# Ventilatory efficiency in cardiac amyloidosis—A systematic review and meta‐analysis

## TL;DR

This study finds that patients with cardiac amyloidosis have poor ventilatory efficiency during exercise, with differences between disease subtypes and exercise testing methods.

## Contribution

The study provides the first meta-analysis of ventilatory efficiency in cardiac amyloidosis, comparing subtypes and exercise testing modalities.

## Key findings

- Patients with transthyretin amyloidosis (ATTR) have elevated VE/VCO2 slopes, indicating ventilatory inefficiency.
- ATTR patients are older and have higher VE/VCO2 slopes compared to AL amyloidosis patients.
- Peak oxygen uptake (VO2) varies by exercise modality, with treadmill testing showing the lowest values in ATTR patients.

## Abstract

In cardiac amyloidosis (CA) cardiopulmonary exercise testing (CPET) is underexplored. This study evaluated exercise limitations in CA using CPET, focusing on the ventilation‐to‐carbon dioxide production (VE/VCO2) slope and peak oxygen uptake (VO2). Seventeen studies involving 1505 patients were analyzed and systematically reviewed according to PRISMA reporting guidelines. Subgroup analyses assessed differences by diagnosis (ATTR vs. AL), CPET modality, and age. The cohort included 12% with AL, 80% with ATTR (23% hereditary [ATTRv], 70% wild‐type [ATTRwt], 7% unspecified), and 8% unidentified subtypes. VE/VCO2 slope was elevated across ATTR subgroups: 38.4 (95% CI: 36.9–40.0, I
2 = 57%) in ATTRwt and 37.9 (95% CI: 35.1–40.7, I
2 = 70%) in ATTRv. ATTR patients were older than AL patients by 9.0 years (95% CI: 0.4–17.6, I
2 = 88%) and had a higher VE/VCO2 slope: 2.5 (95% CI: 0.2–4.8, I
2 = 0%). CPET modality influenced peak VO2, which was lowest for treadmill exercise (13.7, 95% CI: 12.7–14.8, I
2 = 0%, mL/min/kg) compared to upright cycle ergometry (14.7, 95% CI: 14.3–15.1, I
2 = 33%) and semi‐recumbent cycle ergometry (14.5, 95% CI: 14.1–14.9, I
2 = 28%). A high VE/VCO2 slope characterizes both ATTRwt and ATTRv, while AL patients are younger with lower VE/VCO2 slope levels. Peak VO2 in ATTR patients may depend on exercise modality.

Exercise limitations and ventilatory efficiency in cardiac amyloidosis. This illustration summarizes CPET findings in cardiac amyloidosis. Patients with transthyretin amyloidosis, both wild‐type and variant, exhibit elevated VE/VCO₂ slopes, indicating ventilatory inefficiency. Light‐chain amyloidosis patients are younger and show comparatively lower VE/VCO₂ slopes. Peak VO₂ differs by CPET modality in ATTR patients, being lowest for treadmill. These findings emphasize disease mechanisms on ventilatory efficiency and the influence of CPET modality on exercise capacity. AL, amyloid light chain amyloidosis; ATTR, transthyretin amyloidosis; ATTRv, variant transthyretin amyloidosis; ATTRwt, wild‐type transthyretin amyloidosis; CA, cardiac amyloidosis; CPET, cardiopulmonary exercise testing; VE, minute ventilation; VE/VCO₂ slope, ventilatory efficiency; VO₂, oxygen uptake.