Determinants and Monitoring of Response to Disease-Modifying Therapy for Transthyretin Amyloidosis Cardiomyopathy: The ATTR-CM Therapy Study
Date
2024-01-24
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Abstract
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a heart muscle disease characterized by the accumulation of misfolded transthyretin proteins as amyloid plaques in the myocardial interstitium. In 2020, tafamidis, a medication inhibiting the misfolding of transthyretin, received Health Canada's approval for treating ATTR-CM. However, substantial knowledge gaps persist in delivering optimal care and understanding predictors of response to tafamidis therapy. Over the past few years, there have been significant advancements in the clinical care of ATTR-CM. Improved diagnostic and staging techniques have resulted in higher rates of diagnosis, even among older patients not previously considered for invasive evaluation. Notably, tafamidis is the most expensive cardiovascular medication approved, with a list price of approximately $200,000 per patient per year. While Health Canada has defined criteria for initiating tafamidis, these are directly based on enrolment criteria for the international ATTR-ACT trial and may not fully reflect the current ATTR-CM patient population in the community. This project aimed to determine baseline predictors of adverse events in ATTR-CM patients treated with disease-modifying therapy, providing insights into determinants of prognosis and how markers of disease burden are serially impacted by treatment. The study's findings contribute to the development of evidence-based recommendations for guiding ATTR-CM disease monitoring and establish goals of therapy. These recommendations, rooted in evidence, seek to optimize patient care by offering a structured framework for monitoring ATTR-CM. Conducted as a retrospective cohort study, this research included 145 ATTR-CM patients followed by the Cardiac Amyloidosis Clinic, at the Libin Cardiovascular Institute (UofC). The results presented in this thesis contribute to an evidence-based approach for determining and monitoring the response to tafamidis therapy in ATTR-CM patients. The study reveals multiple parameters across clinical, biochemical, and cardiac imaging domains as predictors of major adverse outcomes (all-cause mortality, cardiovascular mortality and hospitalization). Tafamidis proves effective in attenuating disease progression, and specific baseline parameters can be used to assess variations in treatment. Importantly, initiating treatment during the early stages of the disease is pivotal, underscoring the critical role of early diagnosis. This conclusion emphasizes the imperative nature of timely intervention and ongoing observation in managing patients with ATTR-CM.
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Keywords
ATTR-CM, Amyloidosis, Heart Failure, Cardiology, Cardiomyopathy, Transthyretin Amyloidosis
Citation
Shahi, K. (2024). Determinants and monitoring of response to disease-modifying therapy for transthyretin amyloidosis cardiomyopathy: the ATTR-CM therapy study (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.