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Updated: Jul 4, 2026

Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
06:33

Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis

Published on: June 9, 2018

Prognostic impact of chronotropic incompetence in transthyretin cardiac amyloidosis: a multicentre study

Damiano Magrì1, Nikita Ermolaev2, Vincenzo Castiglione3,4

  • 1Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, 'Sapienza' University of Rome, Via Giorgio Nicola Papanicolau, 00189 Rome, Italy.

ESC Heart Failure
|July 3, 2026
PubMed

Insights

Chronotropic incompetence (CI) is common in transthyretin amyloid cardiomyopathy and predicts poor outcomes. A peak heart rate percentage ≤75% identifies patients at higher risk for cardiovascular death.

Area of Science:

  • Cardiology
  • Cardiovascular Disease
  • Exercise Physiology

Background:

  • Chronotropic incompetence (CI) is a frequent but underappreciated feature of cardiac amyloidosis, potentially contributing to exercise intolerance.
  • The prognostic significance of CI in transthyretin (ATTR) amyloid cardiomyopathy is not well-defined.

Purpose of the Study:

  • To investigate the prevalence, functional correlates, and prognostic value of CI in patients with ATTR amyloid cardiomyopathy.
  • To assess the association between CI and 1-year cardiovascular mortality.

Main Methods:

  • A multicentre retrospective study of 212 stable outpatients with ATTR cardiomyopathy undergoing maximal cardiopulmonary exercise testing (CPET).
  • Chronotropic response assessed as peak heart rate percentage (pHR%) of age-predicted value.
  • Prognostic performance evaluated using Cox regression, ROC analysis, and Kaplan-Meier estimates for 1-year CV mortality.

Main Results:

  • CI (pHR% ≤75%) was present in 35% of patients, associated with impaired functional capacity (lower peak oxygen uptake, reduced ventilatory efficiency).
  • pHR% demonstrated strong prognostic value; each 1% increase reduced CV mortality risk by 5.5% (HR 0.945; p=0.011).
  • A pHR% threshold of 75% optimally discriminated risk (AUC 0.71) and identified a subgroup with significantly lower survival.

Conclusions:

  • A blunted chronotropic response is common in ATTR cardiomyopathy and indicates adverse short-term prognosis.
  • A pHR% ≤75% is a clinically meaningful and easily obtainable threshold for functional and prognostic stratification.
  • This threshold offers a pragmatic alternative for risk assessment when comprehensive CPET is unavailable.
Abstract

Keywords:
Cardiac amyloidosisCardiopulmonary exercise testChronotropic incompetencePrognosis

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