients who are homozygous for the disease present with symptoms at earlier onset with more progressive illness or die sooner than those who are heterozygous.33 Nevertheless, once the diagnosis is confirmed, it is important to determine the patient’s specific variant type by DNA testing so that appropriate treatment can be initiated and the patient’s prognosis evaluated.5,10,13
Treatment
For familial amyloidosis in general, some researchers advocate liver transplantation to remove the source of mutant amyloid protein and stop all deposition of amyloid fibrils; this procedure can be followed later by transplantation of other affected organs (including the heart).5,23 Maurer et al34 have reported improved one-year survival rates among patients with ATTR amyloidosis who underwent both cardiac and liver transplantation: 75%, versus 23% in patients who did not receive transplanted organs.
Management of cardiac amyloidosis usually requires a twofold approach: treating associated congestive heart failure, and preventing further deposition of amyloid.24 In the case patient (as in most patients with ATTR amyloidosis), heart transplantation was deemed the only life-sustaining treatment option.11,19,33
Pharmacotherapeutic options are limited for patients with ATTR Val122Ile familial amyloidosis. Conventional heart failure agents (eg, ACE inhibitors, angiotensin receptor blockers, digoxin, β-blockers, calcium channel blockers) can exacerbate heart failure symptoms, leading to a potentially life-threatening arrhythmia.3,11,19,24,35 Amyloid fibrils bind to digitalis, increasing susceptibility to digitalis toxicity; and to nifedipine, causing hemodynamic deterioration. Verapamil should be avoided, as it may induce severe left ventricular dysfunction. ACE inhibitors often provoke profound hypotension in primary amyloidosis.24,35
Diuretics, too (eg, furosemide, as was prescribed for the case patient), must be used with caution.3 These agents have been used to treat fluid overload and the resulting peripheral edema and shortness of breath found in ATTR Val122Ile patients who experience heart failure.36 According to Dubrey et al,5 cautious use of diuretics is necessary for management of heart failure symptoms in these patients.
Because the risk for intracardiac thrombus is high, anticoagulation (using agents other than β-blockers or calcium channel blockers) should be implemented unless compelling risks are involved.11,24 Amiodarone is relatively well tolerated for ventricular tachydysrhythmias and in atrial fibrillation if the goal is maintaining sinus rhythm.37
Regarding heart transplantation in patients with familial amyloidosis, Jacob et al33 hypothesize that since mutant amyloid protein is synthesized by the liver, it would take approximately 50 years for a transplanted heart to become affected by amyloid deposition. In a 59-year-old Afro-Caribbean man with familial amyloidosis who underwent cardiac transplantation, Hamour et al11 reported that the donor heart remained amyloid-free three years posttransplantation, as demonstrated by serial cardiac biopsy.