Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: diagnostic yield, novel mutations and genotype phenotype correlations

Additional file 1. Complementary data on primer sequences, SKI amplification and survival analyses

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVE: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Fishing and environment drive spatial heterogeneity in celtic sea fish community size structure

The Large Fish Indicator (LFI) is a univariate size-based indicator of fish community state that has been selected to support the OSPAR fish community Ecological Quality Objective (EcoQO). To operate this EcoQO, a survey-based LFI for each OSPAR region needs to be developed. However, fish communities in these regions are spatially heterogeneous, and there is evidence of within-region spatial variation in the LFI that could confound an overall indicator series. For Celtic Sea trawl-survey sites, spline correlograms indicate positive spatial autocorrelation at a similar range (similar to 40 km) for the LFI and for fishing effort (h year(-1)) from vessel monitoring systems. Statistical models reveal a strong negative effect on annual LFI by site of fishing effort within a radius of 40 km. There was a weak effect of fishing within 20 km and no effect at 10 km. LFI also varied significantly with substratum and with local fish community composition identified by a resemblance matrix derived from the survey data. Finally, there was a weak effect of survey year on LFI. Spatial stratification of LFI calculations may be necessary when developing size-based indicators for OSPAR or Marine Strategy Framework Directive regions

Fishing and environment drive spatial heterogeneity in celtic sea fish community size structure

The Large Fish Indicator (LFI) is a univariate size-based indicator of fish community state that has been selected to support the OSPAR fish community Ecological Quality Objective (EcoQO). To operate this EcoQO, a survey-based LFI for each OSPAR region needs to be developed. However, fish communities in these regions are spatially heterogeneous, and there is evidence of within-region spatial variation in the LFI that could confound an overall indicator series. For Celtic Sea trawl-survey sites, spline correlograms indicate positive spatial autocorrelation at a similar range (similar to 40 km) for the LFI and for fishing effort (h year(-1)) from vessel monitoring systems. Statistical models reveal a strong negative effect on annual LFI by site of fishing effort within a radius of 40 km. There was a weak effect of fishing within 20 km and no effect at 10 km. LFI also varied significantly with substratum and with local fish community composition identified by a resemblance matrix derived from the survey data. Finally, there was a weak effect of survey year on LFI. Spatial stratification of LFI calculations may be necessary when developing size-based indicators for OSPAR or Marine Strategy Framework Directive regions