Phenotyping and Characterization of wtATTR-CM (TRACE 1)

Phenotyping and Characterization of Danish Wild-type Transthyretin Amyloidosis Cardiomyopathy Patients: A Cross-sectional Study

Descriptive cross-sectional study on 100 consecutive ATTRwt-CM patients reflecting all NAC stages aiming primarily to investigate ATTRwt-CM patient's quality of life (QoL) measures and their relation to ATTRwt-CM severity. Secondarily aiming to investigate the possibility to measure misTTR and fragTTR in plasma and urine and to detect fragTTR in endomyocardial biopsies from ATTRwt-CM patients. To investigate whether misTTR and fragTTR levels are correlated with ATTRwt-CM severity.

Hypothesis:

1. We hypothesize that more severe wild-type amyloidosis cardiomyopathy (ATTRwt-CM) according to clinical, biochemical, and diagnostic imaging parameters are correlated with worse quality of life (QoL) for patients.
2. We expect misfolded (misTTR) and/or fragmented transthyretin (fragTTR) to be measurable in plasma and/or urine and fragTTR to be detectable in endomyocardial biopsies from patients with ATTRwt-CM. We expect the values of misTTR and fragTTR to be correlated with the severity of ATTRwt-CM according to clinical, biochemical, and diagnostic imaging parameters. We expect the level of fragTTR from endomyocardial biopsies to be correlated with plasma levels of fragTTR.

Method:

ATTRwt-CM patients: Prospective inclusion of 100 consecutive ATTRwt-CM patients reflecting all NAC stages (40 patients from NAC disease stage 1, 40 patients from NAC disease stage II and 20 patients from NAC disease stage III). Patients will be recruited from the out-patient amyloidosis clinic at Aarhus University hospital. Patients will be thoroughly clinically assessed.

Control patients:

A control cohort of 20 age- and gender-matched heart-healthy patients will be included for comparison of total/mis-/fragTTR values.

The investigating into QoL, bio markers and the analyses on cardiac MR imaging markers will hopefully provide us with tools to evaluate and monitor disease progression and response to treatment.

Group 1: wtATTR-CM patients

Inclusion Criteria:

• Patients > 18 years diagnosed with ATTRwt-CM by:
• endomyocardial biopsy
• DPD scintigraphy with Perugini grade 2-3 where variant amyloidosis is ruled out due to genetic testing.
• Informed oral and written consent

Exclusion Criteria:

• AL amyloidosis (light-chain amyloidosis).
• Myelomatosis
• Waldenström macroglobulinemia

Group 2: Control group

Inclusion Criteria:

• Patients > 18 years
• Informed oral and written consent

Exclusion Criteria:

• Known cardiovascular disease including ischemic heart disease, heart failure, atrial fibrillation, presence of a pacemaker, or malignant hypertension. Well-controlled hypertension is acceptable.
• Suspicion of cardiac amyloidosis assessed through clinical history, physical examination, ECG, and echocardiography focusing on "red flags":
• Echocardiography with:
• Myocardial hypertrophy (septum >11 mm)
• Apical sparing in LV-GLS
• Infiltrative changes in the right ventricle free wall, thickened atrioventricular valves, or thickened atrial septum
• Symptoms of polyneuropathy
• Low voltage on ECG or discrepancy between left ventricular thickness and ECG amplitude indicative of low voltage
• Atrioventricular block (AV block)
• Bilateral carpal tunnel syndrome
• Surgery for spinal stenosis
• Elevated troponin I or NT-pro-BNP