Non-invasive imaging in congenital heart disease

The care of the adult patient with congenital heart disease is becoming increasingly complex. In many of these patients re-intervention, heart failure and arrhythmias are inevitable consequences of successful repair in childhood. Specialist imaging is integral to accurate diagnosis and in establishing optimal management plans for these long-term complications. Fortunately there are now a whole series of imaging techniques available to the clinician – each with its own inherent strengths and limitations. These modalities are complementary and offer fresh insight into the unique anatomy and physiology of these conditions. This paper reviews the most commonly employed imaging techniques and their contribution to assessing a patient with a congenital heart lesion

The Inheritance of Atherosclerosis and Left Ventricular Structure: A Scottish Twin Study

Cardiovascular disease is a major cause of morbidity and mortality in Scotland. Coronary atherosclerosis alone accounts for 450 premature deaths per 100,000 males and 180 per 100,000 in females each year. The pathological processes underlying these clinical manifestations of cardiovascular disease are multifactorial in causation. However, it is unclear to what extent the Scottish population has a genetic predisposition to these disorders. Twin studies are a highly informative method of delineating the varying genetic and environmental contributions to non-Mendelian parameters. Utilising a population of monozygotic and dizygotic twins allows the contribution of genetic factors to be quantified by comparing intra-class correlations between the monozygotic and dizygotic groups. Previous twin studies have primarily evaluated the genetic influences over known cardiovascular risk factors but little is known about the interplay of these factors in a population from the West of Scotland with its high prevalence of cardiovascular pathology. Few studies have focused on the inheritance of the actual extent of arterial disease. The determination of degree of heritability over a given phenotype is an important first step before embarking on the investigation of potential candidate genes. The cohort investigated in this study consisted of 151 pairs of monozygotic and dizygotic twins aged 30-85 years old (82 monozygotic pairs and 68 dizygotic pairs). All pairs were; recruited from the general population and were of Caucasian origin. Using a classic twin methodology the heritability of a wide range of cardiovascular phenotypes were assessed. Resting and 24-hour assessments of blood pressure were performed. 24-hour measures of diastolic and mean blood pressure were under a significant degree of genetic control. This was particularly true for night-time measurements (night-time mean and diastolic pressures - heritability of 0.53 (p=0.03) and 0.58 (p=0.02) respectively). The degree of heritability was stronger for these parameters than resting or 24-hour measures of systolic blood pressure. Genes were important in the aetiology of left ventricular (LV) mass in this cohort. Heritability for LV mass was 0. 69 (p=0.008). This genetic influence was not explained by similarities In age, sex, size or blood pressure and persisted following correction for these potential confounders (h2 = 0.53; p=0.006). Impaired lung function, as measured by spirometry, is a risk factor for cardiovascular events. Intra-class correlation coefficients were measured for FEV1 and FVC in the monozygotic and dizygotic groups. The baseline data and the data corrected for height both showed a significant percentage of the variability in these measurements were under genetic control. The heritability estimates for the height corrected spirometry variables were 0.61 (p=0.02) for FEV1 and 0.71 (p=0.007) for FVC. When these variables were expressed as a percentage of their predicted value only the FEV1 result remained significant (h2=0.61, p=0.002). The genetic contribution towards the extent of atheroma formation was assessed using B-mode ultrasound of the carotid arteries. This technique measures carotid intima media thickness a marker of atherogenesis in the cerebral and coronary beds. None of the carotid measurements revealed any degree of genetic control. Environmental and familial influences appeared to be more important than narrow-sense heritability in the determination of carotid intima media thickness. Numerous biochemical and haematological parameters were assessed in the twin cohort. A genetic basis was established for many of them including Lipoprotein A, HDL-Cholesterol, urate, haematocrit and platelet level. In summary this population-based adult twin study, which recruited subjects from a high-risk catchment area (the West of Scotland) demonstrated that many important risk factors are genetically determined. Candidate gene investigations should be directed towards the study of phenotypes with the strongest heritability estimates. A clearer understanding of the aetiology of, and relationships between, the risk factors investigated in this study is necessary to enable effective targeting of preventative and therapeutic strategies

Pregnancy and Congenital Heart Disease: Moving Beyond the Current Risk Stratification Tools

Women with congenital heart disease have increased risks of complications during pregnancy. Several risk scoring tools have been developed to quantify the likelihood of adverse cardiac outcomes during pregnancy. This article describes how comprehensive pre-pregnancy or early pregnancy counseling needs to go well beyond these risk scores. Non-cardiac risk factors and adverse obstetric and fetal outcomes are vital components of the dialogue between the multidisciplinary team and the patient embarking on, or contemplating, pregnancy

Transfer of congenital heart patients from paediatric to adult services in England

OBJECTIVE: This study assessed the transfer of patients from paediatric cardiac to adult congenital heart disease (ACHD) services in England and the factors impacting on this process. METHODS: This retrospective cohort study used a population-based linked data set (LAUNCHES QI data set: 'Linking Audit and National datasets in Congenital Heart Services for Quality Improvement') including all patients born between 1987 and 2000, recorded as having a congenital heart disease (CHD) procedure in childhood. Hospital Episode Statistics data identified transfer from paediatric to ACHD services between the ages of 16 and 22 years. RESULTS: Overall, 63.8% of a cohort of 10 298 patients transferred by their 22nd birthday. The estimated probability of transfer by age 22 was 96.5% (95% CI 95.3 to 97.7), 86.7% (95% CI 85.6 to 87.9) and 41.0% (95% CI 39.4 to 42.6) for severe, moderate and mild CHD, respectively. 166 patients (1.6%) died between 16 and 22 years; 42 of these (0.4%) died after age 16 but prior to transfer. Multivariable ORs in the moderate and severe CHD groups up to age 20 showed significantly lower likelihood of transfer among female patients (0.87, 95% CI 0.78 to 0.97), those with missing ethnicity data (0.31, 95% CI 0.18 to 0.52), those from deprived areas (0.84, 95% CI 0.72 to 0.98) and those with moderate (compared with severe) CHD (0.30, 95% CI 0.26 to 0.35). The odds of transfer were lower for the horizontal compared with the vertical care model (0.44, 95% CI 0.27 to 0.72). Patients who did not transfer had a lower probability of a further National Congenital Heart Disease Audit procedure between ages 20 and 30 compared with those who did transfer: 12.3% (95% CI 5.1 to 19.6) vs 32.5% (95% CI 28.7 to 36.3). CONCLUSIONS: Majority of patients with moderate or severe CHD in England transfer to adult services. Patients who do not transfer undergo fewer elective CHD procedures over the following decade

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice