Cardiac transthyretin (ATTR) amyloidosis - clinical and echocardiographic findings from the largest single cohort worldwide

Abstract

Purpose: Cardiac transthyretin (ATTR) amyloidosis, also known as senile systemic/cardiac amyloidosis, is a rarely diagnosed late onset progressive cardiomyopathy. Clinical features and outcome data have been characterised only in small groups of patients. Various observations suggest that it may in fact be far more common, and several promising specific new therapies, including transthyretin stabilizers and RNA inhibitors, are now in clinical development. Our aim here was to review and better characterise the clinical features of the disease in a large single centre series. Methods: More than 200 patients have been diagnosed at our UK tertiary centre during the past 5 years, comprising the largest cohort worldwide. Analyses of clinical data and echocardiography performed at our centre in the first 155 patients are presented here, and will be updated to include all cases prior to the ESC Congress. Survival was estimated using Kaplan-Meier analysis. Results: The number of new patients has increased year on year, from 16 in 2007 to 60 in 2012. Of 155 patients, 144 were male (93%). Median age at diagnosis was 77 yr (IQ range 72-81) and at death was 81 yr (IQ range 77-84). Twenty three patients (15%) were younger than 70 yr at diagnosis. Forty five patients have died. Median survival was 51.2 months (95% CI 40.9 to 67.5). Sixty seven (43%) patients had atrial fibrillation at diagnosis. Median serum NT-pro BNP at diagnosis was 329pmol/L (IQ range 208-658), and serum Troponin-T was elevated in 131 (86%) patients. Transthoracic echocardiography showed median EF of 48% (IQ range 40-55), median IVSd 1.7cm (IQ range 1.5-1.8) and median LVPWd 1.7cm (IQ range 1.5-1.8). Median E/E' was 15.7 (IQ range 12.2-19.3), lateral S' TDI 0.05m/s (IQ range 0.04-0.06) and septal S' TDI 0.04 m/s (IQ range 0.03-0.05). Conclusions: Cardiac ATTR amyloidosis is a cause of heart failure with preserved EF that typically affects older men, but it does occur in women and younger patients. The clinical phenotype is rather non-specific, and although concentric LV wall thickening and reduced longitudinal systolic function with moderate to severe diastolic dysfunction in association with elevated cardiac biomarkers are characteristic, the range of echocardiography findings was wide. Many recent referrals were prompted following CMR, which had strongly suggested amyloid infiltration in most cases. These observations, coupled with the promise of specific new therapies in the near future, encourage a high index of suspicion for cardiac ATTR amyloidosis among older patients with heart failure and preserved EF.