The purpose of this study is to:

* Describe epidemiological and clinical characteristics, natural history and real-world clinical management of ATTR amyloidosis patients
* Characterize the safety and effectiveness of patisiran and vutrisiran as part of routine clinical practice in the real-world clinical setting
* Describe disease emergence/progression in pre-symptomatic carriers of a known disease-causing transthyretin (TTR) variant

The study will enroll subjects with systemic amyloidosis who have participated in AT02-001 study.

The study includes screening period (56 days), treatment period (week 104), follow up (week 112).

The total duration of participant in study is up to 120 weeks.

A Safety Review Committee (SRC) will periodically convene and review all available clinical and laboratory data during the study. A single SRC will monitor safety across all AT-02 studies to ensure that safety signals are assessed in aggregate.

This is a Phase 2 open-label extension study to evaluate the long-term safety, tolerability, and clinical activity of AT-02.

AT-02 is an investigational medicinal product being developed to treat systemic amyloidosis.

Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease.

This is a multicenter trial of 80 subjects enrolled in the CARDIO-TTRansform randomized clinical trial (NCT04136171) who will undergo baseline and follow up Tc-99m PYP to assess for the change in myocardial uptake of the tracer.

The investigators will evaluate the change in myocardial uptake of 99m-technetium pyrophosphate (Tc-99m PYP) tracer on serial planar and SPECT imaging in patients enrolled in the CARDIO-TTRansform clinical trial (NCT04136171).

A. Primary Aim

To determine the safety and efficacy of tafamidis in patients who have undergone heart or combined heart/liver transplantation for ATTR (wild-type or variant) cardiac amyloidosis.

Primary Hypothesis. Initiation of the TTR stabilizer, tafamidis, post heart or heart/liver transplant for ATTR cardiac amyloidosis, (wild-type or variant disease) will be associated with an increase in plasma transthyretin levels during 12 months of therapy.

B. Secondary Aims

Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival.

The objective of the study is to characterize adverse events (AEs) occurring within one day of TEGSEDI administration to adult patients with hATTR-PN overall and in individual patients with respect to time course of AE onset, vital sign changes, preventive measures, treatment required, risk factors, and subsequent adverse outcomes.

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD)/ the recommended phase 2 dose (RP2D) of venetoclax (VEN) with or without daratumumab subcutaneous (DARA SC) and dexamethasone (DEX), in previously treated light chain (AL) amyloidosis (PTAL) participants with t(11;14). (Phase I).

II. To evaluate the efficacy of the combination VEN/DARA SC and DEX as measured by Complete Hematologic Response (CHR rate) in PTAL participants with t(11;14). (Phase II)

SECONDARY OBJECTIVES:

This phase I/II trial tests the safety, side effects, and best dose of venetoclax, daratumumab, and dexamethasone for the treatment of systemic light-chain amyloidosis in patients with a deoxyribonucleic acid (DNA) abnormality called a translocation involving chromosomes 11 and 14, or "t(11;14)". Venetoclax works by attaching to a protein called Bcl-2, in order to kill cancer cells. Daratumumab works by binding to a target on the surface of cancer cells called Cluster of differentiation 38 (CD38).

\[68Ga\]CBP8 is a novel gallium-68 labeled positron emission tomography (PET) probe that selectively binds collagen type I, which constitutes the majority of fibrotic tissue. In pre-clinical mouse models, \[68Ga\]CBP8 had the sensitivity to detect pulmonary fibrosis even at early stages and specificity for collagen uptake with low non-specific uptake in background tissues and organs.

The primary aim of our pilot study is to determine whether fibrosis in the heart can be measured with \[68Ga\]CBP8, a positron emission tomography (PET) probe, using PET/magnetic resonance imaging (MRI) imaging, in 30 individuals with documented cardiac amyloidosis. The investigators will also enroll 15 individuals with recent myocardial infarction and 15 individuals with hypertrophic cardiomyopathy as positive controls for fibrosis, and the investigators will enroll 5 individuals without cardiovascular disease to undergo \[68Ga\]CBP8 PET/MRI imaging as a healthy control group.

The goal of this project is to perform a proof-of-concept study to compare the ability of quantitative parametric cardiac 18F-flutemetamol positron emission tomography (PET) to assess baseline and change in disease burden after six months of therapy with tafamidis treatment in 12 patients diagnosed with transthyretin cardiac amyloidosis (ATTR-CA) at Yale-New Haven Hospital.

18F-Flutemetamol (Vizamyl) is a radioactive diagnostic agent indicated and FDA-approved for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. This study is designed to evaluate a novel use for 18F-Flutemetamol in cardiac amyloidosis.

This is a prospective study enrolling patients referred for or undergoing cardiac amyloidosis or cardiovascular treatment at the University of Kentucky. The study aims to facilitate the discovery of novel diagnostic biomarkers and therapeutic targets and improve the pathophysiological understanding of cardiac amyloidosis.

Use samples procured from patients to improve understanding of molecular, cellular, and tissue-level processes produced by cardiac amyloidosis and therapeutic interventions.