Clinical Profile and Prognosis of Hereditary Transthyretin Amyloid Cardiomyopathy: A Single-Center Study in South China

Abstract

BackgroundHereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a genotypically heterogeneous disorder with a poor prognosis. There is limited literature describing the variants responsible for ATTRv in areas outside the United State, the United Kingdom and Europe. This study was performed to describe the clinical characteristics and genotypic profiles of this disease in South China.MethodsThis was a single-center retrospective study that evaluated 29 patients with a confirmed diagnosis of hereditary transthyretin amyloid cardiomyopathy enrolled from January 2016 to November 2021.Results93.1% patients were male and the median age of symptom onset was 53 (46, 62.5) years old. The initial manifestations of ATTR-CM were cardiovascular symptoms (55.2%), neuropathy (41.4%) and vitreous opacity (3.4%). Phenotypes at diagnosis were mixed (82.8%), predominant cardiac (6.9%), neurological (6.9%) and ophthalmic (3.4%). Poor R-wave progression (41%), pseudo-infarct (31%) and low-voltage (31%) patterns were common findings on electrocardiogram. Unexplained increased wall thickness was observed in all 29 patients, with mean septal and posterior wall thicknesses of 14.25 ± 6.26 mm and 15.34 ± 2.84 mm, respectively. Diastolic dysfunction was also seen in all 29 patients, and 17 (58%) had a restrictive fill pattern at diagnosis. Nine different missense mutations of the TTR gene were found in 29 patients from 23 families, with c.349G>T (p.Ala117Ser) the most common mutation. The median survival time after diagnosis was 47.6 (95% CI 37.9-57.4) months, with 1, 3 and 5-year survival rates of 91.2%, 74% and 38% respectively. Patients with advanced heart failure (National Amyloidosis Staging stage II/III) had worse survival than stage I [Breslow (Generalized Wilcoxon), χ2 = 4.693, P = 0.03)].ConclusionsATTR amyloidosis genotypes and phenotypes are highly heterogeneous. Advanced heart failure predicts a poor prognosis. Understanding the different clinical profiles of ATTR cardiac amyloidosis with different genotype is important to its early recognition.

Musculoskeletal co‐morbidities in patients with transthyretin amyloid cardiomyopathy: a systematic review

“…In addition to CTS, it is consistently more prevalent among patients with ATTRwt with cardiac involvement; for patients with ATTRv the prevalence is more variable, depending on the mutation. While no cases of CTS were recorded in patients with the Val30Met mutation (a variant without cardiac involvement), [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] it was described in the 19.7% of those with the Ile68Leu mutation. 34 With reference to the prognostic implication of CTS, Milandri et al 34 showed that CTS might be an independent risk factor for mortality in patients with ATTR, especially when secondary to deposits of the ATTRwt form (HR 3.36, 95% CI 1.27-10.3).…”

“…26 In terms of SS, the lumbar spinal canal stenosis is the correlated with ATTR-CM. Several studies only looked for SS in the lumbar section, 20,25,30,31 some others did not specify where the stenosis was located 24,27,33 and just Nakagawa et al 17 studied all the spinal sections. They observed four patients with SS in their series, two of them had lumbar spinal canal stenosis, and the other two had cervical spinal canal stenosis.…”

Negative methylene diphosphonate scintigraphy in biopsy-confirmed hereditary transthyretin Ala117Ser cardiac amyloidosis: a case report

“…ATTR-CA can be classified into two types: hereditary/mutant (ATTRm) and wild type (ATTRwt) [2] . A total of 120 transthyretin gene mutations have been reported up to date [3] . In China, the most common ATTR mutation is Ala117Ser (previously Ala97Ser) substitution [3][4][5][6][7][8][9][10] .…”

“…A total of 120 transthyretin gene mutations have been reported up to date [3] . In China, the most common ATTR mutation is Ala117Ser (previously Ala97Ser) substitution [3][4][5][6][7][8][9][10] .…”

Clinical and biochemical characterization of hereditary transthyretin amyloidosis caused by E61K mutation

“…Sensorimotor polyneuropathy, autonomic dysfunction, and gastrointestinal disturbances are the main clinical manifestations of the disorder, which may lead to death after 7.3 years of the disease onset (Conceição and De Carvalho, 2007 ; Koike et al, 2012 ). For ATTRv-CM, amyloidogenic fibers can infiltrate all cardiovascular structures, including the conduction system, atrial and ventricular myocardium, valvular tissue, and coronary and aortic arteries (Wang et al, 2022 ), with myocardial infiltration leading to a progressive increase in the thickness of the right and left ventricular walls, ultimately leading to heart failure (Buxbaum et al, 2006 ).…”