The aim of this study is to investigate the association between increased lifetime physical activity and the development of wild-type transthyretin amyloid cardiomyopathy.

Transthyretin amyloidosis is considered to be the most common cause of cardiac amyloidosis, with an increasing diagnosis rate over the last decade. Though once considered to be a rare disease, recent data suggest it is underappreciated as a common cause of cardiac diseases and syndromes such as left ventricular hypertrophy, aortic stenosis, and heart failure with preserved ejection fraction, especially in the elderly. Wild-type transthyretin amyloidosis, which is associated with ageing, is currently considered to be the most frequent form of amyloidosis worldwide, and is dominated by cardiac symptoms. Other than male gender and advanced age, risk factors for the development of wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) are largely unknown. There is rising empirical observation that patients with wtATTR-CM frequently have a substantial history of athletic activity, which might contribute to the manifestation of the disease.

This study aims to create evidence of a correlation between increased lifetime physical activity and the development of wtATTR-CM. Furthermore, the investigators aim to explore the association between certain sport disciplines and disease development.

Inclusion Criteria:

1. Confirmed diagnosis of wtATTR-CM including sequencing of the TTR gene; or HF; or healthy proband without a diagnosis of heart disease*
2. Initial diagnosis of respective cardiac disease (wtATTR-CM, HF) after the 6th decade of life; or no cardiac disease (healthy control)
3. Willingness and ability to provide signed informed consent form (ICF)
4. Age > 60 years

Exclusion Criteria:

1. History of severe chronic illness limiting the ability to perform physical activity during the 3rd to 6th decade

2. A diagnosis of dementia or cognitive impairment

3. Any other reason resulting in the inability to perform the questionnaire and/or interview

4. Known disease-causing variant (pathogenic or likely-pathogenic) in the TTR gene

   • defined as an individual without one of the following diagnoses:

     • Cardiomyopathy of any origin, defined as a myocardial disorder with structural and functional abnormalities in the absence of coronary artery disease, hypertension, valvular disease, and congenital heart disease sufficient to cause the observed myocardial abnormality; or
     • Heart failure regardless of aetiology, defined as presence of distinct cardinal symptoms (e.g. breathlessness, ankle swelling, fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, peripheral oedema), due to a structural and/or functional abnormality of the heart, regardless of systolic function or aetiology; or
     • Clinically significant coronary artery disease, defined as 1) a history of coronary intervention; or 2) inducible myocardial ischemia and ischaemic chest pain (angina pectoris) due to flow-limiting stenoses, diffuse atherosclerotic lesions, structural abnormalities, congenital anomalies, dynamic epicardial vasospasm; or
     • Clinically significant valvular heart disease, defined as 1) a history of valvular surgery or intervention; or 2) moderate or severe stenosis or regurgitation; or
     • Hypertrophic phenotype defined as enddiastolic maximal wall thickness ≥ 15mm; or
     • History of arrhythmias or significant conduction disease, defined as ventricular brady- or tachyarrhythmias, atrial flutter or atrial fibrillation, sick sinus syndrome, or atrioventricular block greater than 1st degree block; or
     • History of sudden cardiac arrest, defined as sudden cessation of normal cardiac activity with haemodynamic collapse

Number of participants: 180 The study population will comprise three subgroups (n=60 in each group)

1. cardiac wild type transthyretin amyloidosis (wtATTR-CM);
2. heart failure (HF);
3. healthy individuals without heart disease