Background The genetic mutation encoding transthyretin (TTR) isoleucine 122 (V122I) is present in 3.9% of African-Americans and associated with cardiac TTR amyloidosis, but penetrance is unknown. Little is known about the frequency or clinical phenotype of TTR V122I amyloidosis in the British Afro-Caribbean population.
Methods We reviewed the primary diagnoses of 1142 patients admitted with heart failure between September 2005 and February 2011. The diagnosis was supported by echocardiography, cardiac MRI (in patients without contraindications) and genetic testing; endomyocardial biopsies were performed in 68 patients (6%) in whom amyloidosis was suspected or uncertainty about diagnosis remained. Survival analysis was performed to August 2011.
Results The median age was 72 years (range 18–98) with male (66.7%) and Caucasian (71.0%) predominance. Ischaemic cardiomyopathy (ICM) was the primary diagnosis in 428 patients (37%). There were 170 Afro-Caribbean patients (14.9%) among whom ICM was less common (22 patients (13%), p<0.01). Seventeen Afro-Caribbean patients (10%) were confirmed to have cardiac ATTR V122I amyloidosis. Survival of Afro-Caribbean patients with ICM and ATTR V122I amyloidosis was similar (45 vs 36 months, p=0.54), but overall survival (n=1142) was significantly inferior in cardiac amyloidosis compared to non-amyloid cardiomyopathy (34 vs 59 months, p<0.01).
Conclusion ATTR V122I amyloidosis is an important cause of heart failure in the British Afro-Caribbean population, but it is commonly misdiagnosed as hypertensive cardiomyopathy. Diagnosis requires specialist multidisciplinary investigation including CMR, genetic testing and histology, enabling appropriate management in an era when novel treatments for amyloidosis are entering the clinic.
- Cardiac amyloidosis
- heart failure