Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups

Abstract

Background Transthyretin amyloidosis, or ATTR, is a progressive and debilitating rare proteopathy generally manifested as either transthyretin amyloid polyneuropathy (ATTR-PN) or transthyretin amyloid cardiomyopathy (ATTR-CM). Irrespective of the clinical presentation, affected patients manage a chronic and life-threatening condition that severely impacts their quality of life. Although the primary symptoms and diagnostic criteria for ATTR are increasingly being discussed in the medical literature, due in large part by continual advances in uncovering disease pathophysiology, there exists a surprising paucity of published data on the patient journey and family experience. In order to address this disparity, two focus groups, one for ATTR-CM and one for ATTR-PN, were convened and asked to describe the diagnostic process, symptoms, and impact on their own quality of life that was experienced from these rare and typically misdiagnosed illnesses. Results Patients in both ATTR groups often underwent a long and difficult diagnostic odyssey characterized by seemingly nonspecific physical manifestations resulting in mismanagement and suboptimal care, inadequate interventions, and delays in establishing the correct diagnosis, which was integral to determining the specialized treatment they needed. Collectively, patients with ATTR-CM and patients with ATTR-PN reported a similar number of symptoms, but the type of symptoms varied. The ATTR-CM group identified intolerance to activity, inability to exercise, insomnia and fatigue as the most challenging symptoms. The ATTR-PN group identified fatigue, diarrhea/constipation and sensory deficits as the most difficult symptoms. In general, ATTR was reported to be highly stressful for both patients and their families. Spouses of patients with ATTR-CM were often in a caregiver role and reported experiencing considerable anxiety. Patients with ATTR-PN were stressed not only by the physical consequences of their illness, but also by its effects on their parents and other relatives, as well as concerns about children and grandchildren inheriting the disease-causing mutations associated with ATTR. Despite such challenges, family members are identified as an important resource of coping, motivation, inspiration and support. Conclusions Several steps can be taken to reduce the challenges and burdens of living with ATTR, including increased education for primary care physicians and specialists who unknowingly encounter ATTR, increased access to and ready availability of mental health services and support, and increased engagement with support groups and advocacy organizations. Input from patients and their representatives should guide clinical trials, increase the availability of genetic testing, and generate natural history and qualitative studies detailing patients’ experience. Although each recommendation is impactful in itself, taken together they would jointly facilitate a shortened and ameliorated patient journey through more timely diagnosis and greater access to personalized medical care.

Healthcare resource use of patients with transthyretin amyloid cardiomyopathy

“…ATTR-CM is often diagnosed late due to low awareness, or vague initial symptoms that affect several organs mimicking more common comorbidities. [1][2][3][4] It typically presents as heart failure with preserved ejection fraction, representing one of the few cases of heart failure with preserved ejection fraction where a disease-modifying treatment is now available. 5 Diagnostic delay and misdiagnosis is common 6 and contributes to low median survival, which has been estimated to be as short as 2.5-3.6 years depending on disease stage at diagnosis and to be half of that in other HF patients.…”

“…Transthyretin amyloid cardiomyopathy (ATTR‐CM) is the cardiac manifestation of transthyretin amyloidosis (ATTR), a disease characterized by tissue deposition of transthyretin fibrils that may affect several organs. ATTR‐CM is often diagnosed late due to low awareness, or vague initial symptoms that affect several organs mimicking more common comorbidities 1–4 . It typically presents as heart failure with preserved ejection fraction, representing one of the few cases of heart failure with preserved ejection fraction where a disease‐modifying treatment is now available 5 .…”

Clinical manifestation, economic burden, and mortality in patients with transthyretin cardiac amyloidosis

“…Transthyretin amyloidosis (ATTR) is caused by the deposition of the misfolded tetrameric protein transthyretin in the peripheral nerves and organs [ 1 ]. The signs and symptoms are not specific, and the condition can be insidious as the deposition can occur in any part of the body [ 2 ]. The most prevalent areas for deposition are the heart tissues, which cause ATTR-cardiomyopathy (CM), and the peripheral nerves, resulting in ATTR-polyneuropathy (PN) [ 2 ].…”

“…The signs and symptoms are not specific, and the condition can be insidious as the deposition can occur in any part of the body [ 2 ]. The most prevalent areas for deposition are the heart tissues, which cause ATTR-cardiomyopathy (CM), and the peripheral nerves, resulting in ATTR-polyneuropathy (PN) [ 2 ]. ATTR-CM is fatal and poorly recognized; it is a late-onset disease with cardiac symptoms generally occurring in patients over 60 years old [ 1 , 3 ].…”

Genomic Screening for Pathogenic Transthyretin Variants Finds Evidence of Underdiagnosed Amyloid Cardiomyopathy From Health Records

“…Most commonly, hATTR clinically manifests as polyneuropathy and/or cardiomyopathy, with an estimated prevalence of 1:100,000 in the United States ( 3 ). However, this prevalence is likely underestimated due to the challenges of diagnosing patients with hATTR-associated cardiomyopathy and polyneuropathy ( 4 ).…”