Around one-fifth of elderly patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) have a pathogenic TTR variant, according to a study published in the European Journal of Heart Failure.

ATTR-CM has gained increasing recognition in recent years, aided by advances in imaging studies, such as cardiac magnetic resonance and scintigraphy with bone tracers. This has coincided with the development of more effective treatments for this condition. 

Studies recommend sequencing the TTR gene for all patients with a diagnosis of ATTR-CM because it allows clinicians to differentiate between the wild-type and hereditary forms of this condition. However, in real-world clinical practice, TTR sequencing is rarely offered, especially in elderly patients with ATTR-CM. This is because they are often assumed to have the wild-type form of the disease, which is not necessarily the case. 

Read more about hereditary transthyretin amyloidosis etiology

The authors of this study hence aimed to establish the prevalence of variant ATTR-CM (ATTRv-CM) among patients aged 70 or more years in the United Kingdom. They also sought to understand the clinical implications of such a diagnosis. 

They conducted a retrospective, observational study of consecutive patients who were referred to the UK National Amyloidosis Center (NAC) between January 2010 and August 2022 and diagnosed with ATTR-CM. Patients underwent an echocardiogram and/or a cardiac magnetic resonance scan for diagnostic purposes. In addition, all patients diagnosed with ATTR-CM underwent TTR gene sequencing. The primary outcome of this study was the impact of ATTRv-CM on all-cause mortality. 

The research team identified 2729 consecutive patients who were referred to the UK NAC for suspected ATTR-CM. They analyzed the data of 2029 patients diagnosed with this condition who were 70 or more years of age. Of the 2029 patients with ATTR-CM, 421 individuals were diagnosed with ATTRv-CM (20.7%). 

“Among patients diagnosed with ATTR-CM, younger age at diagnosis, female gender, Afro-Caribbean ethnicity, [atrial fibrillation], [ischemic heart disease], polyneuropathy, and orthostatic hypotension are independently associated with ATTRv-CM,” the authors of the study wrote.

During a median follow-up period of 29 months, the researchers found, ATTRv-CM was associated with increased all-cause mortality, compared to the wild type of the condition. Survival was the poorest in those with the V122I TTR variant.

The research team recommends that all patients with a diagnosis of ATTR-CM receive prompt sequencing of the TTR gene to allow their physicians to better understand their risk of morbidity and mortality.


Porcari A, Razvi Y, Masi A, et al. Prevalence, characteristics and outcomes of older patients with hereditary versus wild-type transthyretin amyloid cardiomyopathyEur J Heart Fail. Published online January 16, 2023. doi:10.1002/ejhf.2776