158 Racial differences in val122Ile associated transthyretin cardiac amyloidosis

Abstract

Abstract Aims The valine-to-isoleucine substitution (Val122Ile) is the most common variant of transthyretin (TTR) amyloidosis in the USA, primarily affecting individuals of African descent and leading to a restrictive cardiomyopathy. This variant has recently been identified in a cluster of White individuals in Italy. In this study we aimed to investigate differences in the clinical phenotype of Val122Ile associated TTR cardiac amyloidosis (ATTR-CA) between Black and White individuals. Methods and results In this retrospective study of 70 patients (mean age 72 years) with Val122Ile associated TTR ATTR-CA, cardiac chamber performance was compared using noninvasive pressure-volume analysis. Compared to White patients (n = 17), Black individuals (n = 53) had lower systolic blood pressures (110 vs. 131 mmHg, P < 0.001), reduced pulse pressures (41 vs. 58 mmHg, P < 0.001), and impaired renal function (eGFR 46 vs. 67 mL/min/1.73 m2, P < 0.001) at presentation. Systolic properties and arterial elastance were similar. Black patients had an end-diastolic pressure-volume relationship shifted upward and leftward relative to White patients, indicating reduced left ventricular chamber capacitance. Pressure-volume area at a left ventricular end-diastolic pressure of 30 mmHg was lower in Black compared to White individuals (8055 mmHg*ml vs. 11 538 mmHg*ml, P = 0.008). Conclusions Despite presenting at a similar age to White patients, Black individuals with Val122Ile associated ATTR-CA have a greater degree of cardiac chamber dysfunction at the time of diagnosis due to impaired ventricular capacitance. Whether these differences are attributable to amyloidosis or other cardiovascular disease requires further study.