Baseline characteristics of HCM patients.

<p>Values are given as total number of patients (n) or as mean ± SD.</p

Impact of QTc prolongation on the occurrence of adverse events in HCM patients.

<p>Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value) and OR (odds ratio; adjusted for age and sex) with 95%-CI (confidence intervals) are given in the table below. AE = adverse events (syncope, presyncope, VT).</p

Influence of disease related factors and medication on the QTc interval in 100 HCM patients.

<p>Values are given as total number of patients (n) or as mean ± SD.</p><p>Influence of disease related factors and medication on the QTc interval in 100 HCM patients.</p

Influence of disease related factors and medication on the orthostatic test result in 69 HCM patients older than or equal to 40 years.

<p>Values are given as total number of patients (n) or as mean ± SD.</p><p>Influence of disease related factors and medication on the orthostatic test result in 69 HCM patients older than or equal to 40 years.</p

Impact of orthostatic test on the occurrence of adverse events in HCM patients for all patients (A) and for the subgroup of patients > 40 yrs (B).

<p>Sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value) and OR (odds ratio; adjusted for age and sex) with 95%-CI (confidence intervals) are given in the table below. AE = adverse events (syncope, presyncope, VT).</p

Relationship between orthostatic test result and QTc prolongation.

<p>The percentages of patients with a positive and negative orthostatic test result are given for the group with and without QTc prolongation.</p

Hereditary transthyretin-related amyloidosis is frequent in polyneuropathy and cardiomyopathy of no obvious aetiology

Hereditary Transthyretin-Related Amyloidosis, a clinically heterogeneous autosomal dominant disease caused by pathogenic variants in the TTR gene, is characterized by the deposition of insoluble misfolded protein fibrils. The diagnosis, especially in non-endemic areas, is typically delayed by 4–5 years; a misdiagnosis due to clinical heterogeneity is common. The study objective was to define the prevalence of Hereditary Transthyretin-Related Amyloidosis in patients with polyneuropathy and/or cardiomyopathy of no obvious aetiology. A multicenter observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis”—TRAM study was performed in Germany, Austria, and Switzerland. A total of 5141 participants were recruited by 50 neurologic and 27 cardiologic specialized centres. Genetic analysis demonstrated a 1.1% Hereditary Transthyretin-Related Amyloidosis positivity rate among patients with polyneuropathy and/or cardiomyopathy of not obvious aetiology. Twenty-one various TTR variants (TTR-positive) were identified. Body Mass Index was lower in the TTR-positive patients as an indicator for the involvement of the autonomic nervous system; the age of onset of clinical manifestations was higher in TTR-positive patients. There were no other genotype-phenotype correlations or the prevalence of specific clinical manifestations in TTR-positive patients. Our data support the fact that Hereditary Transthyretin-Related Amyloidosis is underdiagnosed in polyneuropathy and cardiomyopathy patients. Routine implementation of genetic testing is recommended in patients with unexplained polyneuropathy and/or cardiomyopathy to accelerate the earlier diagnosis and the time-sensitive treatment initiation.KEY MESSAGESMore than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis” TRAM study and screened for pathogenic TTR variants.The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant.Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation. More than 5.000 participants with CM and/or PNP of no obvious aetiology were recruited in the observational “Epidemiological analysis for the hereditary Transthyretin-Related AMyloidosis” TRAM study and screened for pathogenic TTR variants. The study demonstrated >1% of patients with CM and/or PNP of unclear aetiology are positive for a pathogenic TTR variant. Routine genetic testing is recommended in patients with unexplained CM and/or PNP to accelerate the initial diagnosis and timely treatment initiation.</p