ImportanceCardiopulmonary exercise testing (CPET) has an established role in the assessment of patients with heart failure. However, data are lacking in patients with transthyretin (ATTR) amyloidosis.ObjectiveTo use CPET to characterize the spectrum of functional phenotypes in patients with ATTR amyloidosis and assess their association with the cardiac amyloid burden as well as the association between CPET parameters and prognosis.Design, Setting and ParticipantsThis single-center study evaluated patients diagnosed with ATTR amyloidosis from May 2019 to September 2022 who underwent CPET at the National Amyloidosis Centre. Of 1045 patients approached, 506 were included and completed the study. Patients were excluded if they had an absolute contraindication to CPET or declined participation. The mean (SD) follow-up period was 22.4 (11.6) months.Main Outcomes and MeasuresComparison of CPET parameters across disease phenotypes (ATTR with cardiomyopathy [ATTR-CM], polyneuropathy, or both [ATTR-mixed]), differences in CPET parameters based on degree of amyloid infiltration (as measured by cardiovascular magnetic resonance [CMR] with extracellular volume mapping), and association between CPET parameters and prognosis.ResultsAmong the 506 patients with ATTR amyloidosis included in this study, the mean (SD) age was 73.5 (10.2) years, and 457 participants (90.3%) were male. Impairment in functional capacity was highly prevalent. Functional impairment in ATTR-CM and ATTR-mixed phenotypes (peak mean [SD] oxygen consumption [VO2], 14.5 [4.3] mL/kg/min and 15.7 [6.2] mL/kg/min, respectively) was observed alongside impairment in the oxygen pulse, with ventilatory efficiency highest in ATTR-CM (mean [SD] ventilatory efficiency/volume of carbon dioxide expired slope, 38.1 [8.6]). Chronotropic incompetence and exercise oscillatory ventilation (EOV) were highly prevalent across all phenotypes, with both the prevalence and severity being higher than in heart failure from different etiologies. Worsening of amyloid burden on CMR was associated with decline in multiple CPET parameters, although chronotropic response and EOV remained abnormal irrespective of amyloid burden. On multivariable Cox regression analysis, peak VO2 and peak systolic blood pressure (SBP) were independently associated with prognosis (peak VO2: hazard ratio, 0.89 [95% CI, 0.81-0.99; P = .03]; peak SBP: hazard ratio, 0.98 [95% CI, 0.97-0.99; P < .001]).Conclusions and RelevanceIn this study, ATTR amyloidosis was characterized by distinct patterns of functional impairment between all disease phenotypes. A high prevalence of chronotropic incompetence, EOV, and ventilatory inefficiency were characteristic of this population. CPET parameters were associated with amyloid burden by CMR and with peak VO2, and SBP, which have been shown to be independent predictors of mortality. These findings suggest that CPET may be useful in characterizing distinct patterns of functional impairment across the spectrum of amyloid infiltration and predicting outcomes, and potentially offers a more comprehensive method of evaluating functional capacity for future prospective studies.

中文翻译：

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心肺运动试验评估转甲状腺素蛋白淀粉样变性

重要性心肺运动试验 (CPET) 在心力衰竭患者的评估中具有明确的作用。然而，转甲状腺素蛋白（ATTR）淀粉样变性患者的数据缺乏。目的利用CPET表征ATTR淀粉样变性患者的功能表型谱，评估其与心脏淀粉样蛋白负荷的关系以及CPET参数与预后的关系。 、设置和参与者这项单中心研究评估了 2019 年 5 月至 2022 年 9 月期间在国家淀粉样变性中心接受 CPET 诊断的 ATTR 淀粉样变性患者。在 1045 名患者中，有 506 名被纳入并完成了研究。如果患者有 CPET 的绝对禁忌症或拒绝参与，则被排除在外。平均 (SD) 随访期为 22.4 (11.6) 个月。 主要结果和测量不同疾病表型（ATTR 与心肌病 [ATTR-CM]、多发性神经病或两者 [ATTR-混合]）的 CPET 参数比较、CPET 差异基于淀粉样蛋白浸润程度的参数（通过心血管磁共振 [CMR] 和细胞外体积图测得）以及 CPET 参数与预后之间的关联。 结果在本研究中纳入的 506 名 ATTR 淀粉样变性患者中，平均 (SD) 年龄为73.5（10.2）岁，457 名参与者（90.3%）为男性。功能能力受损非常普遍。ATTR-CM 和 ATTR 混合表型的功能障碍（峰值平均 [SD] 耗氧量 [VO2]，分别为 14.5 [4.3] mL/kg/min 和 15.7 [6.2] mL/kg/min），同时观察到氧脉冲受损，ATTR-CM 中通气效率最高（平均 [SD] 通气效率/容量）二氧化碳呼出斜率，38.1 [8.6]）。变时性功能不全和运动振荡通气（EOV）在所有表型中都非常普遍，其患病率和严重程度均高于不同病因引起的心力衰竭。CMR 淀粉样蛋白负荷的恶化与多个 CPET 参数的下降相关，尽管变时反应和 EOV 仍然异常，而与淀粉样蛋白负荷无关。多变量 Cox 回归分析，峰值 VO2和峰值收缩压 (SBP) 与预后独立相关（峰值摄氧量2：风险比，0.89 [95% CI，0.81-0.99；磷=.03]；峰值 SBP：风险比，0.98 [95% CI，0.97-0.99；磷< .001]).结论和相关性在这项研究中，ATTR 淀粉样变性的特点是所有疾病表型之间都有不同的功能损害模式。该人群的特点是变时性功能不全、EOV 和通气效率低下。CPET 参数与 CMR 测得的淀粉样蛋白负荷以及峰值 VO2 相关2和 SBP，已被证明是死亡率的独立预测因子。这些发现表明，CPET 可能有助于表征淀粉样蛋白浸润范围内不同的功能损伤模式和预测结果，并有可能为未来的前瞻性研究提供一种更全面的功能能力评估方法。