Anderson-Fabry Disease
Conditions
Keywords
Anderson-Fabry Disease, Cardiac Involvement, CMR, CPET
Brief summary
The goal of this observational study is to observe the relation between excercise parameters - assessed by CPET - and rest/stress hemodynamic parameters - assessed by echocardiogram and CMR - in patients with a genetic diagnosis of Anderson-Fabry Disease. Participants will undergo: * baseline evaluation: clinical evaluation, disease staging with FASTEX and MSSI, KCCQ for quality of life assessment, resting 12-leads ECG, 6MWT, CPET-ESE and contrast-enhanced CMR; * before 36 months from baseline: resting 12-leads ECG, 2D rest and stress echocardiogram, CPET-ESE, contrast-enhanced CMR, disease staging with FASTEX and MSSI and KCCQ for quality of life assessment; * up to 7 years from baseline: clinical follow-up.
Interventions
None listed
Sponsors
IRCCS Policlinico S. Donato
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with a genetic diagnosis of AFD, according to current guidelines; * Informed written consent with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care (for patients age \<18 years old, written consent from a caregiver is mandatory).
Exclusion criteria
* eGFR \<30 ml/min and other contraindications for CMR (relative controindication: patients with implantable device); * Musculoskeletal limitation for exercise test on the cyclo ergometer; * Pregnant or breastfeeding women; * Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with a full comprehension of the written consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CMR parameters - ECV | At baseline and before 36 months from baseline. | Extracellular volume (%) |
| CPET parameters- peak Vo2 | At baseline and before 36 months from baseline. | Peak VO2 ml/Kg/min |
| CPET parameters- predicted peak Vo2 | At baseline and before 36 months from baseline. | Predicted peak VO2 (%). |
| CPET parameters- VE/VCO2 slope | At baseline and before 36 months from baseline. | VE/VCO2 slope |
| CPET parameters- oxygen pulse | At baseline and before 36 months from baseline. | 02 pulse (ml/beat) |
| CPET parameters- heart rate during exercise | At baseline and before 36 months from baseline. | Heart rate reserve (beats/minute) Heart rate recovery (beat/minute) Heart rate recovery at one minute (beat/minute) |
| CPET parameters- presence of chronotropic incompetence, O2 pulse flattening and exercise oscillatory ventilation | At baseline and before 36 months from baseline. | Chronotropic incompetence (yes/no) 02 pulse flattening (yes/no) exercise oscillatory ventilation (yes/no) |
| CPET parameters- VO2/work slope | At baseline and before 36 months from baseline. | VO2/work slope (ml/min/watt) |
| Echocardiogram parameters- diastolic function at rest | At baseline and before 36 months from baseline. | At rest E/A ratio. At rest mean E/E'. At rest left atrial reservoir function (%). At rest sPAP (mmHg). |
| Echocardiogram parameters- systolic function of the left and right ventricle at rest | At baseline and before 36 months from baseline. | At rest TAPSE (mm) At rest LV ejection fraction (%) At rest LV stroke volume indexed for body mass surface (ml/mq) At rest right ventricular free wall strain (%) |
| Echocardiogram parameters- right ventricle-pulmonary artery coupling at rest. | At baseline and before 36 months from baseline. | At rest TAPSE/sPAP (mm/mmHg) |
| Echocardiogram parameters- exertional diastolic function | At baseline and before 36 months from baseline. | exertional E/A, exertional mean E/E' exertional TAPE/sPAP (mm/mmHg) mPAP/CO (mmHg/L/min) |
| CMR parameters - LV Mass and LV Max Wall Thickness | At baseline and before 36 months from baseline. | LV mass (gr) and LV max wall thickness (mm). |
| CMR parameters - Systolic Function | At baseline and before 36 months from baseline. | Stroke volume indexed to body surface (ml/m2) and left ventricular ejection fraction (%). |
| CMR parameters - T1 and T2 Mapping | At baseline and before 36 months from baseline. | T1 and T2 mapping (msec). |
| CMR parameters - presence of late gadolinium enhancement | At baseline and before 36 months from baseline. | late gadolinium enhancement (yes/no) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Cardiovascular Events | Up to 7 years follow-up. | Absolute number of all-cause mortality, CV death, ventricular arrhytmias (sustained and non-sustained VT and VF), bradyarrhytmias requiring permanent pacing, new-onset of atrial fibrillation/atrial flutter, myocardial infarction and stroke. |
Countries
Italy
Contacts
CONTACTMassimo Piepoli, MD, PhD
CONTACTGianluigi Guida, MD
Outcome results
None listed