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Non-cardiac chest pain (NCCP) is defined as recurring, angina-like, chest pain of non-cardiac origin. Studies have estimated that gastroesophageal reflux disease (GERD) is the most common contributing factor for NCCP. In patients with non-GERD related NCCP, esophageal motility disorders, and functional chest pain of presumed esophageal origin are the main underlying mechanisms for symptoms. Epidemiologic studies show a high prevalence of panic disorder, anxiety and major depression in NCCP patients. The diagnostic esophageal workup starts only after that cardiac and pulmonary diseases have been ruled out. NCCP patients with typical reflux symptoms are more likely to have GERD-related NCCP than those without typical reflux symptoms. High-dose proton pump inhibitor trial (PPI test) can be used to confirm the diagnosis of GERD-related NCCP. Negative upper endoscopy is quite common. For patients unresponsive to antireflux treatment and with negative endoscopy, impedance-pH monitoring should be done. Treatment of patients with non-GERD-related NCCP has focused on esophageal (hypercontractile or spastic) motility disorders and esophageal visceral hypersensitivity. In the first case, several trials using calcium channel blockers, nitrates, anticholinergics, or botulinum toxin injection and recent trials with endoscopic myotomy have been conducted. In case of visceral hypersensitivity, studies found that the amelioration, when compared to placebo, was significant with venlafaxine, sertraline, and imipramine. In this context, also cognitive behavioral therapy has been proposed.

Platelet aggregation plays a pivotal role in acute coronary syndrome (ACS). In this setting, β-blockers (BBs) are used to counteract the effects of catecholamines on heart. Circulating catecholamines can also potentiate platelet reactivity, mainly through α2- and β2-adrenoceptors on human platelets' surface, thus BB may affect platelet aggregation; however, the effects of different BBs on platelet aggregation in contemporary-treated patients with ACS have been poorly investigated. One hundred patients with ACS on dual antiplatelet therapy with aspirin and ticagrelor were randomized to receive treatment with carvedilol, a nonselective BB (n = 50), or metoprolol, a selective β1-blocker (n = 50), at maximum tolerated dose. Light transmission aggregometry was performed at randomization (T0) and at 30-day follow-up (T30), and the results were expressed as a percentage of maximum platelet aggregation (MPA). The primary end point was epinephrine-induced MPA at 30 days. Patients were predominantly men (80%), and mean age was 57.3 ± 9.7 years. The 2 randomized groups were well balanced for baseline characteristics. At T0, mean MPA was similar between the groups (18.96 ± 9.05 vs 18.32 ± 9.21 with 10 µM epinephrine, 14.42 ± 9.43 vs 15.98 ± 10.08 with 20 µM adenosine diphophate (ADP), and 13.26 ± 9.83 vs 14.30 ± 9.40 with 10 µM ADP for carvedilol and metoprolol, respectively, all p = NS). At 30 days, platelet aggregation induced by epinephrine was significantly lower in the carvedilol group than in the metoprolol group (23.52 ± 10.25 vs 28.72 ± 14.37, p = 0.04), with a trend toward the lower values of ADP-induced MPA (20 µM ADP 19.42 ± 13.84 vs 24.16 ± 13.62, p = 0.09; 10 µM ADP 19.12 ± 12.40 vs 22.57 ± 13.59, p = 0.19). In conclusion, carvedilol, a nonselective BB, reduces residual platelet reactivity in patients with ACS compared with the selective BB, metoprolol.

Background Peridevice leaks after left atrial appendage closure (LAAC) may increase the risk of embolic stroke. This study appraises the value of a clinically indicated angio-computed tomography (CT) to assess the presence and size of LAA patency after percutaneous closure. Methods We retrospectively analysed patients who underwent LAAC in our centre for a clinically indicated angio-CT to quantify Hounsfield units (HU) in LAA and in the left atrium (LA) and correlated them with the presence and size of LAA leaks at TEE. Results CT scan was available in 56 patients of whom 40 also underwent TEE assessment. Any LAA leak at TEE was present in 9/40 (22.5%) patients of whom all had HU >100 in the LAA. However, HU measured in the LAA was >100 HU in 8 additional patients with no leak at TEE, leading to a sensitivity of 100% (9/9), specificity of 74.1% (23/31) and diagnostic accuracy of 80% (32/40). LAA HU or LAA/LA HU ratio did not discriminate LAA leak size at angio-CT. However, a coaptation gap >3 mm at angio-CT between device and LAA ostium was present in all cases with leak size >3 mm at TEE. Conclusions HU > 100 in the LAA and a coaptation gap >3 mm between device and LAA ostium at angio-CT identified all LAA leaks and those >3 mm at TEE, respectively.

MitoAKAPs (mitochondrial A kinase anchoring proteins), encoded by the Akap1 gene, regulate multiple cellular processes governing mitochondrial homeostasis and cell viability. Although mitochondrial alterations have been associated to endothelial dysfunction, the role of mitoAKAPs in the vasculature is currently unknown. To test this, postischemic neovascularization, vascular function, and arterial blood pressure were analyzed in Akap1 knockout mice ( Akap1 −/− ) and their wild-type (wt) littermates. Primary cultures of aortic endothelial cells (ECs) were also obtained from Akap1 −/− and wt mice, and ECs migration, proliferation, survival, and capillary-like network formation were analyzed under different experimental conditions. After femoral artery ligation, Akap1 −/− mice displayed impaired blood flow and functional recovery, reduced skeletal muscle capillary density, and Akt phosphorylation compared with wt mice. In Akap1 −/− ECs, a significant enhancement of hypoxia-induced mitophagy, mitochondrial dysfunction, reactive oxygen species production, and apoptosis were observed. Consistently, capillary-like network formation, migration, proliferation, and AKT phosphorylation were reduced in Akap1 −/− ECs. Alterations in Akap1 −/− ECs behavior were also confirmed in Akap1 −/− mice, which exhibited a selective reduction in acetylcholine-induced vasorelaxation in mesenteric arteries and a mild but significant increase in arterial blood pressure levels compared with wt. Finally, overexpression of a constitutively active Akt mutant restored vascular reactivity and ECs function in Akap1 −/− conditions. These results demonstrate the important role of mitoAKAPs in the modulation of multiple ECs functions in vivo and in vitro, suggesting that mitochondria-dependent regulation of ECs might represent a novel therapeutic approach in cardiovascular diseases characterized by endothelial dysfunction.

The abnormal wing discs (awd) gene encodes the Drosophila homolog of NME1/NME2 metastasis suppressor genes. Awd acts in multiple tissues where its function is critical in establishing and maintaining epithelial integrity. Here, we analysed awd gene function in Drosophila epithelial cells using transgene-mediated RNA interference and genetic mosaic analysis. We show that awd knockdown in larval wing disc epithelium leads to chromosomal instability (CIN) and induces apoptosis mediated by activation of c-Jun N-terminal kinase. Forced maintenance of Awd depleted cells, by expressing the cell death inhibitor p35, downregulates atypical protein kinase C and DE-Cadherin. Consistent with their loss of cell polarity and enhanced level of matrix metalloproteinase 1, cells delaminate from wing disc epithelium. Furthermore, the DNA content profile of these cells indicates that they are aneuploid. Overall, our data demonstrate a novel function for awd in maintenance of genomic stability. Our results are consistent with other studies reporting that NME1 down-regulation induces CIN in human cell lines and suggest that Drosophila model could be successfully used to study in vivo the impact of NME/Awd - induced genomic instability on tumour development and metastasis formation.

Background Operator experience influences outcomes after percutaneous coronary intervention, but this association in the controlled setting of a randomized, clinical trial is unclear. Methods and Results We investigated operator‐related outcomes (30‐day and 2‐year efficacy and safety end points) among patients undergoing percutaneous coronary intervention and randomized to different dual antiplatelet therapy durations and stent types. A total of 2003 patients were analyzed, and 7 operator groups were compared. The majority of preprocedural and postprocedural characteristics were imbalanced. The primary end point of the study, the composite of death, myocardial infarction, or cerebrovascular accidents, did not differ among operators at 30 days or 2 years. There were no significant differences also for all other individual and composite end points analyzed at 30 days and 2 years, except for 2‐year stent thrombosis ( P =0.048) and bleeding events ( P =0.022 for Bleeding Academic Research Consortium type 2, 3, or 5). Adjusted comparisons for the main end points showed slight differences among operators at 30 days, but not at 2 years. There was no interaction of operator with dual antiplatelet therapy duration ( P =0.112) or stent type ( P =0.300). Results remained entirely consistent when operators were stratified by their experience. Conclusions There was a weak signal of heterogeneity across study operators for the 30‐day, but not the 2‐year, main study outcomes. No clear effect of operator or operator experience was observed for the comparative efficacy and safety profile of the randomized stent types or dual antiplatelet therapy duration regimens. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00611286.

Epithelial morphogenesis contributes greatly to the development and homeostasis of the organs and body parts. Here, we analysed the consequences of impaired ecdysone receptor (EcR) signalling in the Drosophila follicular epithelium. Besides governing cell growth, the three EcR isoforms act redundantly in controlling follicle cell positioning. Flattening of the microvilli and an aberrant actin cytoskeleton arise from defective EcR signalling in follicle cells, and these defects impact on the organisation of the oocyte membrane. We found that this signalling governs a complex molecular network since its impairment affects key molecules as atypical protein kinase C and activated Moesin. Interestingly, the activity of the transcription factor Tramtrack69 isoform is required for microvilli and their actin core morphogenesis as well as for follicle cell positioning. In conclusion, our findings provide evidence of novel roles for EcR signalling and Tramtrack69 transcription factor in controlling stage-specific differentiation events that take place in the follicular epithelium.

Bifurcation geometry and plaque distribution in a diseased left main artery (LM) have the potential to drive operators' decisions regarding treatment strategies, techniques, and material selection. The three-dimensional (3D) geometry of the LM bifurcation typically results in specific patterns of plaque distribution. Plaque distribution may, in turn, significantly affect the procedural and long-term clinical and angiographic outcomes of LM percutaneous coronary intervention. Each LM bifurcation must be treated according to its unique anatomic and pathologic characteristics. Novel classification schemes of plaque distribution and 3D assessment may be valuable aids to obtaining a working picture of the bifurcation geometry.

AIMS: Coronary artery disease is the leading cause of death in western countries, and its association with lower extremity peripheral artery disease (LE-PAD) represents an independent predictor of worse outcome. However, the molecular mechanisms underlying these effects are currently unknown. METHODS AND RESULTS: To investigate these processes, we used in vitro approaches and several mouse models: (i) unilateral limb ischaemia by left common femoral artery ligation [peripheral ischaemia (PI), n = 38]; (ii) myocardial infarction by permanent ligation of the left descending coronary artery (MI, n = 40); (iii) MI after 5 weeks of limb ischaemia (PI + MI, n = 44); (iv) sham operation (SHAM, n = 20). Compared with MI, PI + MI hearts were characterized by a significant increase in cardiomyocyte apoptosis, larger infarct areas, and decreased cardiac function. By using a proteomic approach, we identified a congruent with 8 kDa circulating peptide, Dermcidin (DCD), secreted by ischaemic skeletal muscles, enhancing cardiomyocytes apoptosis under hypoxic conditions and infarct size after permanent coronary artery ligation. siRNA interference experiments to reduce DCD circulating levels significantly reduced infarct size and ameliorated cardiac function after MI. CONCLUSION: Our data demonstrate that chronic limb ischaemia activates detrimental pathways in the ischaemic heart through humoral mechanisms of remote organ crosstalk. Thus, DCD may represent a novel important myokine modulating cardiomyocyte survival and function.

Background: The aim of this study was to assess the feasibility and the safety of early discharge (within 72 h) after transfemoral transcatheter aortic valve implantation (TAVI) and to identify baseline features and/or periprocedural variables, which may affect post-TAVI lengthofstay (LoS) duration. Methods and results: Patients discharged within 72 h of TAVI (early discharge group) were compared with consecutive patients discharged after 3 days (late discharge group). Propensity-matched cohorts of patients with a 2:1 ratio were created to better control confounding bias. Among 465 patients, 107 (23.0%) were discharged within 3 days of the procedure. Multivariable regression analysis of unmatched patients demonstrated that baseline New York Heart Association (NYHA) class IV (OR:0.22, 95% CI 0.05 to 0.96; p=0.045) and any bleeding (OR:0.31, 95% CI 0.74 to 0.92; p=0.031) were less likely to be associated with early discharge after TAVI. Conversely, the year of procedure (OR:1.66, 95% CI 1.25 to 2.20; p

Aims: To evaluate the impact of bivalirudin versus heparin on efficacy and safety outcomes of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (bailout vs. routine) of glycoprotein IIb/IIIa inhibitors (GPI). Methods and Results: Five randomized controlled trials encompassing 10,350 patients were included. Primary efficacy and safety endpoints were all-cause death and major bleeding, respectively. All-cause death at 30 days did not significantly differ with bivalirudin compared to heparin (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.74–1.28; P=0.84). Major bleeding was significantly reduced by bivalirudin compared to heparin (OR 0.58, 95% CI 0.40–0.85; P=0.005). Bivalirudin use was associated with non-significantly different rates of 30-day definite stent thrombosis (ST) (OR 1.71, 95% CI 0.84–3.49; P=0.14), albeit with higher rates of acute ST (OR 3.55, 95% CI 1.67–7.56; P=0.001) and non-significantly different rates of subacute ST (OR 0.86, 95% CI 0.46–1.61; P=0.64). There were non-significant differences in the 30-day rates of reinfarction (OR 1.47, 95% CI 0.94–2.30; P=0.10) and cardiovascular death (OR 0.76, 95% CI 0.56–1.02; P=0.07). There were no significant interactions between bailout versus routine GPI use in the heparin arm for any of the safety or efficacy outcomes (all Pinteraction>0.10). Conclusions: Bivalirudin compared with heparin was associated with comparable 30-day rates of mortality with reduced major bleeding, at the price of an increased risk of acute ST, with non-significant differences in the overall 30-day rates of ST and reinfarction. Intended use of GPI in the heparin arm did not significantly modify the treatment effects of bivalirudin. Given the important differences between trials, as well as evolution in technique and adjunct pharmacotherapy, further randomized trials are warranted to discriminate whether there are substantial safety and efficacy differences between these agents during primary PCI in STEMI.

Background There is conflicting evidence on the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with postoperative acute kidney injury (AKI). Therefore, we conducted a meta-analysis on the impact of AKI on clinical outcomes after TAVI. Methods and Results Twenty-four studies including 5,971 patients were analyzed. The mean incidence of AKI in this population was 22.1% ± 11.2. Postoperative AKI significantly increased early (odds ratio [OR] 5.09; 95% confidence interval [CI], 4.03–6.43 and OR 6.14; 95% CI, 3.26–11.55) and 1-year (OR 3.27; 95% CI, 2.42–4.42 and OR 1.93; 95% CI, 1.38–2.71) all-cause and cardiovascular mortality respectively, but also early myocardial infarction (OR 3.30; 95% CI, 1.44–7.57), life-threatening bleeding (OR 2.90; 95% CI, 1.67–5.05), need for transfusion (OR 2.42; 95% CI, 1.96–2.99), and dialysis (OR 14.35; 95% CI, 6.21–33.20), with a non-significant increase of stroke (OR 1.66; 95% CI, 0.94–2.95), hospitalization (mean difference [MD] 1.73; 95% CI, −0.31 to 3.77) and contrast medium received (MD 4.74; 95% CI, −2.33 to 11.81). Conclusions Postoperative AKI seems to significantly worsen TAVI prognosis. The results of the present meta-analysis should be considered hypothesis-generating and future studies on risk stratification, prevention, and postoperative management are needed. © 2015 Wiley Periodicals, Inc.

The Absorb bioresorbable vascular scaffold (Absorb BVS, Abbott Vascular, Santa Clara, California) promises to address some of the residual shortcomings of existing metallic stents, such as late events induced by permanent caging of the coronary vessel. Scaffold restenosis (ScR) of BVS has been poorly described so far and treatment strategies for this event remain to be codified. We report on a case series of 14 lesions in 12 patients presenting with ScR and discuss their anatomical features and management strategies. © 2015 Wiley Periodicals, Inc.

The optimal antithrombotic therapy for preventing ischemic complications while limiting bleeding risk in patients with acute coronary syndrome (ACS) who are undergoing primary percutaneous coronary intervention (pPCI) remains an area of great controversy [(1)][1]. The quest for an ideal parenteral

The dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor exerts protection against ischemic myocardial recurrences. During last two decades, DAPT has become the mainstay for treating patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), following the initial demonstration that DAPT was superior to anticoagulant therapy in these patients. Initially, and for many years, DAPT was prescribed for 2 to 6 months after PCI in important trials of stent implantation leading to the approval of early-generation drug-eluting stents (DES) by the US Food and Drug Administration. However, the subsequent increasing safety concerns related to the potential occurrence of late and very late stent thrombosis (ST) after implantation of early-generation DES lead to the recommendation of prolonging DAPT to 12 months by the American guidelines (1).

Background The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score

Advanced chronic kidney disease (CKD) is an independent predictor of mortality in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to identify predictors of 1-year mortality in patients after TAVI stratified by the presence or absence of advanced CKD (defined as estimated glomerular filtration rate

Background Adenosine-free coronary pressure wire metrics have been proposed to test the functional significance of coronary artery lesions, but it is unexplored whether their diagnostic performance might be altered in patients with diabetes. Methods We performed a post-hoc analysis of the CONTRAST study, which prospectively enrolled an international cohort of patients undergoing routine fractional flow reserve (FFR) assessment for standard indications. Paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, contrast-based FFR, and FFR) were made. A central core laboratory analyzed blinded pressure tracings in a standardized fashion. Results Of 763 subjects enrolled at 12 international centers, 219 (29%) had diabetes. The two groups were well-balanced for age, clinical presentation (stable or unstable), coronary vessel studied, volume and type of intracoronary contrast, and volume of intracoronary adenosine. A binary threshold of cFFR ≤ 0.83 produced an accuracy superior to both Pd/Pa and iFR when compared with FFR ≤ 0.80 in the absence of significant interaction with diabetes status; indeed, accuracy in subgroups of patients with or without diabetes was similar for cFFR (86.7 vs 85.4% respectively; p = 0.76), iFR (84.2 vs 80.0%, p = 0.29) and Pd/Pa (81.3 vs 78.9%, p = 0.55). There was no significant heterogeneity between patients with or without diabetes in terms of sensitivity and specificity of all metrics. The area under the receiver operating characteristic (ROC) curve was largest for cFFR compared with Pd/Pa and iFR which were equivalent (cFFR 0.961 and 0.928; Pd/Pa 0.916 and 0.870; iFR 0.911 and 0.861 in diabetic and non-diabetic patients respectively). Conclusions cFFR provides superior diagnostic performance compared with Pd/Pa or iFR for predicting FFR irrespective of diabetes (clinicaltrials.gov identifier NCT02184117).

AIMS The aim of this study was to evaluate the efficacy and safety of 24-month vs. six-month dual antiplatelet therapy (DAPT) among elderly (≥75 years) and non-elderly patients (

The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death.Few data exist on the optimal antithrombotic therapy following TAVR.This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population.A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR.This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE Trial [ARTE], NCT01559298; Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI [ARTE], NCT02640794).

Purpose of Review: This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD). Recent Findings: Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y12-platelet receptor. Long-term use of ticagrelor in patients with previous myocardial infarction (MI) has been investigated in the PEGASUS-TIMI-54 trial. Overall, 21,162 patients with a spontaneous MI 1 to 3 years before randomization were randomly assigned to ticagrelor 90 mg bid, ticagrelor 60 mg bid, or placebo. Compared with placebo, both doses of ticagrelor showed that they were capable of significantly reducing the primary efficacy endpoint, although with a significant increase in TIMI major bleeding. Intracranial hemorrhage or fatal bleeding did not differ across groups. Summary: These findings establish clear benefit of DAPT extension with ticagrelor beyond 1 year of treatment, which comes with a tradeoff of clinically meaningful bleeding. Altogether, current evidence suggests that the duration of DAPT remains a patient-by-patient decision based on thrombotic and bleeding risk profiles.

This meta-analysis compares the benefits and harms of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) for adults with severe aortic stenosis and found...

Evidence from studies published more than 10 years ago suggested that patients receiving first-generation drug-eluting stents (DES) needed dual antiplatelet therapy (DAPT) for at least 12 months. Current evidence from randomised controlled trials (RCT) reported within the past five years suggests that patients with stable ischaemic heart disease who receive newer-generation DES need DAPT for a minimum of three to six months. Patients who undergo stenting for an acute coronary syndrome benefit from DAPT for at least 12 months, but a Bayesian network meta-analysis confirms that extending DAPT beyond 12 months confers a trade-off between reduced ischaemic events and increased bleeding. However, the network meta-analysis finds no credible increase in all-cause mortality if DAPT is lengthened from three to six months to 12 months (posterior median odds ratio [OR] 0.98; 95% Bayesian credible interval [BCI]: 0.73-1.43), from 12 months to 18-48 months (OR 0.87; 95% BCI: 0.64-1.17), or from three to six months to 18-48 months (OR 0.86; 95% BCI: 0.63-1.21). Future investigation should focus on identifying scoring systems that have excellent discrimination and calibration. Although predictive models should be incorporated into systems of care, most decisions about DAPT duration will be based on clinical judgement and patient preference.

Objectives The aim of this meta-analysis was to evaluate and compare the efficacy of the 2 different neuroprotection systems in preventing embolization during carotid artery stenting (CAS), as detected by diffusion-weighted magnetic resonance imaging (DW-MRI). Background Data from randomized and nonrandomized studies comparing both types of embolic protection devices revealed contrasting evidence about their efficacy in neuroprotection, as assessed by the incidence of new ischemic lesions detected by DW-MRI. Methods Eight studies, enrolling 357 patients, were included in the meta-analysis. Our study analyzed the incidence of new ischemic lesions/patient, comparing filter cerebral protection and proximal balloon occlusion. Results Following CAS, the incidence of new ischemic lesions/patient detected by DW-MRI was significantly lower in the proximal balloon occlusion group (effect size [ES]: −0.43; 95% confidence interval [CI]: −0.84 to −0.02, I2 = 70.08, Q = 23.40). Furthermore, following CAS, the incidence of lesions at the contralateral site was significantly lower in the proximal protection group (ES: −0.50; 95% CI: −0.72 to −0.27, I2 = 0.00, Q = 3.80). Conclusions Our meta-analysis supports the concept that the use of proximal balloon occlusion compared with filter cerebral protection is associated with a reduction of the amount of CAS-related brain embolization. The data should be confirmed by a randomized clinical trial.

NSAIDs are used worldwide by more than 30 million people everyday, given their anti-inflammatory, analgesic and antipyretic effects. NSAIDs are approved for several common adult diseases, including acute and chronic musculoskeletal or inflammatory disease, osteoarthritis, rheumatoid arthritis and other arthritic conditions, as well as for children with juvenile idiopathic arthritis. Importantly, the population commonly taking NSAIDs is that of older individuals who also represent the population with the highest risk for cardiovascular (CV) and gastrointestinal adverse effects. In recent years, a growing body of evidence regarding potential risks from chronic use of NSAIDs has emerged. The aim of this review is to update the available data concerning chronic use of NSAIDs in patients with and without CV disease by analyzing the mechanisms of action, the interference of specific NSAIDs with the established CV protective role of low-dose aspirin, and the potential increased risk of myocardial infarction, stroke, hypertension, heart failure and atrial fibrillation.

There is conflicting evidence regarding the safety and efficacy of transcatheter aortic valve implantation (TAVI) procedures in patients with severe aortic stenosis and low left ventricular ejection fraction (EF). The primary aim of this study was to determine the impact of TAVI on short- and long-term mortality in patients with low EF (EF50%); the secondary aim was to analyze the impact of TAVI procedure on EF recovery in the same setting of patients.Twenty-six studies enrolling 6898 patients with severe aortic stenosis undergoing TAVI procedure were included in the meta-analysis and analyzed for 30-day, 6-month and 1-year all-cause and cardiovascular mortality; a further meta-analysis was also performed in patients with low EF to assess EF changes post TAVI. In low EF patients, both all-cause and cardiovascular short- and long-term mortality were significantly higher when compared to patients with normal EF (30-day-all-cause mortality: 0.13; 95% confidence interval [CI]: 0.01 to 0.25, I(2)=49.65, Q=21.85; 1-year-all-cause mortality: 0.25; 95% [CI]: 0.16 to 0.34, I(2)=25.57, Q=16.12; 30-day-cardiovascular mortality: 0.03; 95% [CI]: -0.31 to 0.36, I(2)=66.84, Q=6.03; 1-year-cardiovascular mortality: 0.29; 95% [CI]: 0.12 to 0.45, I(2)=0.00, Q=1.88). Nevertheless, in low EF patients TAVI was associated with a significant recovery of EF, which started at discharge and proceeded up to 1-year-follow-up.Patients with low EF severe aortic stenosis have higher mortality following TAVI compared to normal EF patients, despite a significant and sustained improvement in EF.

In recent years, the development of more effective drugs has provided a better prognosis and an increase in life expectancy for patients at all-stages of cancer. On the other hand, the price for the improving effectiveness of therapies against malignant tumors is the development of severe and potentially life-threatening drug reactions. Among these, cardiac toxic effects have recently gained particular attention. The term cardiotoxicity includes many possible pathological manifestations, but the most frequent is the reduction in cardiac function, potentially leading to heart failure and death. Importantly, the development of cardiac dysfunction may occur immediately after drug administration, or after years. The purpose of this review is to discuss the clinical features of cardiotoxicity, its molecular basis and novel possible strategies to reduce the likelihood of serious cardiac complications.

A 48-year-old woman with history of multiple percutaneous coronary interventions and bypass grafting on the left anterior descending coronary artery presented with unstable angina. Coronary angiography showed a patent left internal mammary artery and de novo critical stenoses of the mid-shaft left

Background Lower extremity peripheral arterial disease (LE-PAD) reduces walking capacity and is associated with an increased cardiovascular risk. Endovascular revascularization of LE-PAD improves walking performance and quality of life. In the present study, we determined whether successful lower limbs revascularization also impacts cardiovascular outcome in LE-PAD patients. Methods 479 consecutive LE-PAD patients at stage II of Fontaine's classification, with ankle/brachial index ≤0.90 and one or more stenosis >50% in at least one leg artery, were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 264 (55.1%) underwent percutaneous lower extremity angioplasty (PTA group), while 215 (44.9%) were managed with conservative therapy (MT group). The incidence of major cardiovascular events (including cardiovascular death, myocardial infarction, ischemic stroke, coronary and carotid revascularizations) was prospectively analyzed by Kaplan–Meier curves. Crude and adjusted HRs (95% CI) of developing a cardiovascular event were calculated by Cox analysis. Results No baseline differences were observed among the groups, except for a lower maximum walking distance in the PTA group. During a median follow-up of 21months (12.0–29.0), the incidence of cardiovascular events was markedly lower in PTA compared to MT patients (6.4% vs. 16.3%; p=0.003), and patients in the MT group showed a 4.1-fold increased cardiovascular risk compared to patients in the PTA group, after adjustment for potential confounders (95% CI 1.22–13.57, p=0.023). Conclusions This study shows that successful revascularization of LE-PAD patients affected by intermittent claudication, in addition to improving functional status, reduces the occurrence of future major cardiovascular events.

OBJECTIVE To compare clinical outcomes between short term (up to 6 months) and long term (12 months) dual antiplatelet therapy (DAPT) after placement of a drug eluting stent in patients with and without diabetes. DESIGN Individual participant data meta-analysis. Cox proportional regression models stratified by trial were used to assess the impact of diabetes on outcomes. DATA SOURCE Medline, Embase, and Cochrane databases and proceedings of international meetings searched for randomised controlled trials comparing durations of DAPT after placement of a drug eluting stent. Individual patient data pooled from six DAPT trials. PRIMARY OUTCOME Primary study outcome was one year risk of major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, or definite/probable stent thrombosis. All analyses were conducted by intention to treat. RESULTS Six trials including 11 473 randomised patients were pooled. Of these patients, 3681 (32.1%) had diabetes and 7708 (67.2%) did not (mean age 63.7 (SD 9.9) and 62.8 (SD 10.1), respectively), and in 84 (0.7%) the information was missing. Diabetes was an independent predictor of MACE (hazard ratio 2.30, 95% confidence interval 1.01 to 5.27; P=0.048 At one year follow-up, long term DAPT was not associated with a decreased risk of MACE compared with short term DAPT in patients with (1.05, 0.62 to 1.76; P=0.86) or without (0.97, 0.67 to 1.39; P=0.85) diabetes (P=0.33 for interaction). The risk of myocardial infarction did not differ between the two DAPT regimens (0.95, 0.58 to 1.54; P=0.82; for those with diabetes and 1.15, 0.68 to 1.94; P=0.60; for those without diabetes (P=0.84 for interaction). There was a lower risk of definite/probable stent thrombosis with long term DAPT among patients with (0.26, 0.09 to 0.80; P=0.02) than without (1.42, 0.68 to 2.98; P=0.35) diabetes, with positive interaction testing (P=0.04 for interaction), although the landmark analysis showed a trend towards benefit in both groups. Long term DAPT was associated with higher rates of major or minor bleeding, irrespective of diabetes (P=0.37 for interaction). CONCLUSIONS Although the presence of diabetes emerged as an independent predictor of MACE after implantation of a drug eluting stent, compared with short term DAPT, long term DAPT did not reduce the risk of MACE but increased the risk of bleeding among patients with stents with and without diabetes.

It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI).The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial.Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (0.5 mg/dl) or a relative (25%) increase in serum creatinine (sCr).AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI.In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Controversial data exist regarding the impact of body mass index (BMI) on TAVI outcomes. Thirteen TAVI studies were included and analyzed for the incidence of procedural complications, 30-day, and long-term all-cause mortality. Three comparisons were executed: (1) underweight versus normal weight, (2) overweight versus normal weight, and (3) obese versus normal weight patients. Underweight patients (BMI 30 kg/m(2)) had similar 30-day all-cause mortality rates compared with the normal weight category, whereas they displayed a significant better survival at long-term (hazard ratio 0.79, 95% CI 0.67 to 0.93, p = 0.004). Procedural complications did not differ between obese and normal body weight patients. In conclusion, a low BMI is linked to a significantly worse prognosis after TAVI. Therefore, BMI represents an important and handily tool that might be used in the risk prediction of patients to be addressed for TAVI.

Background— The effectiveness of currently available effective preventive strategies for contrast-induced acute kidney injury (CIAKI) is a matter of debate. Methods and Results— We performed a Bayesian random-effects network meta-analysis of 124 trials (28 240 patients) comparing a total of 10 strategies: saline, statin, N-acetylcysteine (NAC), sodium bicarbonate (NaHCO 3 ), NAC+NaHCO 3 , ascorbic acid, xanthine, dopaminergic agent, peripheral ischemic preconditioning, and natriuretic peptide. Compared with saline, the risk of CIAKI was reduced by using statin (odds ratio [OR], 0.42; 95% credible interval [CrI], 0.26–0.67), xanthine (OR, 0.32; 95% CrI, 0.17–0.57), ischemic preconditioning (OR, 0.48; 95% CrI, 0.26–0.87), NAC+NaHCO 3 (OR, 0.50; 95% CrI, 0.33–0.76), NAC (OR, 0.68; 95% CrI, 0.55–0.84), and NaHCO 3 (OR, 0.66; 95% CrI, 0.47–0.90). The benefit of statin therapy was consistent across multiple sensitivity analyses, whereas the efficacy of all the other strategies was questioned by restricting the analysis to high-quality trials. Overall, high heterogeneity was observed for comparisons involving xanthine and ischemic preconditioning, although the impact of NAC and xanthine was probably influenced by publication bias/small-study effect. Hydration alone was the least effective preventive strategy for CIAKI. Meta-regressions did not reveal significant associations with baseline creatinine and contrast volume. In patients with diabetes mellitus, no strategy was found to reduce the incidence of CIAKI. Conclusions— In patients undergoing percutaneous coronary procedures, statin administration is associated with a marked and consistent reduction in the risk of CIAKI compared with saline. Although xanthine, NAC, NaHCO 3 , NAC+NaHCO 3 , ischemic preconditioning, and natriuretic peptide may have nephroprotective effects, these results were not consistent across multiple sensitivity analyses.

Transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to surgical replacement in patients with severe aortic stenosis. Bleeding and cerebral ischemic events remain frequent complications of this procedure during the periprocedural period and at follow-up with a severe impact on survival. Therefore, there is growing interest towards the optimal antithrombotic therapy to manage patients undergoing TAVI. International guidelines support the adoption of a dual antiplatelet therapy after TAVI, although there is heterogeneity in the suggested duration and the concomitant association with an oral anticoagulant in patients with specific indications, mainly those with atrial fibrillation. Recent data have questioned the benefits of adding clopidogrel to aspirin, showing a slight increase in bleeding compared with aspirin therapy alone. Importantly, recent studies have also underlined the risks of valve thrombosis and the potential benefits of oral anticoagulant therapy in patients undergoing TAVI. Currently, large randomized trials are ongoing and are expected to provide relevant information to guide recommendations on the most appropriate antithrombotic therapy in these patients. Tailored therapy based on the patient's risk profile remains relevant in daily clinical practice.

Aims: Our aim was to report one-year outcomes of Absorb bioresorbable scaffold implantation under realworld conditions in an all-comers population of patients with high proportions of complex lesions. Methods and results: Patients undergoing Absorb 1.1 implantation were included in a single-centre, prospective, all-comers registry. The primary outcome was target lesion failure (TLF), defined as the combination of cardiac death, target vessel myocardial infarction (MI), or clinically driven target lesion revascularisation (TLR). A total of 319 patients received 604 Absorb BVS in 406 lesions. Of note, 24.8% of patients had diabetes and 49.5% presented with an acute coronary syndrome. A total of 51% of lesions were type B2/C. The reference vessel diameter and lesion length were 2.9±0.5 and 21.2±16.8 mm, respectively. The one-year cumulative rate of TLF was 4.9%. Rates of cardiac death, target vessel MI and TLR were 0.9%, 1.3% and 4.2%, respectively. The cumulative one-year rate of definite/probable scaffold thrombosis was 1.3%, with all events occurring within 30 days. Conclusions: These data suggest that twelve-month clinical outcomes of Absorb use in "real-world" unselected patients with high proportions of complex lesions are reasonably good.

Radial approach has been used since 1989 to perform coronary angiography as an alternative to femoral access. During past decades, the development of dedicated equipment has led to high efficacy also in complex procedures. ST elevation myocardial infarction (STEMI) is known to be a high bleeding risk setting and in turn bleeding events can negatively impact on outcomes. Observational studies have demonstrated feasibility, efficacy and safety of radial approach when compared to femoral access in STEMI patients, with benefit in bleeding rates. These advantages have also been described in specific populations such as in the elderly and in patients with cardiogenic shock. Some large randomized trials have been conducted to assess outcomes of transradial access versus transfemoral access, with RIVAL and MATRIX representing the largest two studies. The RIVAL documented a significant reduction in access site-related complications in the global population of acute coronary syndrome (ACS) patients, with also lower mortality and net clinical adverse events (NACE), mainly driven by significant reduction of bleeding and all-cause mortality, in the STEMI sub-group. Overall, the MATRIX trial confirmed that radial access decreased bleeding and all-cause death thus reducing the rate of NACE and supporting the transradial access as the one to be preferred in ACS patients. Clinical advantages of radial access have been also tested in smaller randomized trials corroborating the evidence of radial access as a highly recommendable alternative to femoral access in the setting of primary percutaneous coronary intervention (p-PCI). The current evidence suggests that radial access should become the default access for patients with ACS undergoing invasive management.

The aim of this study was to assess the impact of sex on 2-year outcomes after percutaneous coronary intervention (PCI) in patients randomly allocated to 24-month versus 6-month dual-antiplatelet therapy (DAPT).The optimal duration of DAPT after PCI is highly debated. Whether sex per se should drive decision making on DAPT duration remains unclear.The primary efficacy endpoint of PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3, or 5 bleeding according to the Bleeding Academic Research Consortium criteria.Women (n = 459 [23.3%]) were older and more likely to have hypertension, lower creatinine clearance, and acute coronary syndrome but had a lower severity of coronary artery disease. After adjustment, prolonged DAPT, compared with 6-month treatment, did not reduce the primary endpoint in both men (adjusted hazard ratio: 1.080; 95% confidence interval: 0.766 to 1.522; p = 0.661) and women (adjusted hazard ratio: 1.013; 95% confidence interval: 0.588 to 1.748; p = 0.962) (interaction p = 0.785). No sex disparity was identified across multiple secondary ischemic endpoints, including overall or cardiovascular mortality, myocardial infarction, and stent thrombosis. There was also no clear sex-related effect on clinically relevant bleeding, including Bleeding Academic Research Consortium type 3 or 5, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales.The present findings suggest that men and women undergoing PCI have similar adjusted 2-year ischemic and bleeding outcomes, despite being characterized by different clinical presentation. Sex failed to emerge as a treatment modifier with respect to DAPT duration, suggesting that decision making on DAPT duration in female patients should weigh ischemic versus bleeding risks.

We describe the case of a 50-year-old man with an isolated plaque of the left distal superficial femoral artery (SFA), probably not related to atherosclerosis, but rather to a traumatic event. He was admitted to our hospital because of intermittent claudication. The critical distal SFA stenosis was documented by angiography and the lesion was treated by rotational atherectomy without stent implantation. At 1-year follow up, Doppler Ultrasound scan demonstrated a normal flow pattern of the left SFA and downstream districts in the absence of any complication. Therefore, rotational atherectomy is a safe and effective technique particularly in cases of peripheral arterial disease wherein stent implantation is dangerous.