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Coronary atherosclerosis results from the delicate interplay of genetic and exogenous risk factors, principally taking place in metabolic organs and the arterial wall. Here we show that 224 gene-regulatory coexpression networks (GRNs) identified by integrating genetic and clinical data from patients with (n = 600) and without (n = 250) coronary artery disease (CAD) with RNA-seq data from seven disease-relevant tissues in the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study largely capture this delicate interplay, explaining >54% of CAD heritability. Within 89 cross-tissue GRNs associated with clinical severity of CAD, 374 endocrine factors facilitated inter-organ interactions, primarily along an axis from adipose tissue to the liver (n = 152). This axis was independently replicated in genetically diverse mouse strains and by injection of recombinant forms of adipose endocrine factors (EPDR1, FCN2, FSTL3 and LBP) that markedly altered blood lipid and glucose levels in mice. Altogether, the STARNET database and the associated GRN browser (http://starnet.mssm.edu) provide a multiorgan framework for exploration of the molecular interplay between cardiometabolic disorders and CAD.

Few randomized controlled trials (RCTs) and observational studies had shown acceptable short-term efficacy and safety of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) compared with coronary artery bypass grafting (CABG) in selected patients with left main coronary artery disease (LMCAD). We aimed to evaluate long-term outcomes of PCI using DES compared with CABG in patients with LMCAD. On November 1, 2016, we searched available databases for published RCTs directly comparing DES PCI with CABG in patients with LMCAD. Odds ratios (ORs) were used as the metric of choice for treatment effects using a random-effects model. I-squared index was used to assess heterogeneity across trials. Prespecified end points were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, and repeat revascularization at maximal available follow-up. We identified 5 RCTs including a total of 4,595 patients, with a median follow-up of 60 months. The risk of all-cause mortality (OR 1.01; 95% confidence interval [CI] 0.76 to 1.34) and cardiovascular mortality (OR 1.02; 95% CI 0.73 to 1.42) were comparable between PCI with DES and CABG. Similarly, there were no statistically significant differences between PCI with DES and CABG for MI (OR 1.45; 95% CI 0.87 to 2.40) and stroke (OR 0.87; 95% CI 0.38 to 1.98). Conversely, repeat revascularization was significantly higher with PCI compared with CABG (OR 1.82; 95% CI 1.51 to 2.21). In conclusion, in patients with LMCAD, PCI with DES appears to be a viable alternative to CABG at long-term follow-up, with similar risks of ischemic adverse events (mortality, MI, and stroke) but a higher risk of repeat revascularization.

AIMS Patients with human immunodeficiency virus (HIV) infection have an increased risk of acute myocardial infarction (MI), and 6.5-15% of mortality in this population is attributable to cardiovascular disease. However, the angiographic pattern of coronary artery disease (CAD) in patients with HIV undergoing percutaneous coronary intervention (PCI) remains unknown. We sought to assess and describe the angiographic features and burden of CAD in patients with HIV as compared to those without HIV infection. METHODS AND RESULTS This is a retrospective, single-centre study comparing 93 patients with HIV infection who underwent PCI between 2003 and 2011 with 93 control patients without HIV infection matched for age (±3 years), gender, diabetes, and year of PCI (±2 years). Quantitative coronary angiography (QCA) was performed for all treated lesions at baseline and following PCI in both groups. One-year clinical outcomes post PCI were also analysed and compared. The mean age for both study populations was 57 years; patients with HIV were more likely to present with ST-segment elevation myocardial infarction (STEMI). Patients had a similar extent of CAD as measured by the presence of multivessel disease as well as SYNTAX score; however, patients with HIV were more likely to have lesions in the proximal segment of the respective coronary artery. While both groups mostly displayed none/mild calcified lesions, HIV+ patients had longer and fewer stenotic lesions. Clinical outcomes at one year were similar. CONCLUSIONS While HIV+ patients were more likely to present with STEMI, detailed coronary angiographic analysis revealed less complex lesions and favourable anatomy. This paradox may suggest alterations in genesis and progression of atherosclerosis in this clinical setting.

Key Clinical Message Possible links between inflammatory stimuli and atherothrombotic disease in the context of gallbladder pathology are not well understood. Our case demonstrates that clinical suspicion of cardiac disease after a diagnosis of acute cholecystitis should remain high in light of the dire consequences of a missed diagnosis.

In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same coronary lesion, despite percutaneous coronary intervention (PCI), is a rare but challenging problem that has not been reported. We aim to describe what we propose as the occurrence of "resistant"-ISR (R-ISR) in the DES era, including angiographic patterns and outcomes. We defined R-ISR as the recurrence of an ISR episode after successful treatment of the same lesion. We identified 276 consecutive patients with 291 lesions who had R-ISR between May 2003 and June 2012. Quantitative coronary angiography (QCA) was performed for the first and second ISR episodes. Outcomes at one year, including death, myocardial infarction (MI), and target lesion failure (TLF), were analyzed. Patients with R-ISR had a high frequency of diabetes (62%), chronic kidney disease (39%), bifurcation lesions (51%), and moderate to severe calcified lesions (52%). The most common pattern of R-ISR was focal (77%). R-ISR lesions were treated with DES implantation (55%) or balloon-only strategy (45%). The mortality rate and TLF at 2-years were 9.3% and 51% respectively. The overall 2-year TLF rate did not vary with the originally implanted stent, angiographic pattern (focal versus diffuse), or revascularization strategy. R-ISR appears to consist predominantly of focal lesions and occurs in patients at high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. Clinical outcomes are suboptimal irrespective of angiographic pattern or treatment strategy, indicating the recalcitrant nature of the disease, and need for aggressive treatment of cardiovascular risk factors and novel interventional approaches. In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same lesion, despite percutaneous coronary intervention, is a rare and challenging problem. We described the "resistant"-ISR (R-ISR) phenomena in the DES era, i.e. the recurrence of an ISR after a successful treatment of that same episode. We identified 276 consecutive patients with R-ISR, who presented with a high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. The most common pattern of R-ISR was focal. The overall 2-year TLF rate exceeded 50% and did not vary significantly with the original stent implanted, angiographic pattern, or type of percutaneous revascularization. © 2016 Wiley Periodicals, Inc.

Objectives This study sought to assess the mechanistic effect of rotational atherectomy (RA) and orbital atherectomy (OA) on heavily calcified coronary lesions and subsequent stent placement using optical coherence tomography (OCT). Background RA and OA are two main approaches to ablate coronary calcium. While small case reports have described the mechanistic effect of RA in calcified coronary lesions, there has been no imaging study to assess the effect of OA on coronary artery architecture and/or compare the effects of two atherectomy devices. Methods This study analyzed 20 consecutive patients with OCT imaging performed after atherectomy and after stent implantation, RA (n = 10) and OA (n = 10). Results Postatherectomy OCT analysis identified tissue modification with deep dissections in around a third of lesions after RA and OA; however, post OA dissections (“lacunae”) were significantly deeper (1.14 vs. 0.82 mm, P = 0.048). Post OA/RA lesions with dissections had significantly higher percentage of lipid rich plaques and smaller calcification arcs as compared to plaques without dissections. Stents after OA were associated with a significantly lower percent of stent strut malapposition than post RA stents (4.36 vs. 8.02%, P = 0.038). Conclusions Although the incidence of dissections was comparable between RA and OA cases, OA resulted in deeper tissue modifications (lacunae) as shown by OCT imaging. The finding might provide an explanation for a better stent apposition after OA as compared to RA. Their impact on long-term outcome needs to be determined. © 2015 Wiley Periodicals, Inc.

Background: Whereas statins are well-known to contribute to atheromatic plaque stability and regression of atherosclerosis burden, possible interactions with anti-retroviral therapy have led to sub-prescription in this cohort. However, exactly how statins affect the angiographic phenotype, coronary lesion characteristics and clinical outcomes in HIV patients undergoing PCI has not yet been investigated. Aim: To assess and describe the angiographic features and burden of Coronary Artery Disease (CAD) between HIV patients pre-treated with statins as compared to statin naïve patients undergoing Percutaneous Coronary Intervention (PCI). Methods: This is a retrospective, single-center study comparing pre-treated with statin to statin-naïve HIV patients who underwent PCI between 2003-2011. Quantitative coronary angiography (QCA) was performed for all treated lesions at baseline and following PCI in both groups. 1- Year clinical outcomes post-PCI were also analyzed and compared. Results: Statin pre-treated patients (n=47, 51%) had more frequently hyperlipidemia (95% vs. 50%, p Conclusion: While statin pre-treatment HIV patients were more likely to present with ACS and had worse cardiovascular risk profile, detailed coronary angiographic analysis reveals no significant differences in CAD burden and lesion characteristics. Statin use is associated with more favorable clinical outcomes at 1 year post-PCI suggesting the beneficial effects of statins in atherosclerosis progression in HIV patients.

Aims The aim of this study was to evaluate the safety and efficacy profile of new-generation, SYNERGY everolimus-eluting stents (S-EES) as compared to XIENCE everolimus-eluting stents (X-EES) with a durable polymer coating in "complex patients". Methods and results We included 2,001 consecutive patients treated with S-EES (n=400) or X-EES (n=1,601) at two Italian centres between May 2013 and May 2015. We used propensity score matching to obtain two cohorts of patients with similar baseline risk profiles. Patients were stratified according to baseline complexity based on the EVOLVE II trial exclusion criteria. The primary outcome was major adverse cardiac events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), and target lesion revascularisation (TLR), at one year. Among 391 matched pairs of patients treated with S-EES or X-EES, we identified 253 (63%) as complex. At one-year follow-up, among "complex" patients, MACE rates did not differ between the S-EES and X-EES groups (9.9% vs. 9.5%, p=0.830, HR 1.04, CI: 0.72-1.48). Similarly, death, MI, and TLR, stratified for complexity, were comparable between S-EES and X-EES treated patients at one year. Of note, no definite ST was observed in either the S-EES or the X-EES cohort. Conclusions New-generation S-EES with a bioresorbable polymer coating appear to be safe and effective irrespective of patient complexity as compared to X-EES.

Objective: To elucidate a proposed role of TACI, a tumor necrosis factor (TNF) family member of human B cells, in atherosclerosis. Whereas atherosclerosis has been characterized by inflammation, adaptive immunity, and specifically the role of B cells and their respective cytokine processes have not, and thus we focused on the role of a B cell homeostasis regulator, TACI. We chose TACI because it has been shown, in combination with immunoglobulins, to inhibit cells involved in the innate response, known to be the initial responders to atherosclerosis. Approach and Results: As there are two isoforms of TACI in mice, we needed to first confirm whether human B cells had one or two isoforms, before understanding preferential expression. To this end, we examined peripheral blood mononuclear cells (PBMCs), multiple myeloma cell lines and Hodgkin’s disease cells and found that both the longer and the shorter isoform of TACI are expressed. We did this by: stimulation of cell lines with IL-6, western blot analysis and densitometry, polymerase chain reaction. Student’s t-test, with the use of Statistical Analysis System (Cray, NC), for statistical analysis. Conclusion: Thus, based on our findings of the existence of both isoforms, functional analyses in cardiomyocytes would shed light on any proposed role of TACI in the context if coronary artery disease.

In the drug eluting stent (DES) era, repeat in-stent restenosis (ISR) of the same coronary lesion, despite percutaneous coronary intervention (PCI), is a rare but challenging problem that has not been reported. We aim to describe what we propose as the occurrence of "resistant"-ISR (R-ISR) in the DES era, including angiographic patterns and outcomes.We defined R-ISR as the recurrence of an ISR episode after successful treatment of the same lesion. We identified 276 consecutive patients with 291 lesions who had R-ISR between May 2003 and June 2012. Quantitative coronary angiography (QCA) was performed for the first and second ISR episodes. Outcomes at one year, including death, myocardial infarction (MI), and target lesion failure (TLF), were analyzed.Patients with R-ISR had a high frequency of diabetes (62%), chronic kidney disease (39%), bifurcation lesions (51%), and moderate to severe calcified lesions (52%). The most common pattern of R-ISR was focal (77%). R-ISR lesions were treated with DES implantation (55%) or balloon-only strategy (45%). The mortality rate and TLF at 2-years were 9.3% and 51% respectively. The overall 2-year TLF rate did not vary with the originally implanted stent, angiographic pattern (focal versus diffuse), or revascularization strategy.R-ISR appears to consist predominantly of focal lesions and occurs in patients at high clinical and angiographic risk, conceivably owing to their unique diabetic and coronary calcification profile. Clinical outcomes are suboptimal irrespective of angiographic pattern or treatment strategy, indicating the recalcitrant nature of the disease, and need for aggressive treatment of cardiovascular risk factors and novel interventional approaches. © 2016 Wiley Periodicals, Inc.

Whereas statins are well-known to contribute to atheromatic plaque stability and regression of atherosclerosis burden, possible interactions with anti-retroviral therapy have led to sub-prescription in this cohort. However, exactly how statins affect the angiographic phenotype, coronary lesion

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are at high-risk for thromboembolic and bleeding events. However, the influence of left ventricular dysfunction (LVD) on PCI outcomes and the post-procedural anti-thrombotic strategy in AF patients remains

Patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) are at elevated risk for bleeding and thromboembolic ischemic events. Currently, guidelines on antithrombotic treatment for these patients are based on weak consensus. We describe patterns and determinants of antithrombotic prescriptions in this population. The Antithrombotic Strategy Variability in Atrial Fibrillation and Obstructive Coronary Disease Revascularized with PCI Registry was an international observational study of 859 consecutive patients with AF who underwent PCI from 2009 to 2011. Patients were stratified by treatment at discharge with either dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) or triple therapy (TT; warfarin plus DAPT). Bleeding and thromboembolism risks were assessed by the HAS-BLED and CHADS2 scores, respectively, and predictors of TT prescription at discharge were identified. Major adverse cardiovascular events and clinically relevant bleeding (Bleeding Academic Research Consortium score ≥2) at 1-year follow-up were compared across antithrombotic regimens. Compared with patients on DAPT (n = 488; 57%), those given TT (n = 371; 43%) were older, with higher CHADS2 scores, lower left ventricular ejection fraction, and more often had permanent AF, single-vessel coronary artery disease, and bare-metal stents. In multivariate analysis, increasing thromboembolic risk (CHADS2) was associated with a higher rate of TT prescription at discharge (intermediate vs low CHADS2: odds ratio 2.2, 95% confidence interval [CI] 2.0 to 3.3, p0.01; high vs low CHADS2: odds ratio 1.6, 95% CI 2.6 to 4.3, p0.01 for TT). However, there was no significant association between bleeding risk and TT prescription in the overall cohort or within each CHADS2 risk stratum. The rates of major adverse cardiovascular events were similar for patients discharged on TT or DAPT (20% vs 17%, adjusted hazard ratio 0.8, 95% CI 0.5 to 1.1, p = 0.19), whereas the rate of Bleeding Academic Research Consortium ≥2 bleeding was higher in patients discharged on TT (11.5% vs 6.4%, adjusted hazard ratio 1.8, 95% CI 1.1 to 2.9, p = 0.02). In conclusion, the choice of the intensity of antithrombotic therapy correlated more closely with the risk of ischemic rather than bleeding events in this cohort of patients with AF who underwent PCI.

Percutaneous coronary intervention (PCI) of true bifurcation lesions (Medina classification 1, 1, 1; 1, 0, 1; or 0, 1, 1) is challenging and may involve either a 1-stent strategy with provisional side branch stenting, or a 2-stent strategy. Diabetes mellitus is associated with greater atherosclerotic burden and higher incidence of bifurcation lesions, and unfavorable outcomes after PCI. It is unknown whether use of newer everolimus-eluting stent (EES) implantation impacts relative outcomes of 1-stent and 2-stent strategies in patients with diabetes.We performed a retrospective analysis of consecutive patients with diabetes mellitus and complex true bifurcation lesions (side branch diameter2.0 mm) who underwent PCI with EES between February 2010 and December 2011. We grouped subjects based on initial treatment to a 1-stent (n = 81) or 2-stent (n = 54) strategy, and compared baseline characteristics, quantitative coronary angiography, and 1-year major adverse cardiovascular event (MACE) rates, defined as death, myocardial infarction, target lesion revascularization (TLR), or target vessel revascularization (TVR).Baseline characteristics were well matched. A 2-stent strategy was associated with larger side-branch reference vessel diameter at baseline and post PCI. In-hospital events included 1 periprocedural myocardial infarction in each group and no deaths. At 1 year, there was no significant difference between 1-stent and 2-stent strategies in TVR rates (6.2% vs 3.7%; P=.53), TLR (both 3.7%; P.99), or MACE (7.4% vs 3.7%; P=.37).In this series of diabetic patients undergoing complex bifurcation PCI using EES implantation, there was no difference between 1-stent and 2-stent strategies with respect to ischemic events at 1 year.

Whereas the effects of stent thrombosis in bare metal stents and drug eluting stents on mortality and myocardial infarction have been well documented in the literature, there are currently no reports of the effects of scaffold thrombosis on these outcomes of the newest stents in ABSORB bioresorbable

Cardiovascular risk in patients with advanced aortic stenosis (AS) remains substantial following treatment with balloon aortic valvuloplasty (BAV). While concomitant atrial fibrillation or flutter (AF/AFL) is frequent among patients with AS, the impact of AF/AFL on outcomes following BAV remains

This study sought to assess the mechanistic effect of rotational atherectomy (RA) and orbital atherectomy (OA) on heavily calcified coronary lesions and subsequent stent placement using optical coherence tomography (OCT).RA and OA are two main approaches to ablate coronary calcium. While small case reports have described the mechanistic effect of RA in calcified coronary lesions, there has been no imaging study to assess the effect of OA on coronary artery architecture and/or compare the effects of two atherectomy devices.This study analyzed 20 consecutive patients with OCT imaging performed after atherectomy and after stent implantation, RA (n = 10) and OA (n = 10).Postatherectomy OCT analysis identified tissue modification with deep dissections in around a third of lesions after RA and OA; however, post OA dissections ("lacunae") were significantly deeper (1.14 vs. 0.82 mm, P = 0.048). Post OA/RA lesions with dissections had significantly higher percentage of lipid rich plaques and smaller calcification arcs as compared to plaques without dissections. Stents after OA were associated with a significantly lower percent of stent strut malapposition than post RA stents (4.36 vs. 8.02%, P = 0.038).Although the incidence of dissections was comparable between RA and OA cases, OA resulted in deeper tissue modifications (lacunae) as shown by OCT imaging. The finding might provide an explanation for a better stent apposition after OA as compared to RA. Their impact on long-term outcome needs to be determined.