Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild-type transthyretin amyloidosis is the most frequent form of ATTR-CM found in the elderly, hereditary transthyretin amyloidosis (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR-CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population.

Prevalence, characteristics and outcomes of older patients with hereditary versus wild‐type transthyretin amyloid cardiomyopathy

“…Awareness of the clinical features associated with presence of a TTR variant among patients diagnosed with ATTR‐CM might be useful to stratify the likelihood of ATTRv amyloidosis at first clinical evaluation in the ambulatory setting, to provide more accurate information on the likelihood of diagnosing ATTRv‐CM to patients who are reluctant to proceed with TTR gene sequencing and lastly, to enable prioritization of TTR gene sequencing in centres with limited resource. Our results confirm on multivariable analysis in a far larger population the findings of a single‐centre study on 279 ATTR‐CM patients ≥70 years 18 and further expand the range of clinical features associated with ATTRv‐CM. Of note, the present study provides new evidence for the independent impact of ATTRv‐CM on long‐term survival along with other established independent prognostic parameters.…”

“…In most elderly patients diagnosed with ATTR-CM, the condition is assumed to be of wild-type origin (acquired) and outside specialist referral centres for amyloidosis, patients ≥70 years are not always offered TTR genotyping on this basis. 18 In the present study, ATTR-CM was associated with a pathogenic TTR mutation in 20.7% of the population although the authors acknowledge that this proportion may fall as ATTRwt-CM is more widely diagnosed. ATTRv amyloidosis was most common in the 70-74 year old sub-group of this cohort among whom nearly one third had ATTRv-CM (Figure 1) although the prevalence of ATTRv-CM was >10% throughout all age groups with the exception of those ≥90 years.…”

“…In recent years, major advances in disease awareness and cardiac imaging, 23 the latter enabling accurate non‐invasive diagnosis, have identified ATTR‐CM to be relatively prevalent compared to the past. In most elderly patients diagnosed with ATTR‐CM, the condition is assumed to be of wild‐type origin (acquired) and outside specialist referral centres for amyloidosis, patients ≥70 years are not always offered TTR genotyping on this basis 18 . In the present study, ATTR‐CM was associated with a pathogenic TTR mutation in 20.7% of the population although the authors acknowledge that this proportion may fall as ATTRwt‐CM is more widely diagnosed.…”

“…All patients underwent sequencing of the TTR gene. Age ≥70 years at diagnosis was used to define the elderly cohort as (i) it was the median age of symptom onset in the Transthyretin Amyloid Outcome Survey (THAOS) registry, 17 and (ii) nowadays, the majority of individuals <70 years are not considered ‘elderly’ from a clinical perspective 18 …”

December 2022 at a glance: heart failure with preserved ejection fraction, sodium–glucose cotransporter 2 inhibitors and cardiac amyloidosis

“…The prevalence of hereditary transthyretin CA [(h)ATTR‐CA] has been investigated in a cohort of 300 patients affected by ATTR‐CA. hATTR‐CA was diagnosed in 12% of the overall cohort and in 5.3% of patients aged ≥70 years 31 . Patel et al 32 .…”