Transthyretin cardiac amyloidosis

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure (HF) and mortality worldwide. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have shifted ATTR-CA from a rare and untreatable disease to a relatively prevalent condition that clinicians should consider on a daily basis. Amyloid fibril formation results from age-related failure of homoeostatic mechanisms in wild-type ATTR (ATTRwt) amyloidosis (non-hereditary form) or destabilizing mutations in variant ATTR (ATTRv) amyloidosis (hereditary form). Longitudinal large-scale studies in the United States suggest an incidence of cardiac amyloidosis in the contemporary era of 17 per 100 000, which has increased from a previous estimate of 0.5 per 100 000, which was almost certainly due to misdiagnosis and underestimated. The presence and degree of cardiac involvement is the leading cause of mortality both in ATTRwt and ATTRv amyloidosis, and can be identified in up to 15% of patients hospitalized for HF with preserved ejection fraction. Associated features, such as carpal tunnel syndrome, can preceed by several years the development of symptomatic HF and may serve as early disease markers. Echocardiography and cardiac magnetic resonance raise suspicion of disease and might offer markers of treatment response at a myocardial level, such as extracellular volume quantification. Radionuclide scintigraphy with ‘bone’ tracers coupled with biochemical tests may differentiate ATTR from light chain amyloidosis. Therapies able to slow or halt ATTR-CA progression and increase survival are now available. In this evolving scenario, early disease recognition is paramount to derive the greatest benefit from treatment.

Prevalence, characteristics and outcomes of older patients with hereditary versus wild‐type transthyretin amyloid cardiomyopathy

“…Therefore, other factors rather than a direct protective effect of TTR mutations against ischaemia may have affected the association between IHD and ATTRwt‐CM. Finally, AF is the most common arrhythmias in ATTR‐CM and its incidence is known to increase with aging, providing an explanation for the association with ATTRwt‐CM in this cohort 13 . The aforementioned independent predictors of ATTRv‐CM were further confirmed in an analysis in which patients with Afro‐Caribbean ancestries were excluded.…”

“…26 However, underdiagnosis of ATTRwt-CM in females is highly likely to be a significant contributor since current criteria to define cardiac hypertrophy (i.e. interventricular thickness >12 mm), 13 the usual reason for suspecting cardiac amyloidosis in the first place, do not take gender into account. Studies to establish the true prevalence of ATTR-CM, particularly ATTRwt-CM, among females are urgently required.…”

Evolving trends in epidemiology and natural history of cardiac amyloidosis: 30-year experience from a tertiary referral center for cardiomyopathies

“…The major findings of the present study are that (a) the number of patients diagnosed with CA progressively increased over time, mostly related to ATTR-CA; (b) CA patients from the contemporary cohort presented with less symptomatic HF compared to those from the historical cohort; (c) although an early increase in the event-rate was found in AL-CA, long-term survival rates among ATTR-CA and AL-CA were similar in the historical cohort, while, in the contemporary cohort, ATTR-CA was associated with reduced all-cause mortality and cardiac mortality compared to AL-CA; and, (d) in the contemporary cohort, ATTR-CA, higher eGFR and therapy with ACE-inhibitors were associated with a more favorable global and cardiovascular outcome. Rather than a change in natural history of the disease, we believe that the observed increase in incidence and prevalence of CA is likely related to a number of factors including (1) heightened awareness of disease, (2) recognition of clinical and instrumental red-flags and subgroups of patients at higher risk of CA, and (3) development of non-invasive criteria for the diagnosis and specific treatments ( 25 , 26 ).…”

“…In this study, the type of amyloidosis (AL vs. ATTR amyloidosis), renal function and tolerability of ACE-inhibitor therapy were associated with a better global and cardiac outcome in the contemporary cohort ( Table 2 ). The prognostic role of renal function has been largely investigated and this parameter is included in validated prognostic scores ( 26 , 33 ).…”

Amyloid deposition at the carotid artery in an ATTRwt amyloidosis patient: a case report

“…ATTR amyloidosis can be either an age-related amyloid formation from misfolded wild-type TTR (ATTRwt) or by hereditary TTR malfunction due to mutation in the TTR gene (ATTRv) [ 3 ]. Although ATTRwt amyloidosis can cause various diseases, such as cardiac failure, conduction disturbances, arrhythmias and carpal tunnel syndrome, it is still under-recognised, considering its clinical significance with increasing prevalence in the aged population [ 4 ]. Here the authors report a case of ATTRwt amyloidosis leading to carotid stenosis requiring surgical intervention.…”