There are on-going preclinical and clinical studies to develop better stent platforms, more biocompatible polymers, novel anti-proliferative and anti-platelet drugs, pro-healing stents and bioresorbable scaffolds.

Patients with severely calcified lesions have worse clinical outcomes compared to those without severe coronary calcification. Severe coronary calcification appears as an independent predictor of worse prognosis, and should be considered as a marker of advanced atherosclerosis.

Current generation of drug-eluting stents has significantly improved the outcomes of percutaneous coronary intervention by substantially reducing in-stent restenosis and stent thrombosis. However, a potential limitation of these stents is the permanent presence of a metallic foreign body within the artery, which may cause vascular inflammation, restenosis, thrombosis, and neoatherosclerosis. The permanent stents also indefinitely impair the physiological vasomotor function of the vessel and future potential of grafting the stented segment. Bioresorbable scaffolds (BRSs) have the potential to overcome these limitations as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage and restoring pulsatility, cyclical strain, physiological shear stress, and mechanotransduction. While a number of BRSs are under development, two devices with substantial clinical data have already received a Conformité Européenne marking. This review article presents the current status of these devices and evaluates the challenges that need to be overcome before BRSs can become the workhorse device in coronary intervention.

AimsChronic heart failure (CHF) due to left ventricular systolic dysfunction is associated with poor quality of life (QoL). This study aimed to assess factors affecting health-related QoL in CHF patients and their carers and the impact of QoL on clinical outcomes. Methods and resultsDemographic, social, and clinical data were collected for consecutive CHF patients in an academic hospital setting. All patients (n ¼ 179) and informal carers (n ¼ 131) completed a generic QoL questionnaire (EQ-5D) and patients also completed a CHF-specific QoL questionnaire (Minnesota Living with Heart Failure Questionnaire, MLHFQ). Patients were then followed up for 3 years to assess subsequent hospitalizations and mortality. Minnesota Living with Heart Failure Questionnaire score was independently predicted by NYHA class, socioeconomic deprivation and lack of an informal carer. Severity of heart failure, anaemia, and cancer co-morbidity in CHF patients were associated with poor QoL in carers. Chronic heart failure patients with poor baseline QoL (MLHFQ . median) were at increased risk of hospital admissions [hazard ratios (HR) 7.3, P , 0.001] and death (HR 1.5, P ¼ 0.09). Mortality was also independently associated with repeat hospitalization (HR 6.0, P , 0.001) and lack of beta-blocker therapy (HR 1.8, P ¼ 0.03). ConclusionSevere heart failure, poor socioeconomic status and lack of social support results in poor QoL in CHF patients which in turn leads to an increased risk of hospital admissions and death. Quality of life in carers is lower in female carers, those with socioeconomic deprivation and those caring for patients with higher NYHA class or having a cancer. Quality of life assessment may complement clinical prognostic markers to identify CHF patients at high risk of adverse events.--

Background-There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results-The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions-The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted. Clinical Trial Registration-URL: http://www.clinicaltrials.gov.

The therapeutic potential for manipulation of glucocorticoid metabolism in cardiovascular disease was revolutionized by the recognition that access of glucocorticoids to their receptors is regulated in a tissue-specific manner by the isozymes of 11b-hydroxysteroid dehydrogenase. Selective inhibitors of 11b-hydroxysteroid dehydrogenase type 1 have been shown recently to ameliorate cardiovascular risk factors and inhibit the development of atherosclerosis. This article addresses the possibility that inhibition of 11b-hydroxsteroid dehydrogenase type 1 activity in cells of the cardiovascular system contributes to this beneficial action. The link between glucocorticoids and cardiovascular disease is complex as glucocorticoid excess is linked with increased cardiovascular events but glucocorticoid administration can reduce atherogenesis and restenosis in animal models. There is considerable evidence that glucocorticoids can interact directly with cells of the cardiovascular system to alter their function and structure and the inflammatory response to injury. These actions may be regulated by glucocorticoid and/or mineralocorticoid receptors but are also dependent on the 11b-hydroxysteroid dehydrogenases which may be expressed in cardiac, vascular (endothelial, smooth muscle) and inflammatory (macrophages, neutrophils) cells. The activity of 11b-hydroxysteroid dehydrogenases in these cells is dependent upon differentiation state, the action of pro-inflammaotory cytokines and the influence of endogenous inhibitors (oxysterols, bile acids). Further investigations are required to clarify the link between glucocorticoid excess and cardiovascular events and to determine the mechanism through which glucocorticoid treatment inhibits atherosclerosis/restenosis. This will provide greater insights into the potential benefit of selective 11b-hydroxysteroid dehydrogenase inhibitors in treatment of cardiovascular disease.

The hemodynamic microenvironment appears to regulate neointimal response following an Absorb BVS implantation. These findings underline the role of the ESS patterns on vessel wall healing and should be taken into consideration in the design of bioresorbable devices.

11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) is a therapeutic target in metabolic syndrome because it catalyses reductase regeneration of cortisol from cortisone in adipose and liver. 11βHSD1 can also catalyze the reverse dehydrogenase reaction in vitro (e.g., if cofactor is limited). We used stable isotope tracers to test the hypothesis that both 11βHSD1-reductase and -dehydrogenase activities occur in human metabolic tissues in vivo. 1,2-[2H]2-Cortisone (d2-cortisone) was validated as a tracer for 11β-dehydrogenase activity and its inhibition by licorice. d2-Cortisone and 9,11,12,12-[2H]4-cortisol (d4-cortisol) (to measure 11β-reductase activity) were coinfused and venous samples obtained from skeletal muscle, subcutaneous adipose (n = 6), and liver (n = 4). Steroids were measured by liquid chromatography–tandem mass spectrometry and arteriovenous differences adjusted for blood flow. Data are means ± SEM. 11β-Reductase and -dehydrogenase activities were detected in muscle (cortisol release 19.7 ± 4.1 pmol/100 mL/min, d3-cortisol 5.9 ± 1.8 pmol/100 mL/min, and cortisone 15.2 ± 5.8 pmol/100 mL/min) and splanchnic (cortisol 64.0 ± 11.4 nmol/min, d3-cortisol 12.9 ± 2.1 nmol/min, and cortisone 19.5 ± 2.8 nmol/min) circulations. In adipose, dehydrogenase was more readily detected than reductase (cortisone release 38.7 ± 5.8 pmol/100 g/min). Active recycling between cortisol and cortisone in metabolic tissues in vivo may facilitate dynamic control of intracellular cortisol but makes consequences of dysregulation of 11βHSD1 transcription in obesity and diabetes unpredictable. Disappointing efficacy of 11βHSD1 inhibitors in phase II studies could be explained by lack of selectivity for 11β-reductase.