Care of Patients With Transthyretin Amyloidosis: the Roles of Nutrition, Supplements, Exercise, and Mental Health
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.
References (70)
- et al.
Diagnosis, prognosis, and therapy of transthyretin amyloidosis
J Am Coll Cardiol
(2015) - et al.
Exercise intolerance in patients with heart failure: JACC State-of-the-Art Review
J Am Coll Cardiol
(2019) - et al.
Parenteral nutrition improves nutritional status, autonomic symptoms and quality of life in transthyretin amyloid polyneuropathy
Neuromuscul Disord
(2016) - et al.
Natural product-based amyloid inhibitors
Biochem Pharmacol
(2017) - et al.
Novel pharmacotherapies for cardiac amyloidosis
Pharmacol Ther
(2017) - et al.
Anti-apoptotic treatment reduces transthyretin deposition in a transgenic mouse model of familial amyloidotic polyneuropathy
Biochim Biophys Acta
(2008) - et al.
Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction
JACC Heart Fail
(2014) - et al.
Symptomatic conduction system disease in cardiac amyloidosis
Am J Cardiol
(1997) - et al.
Screening for transthyretin amyloid cardiomyopathy in everyday practice
JACC Heart Fail
(2019) - et al.
Systemic amyloidoses
Annu Rev Biochem
(2013)
The pathology of amyloidosis in classification: a review
Acta Haematol
Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases
Eur J Heart Fail
Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs
Heart Fail Rev
Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy
J Neurol
Burden of hereditary transthyretin amyloidosis on quality of life
Muscle Nerve
Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups
Orphanet J Rare Dis
Abnormal small bowel motility in patients with hereditary transthyretin amyloidosis
Neurogastroenterol Motil
Systemic amyloidosis and the gastrointestinal tract
Nat Rev Gastroenterol Hepatol
Diagnosis and treatment of gastrointestinal dysfunction in hereditary TTR amyloidosis
Clin Auton Res
Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy
Neurogastroenterol Motil
Familial amyloidosis with polyneuropathy. A long-term follow-up of 21 patients with special reference to gastrointestinal symptoms
Acta Med Scand
THAOS investigators. THAOS: gastrointestinal manifestations of transthyretin amyloidosis - common complications of a rare disease
Orphanet J Rare Dis
Markers of nutritional status and inflammation in transthyretin cardiac amyloidosis: association with outcomes and the clinical phenotype
Amyloid
Malnutrition and gastrointestinal dysfunction as prognostic factors for survival in familial amyloidotic polyneuropathy
J Intern Med
Clinical measures in transthyretin familial amyloid polyneuropathy
Muscle Nerve
Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy
J Neurol
Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis
N Engl J Med
Inotersen treatment for patients with hereditary transthyretin amyloidosis
N Engl J Med
Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy
N Engl J Med
Emerging advances in the management of cardiac amyloidosis
Curr Cardiol Rep
Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial
Amyloid
Post hoc analysis of nutritional status in patients with transthyretin familial amyloid polyneuropathy: impact of tafamidis
Neurol Ther
Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome
Postgrad Med
Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies
N Engl J Med
Medical management of constipation
Clin Colon Rectal Surg
Cited by (1)
The Relationship Between Sports And Mental Health: Literature Analysis And Empirical Study
2023, Health Education and Health Promotion
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.