Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis

• Published in: The American heart journal Vol. 158; no. 4; pp. 607 - 614
• Main Authors: Connors, Lawreen H., Prokaeva, Tatiana, Lim, Amareth, Théberge, Roger, Falk, Rodney H., Doros, Gheorghe, Berg, Alan, Costello, Catherine E., O'Hara, Carl, Seldin, David C., Skinner, Martha
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.10.2009; Elsevier Limited
• Subjects: African Americans; Aged; Alleles; Amyloidosis - ethnology; Amyloidosis - genetics; Amyloidosis - metabolism; Cardiomyopathies - ethnology; Cardiomyopathies - genetics; Cardiomyopathies - metabolism; Cardiovascular; DNA - genetics; Female; Follow-Up Studies; Gene Frequency; Humans; Immunoglobulin Light Chains - blood; Immunohistochemistry; Male; Mass Spectrometry; Massachusetts - epidemiology; Medical treatment; Middle Aged; Mutation; Prealbumin - genetics; Prealbumin - metabolism; Prevalence; Prognosis; Retrospective Studies; Sequence Analysis, DNA; Massachusetts
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2009.08.006

Transthyretin (TTR) mutations known to cause cardiac amyloidosis include V122I, found almost exclusively in African Americans at a prevalence of 3-3.9%. This retrospective study describes TTR V122I–associated cardiac amyloid disease (ATTR) in a major amyloid referral clinic population. Self-identified African Americans with amyloidosis (n = 156) were screened for TTR V122I by serum isoelectric focusing; mutant TTR was confirmed by DNA sequencing or mass spectrometry. Cardiac findings in ATTR V122I and immunoglobulin light chain (AL) amyloidoses were compared. TTR V122I was identified in 36/156 (23.1%) of evaluated patients and included 5 homozygotes; the allele frequency was 0.013. One compound heterozygote (F44L/V122I) and 4 patients who had AL and the mutant TTR allele were characterized. In patients negative for V122I, AL was the most frequent diagnosis (86/120). Cardiomyopathy was present in 100% of patients with ATTR and 84% of patients with AL ( P = .01). In patients with dominant cardiac involvement, better survival occurred in ATTR (n = 30) compared to AL (n = 31), (27 vs 5 months, P < .01) although the mean age in ATTR was higher (70.3 vs 56.2 years, P < .01). Congestive heart failure symptoms and electrocardiographic findings were similar in ATTR and AL, but significant differences in echocardiographic measurements were observed. ATTR V122I and AL are equally prevalent as the cause of cardiomyopathy in African Americans referred for a diagnosis of amyloidosis. Available therapy for AL underscores the need for early and accurate determination of amyloid type.