Transthyretin Amyloid Cardiomyopathy

TTR amyloid cardiomyopathy (ATTR-CM) occurs when the heart is predominantly affected. In this disease, which is also known as familial amyloid cardiomyopathy (FAC), TTR amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction progressing to restrictive cardiomyopathy and heart failure. Several single point mutations in TTR have been primarily associated with ATTR-CM: V20I, P24S, A45T, Gly47Val, Glu51Gly, I68L, Gln92Lys, L111M and V122I. One common mutation, V122I (substitution of isoleucine for valine at position 122), occurs with high frequency (prevalence of approximately 3.5%) in African-Americans.

The onset of ATTR cardiomyopathy related to the V122I mutation or wild-type TTR is typically occurs > 60. Patients may present with carpal tunnel syndrome, which has been reported in >40% of patients with ATTR-CM. Cardiac involvement can present with conduction system disease (sinus node or atrioventricular node dysfunction) or congestive heart failure including shortness of breath, peripheral edema, syncope, exertional dyspnea, generalized fatigue or with heart blocks. The echocardiographic findings are indistinguishable from those seen in AL (primary immunoglobulin light chain) amyloidosis and include thickened ventricular walls (concentric hypertrophy, both right and left) with a normal to small left ventricular cavity, increased myocardial echogenicity, normal or mildly reduced ejection fraction, often with evidence of diastolic dysfunction and severe impairment of contraction along the longitudinal axis, and bi-atrial dilation with impaired atrial contraction.

Unlike in AL amyloidosis, the voltage on the ECG is often normal, although low voltage may be seen despite the increased wall thickness on echocardiography. Marked axis deviation, bundle branch block and AV block is common, as is atrial fibrillation.

There is no disease modifying therapy currently available, with available treatment aimed at symptom relief, including diuretic, pacemakers, and arrhythmia management.