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Introduction: Coronary artery disease and malignancy occur more frequently in patients with type 2 diabetes. They may share inflammation as a possible common pathogenetic mechanism, but it is unclear whether a clinical correlation exists between them. Methods: This prospective cohort study followed 735 asymptomatic diabetics, aged 63.4 ± 5.3 years (mean ± standard deviation) for 12.2 ± 0.6 years after baseline coronary artery calcium scoring and cardiac computed tomography angiography. We examined extent and nature of coronary atherosclerosis and incidence of clinical cardiovascular (CV) events (death or myocardial infarction) and sought a relation to incidence of malignancy and malignancy mortality. Results: Total mortality was 16.5% (121/735 patients): malignancy was cause of death in 48/121 (39.7%) of these and CV events in 44/121 (36.3%). There was no relation between extent of coronary atherosclerosis and incident malignancy (plaque volume 127 [21, 427] mm3 (median [interquartile range]) for incident malignancy versus 153 [24, 427] mm3 no malignancy, p = 0.71) or death from malignancy (plaque volume 176 [26, 646] versus 144 [22, 411] mm3, p = 0.32). There was also no relation between presence of high-risk plaque and incident malignancy (high-risk plaque in 27.1% with malignancy vs. 21.6% without, p = 0.18) or fatal malignancy (p = 0.16). Incident and fatal malignancy were not related to clinical CV events. Independent predictors of incident and fatal malignancy were age, smoking at baseline, and elevated C-reactive protein. Conclusion: This study found no relation between extent of coronary atherosclerosis or incidence of CV events and malignancy. Malignancy surpassed CV disease as the commonest long-term cause of mortality in middle-aged and older diabetics. [ABSTRACT FROM AUTHOR]

This study examined the relation between high-sensitivity C-reactive protein (CRP), exercise-induced myocardial ischemia, and exercise tolerance in 288 stable patients who underwent maximal treadmill stress testing. CRP was correlated with peak exercise workload, which was consistent with the long-term predictive value of peak workload and CRP for outcome events. There was no correlation of high-sensitivity CRP with stress-induced ischemia, which is consistent with a lack of correlation between CRP and the degree of chronic luminal coronary arterial narrowing. [Copyright &y& Elsevier]

The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI. The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo. The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis–related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations. [Display omitted] [ABSTRACT FROM AUTHOR]

Integrated myocardial revascularization combines the advantages of angioplasty, stenting, and minimally invasive surgery to revascularize patients with multivessel coronary artery disease without cardiopulmonary bypass. This pilot study showed that a new same-day management strategy, consisting of percutaneous coronary intervention followed immediately by minimally invasive surgery, was feasible and provided complete all-arterial revascularization with minimal surgical trauma, short hospital stay, and excellent early therapeutic result in 14 patients with multivessel coronary disease. [ABSTRACT FROM AUTHOR]

Information on topics discussed at the 11th International Congress on Coronary Artery Disease (ICCAD) that was held in Florence, Italy is presented. Topics discussed at the conference include stem cell therapy, percutaneous coronary interventions, and lecture on reperfusion injury presented by professor Roberto Ferrari.

Information about the 11th International Congress on Coronary Artery Disease (ICCAD) held in Florence, Italy in 2016 is presented. The conference featured a presentation by professor Roberto Ferrari, dean of the University of Ferrara School of Medicine, about reperfusion injury. The other topics discussed at the conference concerned on coronary artery disease.

Aims: Coronary artery disease (CAD) portends worse outcomes in heart failure (HF). We aimed to characterize patients with CAD and worsening HF with reduced ejection fraction (HFrEF) and evaluate post hoc whether vericiguat treatment effect varied according to CAD. Methods and results: Cox proportional hazards were generated for the primary endpoint of cardiovascular death or HF hospitalization (CVD/HFH). CAD was defined as previous myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting. Of 5048 patients in VICTORIA with available data on CAD status, 2704 had CAD and were older, were more frequently male, diabetic, and had a lower glomerular filtration rate than those without CAD (all p <0.0001). Use of implantable cardioverter defibrillators and cardiac resynchronization therapy (CRT) was higher in patients with versus without CAD (33.5% vs. 21.1%; p <0.0001 and 16.3% vs. 12.8%; p = 0.0006). The primary endpoint of CVD/HFH was higher in those with versus without CAD (40.6 vs. 30.1/100 patient‐years; adjusted hazard ratio [HR] 1.23; p <0.001) as was all‐cause mortality (17.9% vs. 12.7%; adjusted HR 1.32; p <0.001). The primary outcome of CVD/HFH associated with vericiguat in patients with or without CAD was 38.8 versus 27.6 per 100 patient‐years and for placebo was 42.6 versus 32.7 per 100 patient‐years (interaction p = 0.78). Conclusion: In this post hoc study, CAD was associated with more CVD and HFH in patients with HFrEF and worsening HF. Vericiguat was beneficial and safe regardless of concomitant CAD. [ABSTRACT FROM AUTHOR]

Abstract: Aims: High-risk patients with severe aortic stenosis (AS) who are candidates for transcatheter valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) may additionally require revascularization of the unprotected left main coronary artery (UPLM). We aimed to assess the feasibility and procedural safety of UPLM stenting in such patients. Methods and Results: Ten cases of UPLM stenting prior to BAV or TAVI at three medical centers over a 2-year period were identified. Mean age was 84±4 years, aortic valve area was 0.70±0.12 cm2, left ventricular ejection fraction was 58%±3%, and logistic EuroScore was 32±17. Intraaortic balloon counterpulsation was used in three patients. A single stent was used in seven patients, and two stents were used in three patients. One patient received a bare-metal stent, and the others received drug-eluting stents. No procedural complications occurred, and the patients were hemodynamically stable. Three patients subsequently underwent BAV, and seven underwent TAVI. During 6 months of follow-up, two patients died: one due to AS restenosis 6 months after BAV and one due to vascular complications 18 days after TAVI (34 days after UPLM stenting). Conclusions: Stenting of the UPLM in patients with severe AS prior to percutaneous valve intervention seems feasible and safe. This approach may enable more patients to achieve comprehensive percutaneous therapy for severe coronary and valvular disease. [Copyright &y& Elsevier]

Abstract: Background and aims: Medical personnel generally believe that non-ST elevation (NSTE) acute coronary syndromes (ACS) are less damaging than ST elevation myocardial infarction (STEMI), in keeping with the lower morbidity and mortality attributed to these subgroups in randomized clinical trials. We examined whether this concept translates into a difference from the patients'' point of view regarding lifestyle modification and return to work following hospitalization for ACS. Methods: A structured anonymous self-completed questionnaire was mailed and returned by 160 consecutive patients (age 64±11 years; 125 (78%) men) 3–12 months after hospitalization for ACS. In 49 patients, the diagnosis was unstable angina pectoris (UAP), in 34 non-ST elevation myocardial infarction (NSTEMI) and in 73, ST elevation myocardial infarction (STEMI). The questionnaire addressed issues relating to demographic data, medical history, occupation, employment and income before the acute event, changes following hospitalization for ACS and questions relating to current perceived health status and return to work. Results: Most (98/159, 62%) patients saw themselves as “heart patients” after hospitalization for ACS. Quality of life was perceived to have decreased in 70 (44%), self-image in 85 (53%), self-confidence in 78 (49%) and sexual function in 75 (48%), with no differences according to ACS type. Anxiety was reported by 85 (54%) patients and anxiety level (1.47±1.25 on the Brief Symptom Inventory scale) was high. Only 38 (49%) of 77 patients who were working prior to the acute event returned to full- or part-time gainful employment. By multivariate analysis, return to work was associated with 3 variables: younger age (p =0.015), shorter duration of hospitalization (p =0.036) and higher income bracket prior to the acute event (p =0.0001), with no relation to gender, in-hospitalization revascularization strategy, rehabilitation program or to underlying cardiac diagnosis (UAP, NSTEMI or STEMI). Conclusions: Hospitalization for ACS had a major negative impact on patient lifestyle and return to work, irrespective of the underlying cardiac diagnosis. The experience of hospitalization for an acute heart condition was uniformly traumatic with in many instances a prolonged adverse effect on patient function. [Copyright &y& Elsevier]

Abstract: Arterial obstructive syndromes result in heart disease, stroke and limb loss, disability, and mortality. Currently available therapeutics for patients with these conditions are inadequate or fail in a significant number of patients. The development of novel therapies for severe coronary arterial disease (CAD), peripheral arterial disease (PAD), and cerebral vascular disease (CVD) is a major goal for modern medicine. Molecular and cell-based therapies for arterial obstructive syndromes have the potential to become clinically useful in the near future. Molecular therapy employs angiogenic proteins and genes in order to initiate the development of new blood vessels that by-pass an arterial occlusion. The induction of a collateral artery system is termed therapeutic angiogenesis or neovascularization. Proteins have been delivered either directly into the ischemic area or via a vector encoding an angiogenic gene. Both protein and gene therapies have been associated with promising preclinical and early phase human trial results in patients with PAD as well as CAD. However, to date, efficacy has not been demonstrated in placebo-controlled, large trails. Today''s cell-based therapy is focused on stem cells (SCs) for the treatment of patients after acute myocardial infarction (AMI) or for patients with severe left ventricular dysfunction. Stem cells have shown to increase cardiac performance in uncontrolled, early phase human studies. This improvement is believed to have its origin in myogenesis and neovascularization. In the following review, we will cover current state of molecular- and cellular-based treatments for PAD and CAD that have reached the clinical arena. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to assess the accuracy of a new generation spiral multidetector computed tomography (MDCT) scanner (Brilliance 40, Philips Medical Systems, Cleveland, Ohio) in the diagnosis of coronary in-stent restenosis (ISR). Background: Noninvasive imaging of ISR would be clinically useful, but artifacts caused by metallic stent struts have limited the role of early generation MDCT scanners. Methods: We examined 65 patients (age 63 ± 12 years, 48 [73.8%] men) with 111 implanted coronary stents who were referred for repeat invasive coronary angiography (ICA). Patients underwent 40-slice MDCT one to three days before scheduled ICA, using intravenous contrast enhancement. Images were reconstructed in multiple formats using retrospective electrocardiographic gating. Stents were viewed in their long and short axes and luminal contrast attenuation graded from MDCT grade 1 (minimal restenosis) to 4 (severe restenosis) by consensus of two observers. Results: In-stent restenosis (≥60% luminal narrowing by quantitative coronary angiography) was found on ICA in 18 (16.2%) of the stented segments and in 16 (24.6%) patients. The MDCT findings correlated with ICA restenosis, with restenosis in only 1 of 59 (1.6%) MDCT grade 1 segments, but in more than three-quarters (12 of 15, 80%) of MDCT grade 4 segments (sensitivity 72.2%, specificity 92.5%, positive predictive value [PPV] 65.0%, negative predictive value [NPV] 94.5% [five stents not assessable by MDCT considered as restenosis]). Using MDCT grades 3 or 4 combined for restenosis, sensitivity of MDCT was 88.9%, specificity 80.6%, PPV 47.1%, and NPV 97.4%. Conclusions: In-stent restenosis can be diagnosed with moderate sensitivity using a new generation 40-slice MDCT scanner. The high NPV implies a significant role for MDCT in excluding ISR. [Copyright &y& Elsevier]

Aims: Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE‐TIMI 58. We hypothesized that baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT‐proBNP and hsTnT levels. Methods and results: This was a pre‐specified biomarker study from DECLARE‐TIMI 58, a randomized, double‐blind, placebo‐controlled CV outcomes trial of dapagliflozin. Baseline NT‐proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT‐proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35–165] and 10.2 pg/mL (IQR 6.9–15.5), respectively. Patients with higher NT‐proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT‐proBNP: 4‐year Kaplan–Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P‐trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT‐proBNP (P‐interaction 0.72) or hsTnT quartiles (P‐interaction 0.93). Given their higher baseline risk, patients with NT‐proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT‐proBNP 1.9% vs. 0%, P‐interaction 0.010; hsTnT 1.8% vs. 0.1%, P‐interaction 0.026). Conclusion: Patients with type 2 diabetes mellitus and higher NT‐proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT‐proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels. [ABSTRACT FROM AUTHOR]

Background: Interleukin-1 has been implicated as a mediator of recurrent pericarditis. The efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β cytokine trap, were studied previously in a phase 2 trial involving patients with recurrent pericarditis.Methods: We conducted a phase 3 multicenter, double-blind, event-driven, randomized-withdrawal trial of rilonacept in patients with acute symptoms of recurrent pericarditis (as assessed on a patient-reported scale) and systemic inflammation (as shown by an elevated C-reactive protein [CRP] level). Patients presenting with pericarditis recurrence while receiving standard therapy were enrolled in a 12-week run-in period, during which rilonacept was initiated and background medications were discontinued. Patients who had a clinical response (i.e., met prespecified response criteria) were randomly assigned in a 1:1 ratio to receive continued rilonacept monotherapy or placebo, administered subcutaneously once weekly. The primary efficacy end point, assessed with a Cox proportional-hazards model, was the time to the first pericarditis recurrence. Safety was also assessed.Results: A total of 86 patients with pericarditis pain and an elevated CRP level were enrolled in the run-in period. During the run-in period, the median time to resolution or near-resolution of pain was 5 days, and the median time to normalization of the CRP level was 7 days. A total of 61 patients underwent randomization. During the randomized-withdrawal period, there were too few recurrence events in the rilonacept group to allow for the median time to the first adjudicated recurrence to be calculated; the median time to the first adjudicated recurrence in the placebo group was 8.6 weeks (95% confidence interval [CI], 4.0 to 11.7; hazard ratio in a Cox proportional-hazards model, 0.04; 95% CI, 0.01 to 0.18; P<0.001 by the log-rank test). During this period, 2 of 30 patients (7%) in the rilonacept group had a pericarditis recurrence, as compared with 23 of 31 patients (74%) in the placebo group. In the run-in period, 4 patients had adverse events leading to the discontinuation of rilonacept therapy. The most common adverse events with rilonacept were injection-site reactions and upper respiratory tract infections.Conclusions: Among patients with recurrent pericarditis, rilonacept led to rapid resolution of recurrent pericarditis episodes and to a significantly lower risk of pericarditis recurrence than placebo. (Funded by Kiniksa Pharmaceuticals; RHAPSODY ClinicalTrials.gov number, NCT03737110.). [ABSTRACT FROM AUTHOR]

Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events.Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding.Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P=0.002; and hazard ratio, 0.77, P=0.005, respectively, Pinteraction=0.77) and all-cause mortality (hazard ratio, 0.81, P=0.05; and hazard ratio, 0.84, P=0.09, respectively; Pinteraction=0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative Pinteraction<0.0001; 1.9% versus 0.6% for all-cause mortality, Pinteraction=0.02; 2.7% versus 1.7% for major vascular events, Pinteraction<0.0001). Because the bleeding hazards were similar among patients with and without diabetes mellitus, the prespecified net benefit for rivaroxaban appeared particularly favorable in the patients with diabetes mellitus (2.7% versus 1.0%; Gail-Simon qualitative Pinteraction=0.001).Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424. [ABSTRACT FROM AUTHOR]

Background: The COMPASS trial (Cardiovascular Outcomes for People using Anticoagulation Strategies) demonstrated that dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily versus aspirin 100 mg once daily reduced the primary major adverse cardiovascular event (MACE) outcome of cardiovascular death, myocardial infarction, or stroke, as well as, mortality, in patients with chronic coronary syndromes or peripheral arterial disease. Whether this remains true in patients with a history of percutaneous coronary intervention (PCI) is unknown.Methods: In a prespecified subgroup analysis from COMPASS, we examined the outcomes of patients with chronic coronary syndrome with or without a previous PCI treated with DPI versus aspirin alone. Among patients with a previous PCI, we studied the effects of treatment according to the timing of the previous PCI.Results: Of the 27 395 patients in COMPASS, 16 560 patients with a chronic coronary syndrome were randomly assigned to DPI or aspirin, and, of these, 9862 (59.6%) had previous PCI (mean age 68.2±7.8, female 19.4%, diabetes mellitus 35.7%, previous myocardial infarction 74.8%, multivessel PCI 38.0%). Average time from PCI to randomization was 5.4 years (SD, 4.4) and follow-up was 1.98 (SD, 0.72) years. Regardless of previous PCI, DPI versus aspirin produced consistent reductions in MACE (PCI: 4.0% versus 5.5%; hazard ratio [HR], 0.74 [95% CI, 0.61-0.88]; no PCI: 4.4% versus 5.7%; HR, 0.76 [95% CI, 0.61-0.94], P-interaction=0.85) and mortality (PCI: 2.5% versus 3.5%; HR, 0.73 [95% CI, 0.58-0.92]; no PCI: 4.1% versus 5.0%; HR, 0.80 [95% CI, 0.64-1.00], P-interaction=0.59), but increased major bleeding (PCI: 3.3% versus 2.0%; HR, 1.72 [95% CI, 1.34-2.21]; no PCI: 2.9% versus 1.8%; HR, 1.58 [95% CI, 1.15-2.17], P-interaction=0.68). In those with previous PCI, DPI compared with aspirin produced consistent (robust) reductions in MACE irrespective of time since previous PCI (as early as 1 year and as far as 10 years; P-interaction=0.65), irrespective of having a previous myocardial infarction (P-interaction=0.64).Conclusions: DPI compared with aspirin produced consistent reductions in MACE and mortality but with increased major bleeding with or without previous PCI. Among those with previous PCI 1 year and beyond, the effects on MACE and mortality were consistent irrespective of time since last PCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01776424. [ABSTRACT FROM AUTHOR]

Background: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI.Methods: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI.Results: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710).Conclusions: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400. [ABSTRACT FROM AUTHOR]

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure. [ABSTRACT FROM AUTHOR]

Background: The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) recently showed that the PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor evolocumab significantly reduced major vascular events in patients with stable atherosclerotic cardiovascular disease, including patients with prior myocardial infarction (MI). Within the broad group of patients with prior MI, we hypothesized that readily ascertainable features would identify subsets who derive greater clinical risk reduction with evolocumab.Methods: The 22 351 patients with a prior MI were characterized on the basis of time from most recent MI, number of prior MIs, and presence of residual multivessel coronary artery disease (≥40% stenosis in ≥2 large vessels). The relative and absolute risk reductions in major vascular events, including the primary end point (cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) and the key secondary end point (cardiovascular death, MI, or stroke), with evolocumab in these subgroups were compared.Results: A total of 8402 patients (38%) were within 2 years of their most recent MI; 5285 patients (24%) had ≥2 prior MIs; and 5618 patients (25%) had residual multivessel coronary artery disease. In a multivariable-adjusted model that simultaneously included all 3 high-risk features and other baseline covariates, more recent MI, multiple prior MIs, and residual multivessel coronary disease remained independent predictors of cardiovascular outcomes, with adjusted hazard ratios (HRs) for the primary end point of 1.37 (95% confidence interval [CI],1.22-1.53), 1.78 (95% CI, 1.59-1.99), and 1.39 (95% CI, 1.24-1.56; all P<0.001). The relative risk reductions with evolocumab for the primary end point tended to be greater in the high-risk subgroups and were 20% (HR, 0.80; 95% CI, 0.71-0.91), 18% (HR, 0.82; 95% CI, 0.72-0.93), and 21% (HR, 0.79; 95% CI, 0.69-0.91) for those with more recent MI, multiple prior MIs, and residual multivessel coronary artery disease, whereas they were 5% (HR, 0.95; 95% CI, 0.85-1.05), 8% (HR, 0.92; 95% CI, 0.84-1.02), and 7% (HR, 0.93; 95% CI, 0.85-1.02) in those without, respectively. Given the higher baseline risk, the respective absolute risk reductions at 3 years exceeded 3% in the high-risk groups (3.4%, 3.7%, and 3.6%) versus ≈1% in the low-risk groups (0.8%, 1.3%, and 1.2%).Conclusions: Patients closer to their most recent MI, with multiple prior MIs, or with residual multivessel coronary artery disease are at high risk for major vascular events and experience substantial risk reductions with low-density lipoprotein cholesterol lowering with evolocumab.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633. [ABSTRACT FROM AUTHOR]

Background: The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events.Methods: FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years. Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of <0.85, or if they had a prior peripheral vascular procedure. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularization. The key secondary end point was a composite of cardiovascular death, myocardial infarction, or stroke. An additional outcome of interest was major adverse limb events defined as acute limb ischemia, major amputation, or urgent peripheral revascularization for ischemia.Results: Three thousand six hundred forty-two patients (13.2%) had PAD (1505 with no prior myocardial infarction or stroke). Evolocumab significantly reduced the primary end point consistently in patients with PAD (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.0098) and without PAD (HR 0.86; 95% CI, 0.80-0.93; P=0.0003; Pinteraction=0.40). For the key secondary end point, the HRs were 0.73 (0.59-0.91; P=0.0040) for those with PAD and 0.81 (0.73-0.90; P<0.0001) for those without PAD (Pinteraction=0.41). Because of their higher risk, patients with PAD had larger absolute risk reductions for the primary end point (3.5% with PAD, 1.6% without PAD) and the key secondary end point (3.5% with PAD, 1.4% without PAD). Evolocumab reduced the risk of major adverse limb events in all patients (HR, 0.58; 95% CI, 0.38-0.88; P=0.0093) with consistent effects in those with and without known PAD. There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events (P=0.026 for the beta coefficient) that extended down to <10 mg/dL.Conclusions: Patients with PAD are at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions. Moreover, lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633. [ABSTRACT FROM AUTHOR]

Background: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.Methods: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Findings: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).Interpretation: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.Funding: Bayer AG. [ABSTRACT FROM AUTHOR]

Objectives: Predictive models for heart failure (HF) in heterogeneous populations have had limited success. We examined cardiac computed tomography angiography (CTA) predictors of HF or cardiovascular death (HF-CVD) in a prospective study of asymptomatic diabetics undergoing baseline assessment by CTA. Methods: The subjects (n = 735, aged 55-74 years, 51.2% women) had no clinical history of cardiovascular disease at study entry. Coronary artery calcium (CAC) score, CTA-defined coronary atherosclerosis, cardiac chamber volumes, and clinical data were collected and late outcome events recorded over 8.4 ± 0.6 years (range 7.3-9.3). Results: HF-CVD occurred in 41 (5.6%) subjects, with HF occurring mostly (19/23, 82.6%) in subjects without preceding myocardial infarction. Baseline univariate clinical outcome predictors of HF-CVD included older age (p = 0.027), the duration of diabetes (p = 0.004), HbA1c (p < 0.0001), mi-crovascular disease (retinopathy, microalbuminuria) (p < 0.0001), and systolic blood pressure (p = 0.035). Baseline univariate CTA predictors included CAC score (p = 0.004), coronary stenosis (p = 0.047), and a CTA-defined left/right atrial (LA/RA) volume ratio >1 (p < 0.0001). Independent predictors were an LA/RA volume ratio >1, microvascular disease, and systolic blood pressure (model C-statistic 0.792, 95% CI 0.758-0.824). Measures of the extent of coronary artery disease (CAD) were not independent predictors of HF-CVD. Conclusions: In a low- to moderate-risk asymptomatic diabetic population, CTA LA enlargement (LA/RA volume ratio) but not the extent of CAD had independent prognostic value for HF-CVD in addition to the clinical variables. [ABSTRACT FROM AUTHOR]

Objectives: Predictive models for heart failure (HF) in heterogeneous populations have had limited success. We examined cardiac computed tomography angiography (CTA) predictors of HF or cardiovascular death (HF-CVD) in a prospective study of asymptomatic diabetics undergoing baseline assessment by CTA. Methods: The subjects (n = 735, aged 55-74 years, 51.2% women) had no clinical history of cardiovascular disease at study entry. Coronary artery calcium (CAC) score, CTA-defined coronary atherosclerosis, cardiac chamber volumes, and clinical data were collected and late outcome events recorded over 8.4 ± 0.6 years (range 7.3-9.3). Results: HF-CVD occurred in 41 (5.6%) subjects, with HF occurring mostly (19/23, 82.6%) in subjects without preceding myocardial infarction. Baseline univariate clinical outcome predictors of HF-CVD included older age (p = 0.027), the duration of diabetes (p = 0.004), HbA1c (p < 0.0001), mi-crovascular disease (retinopathy, microalbuminuria) (p < 0.0001), and systolic blood pressure (p = 0.035). Baseline univariate CTA predictors included CAC score (p = 0.004), coronary stenosis (p = 0.047), and a CTA-defined left/right atrial (LA/RA) volume ratio >1 (p < 0.0001). Independent predictors were an LA/RA volume ratio >1, microvascular disease, and systolic blood pressure (model C-statistic 0.792, 95% CI 0.758-0.824). Measures of the extent of coronary artery disease (CAD) were not independent predictors of HF-CVD. Conclusions: In a low- to moderate-risk asymptomatic diabetic population, CTA LA enlargement (LA/RA volume ratio) but not the extent of CAD had independent prognostic value for HF-CVD in addition to the clinical variables. [ABSTRACT FROM AUTHOR]

Background: Patients with stable ischemic heart disease and previous myocardial infarction (MI) vary in their risk for recurrent cardiovascular events. Atherothrombotic risk assessment may be useful to identify high-risk patients who have the greatest potential to benefit from more intensive secondary preventive therapy such as treatment with vorapaxar.Methods: We identified independent clinical indicators of atherothrombotic risk among 8598 stable, placebo-treated patients with a previous MI followed up for 2.5 years (median) in TRA 2°P-TIMI 50 [Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50]. The efficacy and safety of vorapaxar (SCH 530348; MK-5348) were assessed by baseline risk among patients with previous MI without prior stroke or transient ischemic attack for whom there is a clinical indication for vorapaxar. End points were cardiovascular death, MI, or ischemic stroke and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding.Results: The 9 independent risk predictors were age, diabetes mellitus, hypertension, smoking, peripheral arterial disease, previous stroke, previous coronary bypass grafting, heart failure, and renal dysfunction. A simple integer-based scheme using these predictors showed a strong graded relationship with the rate of cardiovascular death/MI/ischemic stroke and the individual components (P for trend <0.001 for all). High-risk patients (≥3 risk indicators; 20% of population) had a 3.2% absolute risk reduction in cardiovascular disease/MI/ischemic stroke with vorapaxar, and intermediate-risk patients (1-2 risk indicators; 61%) had a 2.1% absolute risk reduction (P<0.001 each), translating to a number needed to treat of 31 and 48. Bleeding increased across risk groups (P for trend<0.01); however, net clinical outcome was increasingly favorable with vorapaxar across risk groups. Fatal bleeding or intracranial hemorrhage was 0.9% with both treatments in high-risk patients.Conclusions: Stratification of baseline atherothrombotic risk can assist with therapeutic decision making for vorapaxar use for secondary prevention after MI.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00526474. [ABSTRACT FROM AUTHOR]

Background: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially.Methods: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years.Results: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups.Conclusions: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.). [ABSTRACT FROM AUTHOR]

Background Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). Objectives We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. Methods This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate. Results At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p interaction = 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p interaction = 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention. Conclusions Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441 ) [ABSTRACT FROM AUTHOR]

Background Despite its well-established prognostic value, cardiorespiratory fitness (CRF) is not incorporated routinely in risk assessment tools. Whether low CRF provides additional predictive information in asymptomatic type 2 diabetics beyond conventional risk scores and coronary artery calcification (CAC) is unclear. Methods We studied 600 type 2 diabetics aged 55–74 years without known coronary heart disease. CRF was quantified in metabolic equivalents (METs) by maximal treadmill testing and categorized as tertiles of percent predicted METs (ppMETs) achieved. CAC was calculated by non-enhanced computed tomography scans. The individual and joint association of both measures with an outcome event of all-cause mortality, myocardial infarction or stroke, was determined over a mean follow-up period of 80 ± 16 months. Results There were 72 (12%) events during follow-up. Low CRF was independently associated with event risk after adjustment for traditional risk factors and CAC (HR 2.25, 95% CI 1.41–3.57, p = 0.001). CRF (unfit/fit) allowed further outcome discrimination both amongst diabetics with low CAC scores (9.5% versus 2.0% event rate), and amongst diabetics with high CAC scores (23.5% versus 12.4% event rate), p < 0.001. The addition of CRF to a model comprising UKPDS and CAC scores improved the area under the curve for event prediction from 0.66 to 0.71, p = 0.03, with a positive continuous net reclassification improvement (NRI) of 0.451, p = 0.002. Conclusions CRF, quantified by ppMETs, provided independent prognostic information which was additive to CAC. Low CRF may identify asymptomatic diabetic subjects at higher risk for all-cause mortality, myocardial infarction or stroke, despite low CAC. [ABSTRACT FROM AUTHOR]

The article discusses a study that added nonstatin drug ezetimibe to determine its ability of reducing absorption of intestinal cholesterol for reducing cardiovascular events. Topics covered include randomized trial on 18,144 patients with acute coronary syndrome and 50-100 milligrams per deciliter (mg/deciliter) low-density lipoprotein (LDL) levels. Results showed lower Kaplan-Meier events in the simvastatin-ezetimibe patients group than those in the simvastatin-monotherapy group.

Background--Diabetes mellitus and heart failure frequently coexist. However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point. Methods and Results--A total of 16492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo (mean follow-up, 2.1 years). The primary end point was the composite of cardiovascular death, myocardial infarction, or ischemic stroke. Hospitalization for heart failure was a predefined component of the secondary end point. Baseline N-terminal pro B-type natriuretic peptide was measured in 12301 patients. More patients treated with saxagliptin (289, 3.5%) were hospitalized for heart failure compared with placebo (228, 2.8%; hazard ratio, 1.27; 95% confidence intercal, 1.07-1.51 ;P=0.007). Corresponding rates at 12monthswere 1.9% versus 1.3% (hazard ratio, 1.46; 95% confidence interval, 1.15-1.88; P=0.002), with no significant difference thereafter (time-varying interaction, P=0.017). Subjects at greatest risk of hospitalization for heart failure had previous heart failure, an estimated glomerular filtration rate ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide. There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin (P for interaction=0.46), although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile (2.1 %). Even in patients at high risk of hospitalization for heart failure, the risk of the primary and secondary end points were similar between treatment groups. Conclusions--In the context of balanced primary and secondary end points, saxagliptin treatment was associated with an increased risk or hospitalization for heart failure. This increase in risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. Methods We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolie events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. Findings 42411 participants received a new oral anticoagulant and 29272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolie events by 19% compared with warfarin (RR 0-81, 95% CI 0-73-0-91; p<0 0001), mainly driven by a reduction in haemorrhagic stroke (0-49, 0-38-0-64; p<0 0001). New oral anticoagulants also significantly reduced all-cause mortality (0-90, 0-85-0-95; p=0-0003) and intracranial haemorrhage (0-48, 0-39-0-59; p<0 0001), but increased gastrointestinal bleeding (1-25, 1-01-1-55; p=0 04). We noted no heterogeneity for stroke or systemic embolie events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0 • 69, 0 • 59-0 • 81 vs 0 • 93, 0 • 76-1 • 13; p for interaction 0 ¦ 022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolie events to warfarin (1-03, 0-84-1-27; p=0-74), and a more favourable bleeding profile (0-65, 0-43-1-00; p=0 05), but significantly more ischaemic strokes (1 • 28,1 • 02-1 • 60; p=0• 045). Interpretation This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolie events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. [ABSTRACT FROM AUTHOR]

The coronary artery calcium score (CS), an independent predictor of cardiovascular events, can be obtained from a stand-alone nonenhanced computed tomography (CT) scan (CSCT) or as an additional nonenhanced procedure before contrast-enhanced coronary CT angiography (CCTA). We evaluated the accuracy of a novel fully automatic tool for computing CS from the CCTA examination. One hundred thirty-six consecutive symptomatic patients (aged 59 ± 11 years, 40% female) without known coronary artery disease who underwent both 256-row CSCT and CCTA were studied. Original scan reconstruction (slice thickness) was maintained (3 mm for CSCT and 0.67 mm for CCTA). CS was computed from CCTA by an automatic tool (COR Analyzer, rcadia Medical Imaging, Haifa, Israel) and compared with CS results obtained by standard assessment of nonenhanced CSCT (HeartBeat CS, Philips, Cleveland, Ohio). We also compared both methods for classification into 5 commonly used CS categories (0, 1 to 10, 11 to 100, 101 to 400, >400 Agatston units). All scans were of diagnostic quality. CS obtained by the COR Analyzer from CCTA classified 111 of 136 (82%) of patients into identical categories as CS by CSCT and 24 of remaining 25 into an adjacent category. Overall, CS values from CCTA showed high correlation with CS values from CSCT (Spearman rank correlation [ 0.95, p <0.0001). In conclusion, CS values automatically computed from 256-row CCTA correlated highly with standard CS values obtained from nonenhanced CSCT. CS obtained directly from CCTA may obviate the need for an additional scan and attendant radiation. [ABSTRACT FROM AUTHOR]

Abstract: Background: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD. Methods and results: In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71–1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81–1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD. Conclusions: In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients. [Copyright &y& Elsevier]

Abstract: Background: Elderly patients with acute coronary syndromes (ACS) are at high risk for death and recurrent thrombotic events. We evaluated the efficacy and safety of intensive treatment with glycoprotein IIb/IIIa inhibitors in an elderly population, and the relationships between age, timing of administration, and clinical outcomes. Methods: We used data from high-risk non–ST-segment elevation ACS patients randomized to early eptifibatide vs. delayed provisional use at percutaneous coronary intervention. In multivariable models, we included age×treatment interaction terms to assess whether treatment effect varied by age after adjusting for confounders. Results: Of 9406 patients, 13.9% were aged <55years; 27.6%, 55–64years; 33.2%, 65–74years; and 25.3%, ≥75years. For each 10-year age increase, the adjusted odds ratio (OR) (95% confidence interval [CI]) for 96-hour death, myocardial infarction (MI), recurrent ischemia requiring urgent revascularization, or thrombotic bailout was 1.13 (1.04–1.23) and for 30-day death or MI was 1.13 (1.04–1.22). Increasing age was also associated with greater 1-year mortality (adjusted hazard ratio per 10years: 1.44, 95% CI 1.30–1.60). There was no interaction between age and treatment (p interaction=0.99, 0.54, and 0.87, respectively). Increasing age was associated with more non‐coronary artery bypass grafting-related TIMI major bleeding (adjusted OR and 95% CI per 10years: 1.54 [1.24–1.92]), GUSTO moderate/severe bleeding (1.52 [1.33–1.75]), and transfusion (1.25 [1.07–1.45]). The amount by which TIMI major bleeding was increased with early vs. delayed provisional eptifibatide use was significantly greater with increasing age (p interaction=0.02), but the age×treatment interactions were not significant for GUSTO moderate/severe bleeding or transfusion (p interaction=0.33 and 0.54, respectively). Conclusion: Increasing age was associated with greater risk for ischemic events and more bleeding. Despite higher baseline ischemic risk in older patients, there was no preferential benefit of early vs. delayed provisional eptifibatide use for ischemic outcomes as age increased, but the incremental bleeding risk was amplified. [Copyright &y& Elsevier]

BACKGROUND: We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial. METHODS AND RESULTS: Of 18 624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; P=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59-0.95; P=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours-30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment >=80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88). CONCLUSION: Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics. [ABSTRACT FROM AUTHOR]

Background--We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods and Results--Of 18624 patients hospitalized for acute coronary syndromes, 11 289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; P=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59-0.95; P=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours-30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment >80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88). Conclusion--Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics. Clinical Trial Registration--URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. [ABSTRACT FROM AUTHOR]

Background: Coronary revascularization is commonly based on the angiographic finding of percent diameter stenosis (%DS) >50 while lesion length (LL), which contributes to flow-limitation according to Poiseuille's equation, is disregarded. Fractional flow reserve (FFR) is superior to assessment of %DS for identifying flow-limiting lesions, but the technology is invasive and relatively expensive. We developed a Poiseuille-based angiographic index, incorporating both minimal lumen diameter (MLD) and LL, for improved assessment of the hemodynamic significance of intermediate coronary lesions. The present study was designed to test the hypothesis that the Poiseuille-based angiographic index correlated better with FFR measurements than angiographic assessment of %DS. Methods: We performed quantitative coronary angiography (QCA) and FFR measurements in 46 intermediate coronary lesions in 41 symptomatic patients referred for diagnostic coronary angiography. From QCA we determined LL, MLD and %DS and calculated an angiographic index, the LL/MLD4 ratio. Results: Mean LL was 14.2±7.8 (range: 4.3–38.8) mm, MLD 1.4±0.4 (range: 0.6–2.3) mm, %DS 46±12 (range: 25–74) and FFR 0.85±0.09 (range: 0.55–1.00). Fractional flow reserve correlated inversely with %DS (R =−0.39, p =0.008) and with the LL/MLD4 ratio (R =−0.66, p <0.0001). An FFR cut-off value of 0.80 corresponded with a LL/MLD4 ratio of 12 (p =0.003) but not with a %DS of 50 (p =NS). A LL/MLD4 ratio ≤12 had a specificity of 94% and negative predictive value of 82% for excluding hemodynamically significant lesions with FFR (≥0.80). Conclusions: The LL/MLD4 ratio was superior to standard angiographic measurement of %DS for exclusion of hemodynamically significant coronary lesions. [ABSTRACT FROM AUTHOR]

We assessed the performance of a new-generation, 256-row computed tomography (CT) scanner for detection of obstructive coronary artery disease (CAD) compared to invasive quantitative coronary angiography. A total 121 consecutive symptomatic patients without known CAD referred for invasive coronary angiography (age 59 ± 12 years, 37% women) underwent clinically driven 256-row coronary computed tomographic angiography (CCTA) before the invasive procedure. Obstructive CAD (>50% diameter stenosis) was assessed visually on CCTA by 2 independent observers using the 18-segment society of cardiovascular CT model and on invasive angiograms using quantitative coronary angiography (the reference standard). Observers were unaware of the findings from the alternate modality. Nonassessable coronary computed tomographic angiographic segments were considered obstructive for the purpose of analysis. Quantitative coronary angiography demonstrated obstructive CAD in 145 segments in 82 of 121 patients (68%). Overall, 1,677 coronary segments were available for comparative analysis, of which 39 (2.3%) were nonassessable by CCTA, mostly because of heavy calcification. Patient-based and segmentbased analysis showed a sensitivity of 100% and 97% (95% confidence interval 95% to 100%) and specificity of 69% (95% confidence interval 55% to 84%) and 97% (confidence interval 96% to 98%), respectively. Four segments with obstructive CAD in 4 patients were not detected by CCTA. All 4 patients had additional coronary obstructions identified by CCTA. The predictive accuracy was 90% (range 85% to 95%) for patient based and 97% (96% to 98%) for segment based analysis. In conclusion, 256-row CCTA showed high sensitivity and high predictive accuracy for detection of obstructive CAD in patients without previously known disease. Although coronary calcification might still interfere with analysis, the rate of nonassessable segments was low. [ABSTRACT FROM AUTHOR]

Abstract: Background: Visceral abdominal adipose tissue (VAT) may play an active role in the progression of coronary atherosclerosis. We examined the relation between VAT, non-alcoholic fatty liver disease and extent of coronary atheroma in patients with type 2 diabetes mellitus but no known coronary artery disease. Methods: Coronary artery calcium and area, distribution and thickness of upper abdominal fat were measured in selected axial cross-sections from non-enhanced computed tomography (CT) scans of the chest. Coronary atheroma was assessed visually on a per vessel basis from 64 slice CT angiography using axial views and multi-format reconstructions. Fatty liver was diagnosed when liver density was <40 Hounsfield units (HU) or ≥10 HU below spleen density. Results: The area of VAT was increased in patients with versus without multi-vessel coronary artery plaque (237.0±101.4 vs 179.2±79.4mm2, p<0.001). Waist circumference (101.6±12.3 versus 95.3±13.8cm) and internal abdominal diameter (218.7±33.0 vs 194.6±25.7mm) (both p<0.001) were increased in patients with multi-vessel plaque whereas subcutaneous fat was unrelated to coronary plaque. Presence of fatty liver (93/318 patients, 29.2%) did not correlate with presence or extent of coronary plaque. The correlation of VAT with multi-vessel plaque although nominally independent of the metabolic syndrome (p=0.04) was not independent of waist circumference. Conclusion: In asymptomatic subjects with DM and no history of CAD area of VAT correlated with the presence and extent of coronary atheroma but as a risk predictor added little independent information to that obtained by more readily obtainable measures of adiposity—waist circumference and internal abdominal diameter. [Copyright &y& Elsevier]

Background: Atrial fibrillation (AF) in patients with heart failure signals poor prognosis. The endothelial nitric oxide synthase (eNOS) enzyme is a key player in the counterregulation of oxidative stress, which is related in part to AF pathogenesis. The purpose of this study was to investigate a possible clinical association in heart failure patients between the presence of exon 7 G894T eNOS polymorphism, known to result in the Glu298Asp protein variant, and the occurrence of AF. Methods: We analyzed the DNA of 344 patients with chronic systolic heart failure for exon 7 G894T eNOS polymorphism, using PCR. Odds ratios for AF were calculated for the homo- and heterozygous G-allele G894T variants relative to the TT variant. Results: Of the 344 patients, 204 (59%) were homozygous for the G allele, 122 (36%) were heterozygous (GT), and 18 (5%) were homozygous for the T allele. AF episodes were documented in 73 patients (36%) with the GG genotype, in 35 (29%) with GT, and in 2 (11%) with TT. The odds ratio for AF, based on the presence of at least one G allele in the eNOS 894 gene, was 3.96 (95% confidence interval, 1.17-13.56, p=0.04). Having two G alleles increased the odds ratio to 4.5 (95% confidence interval, 1.0-20.0, p=0.02). Conclusion: Patients with systolic heart failure demonstrate strong correlation between AF and the presence of a G allele in the exon 7 G894T eNOS genotype. These findings support the importance of eNOS polymorphism in the pathogenesis of AF in heart failure patients. [ABSTRACT FROM AUTHOR]

The article presents information on a study on treatment strategy for long-term secondary prevention of thrombosis for patients with previous myocardial infarction. A randomised, placebo-controlled trial was done in which the patients with a history of atherothrombosis were assigned to receive vorapaxar, an antagonist of protease-activated receptor 1 or matching placebo in equal ratio. INSET: Panel: Research in context.

Summary: Background: In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Methods: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0–3·0). The median duration of follow-up was 1·8 years (IQR 1·4–2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Findings: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI −0·08 to 1·63) in patients with and 0·22 (−0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09–2·04) in patients with and 0·93 (0·54–1·32) in those without previous stroke or TIA. Interpretation: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Funding: Bristol-Myers Squibb and Pfizer. [Copyright &y& Elsevier]

Aims Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non-coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients. Methods and results The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic heart failure patients and 30 controls using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The differences in microRNA levels between the two groups were characterized, and a score, based on the levels of four specific microRNAs with the most significant increase in the heart failure group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined. The score was used to discriminate heart failure patients from controls with a sensitivity and specificity of 90%. Moreover, in the heart failure group, there was a significant association between the score and important clinical prognostic parameters such as elevated serum natriuretic peptide levels, a wide QRS, and dilatation of the left ventricle and left atrium (r = 0.63, P = 3e-4; P = 0.009; P = 0.03; and P = 0.01, respectively). Conclusions Elevated serum levels of specific microRNAs: miR-423-5p, miR-320a, miR-22, and miR-92b, identify systolic heart failure patients and correlate with important clinical prognostic parameters. [ABSTRACT FROM PUBLISHER]

To detect and quantify consistent ECG amplitude changes, the "ECG variability contour" (EVC) method was proposed. Using this method we investigated amplitude changes in subjects undergoing myocardial perfusion imaging (MPI) with Dipyridamole (Dp). Fifty-three patients having reversible perfusion defects and 19 normal subjects (NS) who were free of: perfusion defects on their MPI, standard ST-T changes during Dp stress, and a negative clinical follow up. Mean ∏¹(<∏¹>) was similar for the NS and patient group (6.2 ± 6.1 vs. 6.3 ± 6.2, P = 0.95). <∏¹> was 4.6 ± 3.0 in patients not having ST-T changes during Dp stress (n = 42), whereas in patients having ST-T changes (n = 11) it was 13.1 ± 10.2 (P < 0.001). For both groups <∏(QRS)> was smaller than <∏(ST)>, which in turn was smaller than <∏(T)>. The values of <∏(QRS)>, <∏(ST)>, and <∏(T)> for the NS, patients without and with ST-T changes were: 26.8 ± 28.6, 42.6 ± 41.8, 44.9 ± 36.5; 19.6 ± 20.8, 26.4 ± 31.4, 38.7 ± 27.3; 51.0 ± 30.0, 71.0 ± 36.8, 75.1 ± 20.9, respectively (P < 0.05 for all comparisons of patients with versus without ST-T changes). This study showed that Dp stress, with or without hypoperfusion, had a clear effect on myocyte electrophysiology, expressed by consistent ECG amplitude changes, detected by the EVC method. The EVC method did not distinguish between NS and patients in this clinical setting. [ABSTRACT FROM AUTHOR]

The article presents a study on the assessment of femoral and radial access for percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). It states that radial access for PCI decreases vascular bleeding and complications compared with the femoral access. It mentions the used of RadIal Versus FemorAL access for coronary intervention (RIVAL) trial, a parallel group and multicentre trial, in which patients were enrolled to find out if patients had ACS.

Objectives: Inflammation and serum oxidative stress (OS) are important components in heart failure (HF) deterioration. In this study we tested the hypothesis that an increase in patients' sera OS levels is associated with acute HF (AHF) readmissions. Methods: Thirty consecutive patients (mean age 71 ± 10 years) admitted with AHF were included in the study. Serum OS in these patients was measured in-hospital and repeatedly after discharge over a period of 8 weeks of follow-up in which we reordered patients' HF readmissions. Of the 30 patients, 13 (43%) were readmitted (RAD group) and 17 (57%) did not require readmission (NRAD group). Results: OS levels before discharge from the first hospital admission in the 2 groups were similar (p = 0.84 and p = 0.56, respectively). However, using repeated measures ANOVA, we found that the interaction between the time points and the 2 groups of patients (RAD and NRAD) was statistically significant (p = 0.037). It is important to note that OS serum levels were more predictive of HF readmissions than were repeated simultaneous serum measurements of NT-proBNP (p = 0.97). Conclusions: Increased OS levels in AHF patients, after they have been discharged from the hospital, are associated with higher HF readmission rates. In AHF, OS is a dynamic parameter associated with HF deterioration. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]