Abstract

Senile systemic amyloidosis (SSA) is a rare cause of heart failure due to the deposition of wildtype transthyretin. The clinical features and outcome are ill defined; our aim was to evaluate the natural history of the disease in the UK in a group of thoroughly characterised patients. The series included all cases of biopsy proven transthyretin (TTR) amyloidosis with wildtype TTR gene sequencing who were prospectively followed up between January 2001 and May 2010. Clinical, biochemical, ECG and echocardiographic evaluation were performed at presentation to our centre. Patient survival was estimated using Kaplan–Meier analysis. 55 patients with histologically proven SSA; 36 (65.5%) from cardiac, 14 (25.4%) from GI tract, 3 (5.5%) from bladder, 1 (1.8%) from fat and 1 (1.8%) from carpal tunnel tissue were identified. 49 (89%) were male. The median age at diagnosis and death were 74 (range 66–89) and 79 (range 69–84)  years respectively. Survival from symptom onset and diagnosis was 7.04 (range 0.54–8.41) and 4.58 (range 0.07–5.41) years respectively. In recent years more patients have been diagnosed with 2 (3.6%), 14 (25.5%) and 39 (70.9%) patients between 2001–2003, 2004–2006 and 2007–2009 respectively. The most common presentation was with breathlessness in 28 patients (51%). Twenty-four patients (43.6%) had prior carpal tunnel operations. Twelve (21.8%) patients had a history of ischaemic heart disease. Fifteen had had a coronary angiogram; 8 were reportedly normal and 7 required intervention. Arrhythmias were common, 20 patients (36.3%) had a history of atrial fibrillation and 6 (10.9) had pacemakers in situ. ECG findings were; 24 (43.6%) in AF, 6 (10.9%) first degree block, 10 (18.2%) left bundle and 6 (10.9%) right bundle branch block, 27 (49%) T wave changes, 11 (20%) <5 mm complexes in all inferior leads. Echocardiographic findings revealed the median IVSd was 1.7 (range 1.1–2.5) cm, median E/A ratio was 2.7 (range 0.79–5.4), E/E′ 15.81 (range 7.5–41.1) and ejection fraction was 45.5 (range 13–83)%. Blood results showed; the median baseline NT-proBNP was 356.1 (range 5–2611) and troponin T 0.03 (range 0.01–0.28). Twenty-five patients had a troponin T >0.03 (45%). Ten patients (18%) had a detectable paraprotein and 2 (3.6%) had bence jones proteins. SSA is present in >25% of the very elderly at post mortem but was rarely diagnosed during life. It is becoming more frequently recognised perhaps due to widespread use of cardiac MRI. Most patients are male but women can be affected. A history of carpal tunnel syndrome is common. The diagnosis is often made after the onset of breathlessness. Systolic and diastolic dysfunction can be seen on echocardiogram. A positive troponin is a common finding with a subsequent normal coronary angiogram. Incidental paraproteins are prevalent in up to 8% of this population and it is important to obtain a tissue diagnosis to rule out AL amyloidosis. With supportive management medium term outcomes are good.