Dataset Information

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

ABSTRACT: BACKGROUND:Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (TTR) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria. METHODS:Within the period of 2014-2019, patients with ATTR-associated cardiomyopathy and/or unexplained progressive polyneuropathies were screened for mutations in the TTR gene. RESULTS:We identified 43 cases from 22 families carrying 10 different TTR missense mutations and confirmed two mutational hot spots at c.323A>G (p.His108Arg) and c.337G>C (p.Val113Leu). Two further patients with late onset ATTR carried TTR variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations. CONCLUSIONS:Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the TTR gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.

SUBMITTER: Auer-Grumbach M

PROVIDER: S-EPMC7408866 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

Auer-Grumbach Michaela M Rettl Rene R Ablasser Klemens K Agis Hermine H Beetz Christian C Duca Franz F Gattermeier Martin M Glaser Franz F Hacker Markus M Kain Renate R Kaufmann Birgit B Kovacs Gabor G GG Lampl Christian C Ljevakovic Neira N Nagele Jutta J Pölzl Gerhard G Quasthoff Stefan S Raimann Bernadette B Rauschka Helmut H Reiter Christian C Skrahina Volha V Schuhfried Othmar O Sunder-Plassmann Raute R Verheyen Nicolas D ND Wanschitz Julia J Weber Thomas T Windhager Reinhard R Wurm Raphael R Zimprich Friedrich F Löscher Wolfgang N WN Bonderman Diana D

Journal of clinical medicine 20200714 7

<h4>Background</h4>Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (<i>TTR</i>) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic ...[more]

PMID: 32674397

Similar Datasets

Project description:AimsThe aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA).Methods and resultsA retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (interquartile range 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARBs discontinued. In contrast, only 7.5% had MRAs discontinued. A propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population [hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.66-0.89), P < .001] and in a pre-specified subgroup of patients with a left ventricular ejection fraction (LVEF) >40% [HR 0.75 (95% CI 0.63-0.90), P = .002]; and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% [HR 0.61 (95% CI 0.45-0.83), P = .002]. No convincing differences were found for treatment with ACEi/ARBs.ConclusionConventional heart failure medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.

Project description:BackgroundHereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient's life.ObjectivesThis online international Delphi survey aimed to evolve clinical-patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs).DesignA 14-member joint patient advocate-HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient-doctor dialogue; access to social support and social networking.ParticipantsFrom June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%).Main outcome measureBoth level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds.ResultsBased on an a priori threshold for consensus of ≥75% agreement, the clinical-patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%-45% of HCPs. By comparison, PAGs recorded lower implementation levels.ConclusionsFurther consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.

Dataset Information

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

Publications

Hereditary ATTR Amyloidosis in Austria: Prevalence and Epidemiological Hot Spots.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets