CVI Alterations in FD: a Prospective, Multicenter, Observational Cohort Study

The Characteristics of Cardiovascular Imaging Alterations in Patients with Fabry Cardiomyopathy: a Prospective, Multicenter, Observational Cohort Study

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (GLA) gene mutations leading to reduced or undetectable α galactosidase A (α-Gal A) enzyme activity, resulting in progressive accumulation of globotriaosylceramide (GL3) and its deacylated form globotriaosylsphingosine (Lyso-GL-3) in multiple organs, causing neural, renal, cardiac, dermatological, gastrointestinal and ophthalmic manifestations, even leading to life-threatening complications. Cardiovascular and cerebrovascular complications (i.e. heart failure, stroke, etc.) or end-stage renal disease even premature death can be seen in severe cases. The life expectancy of male patients is reduced by 15~20 years, while that of female patients is reduced by 6~10 years.

The exact prevalence of FD is currently unknown. Based on an estimated prevalence of 1:60,000, there are approximately 23,000 affected FD patients in China. The clinical manifestations of FD are diverse and non-specific, which may lead to misdiagnosis in patients with non-typical clinical manifestations in the absence of a family history of FD. Cardiac involvement can be recognized in up to 68% patients with FD, significantly higher than in other organs, and the positive screening rate for FD in adults with unexplained left ventricular hypertrophy (LVH)/hypertrophic cardiomyopathy was 0.9%.

Cardiovascular disease is the leading cause of death in patients with FD cardiomyopathy (40.2%). The 2020 Expert Consensus Document on the Management of Cardiovascular Manifestations of Fabry Disease recommends early screening in patients with suspected LVH for early diagnosis. Therefore, strengthened screening strategy in high-risk patients with LVH will improve the diagnosis and treatment of FD in China.

Study Overview

• Status: Recruiting
• Conditions: Fabry Disease, Cardiac Variant

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Lei Song; Phone Number: +86 8839 2165; Email: songlqd@126.com

Study Locations

• China
  • Beijing, China, 100037
    • Recruiting
    • Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Lei Song; Phone Number: +86 88392165; Email: songlqd@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Adult patients with a maximum myocardial wall thickness (left ventricular posterior wall or septum) of ≥13 mm at the end diastole on echocardiography, with at least two or more "warning signs" associated with FD ("warning signs" include cardiac "warning signs", extracardiac "warning signs", or family history) who fullfil the standard of screening for Fabry disease will be consecutively recruited.

Description

Inclusion Criteria:

Patients to be enrolled in this study should fulfill all 3 criteria (a, b, and c) at screening:

1. Patients with a maximum myocardial wall thickness (left ventricular posterior wall or septum) of ≥13 mm at the end diastole on echocardiography;
2. At least two or more "warning signs" associated with FD ("warning signs" include cardiac "warning signs", extracardiac "warning signs", or family history)
3. Aged 18 years old or older;

cardiac "warning signs" of FD:

Concentric LVH or papillary hypertrophy or right ventricular hypertrophy on echocardiography

ECG abnormalities (eg, shortened PR interval, wide QRS complex, right bundle branch block, ST-segment depression, etc.)

Extra-cardiac "warning signs" of FD

Angiokeratomas

Acroparesthesia

Hypohidrosis

Premature stroke (<50 years of age)

Corneal verticillate

Renal impairment accompanied by proteinuria

Hearing loss

Family history

Family history of X-linked inherited disorder (renal disease or cardiac disease)

Exclusion Criteria:

1. LVH patients with a clear etiology;
2. Combining any other clinical condition with a life expectancy less than 1 year;
3. Refuse to give informed consent or refuse to be followed-up.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular deaths	Including sudden cardiac death or equivalent events, heart failure-related death, stroke-related death and death from other cardiovascular causes.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart failure	NYHA progression to level III/IV	12 months
Stroke	Including ischemic stroke and hemorrhagic stroke	12 months
Myocardial infarction	Including ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction	12 months
All-cause deaths	Death from all causes	12 months

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Lei Song, Fuwai Hospital, National Centre for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 23, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Fabry Disease
• Other Study ID Numbers: 2023-ZX084

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No