Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM), this study aimed to determine whether there is a differential effect between variant transthyretin amyloidosis ...(ATTRv) and wild-type transthyretin (ATTRwt).
ATTR-CM is a progressive, fatal disorder resulting from mutations in the ATTRv or the deposition of denatured ATTRwt.
In pre-specified analyses from ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), baseline characteristics, all-cause mortality, and change from baseline to month 30 in 6-min walk test distance and Kansas City Cardiomyopathy Questionnaire Overall Summary score were compared in patients with ATTRwt and ATTRv.
There were 335 patients with ATTRwt (201 tafamidis, 134 placebo) and 106 with ATTRv (63 tafamidis, 43 placebo) enrolled in ATTR-ACT. Patients with ATTRwt (vs. ATTRv) had less advanced disease at baseline and a lower rate of disease progression over the study. The reduction in all-cause mortality with tafamidis compared with placebo was not different between ATTRwt (hazard ratio: 0.706 95% confidence interval (CI): 0.474 to 1.052; p = 0.0875) and ATTRv (hazard ratio: 0.690 95% CI: 0.408 to 1.167; p = 0.1667). Tafamidis was associated with a similar reduction (vs. placebo) in the decline in 6-min walk test distance in ATTRwt (mean ± SE difference from placebo, 77.14 ± 10.78; p < 0.0001) and ATTRv (79.61 ± 29.83 m; p = 0.008); and Kansas City Cardiomyopathy Questionnaire Overall Summary score in ATTRwt (12.72 ± 2.10; p < 0.0001) and ATTRv (18.18 ± 7.75; p = 0.019).
Pre-specified analyses from ATTR-ACT confirm the poor prognosis of untreated ATTRv-related cardiomyopathy compared with ATTRwt, but show the reduction in mortality and functional decline with tafamidis treatment is similar in both disease subtypes. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy ATTR-ACT; NCT01994889).
Cardiac amyloidosis (CA) is a complex disease considered to be the most common underdiagnosed form of restrictive cardiomyopathy. Accumulation of misfolded proteins called amyloid fibrils in the ...extracellular space results in clinical deterioration and late diagnosis is associated with morbidity and mortality. Both types of this disease, light chain CA and transthyretin-related CA share many cardiac and extracardiac features that compromise multiple organs such as kidneys, musculoskeletal system, autonomic nervous system, and gastrointestinal tract. Early diagnosis and detection of CA are imperative. Clinicians should maintain a high degree of suspicion among patients with unexplained diastolic heart failure to implement different disease-altering therapies at the early stages of the disease. In this article, we provided a comprehensive review of multiple invasive and non-invasive cardiac imaging modalities with their respective degrees of sensitivities and specificity.
Introduction
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal and under-recognized disease. This targeted literature review assessed the extent and consequences of diagnostic ...delay and misdiagnosis in ATTR-CM.
Methods
The Embase database was searched together with proceedings of eight cardiology conferences to identify publications or abstracts on ATTR-CM. Outcomes of interest were time from symptom onset to diagnosis, rates of delayed diagnosis and misdiagnosis, and costs, healthcare resource use or clinical outcomes whilst undiagnosed/misdiagnosed.
Results
Twenty-three articles were included. Weighted means of reported mean and median diagnostic delays were 6.1 and 3.4 years for wild-type (ATTRwt-CM) and 5.7 and 2.6 years for hereditary (ATTRv-CM). Misdiagnosis occurred in 34–57% of patients when reported. Evaluation and misdiagnosis by multiple healthcare providers before receiving an ATTR-CM diagnosis was common, and there was evidence that patients undergo unnecessary or inappropriate evaluations or treatments while misdiagnosed. Diagnostic “red flags” were reported to be underused. Data on the consequences of delay for patients and health systems were sparse, but given the progressive nature of ATTR-CM, delay is likely to have adverse consequences.
Conclusion
ATTR-CM patients commonly experience diagnostic delay and misdiagnosis. Efforts are required to provide timely diagnosis so that patients can benefit from earlier access to new disease-modifying therapies.
PDF
