Nandi Pooja, Ellis Robert, Hiros Jennifer, Howard Paul, Veleva-Rotse Biliana O
Koneksa Health, New York, NY, USA.
Koneksa Health, One World Trade Center, 285 Fulton St. 77th Floor, New York, NY, 10007, USA.
Orphanet J Rare Dis. 2025 Jul 28;20(1):382. doi: 10.1186/s13023-025-03895-x.
Fabry disease (FD) is an X-linked, multisystemic, progressive lysosomal disorder caused by GLA variants resulting in alpha-galactosidase A deficiency. Although cardiovascular disease is the leading cause of death in people with FD, the progression of cardiac dysfunction remains poorly understood, mainly due to a lack of clinical measurement tools for predicting cardiac progression risk over relevant timescales. New, accessible tools are needed to measure cardiac functional change and predict event risk over shorter timescales. Digital tools allow at-home, frequent data collection that could help detect elevated cardiac event risk, inform treatment and management, and support novel therapy development. Digital measures are designed, developed, and validated using recognized frameworks. We present a novel composite measurement concept aligned to established guidance that utilizes digital tools to improve the monitoring of cardiac function in FD.
A targeted literature search, patient advisory board, and clinician advisory board were conducted to identify important FD signs and symptoms and the most suitable cardiac patient-reported outcomes and digital tools for concurrent remote collection of subjective and objective data.
The literature search highlighted a lack of FD-specific cardiac digital monitoring tools. Patient advisory board discussions and survey responses highlighted pain, gastrointestinal issues, and fatigue as important FD symptoms, and participants expressed a desire to understand how cardiac manifestations impacted these symptoms. The clinician advisory board noted a lack of specific diagnostic, monitoring, and prognosis (especially cardiac) tools in FD. The composite measurement concept was developed to capture the signs and symptoms most important to people living with FD, alongside heart-rate variability, electrocardiograms, blood pressure, and quality of life as relevant measures within the cardiac domain that can be staged in a progression model with clear group boundaries.
Based on work completed to date, developing a composite measurement concept that utilizes digital tools to improve the measurement of cardiac function in FD is conceptually possible and aligns with the evidentiary framework for designing and building a monitoring biomarker. This composite measurement concept could be used for future analytical validation, usability, and clinical validation, seeking to capture progressing cardiac dysfunction in people living with FD.
法布里病（FD）是一种X连锁的多系统进行性溶酶体疾病，由GLA基因变异导致α-半乳糖苷酶A缺乏引起。虽然心血管疾病是FD患者的主要死因，但心脏功能障碍的进展仍知之甚少，主要原因是缺乏在相关时间尺度上预测心脏进展风险的临床测量工具。需要新的、可获取的工具来测量心脏功能变化并在更短的时间尺度上预测事件风险。数字工具允许在家中频繁收集数据，这有助于检测心脏事件风险升高、为治疗和管理提供信息，并支持新疗法的开发。数字测量是使用公认的框架进行设计、开发和验证的。我们提出了一种与既定指南一致的新型综合测量概念，该概念利用数字工具来改善对FD患者心脏功能的监测。
进行了有针对性的文献检索、患者咨询委员会和临床医生咨询委员会，以确定重要的FD体征和症状，以及最适合同时远程收集主观和客观数据的心脏患者报告结局和数字工具。
文献检索突出显示缺乏针对FD的心脏数字监测工具。患者咨询委员会的讨论和调查回复强调疼痛、胃肠道问题和疲劳是重要的FD症状，参与者表示希望了解心脏表现如何影响这些症状。临床医生咨询委员会指出FD缺乏特定的诊断、监测和预后（尤其是心脏方面）工具。开发了综合测量概念，以捕捉对FD患者最重要的体征和症状，以及心率变异性、心电图、血压和生活质量等心脏领域的相关测量指标，这些指标可以在具有明确分组界限的进展模型中进行分期。
基于迄今为止完成的工作，开发一种利用数字工具改善FD患者心脏功能测量的综合测量概念在概念上是可行的，并且与设计和构建监测生物标志物的证据框架一致。这种综合测量概念可用于未来的分析验证、可用性和临床验证，旨在捕捉FD患者进展性心脏功能障碍。
