Advanced therapy for pulmonary arterial hypertension due to congenital heart disease: a clinical perspective in a new therapeutic era

Cardiolog

A 3-SNP gene risk score and a metabolic risk score both predict hypertriglyceridemia and cardiovascular disease risk.

BACKGROUND: Evidence on the causal link between plasma triglyceride (TG) levels and risk for cardiovascular disease (CVD) has recently emerged. Individuals with the metabolic syndrome have an increased risk for acquiring elevated TG levels later in life. Moreover, common DNA sequence variations in genes affecting TG levels identify individuals at risk for elevated plasma TG levels. OBJECTIVE: We evaluated whether a 3-single nucleotide polymorphism (SNP) TG gene risk score (GRS) and a metabolic risk score (MetRS) both improved CVD risk prediction. METHODS: A 3-SNP GRS and MetRS were generated in the EPIC-Norfolk cohort (n = 20,074) based on 3 SNPs in LPL and APOA5 or the number of Metabolic Syndrome criteria present (maximum 5), respectively. The associations between the 3-SNP GRS, MetRS, TG levels, and CVD risk were evaluated. RESULTS: The 3-SNP GRS and MetRS were both linearly associated with plasma TG levels, that is, +0.25 mmol/L [95% CI 0.22-0.27] per allele change (P < .001) and +0.72 mmol/L [95% CI 0.70-0.73] per increase of number of metabolic syndrome risk score points (P < .001), respectively. We observed a positive association between the 3-SNP GRS and the risk of CVD with an adjusted hazard ratio (HR) of 1.35 [95% CI 1.04-1.74] for the highest versus the lowest GRS, which was independent of the MetRS. For the MetRS, the adjusted HR was 2.03 [95% CI 1.73-2.40] for the highest versus the lowest MetRS. CONCLUSION: Both the 3-SNP GRS and the MetRS are associated with increased plasma TG levels and increased risk for CVD

Validation of the Systematic COronary Risk Evaluation - Older Persons (SCORE-OP) in the EPIC-Norfolk prospective population study.

BACKGROUND: The Systematic COronary Risk Evaluation - Older Persons (SCORE-OP) algorithm is developed to assess 10-year risk of death due to cardiovascular disease (CVD) in individuals aged ≥65 years. We studied the performance of SCORE-OP in the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. METHODS: 10-year CVD mortality as predicted by SCORE-OP was compared with observed CVD mortality among individuals in the EPIC-Norfolk cohort. Persons aged 65-79 years without known CVD were included in the analysis. CVD mortality was defined as death due to ischemic heart disease, cardiac failure, cerebrovascular disease, peripheral-artery disease or aortic aneurysm. Predicted 10-year CVD mortality was calculated by the SCORE-OP algorithm, and compared to observed mortality rates. The area under the receiver operator characteristics curve (AUROC) was calculated to evaluate discriminative power. Calibration was evaluated by calculating ratios of predicted vs observed mortality and by Hosmer-Lemeshow tests. RESULTS: A total of 6590 individuals (45.8% men), mean age 70.2 years (standard deviation 3.3) were included. The predicted mortality by SCORE-OP was 9.84% (95% confidence interval (CI) 9.76-9.92) and observed mortality was 10.2% (95% CI 9.52-11.04), ratio 0.96. AUROC was 0.63 (95% CI 0.60-0.65), and X2 was 3.3 (p = 0.92). CONCLUSION: SCORE-OP overall accurately estimates the rate of CVD mortality in a general population aged 65-79 years. However, while calibration is excellent, the discriminative power of the SCORE-OP is limited, and as such cannot be readily implemented in clinical practice for this population

Nasopharyngeal Myoepithelial Carcinoma Mimicking Nasopharyngeal Carcinoma

AbstractMyoepithelial carcinoma (malignant myoepithelioma) (MC) is a rare tumor, defined as a malignant salivary neoplasm composed almost exclusively of tumor cells with myoepithelial differentiation. It can arise in unusual location sites, such as the nasopharynx, and may be difficult to approach. Nasopharyngeal MC can sometimes present as a nasopharyngeal mass which may be mistaken for primary nasopharyngeal carcinoma (NPC). The treatment strategy for nasopharyngeal MC is different from NPC, and maximal surgical resection of the main lesion is still considered as the mainstay of therapy. Herein we present a 32-year-old man with a nasopharyngeal mass which was initially mistaken as NPC, and which was later confirmed as MC after a comprehensive review of the pathology

Long-term cardiac follow-up of athletes infected with SARS-CoV-2 after resumption of elite-level sports

OBJECTIVE: Longitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the highest level of sports and exercise.METHODS: This prospective controlled study included elite athletes from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise cohort. Athletes infected with SARS-CoV-2were offered structured, additional cardiovascular screenings, including cardiovascular MRI (CMR). We compared ventricular volumes and function, late gadolinium enhancement (LGE) and T1 relaxation times, between infected and non-infected elite athletes, and collected follow-up data on cardiac adverse events, ventricular arrhythmia burden and the cessation of sports careers.RESULTS: We included 259 elite athletes (mean age 26±5 years; 40% women), of whom 123 were infected (9% cardiovascular symptoms) and 136 were controls. We found no differences in function and volumetric CMR parameters. Four infected athletes (3%) demonstrated LGE (one reversible), compared with none of the controls. During the 26.7 (±5.8) months follow-up, all four athletes resumed elite-level sports, without an increase in ventricular arrhythmias or adverse cardiac remodelling. None of the infected athletes reported new cardiac symptoms or events. The majority (n=118; 96%) still participated in elite-level sports; no sports careers were terminated due to SARS-CoV-2.CONCLUSIONS: This prospective study demonstrates the safety of resuming elite-level sports after SARS-CoV-2 infection. The medium-term risks associated with SARS-CoV-2 infection and elite-level sports appear low, as the resumption of elite sports did not lead to detrimental cardiac effects or increases in clinical events, even in the four elite athletes with SARS-CoV-2 associated myocardial involvement.</p

Ideal cardiovascular health influences cardiovascular disease risk associated with high lipoprotein(a) levels and genotype: The EPIC-Norfolk prospective population study

BACKGROUND AND AIMS: Lipoprotein(a) (Lp[a]) is a strong genetic risk factor for cardiovascular disease (CVD). The American Heart Association has prioritised seven cardiovascular health metrics to reduce the burden of CVD: body mass index, healthy diet, physical activity, smoking status, blood pressure, diabetes and cholesterol levels (together also known as ideal cardiovascular health). Our objective was to determine if individuals with high Lp(a) levels could derive cardiovascular benefits if characterized by ideal cardiovascular health. METHODS: A total of 14,051 participants of the EPIC-Norfolk study were stratified according to the cardiovascular health score (based on the number of health metrics with an ideal, intermediate or poor status). Of them, 1732 had a CVD event during a mean follow-up of 11.5 years. Cox proportional hazards models were used to describe the association between the cardiovascular health score and Lp(a) level or genotype (as estimated by the rs10455872 variant) with the risk of CVD. RESULTS: We observed little or no differences in serum Lp(a) levels across the seven cardiovascular health metric categories. Among participants with high serum Lp(a) levels ≥50 mg/dl), those in the highest (i.e. healthiest) cardiovascular health score category (10-14) had an adjusted hazard ratio for cardiovascular disease of 0.33 (95% CI = 0.17-0.63, p = 0.001) compared to participants in the lowest (i.e. unhealthiest) cardiovascular health score category(0-4). Similar results were obtained when we replaced Lp(a) with rs10455872. CONCLUSIONS: Although Lp(a) levels are only slightly influenced by cardiovascular health metrics, an ideal cardiovascular health could substantially reduce CVD risk associated with high Lp(a) levels or genotype.EPIC-Norfolk is supported by program grants from the Medical Research Council UK and Cancer Research UK and with additional support from the European Union, Stroke Association, British Heart Foundation, and Research into Ageing. RV is supported by a grant from the European Union [TransCard: FP7-603091-2]. BJA holds a junior scholar award from the Fonds de recherche du Québec: Santé (FRQS)

A 3-slice cardiac quantitative native and post-contrast T1 and T2 MRI protocol requiring only four BHs using a 72-channel receive array coil

Introduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel-imaging approach with a 72-channel receive-array to reduce BHs and demonstrate this in healthy subjects and hypertrophic cardiomyopathy (HCM) patients.Methods: A T1/T2 phantom was scanned at 3 T using a 16-channel and a novel 72-channel coil to assess the impact of different coils and acceleration factors on relaxation times. 16-18 healthy participants (8 female, age 28.4 +/- 5.1 years) and 3 HCM patients (3 male, age 55.3 +/- 4.2 years) underwent cardiac-MRI with the 72-channel coil, using a Modified Look-Locker scan with a shared inversion pulse across 3 slices and a Gradient-Spin-Echo scan. Acceleration was done by sensitivity encoding (SENSE) with accelerations 2, 4, and 6. LV T1 and T2 values were analyzed globally, per slice, and in 16 segments, with SENSE = 2 as the reference.Results: The phantom scans revealed no bias between coils and acceleration factors for T1 or T2, except for T2 with SENSE = 2, which resulted in a bias of 8.0 +/- 6.7 ms (p < 0.001) between coils. SENSE = 4 and 6 enabled T1 mapping of three slices in a single BH, and T2 mapping of three slices within two BHs. In healthy subjects, T1 and T2 values varied. We found an average overestimation of T1 in 3 slices of 25 +/- 87 ms for SENSE = 4 and 30 +/- 103 ms using SENSE = 6, as compared to SENSE = 2. Acceleration resulted in decreased signal-to-noise; however, visually insignificant and without increased incidence of SENSE-artifacts. T2 was overestimated by 2.1 +/- 5.0 ms for SENSE = 4 and 6.4 +/- 9.7 ms using SENSE = 6, as compared to SENSE = 2. Native and post-contrast T1 measurements with SENSE = 4 and ECV quantification in HCM patients was successful.Conclusion: The 72-channel receiver-array coil with SENSE = 4 and 6, enabled LV-tissue characterization in three slices. Pre- and post-contrast T1 maps were obtained in a single BH, while T2 required two BHs.Radiolog

Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease

Objective: This study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD). Methods: Cardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows: men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth's penalised Cox regression. Results: The event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in w