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Introduction Post-operative atrial fibrillation (POAF) occurs in 20–40% of patients in the first week after cardiac surgery, and is associated with longer hospital stay, higher stroke risk, and worse overall prognosis. The surgery-related inflammatory response has been strongly implicated in POAF pathogenesis; however, lower CRP levels resulting from perioperative rosuvastatin therapy in the Statin Therapy In Cardiac Surgery (STICS) randomized trial were not associated with a reduced incidence of POAF. Furthermore, POAF independently predicts subsequent clinical AF and as such may reflect the presence of a subclinical cardiomyopathic substrate. We tested this hypothesis by investigating determinants of POAF in 1613 patients who underwent isolated coronary artery bypass grafting in China in the STICS trial. Methods Clinical data included age, sex, body mass index, medical history, medications, and type of surgery (on-pump vs off-pump). Blood taken prior to surgery was assayed for troponin I, N-terminal pro–brain natriuretic peptide (NT-proBNP), creatinine, low-density lipoprotein (LDL) cholesterol, and serum CD40 ligand. The biomarkers growth differentiation factor 15, interleukin-6, procalcitonin, and placental growth factor were measured at baseline and at 6 hours after surgery. Echocardiography evaluated left ventricular ejection fraction (LVEF) and left atrial (LA) size. POAF was detected by continuous Holter electrocardiographic monitoring for 5 days after surgery. Results POAF occurred in 314 of 1613 patients (19%). As expected, age was the single strongest predictor of POAF (C-statistic 0.66 [95% CI 0.62–0.70]). After adjustment for age, NT-proBNP, LA size, Troponin, LVEF, sex, calcium-channel blocker use, and prior myocardial infarction were all significantly associated with POAF when assessed individually (all P Conclusions A basic model requiring only age, NT-proBNP, and LA size has good predictive value for POAF in this population, comparing well to more complex risk prediction scores. More broadly, these results suggest that systemic inflammation and perioperative myocardial injury may be less relevant to the pathogenesis of POAF than the effects of aging and cardiac structural and functional changes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation

Aims The provision of high-quality education allows the European Society of Cardiology (ESC) to achieve its mission of better cardiovascular practice and provides an essential component of translating new evidence to improve outcomes Methods and results The 4th ESC Education Conference, held in Sophia Antipolis (December 2016), brought together ESC education leaders, National Directors of Training of 43 ESC countries, and representatives of the ESC Young Community. Integrating national descriptions of education and cardiology training, we discussed innovative pathways to further improve knowledge and skills across different training programmes and health care systems. We developed an ESC roadmap supporting better cardiology training and continued medical education (CME), noting: (i) The ESC provides an excellent framework for unbiased and up-to-date cardiovascular education in close cooperation with its National Societies. (ii) The ESC should support the harmonization of cardiology training, curriculum development, and professional dialogue and mentorship. (iii) ESC congresses are an essential forum to learn and discuss the latest developments in cardiovascular medicine. (iv) The ESC should create a unified, interactive educational platform for cardiology training and continued cardiovascular education combining Webinars, eLearning Courses, Clinical Cases, and other educational programmes, along with ESC Congress content, Practice Guidelines and the next ESC Textbook of Cardiovascular Medicine. (v) ESC-delivered online education should be integrated into National and regional cardiology training and CME programmes. Conclusion These recommendations support the ESC to deliver excellent and comprehensive cardiovascular education for the next generation of specialists. Teamwork between international, national and local partners is essential to achieve this objective.

Aim To investigate sex differences in acute myocardial infarction (AMI) guideline-indicated care as defined by the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) quality indicators. Methods Nationwide cohort study comprising 691 290 AMI hospitalisations in England and Wales (n=233 hospitals) from the Myocardial Ischaemia National Audit Project between 1 January 2003 and 30 June 2013. Results There were 34.5% (n=238 489) women (median age 76.7 (IQR 66.3–84.0) years; 33.9% (n=80 884) ST-elevation myocardial infarction (STEMI)) and 65.5% (n=452 801) men (median age 67.1 (IQR 56.9–77.2) years; 42.5% (n=192 229) STEMI). Women less frequently received 13 of the 16 quality indicators compared with men, including timely reperfusion therapy for STEMI (76.8% vs 78.9%; p Conclusion According to the ESC ACCA AMI quality indicators, women in England and Wales less frequently received guideline-indicated care and had significantly higher mortality than men. Greater attention to the delivery of recommended AMI treatments for women has the potential to reduce the sex-AMI mortality gap.

Atrial fibrillation (AF) is associated with increased risk of heart failure and premature death, and is often resistant to treatment. Animal models of pacing-induced AF indicate that AF-induced endothelial dysfunction, impaired coronary reserve, and myocardial remodelling are important in arrhythmia maintenance. However, human AF may reflect a subclinical cardiomyopathy, which persists after sinus rhythm (SR) restoration and provides a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics.

Atrial fibrillation (AF) is associated with subclinical left ventricular (LV) dysfunction and overt heart failure, but causal relationships are incompletely defined. Both AF and LV dysfunction may be tissue-specific manifestations of an underlying subclinical cardiomyopathy.

Patient-specific modelling aims to produce computational models of human physiology tailored to a specific patient. In line with this, we construct multiple human atrial electrophysiological models mimicking the behaviour of single atrial myocytes extracted from a homogeneous patient group. We study cells with the action potential duration being 2-3 times lower than in human atrial electrophysiological models. Assuming such a difference can be rationalized by altering the values of ionic conductances, we generated 15000 models by simultaneously varying conductance values of the most important currents affecting the action potential (AP). We paced the models at different frequencies and conditions, probing the importance of ion concentrations and stimulus strength, and kept the models producing AP biomarkers consistent with experiments. We discovered that both the ionic conductances and external factors play a critical role in producing biomarker values consistent with experiments. By mimicking experimental conditions, we generated 604 models fully covering the experimental range of AP biomarkers. In conclusion, both the ionic conductances and external factors are vital in tailoring single-cell electrophysiological models to a narrow patient group. This has implications in understanding the propensity of subgroups of the total population to disease conditions.

Aim: In healthy hearts, the neuronal nitric oxide synthase (nNOS) is predominantly localised to the sarcoplasmic reticulum (SR), where it regulates the ryanodine receptor Ca2+ release channel (RyR2) and phospholamban (PLB) phosphorylation, and to a lesser extent to the sarcolemmal membrane where it inhibits the L-type Ca2+ current (ICa). However, in failing hearts, impaired relaxation and depressed inotropy are associated with a larger proportion of nNOS being localised to the sarcolemmal membrane. Whether there is a causal relationship between altered myocardial function and subcellular localisation of nNOS remains to be assessed. Methods and Results: Adenoviruses (AdV) encoding for a human nNOS.eGFP fusion protein or eGFP were injected into the left ventricle (LV) of nNOS-/- mice. nNOS.eGFP localised to the sarcolemmal and t-tubular membrane and immunoprecipitated with syntrophin and caveolin-3 but not with RyR2. Myocardial transduction of nNOS.eGFP resulted in a significantly increased NOS activity (10-fold, P

Supplemental Digital Content is available in the text., Background: Lone atrial fibrillation (AF) may reflect a subclinical cardiomyopathy that persists after sinus rhythm (SR) restoration, providing a substrate for AF recurrence. To test this hypothesis, we investigated the effect of restoring SR by catheter ablation on left ventricular (LV) function and energetics in patients with AF but no significant comorbidities. Methods: Fifty-three patients with symptomatic paroxysmal or persistent AF and without significant valvular disease, uncontrolled hypertension, coronary artery disease, uncontrolled thyroid disease, systemic inflammatory disease, diabetes mellitus, or obstructive sleep apnea (ie, lone AF) undergoing ablation and 25 matched control subjects in SR were investigated. Magnetic resonance imaging quantified LV ejection fraction (LVEF), peak systolic circumferential strain (PSCS), and left atrial volumes and function, whereas phosphorus-31 magnetic resonance spectroscopy evaluated ventricular energetics (ratio of phosphocreatine to ATP). AF burden was determined before and after ablation by 7-day Holter monitoring; intermittent ECG event monitoring was also undertaken after ablation to investigate for asymptomatic AF recurrence. Results: Before ablation, both LV function and energetics were significantly impaired in patients compared with control subjects (LVEF, 61% [interquartile range (IQR), 52%–65%] versus 71% [IQR, 69%–73%], P

Although the initiation, development and maintenance of atrial fibrillation (AF) has been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso-redox balance. However, it remains unclear which radical or non-radical species are primarily involved in the underlying mechanisms of AF, or which proteins are targeted for redox modification. In most instances, only free radical oxygen species have been assessed, yet evidence from the redox signalling field suggests that non-radical species are more likely to regulate cellular processes. A wider appreciation for the distinction of these species and how both species may be involved in the development and maintenance of AF could impact treatment strategies. In this review we summarize how redox second-messenger systems are regulated, and discuss the recent evidence for alterations in redox regulation in the atrial myocardium in the presence of AF, while identifying some critical missing links. We also examine studies looking at antioxidants for the prevention and treatment of AF and propose alternative redox targets which may serve as superior therapeutic options for the treatment of AF.

Supplemental Digital Content is available in the text., Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase–derived O2−, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2−. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase–mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2− production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ in EpAT. Conclusions: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress.