Natural History in Fabry Disease With IVS4+919G>A Mutations

The Left Ventricular mass index quantifies the mass of the left ventricle, the heart's main pumping chamber, relative to an individual's body size. This will be measured using cardiac MRI.

Papillary muscle mass refers to the total amount of tissue (mass) in the papillary muscles located within the left ventricle. These muscles help support the mitral valve and play an important role in how the left ventricle pumps blood during systole. This measurement will be obtained using cardiac MRI.

LVEF, or Left Ventricular Ejection Fraction, indicates how well the left ventricle pumps blood. This will be measured using cardiac MRI.

LVEDV, or Left Ventricular End-Diastolic Volume, is the amount of blood in the left ventricle at the end of diastole, right before the heart contracts. This will be measured using cardiac MRI.

LVESV stands for Left Ventricular End-Systolic Volume and refers to the volume of blood remaining in the left ventricle after pumping. This will be measured using cardiac MRI.

Native T1 is a heart MRI measurement that looks at the properties of the heart muscle tissue without using contrast dye. It helps detect early or subtle tissue changes, such as inflammation or remodeling, even when scarring isn't yet obvious. This will be obtained during cardiac MRI.

LGE volume refers to the measurement of Late Gadolinium Enhancement, a cardiac MRI method used to estimate how much heart muscle has developed fibrosis (scarring). This measurement will be obtained using cardiac MRI.

LGE positive refers to Late Gadolinium Enhancement and is used to visualise and assess myocardial damage or scarring. This measurement will be obtained using cardiac MRI.

Extracellular Volume (ECV) it's a measurement from cardiac MRI that estimates how much of the heart muscle's space is in the outside (between-cell) area, which can increase when there's things like fibrosis (scarring) or other tissue remodeling. This measurement will be obtained with T1 mapping during cardiac MRI.

Left Ventricle end-diastolic septal thickness is the thickness of the septum, the wall between the left and right sides of the heart, measured at the end of diastole, just before the heart contracts. This measurement indicates how thick that part of the heart wall is when the ventricle is fully filled. This will be measured during echocardiography.

Left Ventricle end-diastolic posterior wall thickness is a measure of how thick the back wall of the left ventricle is at the end of heart filling. This measurement will be obtained during echocardiography.

Left ventricular maximal wall thickness measures how thick the heart muscle is at its thickest point on the left ventricle wall. This measurement will be taken during echocardiography.

Left Ventricular Ejection Fraction (LVEF) is a measure of how well the left side of the heart pumps. It shows what percentage of blood in the left ventricle is pushed out with each heartbeat. This will be measured during echocardiography.

Left Ventricular End-Diastolic Volume (LVEDV) is the amount of blood left in the left ventricle at the end of diastole. This measurement will be taken during echocardiography.

Left ventricular end-systolic volume (LVESV) is the amount of blood left in the left ventricle right after it contracts. This will be measured during echocardiography.

Left Atrium Volume (LA volume) means the size of the left atrium and is a measurement of how much space or blood the left atrium holds. This will be measured during echocardiography.

Right ventricular volume refers to the amount of blood in the right ventricle, usually measured at end-diastole (when the heart is filling) and end-systole (when it has squeezed). This will be measured during echocardiography.

Right Ventricular Systolic Pressure (RVSP) measures the pressure generated by the right ventricle as it pumps blood into the pulmonary artery. This will be measured during echocardiography.

LV global longitudinal strain (GLS) is a measurement of how well the left ventricle is squeezing by looking at how much the heart muscle shortens in length during each heartbeat. This will be measured during echocardiography.

Left Atrial strains (LA strains) is a measurement of how well the left atrium is working, by tracking how much it stretches and squeezes during the heartbeat. This will be measured during echocardiography.

The Right Ventricle free wall refers to the outer/free edge of the right ventricle and is used to assess how well the right ventricle is contracting and working.

Septal longitudinal strain is a measure of how much the septum (the wall in the middle of the heart that separates the left and right sides) lengthens and shortens from the base to the tip of the heart during each heartbeat. This will be measured during echocardiography.

Plasma lyso-Gb3 is a blood test that measures a substance called lyso-globotriaosylsphingosine (lyso-Gb3). In Fabry disease, the body can't properly break down certain fats, because of that, lyso-Gb3 can build up. This is used as a biomarker to diagnose Fabry disease and to monitor disease progression. This will be obtained during a blood test.

NT-proBNP is a blood biomarker released by the heart that indicates cardiac stress and helps diagnose and monitor heart failure. This will be obtained during a blood test.

Cardiac troponins are proteins that leak into the bloodstream when the heart muscle is injured. They are used to help diagnose heart attacks and other types of heart damage. This will be measured using a blood test.

Measuring urinary protein is an important way to check how well the kidneys are working. This will be measured by collecting a urine sample.

Albumin is a protein made by the liver and is essential for maintaining fluid balance and transporting substances throughout the body. This will be measured by collecting a blood test.

MSSI (Mainz Severity Score Index) will be used to measure how severe the disease is overall and how the participants' health changes overtime or in response to treatment. A higher MSSI score means the disease is more severe.

A NYHA class (New York Heart Association) questionnaire will be used to assess the heart failure severity and the impact on the patients' daily activities and overall functional capacity. The scores are divided into Class I (1) to Class IV (4) with Class I meaning no limitations and Class IV meaning severe limitations.

Mortality will be recorded during the study period.

Any new onset of heart failure will be recorded throughout the study. This will be assessed by capturing evidence of cardiac deterioration and heart failure symptoms using standard tools such as the NYHA questionnaire and echocardiography.

Detected rhythm abnormalities/events during follow-up will be documented and analysed as part of disease progression. This will be assessed using standard 12-lead ECG and 24-hour Holter ECG.

Any hospitalisation due to a cardiac cause will be assessed and recorded throughout the study, and this will be evaluated at the scheduled clinical visits.