Roy Ashwin, Thompson Sophie E, Hodson James, van Vliet Jan, Condon Nicola, Alvior Amor Mia, O'Shea Christopher, Vijapurapu Ravi, Nightingale Tom E, Clift Paul F, Townend Jonathan, Geberhiwot Tarekegn, Steeds Richard Paul
University of Birmingham Institute of Cardiovascular Sciences, Birmingham, UK
Department of Cardiology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
Heart. 2025 Feb 12;111(5):230-238. doi: 10.1136/heartjnl-2024-324553.
Fabry disease (FD) causes multiorgan sphingolipid accumulation, with cardiac involvement responsible for the largest burden of morbidity and mortality. Exercise intolerance in FD is prevalent, yet the mechanisms of this are poorly understood. The aim of this study was to assess exercise intolerance in FD and identify whether this correlates with the phase of cardiomyopathy.
This was a retrospective observational study of adults with FD undergoing cardiopulmonary exercise testing (CPEX) between September 2011 and September 2023 at a national referral centre in the UK. The primary outcome measure was peak oxygen uptake (V̇O), with forced expiratory volume in 1 s (FEV) used to quantify respiratory impairment. Age-normalised/sex-normalised values were additionally calculated, based on published normal ranges for subgroups of age and sex. The cardiomyopathy phase was classified on a 4-point scale by two FD experts using contemporaneous imaging and biochemistry results.
CPEX was completed by 42 patients, with a median age of 54 years and of whom 62% were male. Patients were approximately equally distributed across the four cardiomyopathy phases. At phase I, the mean (±SD) V̇O was 28.7±7.7 mL/kg/min, which represented a significant underperformance of 23%, relative to age-normalised and sex-normalised values (expected mean: 37.3±3.2 mL/kg/min, p=0.006). V̇O declined significantly across the cardiomyopathy phases (p=0.010), reaching a mean of 21.2±6.1 mL/kg/min at phase IV. Normalised FEV was not found to show a corresponding significant change with cardiomyopathy phase (p=0.683). Impaired left atrial global longitudinal strain as well as biochemical markers of inflammation were associated with impaired V̇O.
This study identifies significantly impaired aerobic capacity in FD, even in those without phenotypic cardiomyopathy. No corresponding changes in respiratory impairment were observed, suggesting that exercise intolerance may be due to early cardiac sphingolipid accumulation and subsequent atrial and ventricular dysfunction, which increases as cardiomyopathy progresses. As such, peak V̇O holds promise as a therapeutic marker of response to FD-specific therapy.
法布里病（FD）会导致多器官鞘脂蓄积，其中心脏受累是发病和死亡负担最重的因素。FD患者运动不耐受很常见，但其机制尚不清楚。本研究旨在评估FD患者的运动不耐受情况，并确定其是否与心肌病阶段相关。
这是一项对2011年9月至2023年9月期间在英国一家国家转诊中心接受心肺运动试验（CPEX）的成年FD患者进行的回顾性观察研究。主要结局指标是峰值摄氧量（V̇O），用第1秒用力呼气量（FEV）来量化呼吸功能损害。还根据已发表的年龄和性别亚组正常范围计算了年龄标准化/性别标准化值。由两名FD专家根据同期影像学和生化结果，采用4分制对心肌病阶段进行分类。
42例患者完成了CPEX，中位年龄54岁，其中62%为男性。患者在四个心肌病阶段的分布大致相等。在I期，平均（±标准差）V̇O为28.7±7.7 mL/kg/min，相对于年龄标准化和性别标准化值（预期平均值：37.3±3.2 mL/kg/min，p=0.006），这代表着显著低23%的表现。V̇O在心肌病各阶段显著下降（p=0.010），在IV期降至平均21.2±6.1 mL/kg/min。未发现标准化FEV随心肌病阶段有相应的显著变化（p=0.683）。左心房整体纵向应变受损以及炎症生化标志物与V̇O受损有关。
本研究发现FD患者的有氧能力显著受损，即使是那些没有表型性心肌病的患者。未观察到呼吸功能损害有相应变化，这表明运动不耐受可能是由于早期心脏鞘脂蓄积以及随后的心房和心室功能障碍，随着心肌病进展而加重。因此，峰值V̇O有望作为FD特异性治疗反应的治疗标志物。
