Cardiac amyloidosis is a condition characterised by infiltration of the myocardium with fibrillar proteins. Transthyretin (TTR) is a plasma protein that may form amyloid fibrils and the V122I mutant form of TTR is associated with isolated cardiac amyloidosis. Previous studies have estimated a 4% V122I allele frequency in African Americans. The prevalence of cardiac transthyretin amyloidosis (ATTR) V122I in the British population is not known. I was awarded a British Heart Foundation Clinical Research Fellowship to investigate the diagnosis and prevalence of ATTR V122I in the UK population. More than one million people of Afro-Caribbean ethnicity live in the Greater London area, and in the local ward of Wandsworth make up more than 10% of the population (2011 census data). The prevalence of ATTR V122I at St George's Hospital was high, affecting 12% of all Afro-Caribbean heart failure patients aged ~60 years. The estimated incidence of ATTR V122I in Afro-Caribbean subjects in the St George's Hospital catchment area was over twice the reported incidence of amyloidosis of all types in the general, predominantly Caucasian, UK population. The clinical phenotype is characterised by resistant heart failure, increased wall thickness and diastolic dysfunction on echocardiography and poor outcomes (median survival 29 months). The ECG had poor sensitivity to detect ATTR V122I because 25% of patients present with left ventricular hypertrophy criteria, contrary to the reported low voltage complexes widely reported in AL amyloidosis. Cardiovascular magnetic resonance (CMR) imaging demonstrated extensive late gadolinium enhancement (LGE) and I developed a novel LGE scoring system to differentiate ATTR from AL amyloidosis with high accuracy. A simple diagnostic algorithm to detect new cases of ATTR amyloidosis was retrospectively employed at a separate tertiary heart failure clinic and demonstrated that 5.2% of elderly black patients had ATTR amyloidosis, having previously been given a diagnosis of hypertensive heart failure. Improved detection of ATTR amyloidosis is increasingly important as novel treatments are now undergoing phase 3 clinical trial assessment and newly diagnosed patients now have the potential for disease modifying therapies. This will have implications for counselling and family screening of this inherited autosomal dominant condition in the future.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:676103 |
| Date | January 2014 |
| Creators | Dungu, Jason N. |
| Publisher | St George's, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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