Transthyretin amyloid cardiomyopathy: An uncharted territory awaiting discovery

Porcari, Aldostefano; Merlo, Marco; Rapezzi, Claudio; Sinagra, Gianfranco

doi:10.1016/j.ejim.2020.09.025

Cited by 45 publications

(62 citation statements)

References 47 publications

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“…Patients in this analysis had severe CA; hence, making the correct diagnosis at their last evaluation before death would not have changed their natural history. However, these findings reflect the ominous natural history of untreated CA patients diagnosed in advanced stages of the disease (31). Therefore, there is an urgent need to promote awareness of the disease among physicians of several specialties since many patients with post-mortem evidence of CA could have been considered at suspicion of CA or even diagnosed non-invasively during their lives.…”

Section: Need Of Systematic Evaluation Of Red Flags Of Ca For An Early Diagnosismentioning

confidence: 99%

Incidence and Characterization of Concealed Cardiac Amyloidosis Among Unselected Elderly Patients Undergoing Post-mortem Examination

Porcari

Bussani

Merlo

et al. 2021

Front. Cardiovasc. Med.

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Background: The prevalence of cardiac amyloidosis (CA) is unknown.Aims and Methods: We sought to (a) determine the prevalence of CA in unselected patients ≥75 years undergoing autopsy, (b) characterize cardiological profiles of CA and non-CA patients by providing clinical-histological correlations, and (c) compare their cardiological profiles. After dedicated staining, the localization (interstitial or vascular) and the distribution (non-diffuse or diffuse) of amyloid deposition were analyzed. Cardiological data at last evaluation were retrospectively assessed for the presence of CA red-flags.Results: CA (50% light chains, 50% transthyretin) was found in 43% (n = 24/56) of the autopsied hearts. Atria were involved in 96% of cases. Amyloid localized both at the perivascular and interstitial levels (95.5 and 85%, respectively) with a slightly predominant non-diffuse distribution (58% of cases). Compared to the other patients, CA patients had a more frequent history of heart failure (HF) (79 vs. 47%, p = 0.014), advanced NYHA functional class (III-IV 25 vs. 6%, p = 0.047), atrial fibrillation (68 vs. 36%, p = 0.019), discrepancy between QRS voltage and left ventricular (LV) thickness (70 vs. 12%, p < 0.001), thicker LV walls (15 vs. 11 mm, p < 0.001), enlarged left atrium (49 vs. 42 mm, p = 0.019) and restrictive filling pattern (56 vs. 19%, p = 0.020). The presence of right ventricular amyloidosis seemed to identify hearts with a higher amyloid burden. Among the CA patients, >30% had ≥3 echocardiographic red-flags of disease.Conclusion: CA can be found in 43% of autopsied hearts from patients ≥75 years old, especially in patients with HF, LV hypertrophy and atrial fibrillation.

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Section: Need Of Systematic Evaluation Of Red Flags Of Ca For An Early Diagnosismentioning

confidence: 99%

Incidence and Characterization of Concealed Cardiac Amyloidosis Among Unselected Elderly Patients Undergoing Post-mortem Examination

Porcari

Bussani

Merlo

et al. 2021

Front. Cardiovasc. Med.

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“…The non-heritable, or wild-type, form (ATTRwt-CM) typically presents after the 6th decade of life with the average foundational age being approximately 75 years and is much more pervasive and globally ubiquitous [ 9 ]. Long thought to be an uncommon disorder, emerging findings purport that ATTR-CM, particularly the wild-type variety, will become the dominant diagnosed form of cardiomyopathy resulting from amyloidosis with a variable yet ever-increasing estimated global prevalence [ 11 , 13 ]. Despite the etiological differences in ATTR presentation, all forms of transthyretin amyloidoses (wild type—ATTRwt-CM and hereditary/mutant ATTRm-CM or ATTR-PN) lead to reduced functionality (effort tolerance and activities of daily living) and premature death [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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

Rintell

Heath

Mendendez³

et al. 2021

Orphanet J Rare Dis

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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.

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“…However, some cases have been reported in patients younger than 65 years of age. 1 , 3 We describe a 62-year-old African-American male who was screened with genetic testing for ATTRm. This helped confirm a diagnosis of ATTR-CM after being followed for several years due to arrhythmias.…”

Section: Introductionmentioning

confidence: 99%

A Case of Early Hereditary Transthyretin Amyloid Cardiomyopathy Recognition With Genetic Screening: A Case Report

Juarez¹,

Rio‐Pertuz

Parmar

et al. 2022

J Prim Care Community Health

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Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is one of the most common types of cardiac amyloidosis. Amyloid cardiomyopathy more commonly affects men, elderly, and 3% to 4% of the African-American population. ATTR-CM suspicion and diagnosis is challenging; however, awareness of the disease is increasing, and best practices to identify it are being proposed. The approach to suspected cases of ATTR-CM relies on the presence of heart failure, red flag signs and symptoms, and age >65 or >70 for men and women respectively. Little is known about cases when it presents in early ages. Case: We report a 62-year-old African American male with past medical history of hyperlipidemia, prostate cancer, hypertension, bilateral carpal tunnel surgery that had debuted with a cardiac arrhythmia at age 55 and was diagnosed with heart failure several years later. Restrictive cardiomyopathy was suspected, and genetic screening was sent for ATTRm which confirmed a pathogenic trasnthyretin gene mutation. Endomyocardial biopsy was performed which confirmed cardiac amyloid deposition. Discussion: ATTR-CM is a rare disease with an increasing prevalence. Cases with out of proportion signs and symptoms of heart failure with preserved ejection fractions should raise the suspicion of ATTR-CM despite age.

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Transthyretin amyloid cardiomyopathy: An uncharted territory awaiting discovery

Cited by 45 publications

References 47 publications

Incidence and Characterization of Concealed Cardiac Amyloidosis Among Unselected Elderly Patients Undergoing Post-mortem Examination

Incidence and Characterization of Concealed Cardiac Amyloidosis Among Unselected Elderly Patients Undergoing Post-mortem Examination

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

A Case of Early Hereditary Transthyretin Amyloid Cardiomyopathy Recognition With Genetic Screening: A Case Report

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