Care of Patients With Transthyretin Amyloidosis: the Roles of Nutrition, Supplements, Exercise, and Mental Health

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Transthyretin (ATTR) amyloidosis is a debilitating disease that results in organ failure and eventual death. As the disease progresses, patients experience neurologic, gastrointestinal, and cardiovascular symptoms that increasingly compromise their nutritional status and exercise capacity. These symptoms cause considerable emotional stress and mental health challenges for patients and caregivers. This review summarizes common symptoms and mechanisms associated with malnutrition and exercise intolerance, and sources of emotional stress, and offers therapeutic strategies to address these issues. Although earlier diagnosis and disease-specific treatment are central to caring for patients with ATTR amyloidosis, additional attention to symptom-focused treatments to improve nutritional status, maintain exercise tolerance and capacity, and improve and maintain mental health are also important. In conclusion, a team-based approach involving multiple clinicians and providers can offer more comprehensive and coordinated care, support, and education for patients and caregivers.

Introduction

Amyloidosis is characterized by the extracellular presence of misfolded protein deposits, known as amyloid, in organs and tissue.1 These deposits interfere with normal tissue structure and function, causing organ failure and eventual death. To date, 36 proteins have been identified as being amyloidogenic in humans.2 Amyloid deposits may be localized or systemic and clinical manifestations can vary. Although certain phenotypes may typically be associated with certain amyloid types, considerable clinical overlap exists. The amyloidosis types associated with cardiomyopathy are shown in Table 1.3

Transthyretin (ATTR) amyloidosis results from the deposition of misfolded transthyretin (TTR), a protein that is produced mainly by the liver.4 Transthyretin amyloidosis can either be an inherited condition (hATTR) or result from age-related protein misfolding of normal TTR (wild-type ATTR), and may result in progressive neuropathy and cardiomyopathy.5 Many patients with ATTR polyneuropathy (ATTR-PN) commonly experience neuropathic pain and autonomic symptoms such as gastrointestinal (GI) symptoms, urinary and erectile dysfunction, and orthostatic hypotension.6 As the disease progresses, patients may experience motor involvement and loss of ambulation.7 Transthyretin cardiomyopathy (ATTR-CM) presents with typical heart failure (HF) symptoms including exertional dyspnea, peripheral edema, and fatigue.5,8 These debilitating physical symptoms can progressively compromise patients’ nutritional status and exercise capacity. In addition, as activities of daily living become affected, patients and caregivers often experience considerable emotional stress and mental health challenges.9 The present review summarizes common symptoms and mechanisms associated with malnutrition and exercise intolerance, and sources of emotional stress, and considers therapeutic strategies, including the use of supplements, to address these issues.

Section snippets

Gastrointestinal Involvement and Nutritional Status

Autonomic nervous system damage related to ATTR amyloidosis can result in abnormalities in both GI motility and secretory function.10,11 Impaired gastric emptying is the source of a large spectrum of debilitating symptoms including early satiety, postprandial fullness, nausea, vomiting, bloating, and weight loss.12,13 Abnormal bowel function can lead to constipation, diarrhea, abdominal pain, and fecal incontinence.14 In a global, multicenter, longitudinal survey of 1739 patients with ATTR

Challenges of Exercise

Patients with ATTR amyloidosis often experience exercise intolerance because of multiple pathophysiologic mechanisms.8 During exercise, patients with normal physiology can augment their cardiac output and increase their stroke volume. Generally during exercise, blood pressure and heart rate increase in healthy people. In contrast, patients with heart disease, including those with cardiac involvement caused by amyloidosis, have a diminished ability to increase their stroke volume and cardiac

Sources of Mental Health Challenges for Patients and Their Families

Transthyretin amyloidosis can impose significant mental health burdens on both patients and caregivers. Delays in diagnosis and treatment can be very stressful. Studies have found median diagnostic delays of 34 to 41 months for ATTR amyloidosis.59,60 In a survey of patients with ATTR amyloidosis, the diagnosis was made within 6 months in only 35% of patients with hATTR and 46% with wild-type ATTR.61 In focus groups, patients with ATTR described frustrating and arduous diagnostic journeys in

Conclusions

In addition to earlier diagnosis and disease-specific treatment, clinicians treating patients with ATTR amyloidosis should also focus on supportive treatments and interventions specifically designed to improve nutritional status, maintain exercise tolerance and capacity, and improve and maintain mental health. A team-based approach involving multiple clinicians and providers can offer more comprehensive and coordinated care, support, and education for patients and caregivers.

Disclosures

Dr. Dasgupta has consulted for Alnylum, Eidos, and Intellia.

Acknowledgment

Medical writing and editing assistance was provided by Annie Steffenson and Geoff Marx of BioScience Communications, New York, New York, funded by Eidos.

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  • This article was funded by Eidos Therapeutics, Inc., San Francisco, California. The International Congress on ATTR Amyloidosis was supported by Eidos, and developed and produced in coordination with MedscapeLIVE!

    This article is published as part of a supplement supported by Eidos.

    This article is based on a presentation given at the 1st Annual International Congress on ATTR Amyloidosis on October 16, 2021.

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