Wild-type transthyretin cardiac amyloidosis is not rare in elderly subjects: the CATCH screening study

Eur J Prev Cardiol. 2024 Aug 22;31(11):1410-1417. doi: 10.1093/eurjpc/zwae093.

Abstract

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) affects older adults and is currently considered as a rare disorder. We investigated for the first time the prevalence of ATTRwt-CA in elderly individuals from the general population.

Methods and results: General practitioners from Pisa, Italy, proposed a screening for ATTRwt-CA to all their patients aged 65-90 years, until 1000 accepted. The following red flags were searched: interventricular septal thickness ≥ 12 mm, any echocardiographic, electrocardiographic or clinical hallmark of CA, or high-sensitivity troponin T ≥ 14 ng/L. Individuals with at least one red flag (n = 346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Four patients received a non-invasive diagnosis of ATTRwt-CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (Grade 3), left ventricular (LV) wall thickening, Grade 2 and 3 diastolic dysfunction, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 1000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a Grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT-proBNP < 300 ng/L. The prevalence of ATTR-CA in subjects ≥ 65 years was calculated as 0.46% (i.e. 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2).

Conclusion: Wild-type transthyretin cardiac amyloidosis is uncommon in elderly subjects from the general population, but more frequent than expected for a rare disease.

Keywords: ATTR; Amyloidosis; Disease prevalence; Elderly; Screening; Transthyretin cardiomyopathy; Wild-type.

Plain language summary

Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a heart condition mostly found in older adults. Wild-type transthyretin cardiac amyloidosis is considered a rare disease, although no systematic screening has been performed yet. The study aimed to understand how common this disease is among the general population aged 65–90 years in Pisa, Italy. To do this, general practitioners offered screening for ATTRwt-CA to their patients within this age group. The initial step of the screening involved checking for certain warning signs (red flags), like abnormal thickness in a part of the heart called the interventricular septum, unusual heart function observed through various tests, or elevated levels of a specific heart protein. Out of 1000 individuals who began the screening process, 346 showed at least one of these red flags and were further examined using bone scintigraphy (a type of imaging test) and tests for a specific protein related to this condition. Of these, 216 agreed to proceed with these additional tests. The results showed that four of these patients actually had ATTRwt-CA. Their conditions varied in severity, with some showing more intense signs of the disease on the heart scans, thicker heart walls, and higher levels of heart stress proteins. All four patients experienced mild difficulty in breathing during physical activity. Based on these findings, the study concluded that about 0.46% of elderly individuals in the general population might have ATTRwt-CA, indicating that the disease is somewhat more common in this age group than previously thought.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial* / blood
  • Amyloid Neuropathies, Familial* / diagnosis
  • Amyloid Neuropathies, Familial* / epidemiology
  • Biomarkers / blood
  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / epidemiology
  • Echocardiography
  • Electrocardiography
  • Female
  • Humans
  • Italy / epidemiology
  • Male
  • Mass Screening / methods
  • Prealbumin
  • Predictive Value of Tests
  • Prevalence
  • Ventricular Function, Left

Substances

  • Prealbumin
  • Biomarkers
  • TTR protein, human

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related