COSMIC, the Catalogue Of Somatic Mutations In Cancer (http://cancer.sanger.ac.uk) is the world's largest and most comprehensive resource for exploring the impact of somatic mutations in human cancer. ...Our latest release (v70; Aug 2014) describes 2 002 811 coding point mutations in over one million tumor samples and across most human genes. To emphasize depth of knowledge on known cancer genes, mutation information is curated manually from the scientific literature, allowing very precise definitions of disease types and patient details. Combination of almost 20,000 published studies gives substantial resolution of how mutations and phenotypes relate in human cancer, providing insights into the stratification of mutations and biomarkers across cancer patient populations. Conversely, our curation of cancer genomes (over 12,000) emphasizes knowledge breadth, driving discovery of unrecognized cancer-driving hotspots and molecular targets. Our high-resolution curation approach is globally unique, giving substantial insight into molecular biomarkers in human oncology. In addition, COSMIC also details more than six million noncoding mutations, 10,534 gene fusions, 61,299 genome rearrangements, 695,504 abnormal copy number segments and 60,119,787 abnormal expression variants. All these types of somatic mutation are annotated to both the human genome and each affected coding gene, then correlated across disease and mutation types.
Conclusions: Symptomatic PAD confers independent prognostic implications for perioperative adverse events, longer hospital stay and poorer long term graft survival rates following HT, thereby ...indicating high risk for HT-related morbidity.
Subclinical left ventricular (LV) dysfunction refers to subtle abnormalities in LV function
which typically precede a reduction in the left ventricular ejection fraction (LVEF). The assessment
of ...myocardial function using LVEF, a radial metric of systolic function, is subject to load dependence,
intra-observer and inter-observer variability. Reductions in LVEF typically manifest late in the
disease process thus compromising the ability to intervene before irreversible impairment of systolic
performance sets in. 2-Dimensional speckle tracking echocardiography (2D-STE), a novel strain
imaging modality has shown promise as a sensitive indicator of myocardial contractility. It arms the
clinician with a powerful and practical tool to rapidly quantify cardiac mechanics, circumventing
several inherent limitations of conventional echocardiography. This article highlights the incremental
utility of 2D-STE in the detection of subclinical LV dysfunction.
Background The effect of dual antiplatelet therapy (DAPT) or oral anticoagulation on long term incidence of acute coronary syndromes (ACS) in patients with coronary artery ectasia (CAE) and no ...significant occlusive CAD is not well known. ...a total of 105 among 317 CAE patients (33%) were placed on warfarin or direct-acting oral anticoagulant therapy for atrial arrhythmias or venous thromboembolism but none of these were prescribed for CAE as the primary indication.
Background: Clinical presentation, natural history of coronary artery ectasia (CAE) and prognostic implications of its anatomic classification of are not well known.
Abstract Background Cholesterol management guidelines from the American College of Cardiology/American Heart Association (ACC/AHA-2013) recommend fixed statin dosing (dose depends on age ≤ or >75 ...years) compared to the earlier adult treatment panel III (ATPIII) guidelines which recommended specific low-density lipoprotein-cholesterol (LDL-C) targets. Clinical implications of this recommendation are not known. Methods We retrospectively compared cholesterol levels and statin utilization across cohorts with coronary artery disease (CAD) (n = 9563), peripheral arterial disease (PAD) (n = 596) and CAD + PAD (n = 975) by applying both guidelines. The percentage of patients who achieved guideline-specific targets using 2013 ACC/AHA (use of moderate/high intensity statins) or ATPIII guidelines (LDL-C < 100 mg/dl) was compared between all groups. Results Using both guidelines, the PAD only group demonstrated lower utilization and lower statin doses than the CAD or CAD + PAD groups. When applying the ACC/AHA guidelines, more patients in the CAD only group (age ≤75 years) were considered at goal as compared to the ATPIII guidelines (92.2% vs. 75%), primarily driven by the group placed on moderate/high intensity statins but had an LDL-C level >100 mg/dl. Conclusions Application of the ACC/AHA guidelines results in a higher percentage of patients considered to be ‘at goal’ when compared to the ATP III guidelines without changes in clinical practice. This is due to patients ≤75 years old on adequate statin doses but still have LDL-C levels >100 mg/dl, thereby raising concerns that physicians may not pursue alternate LDL reduction strategies since they are now considered at goal despite LDL-C >100 mg/dl. Lipid management of PAD patients remains sub-optimal as compared to CAD and CAD + PAD.
The ACC/AHA guidelines recommend low-dose dobutamine challenge for hemodynamic assessment of the severity of AS in patients with low flow, low gradient aortic stenosis with reduced ejection fraction ...(EF) (LFLG-AS; stage D2). Inherent pitfalls of echocardiography could result in inaccurate aortic valve areas (AVA), which have downstream prognostic implications. Data on the safety and efficacy of coronary pressure wire and fluid-filled catheter use for low dose dobutamine infusion is sparse.
We retrospectively analyzed 39 consecutive patients with EF<50%, AVA<1cm2 and SVI<35ml/m2 on echocardiography who underwent simultaneous right and left heart catheterization. Hemodynamic assessments were performed at baseline and at every increment in the dobutamine infusion rate (The infusion was continued until maximal dose of dobutamine or a mean AV gradient>40mmHg was attained. The occurrence of sustained ventricular arrhythmias, symptomatic hypotension or intolerable symptoms leading to cessation of infusion was recorded. Transient ischemic attacks (TIAs) or clinically apparent strokes periprocedurally or up to 30days after the procedure were recorded.
Dobutamine challenge confirmed true AS in 26 patients (67%) and pseudosevere AS in 34%. No sustained arrhythmias, hypotension or cessation of infusion from intolerable symptoms were observed. No clinical strokes or TIAs were observed up to 30days after procedure in any of these patients.
Hemodynamic assessment of AS using a pressure wire with dobutamine challenge is a safe and effective tool in identifying truly severe AS in patients with LFLG-AS with reduced EF.
Left ventricular hypertrophy (LVH) has not been evaluated for reclassification improvement in the intermediate Framingham risk category for incident hard coronary events in a large multi ethnic ...population free of cardiovascular disease at baseline.
A post-hoc analysis on the Multi Ethnic Study of Atherosclerosis (MESA) dataset (n = 4921) was performed.
LVH was defined as the upper 95 th percentile of cardiac magnetic resonance imaging derived left ventricular mass (LVM) indexed based on body surface area (BSA) and height. Multivariate Cox proportional hazards models were used to assess the independent association between LVH and composite outcomes like all cardiovascular disease (CVDa) and hard coronary heart disease (CHDh) events over a mean follow-up period of 4.5 years. To assess the incremental value of LVH over traditional CV risk factors for CHDh prediction, we compared the discrimination, calibration and net reclassification index (NRI) of models comprising of traditional CV risk factors with and without LVH.
LVH derived from LVM indexed by BSA (LVH-BSA) and height(1.7)(LVH-height) showed an independent association with CVDa (LVH-BSA: hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.05-2.20, p = 0.03; LVH-height(1.7): HR 1.58, 95% CI 1.14-2.18, p = 0.012) and CHDh (LVH-BSA: HR 2.36, 95% CI 1.37-4.04, p = 0.002; LVH-height(1.7): HR: 1.95, 95% CI: 1.17-3.26, p = 0.01). Addition of LVH to the model based on traditional CV risk factors demonstrated no significant improvement in NRI for CHDh in either the entire cohort (LVH-BSA: NRI 1.7%, 95% CI: -8.3% to 11.7%, p = 0.74; LVH-height(1.7): NRI 2.7%, 95% CI: -5.8% to 11.3%, p = 0.62) or the intermediate risk group (LVH-BSA: NRI 12.0%, 95% CI: -5.7% to 29.8%, p = 0.19; LVH-height(1.7): NRI 14.5%, 0.1% to 28.8%, p = 0.05).
Although an independent predictor of cardiovascular events, LVH does not lead to clinically meaningful reclassification of the overall and intermediate risk population for CHDh.
The current definition of peripartum cardiomyopathy (PC) is restricted to patients with left ventricular systolic dysfunction (ejection fraction EF <45%). Data on peripartum heart failure (HF) with ...normal EF are sparse. We describe clinical characteristics of patients with normal (≥55%) and patients with low (<45%) left ventricular ejection fractions (LVEFs). Electronic medical records (2006 to 2013) of our tertiary care center were retrospectively screened to identify peripartum HF with normal EF, defined as an entity meeting Framingham criteria for HF with symptom onset during the last month of pregnancy or up to 5 months after delivery and with an EF of ≥55%. Clinical characteristics, echocardiographic parameters, and outcomes of these patients were compared with age-matched control patients with traditionally defined PC (EF <45%). A total of 25 patients with PC and EF ≥55% were identified. Exclusion of hypertension (n = 9), preeclampsia (n = 1), and diabetes mellitus (n = 2) yielded 13 patients with PC and EF ≥55%. Age-matched patients with traditional PC (EF <45%) constituted controls (n = 16). Compared with patients with PC and low LVEF, patients with PC and normal LVEF had lower B-type natriuretic peptide levels, systolic and diastolic left ventricular dimensions, left atrial size, and incidence of decompensated HF during delivery (p <0.05). Compared with historical age-matched controls, patients with normal LVEF exhibited attenuated E′ mitral annular velocities. On follow-up, these patients were associated with a lower New York Heart Association functional class. In conclusion, peripartum HF with normal LVEF appears to be a distinct entity.
PDF
