Citations

Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome. Methods and results A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1–5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0–8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively. Conclusion Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

Objective The aim of the study was to perform an economic analysis to identify the clinical and cost determinants of pancreatic cancer (PC) surveillance in high-risk individuals (HRIs). Methods A Markov model was created to compare the following 3 strategies: no screening, endoscopic ultrasound (EUS), and magnetic resonance imaging (MRI) screening. Patients were considered HRIs according to the Cancer of the Pancreas Screening consortium recommendations. Risk for developing PC, survival, and costs data were obtained from the Surveillance, Epidemiology, and End Results and Medicare databases. Surveillance effectiveness was obtained from a recent meta-analysis. Results Analysis of a cohort with fivefold relative risk of PC higher than the US population showed that MRI is the most cost-effective strategy. For those with the highest risk (>×20 relative risk), EUS became the dominant strategy. Our model was impacted by cost and imaging performance, but still cost-effective within the range reported in literature. Threshold analysis showed that if MRI increases greater than US $1600, EUS becomes more cost-effective. Once patients reached the age of 76 years, “no screening” was favored. Both surveillance strategies were cost-effective over a wide range of willingness to pay. Conclusions Abdominal imaging followed by pancreatectomy is cost-effective to prevent PC in HRIs, favoring MRI in moderate risk cases but EUS in those with highest risk.

Abstract BACKGROUND Both stent-assisted coiling (SAC) and flow diversion with the Pipeline Embolization device (PED; Medtronic Inc) have been shown to be safe and clinically effective for treatment of small (<10 mm) unruptured aneurysms. However, the economic impact of these different techniques has not been established. OBJECTIVE To analyze the cost-effectiveness between stent-assisted coiling and flow diversion using PED, including procedural costs, long-term outcomes, and aneurysm recurrence. METHODS A decision-analytical study was performed with Markov modeling methods to simulate patients undergoing SAC or PED for treatment for unruptured aneurysms of sizes 5 and 7 mm. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed. RESULTS In base case calculation and PSA, PED was the dominant strategy for both the size groups, with and without consideration of indirect costs. One-way sensitivity analyses show that the conclusion remained robust when varying the retreatment rate of SAC from 0% to 50%, and only changes when the retreatment rate of PED > 49%. PED remained the more cost-effective strategy when the morbidity and mortality of PED increased by <55% and when those of SAC decreased by <37%. SAC only became cost-effective when the total cost of PED is >$73000 more expensive than the total cost of SAC. CONCLUSION With increasing use of PED for treatment of small unruptured anterior circulation aneurysms, our study indicates that PED is cost-effective relative to stent coiling irrespective of aneurysm size. This is due to lower aneurysm recurrence rate, as well as better health outcomes.

Abstract Background The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. Methods We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. Pairs of reviewers selected and appraised the trials. Results We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

Background Steps towards the development of diagnostic criteria are needed for children with the radiologically isolated syndrome to identify children at risk of clinical demyelination. Objectives To evaluate the 2005 and 2016 MAGNIMS magnetic resonance imaging criteria for dissemination in space for multiple sclerosis, both alone and with oligoclonal bands in cerebrospinal fluid added, as predictors of a first clinical event consistent with central nervous system demyelination in children with radiologically isolated syndrome. Methods We analysed an international historical cohort of 61 children with radiologically isolated syndrome (≤18 years), defined using the 2010 magnetic resonance imaging dissemination in space criteria (Ped-RIS) who were followed longitudinally (mean 4.2 ± 4.7 years). All index scans also met the 2017 magnetic resonance imaging dissemination in space criteria. Results Diagnostic indices (95% confidence intervals) for the 2005 dissemination in space criteria, with and without oligoclonal bands, were: sensitivity 66.7% (38.4–88.2%) versus 72.7% (49.8–89.3%); specificity 83.3% (58.6–96.4%) versus 53.9% (37.2–69.9%). For the 2016 MAGNIMS dissemination in space criteria diagnostic indices were: sensitivity 76.5% (50.1–93.2%) versus 100% (84.6–100%); specificity 72.7% (49.8–89.3%) versus 25.6% (13.0–42.1%). Conclusions Oligoclonal bands increased the specificity of magnetic resonance imaging criteria in children with Ped-RIS. Clinicians should consider testing cerebrospinal fluid to improve diagnostic certainty. There is rationale to include cerebrospinal fluid analysis for biomarkers including oligoclonal bands in planned prospective studies to develop optimal diagnostic criteria for radiologically isolated syndrome in children.

AbstractModeling the flow dynamics in cerebral aneurysms after the implantation of intrasaccular devices is important for understanding the relationship between flow conditions created immediately posttreatment and the subsequent outcomes. This information, ideally available a priori based on computational modeling prior to implantation, is valuable to identify which aneurysms will occlude immediately and which aneurysms will likely remain patent and would benefit from a different procedure or device.In this report, a methodology for modeling the hemodynamics in intracranial aneurysms treated with intrasaccular flow diverting devices is described. This approach combines an image‐guided, virtual device deployment within patient‐specific vascular models with an immersed boundary method on adaptive unstructured grids. A partial mesh refinement strategy that reduces the number of mesh elements near the aneurysm dome where the flow conditions are largely stagnant was compared with the full refinement strategy that refines the mesh everywhere around the device wires.The results indicate that using the partial mesh refinement approach is adequate for analyzing the posttreatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intrasaccular devices were in good qualitative agreement with angiographic observations.Promising results were obtained relating posttreatment flow conditions and outcomes of treatments with intrasaccular devices, which need to be confirmed on larger series.

Background Thoracic aortic aneurysm is common in patients with tetralogy of Fallot ( TOF ); the incidence of thoracic aortic dissection ( TAD ) is unknown, but generally considered to be uncommon. The purpose of this study was to determine incidence and risk factors for TAD in TOF patients. Methods and Results This work is a retrospective review of the National Inpatient Sample ( NIS ) database for cases of ascending TAD among all hospital admissions in adults with TOF , 2000–2014. Of 18 353 admissions in TOF patients, 11 (0.06%; 6 per 10 000 admissions) of these were TAD ‐related admissions. For the TAD ‐related admissions, mean age was 49.8±7.2 years; aortic surgical interventions were performed during 8 of the admissions, and overall in‐hospital mortality was 45% (5 of 11). Risk factors associated with TAD ‐related admission were age >60 years (odds ratio, 2.41; 95% CI, 1.23–3.25; P =0.013), male sex ( odds ratio, 6.91; 95% CI, 4.85–8.54; P <0.001), and hypertension (odds ratio, 1.74; 95% CI, 1.06–3.19; P =0.037). Conclusions This is the first population‐based study of TAD outcomes in patients with TOF , and it showed a low risk of TAD in this population. This has important clinical implication with regard to surveillance and surgical intervention. Given that prevalence of thoracic aortic aneurysm is higher in TOF patients compared with the general population; therefore, making clinical decisions based on outcomes data and practice guidelines derived from patients with degenerative and bicuspid aortic valve–related aortopathies may lead to overtreatment . Further studies are required to better understand the pathobiology of this disease in order to make evidence‐based recommendations for surveillance and treatment.

AbstractBackgroundSevere primary graft dysfunction (PGD) is the leading cause of early death after heart transplant.AimTo examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA‐ECMO) for severe PGD.MethodsWe reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements.ResultsOf 1030 heart transplant patients, 31 (3%) had severe PGD and required VA‐ECMO. The mean (range) age was 59 (43‐69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty‐five patients (81%) were successfully weaned from VA‐ECMO, and 19 (61%) were discharged; the other 12 (39%) died.ConclusionsAlthough VA‐ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.