Myocardial Injury After Noncardiac Surgery in Major General Surgical Patients a Prospective Observational Cohort Study.

OBJECTIVE: The objective of this study was to determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in major general surgery patients. BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in major general surgical patients have not been described. METHODS: This was an international prospective cohort study of a representative sample of 22,552 noncardiac surgery patients 45 years or older, of whom 4490 underwent major general surgery in 24 centers in 13 countries. All patients had fifth-generation plasma high-sensitivity troponin T (hsTnT) concentrations measured during the first 3 postoperative days. MINS was defined as a hsTnT of 20-65 ng/L and absolute change >5 ng/L or hsTnT ≥65 ng/L secondary to ischemia. The objectives of the present study were to determine (1) whether MINS is prognostically important in major general surgical patients, (2) the clinical characteristics of major general surgical patients with and without MINS, (3) the 30-day outcomes for major general surgical patients with and without MINS, and (4) the proportion of MINS that would have gone undetected without routine postoperative monitoring. RESULTS: The incidence of MINS in the major general surgical patients was 16.3% (95% CI, 15.3-17.4%). Thirty-day all-cause mortality in the major general surgical cohort was 6.8% (95% CI, 5.1%-8.9%) in patients with MINS compared with 1.2% (95% CI, 0.9%-1.6%) in patients without MINS ( P <0.01). MINS was independently associated with 30-day mortality in major general surgical patients (adjusted odds ratio 4.7, 95% CI, 3.0-7.4). The 30-day mortality was higher both among MINS patients with no ischemic features (ie, no ischemic symptoms or electrocardiogram findings) (5.4%, 95% CI, 3.7%-7.7%) and among patients with 1 or more clinical ischemic features (10.6%, 95% CI, 6.7%-15.8%). The proportion of major general surgical patients who had MINS without ischemic symptoms was 89.9% (95% CI, 87.5-92.0). CONCLUSIONS: Approximately 1 in 6 patients experienced MINS after major general surgery. MINS was independently associated with a nearly 5-fold increase in 30-day mortality. The vast majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Normoxic low-altitude simulation (at 714 mmHg) improves limb blood perfusion in mice with hindlimb ischemia.

Humans have fewer cardiovascular events and improved outcomes after cardiovascular events when living at low and moderate altitudes (<3000 m) above sea level. We have previously shown that low-altitude simulation using reductions in barometric pressure enhances vasodilation ex vivo in arterial segments and reduces systemic vascular resistance in vivo and can also improve left ventricular function after a myocardial infarction. We hypothesize that low-altitude simulation could also improve hindlimb ischemia, a model of peripheral artery disease in humans. We performed femoral artery ligation to generate hindlimb ischemia in 3-month-old C57BL6 mice. Control group mice (n = 10) recovered at 754 mmHg (control) for 14 days. Treatment group mice (n = 15) were placed in a low-altitude simulation chamber (at 714 mmHg) to recover from surgery for 3-hours daily for 14 days. Hindlimb perfusion imaging using a laser Doppler line scanner was performed for all mice prior to the surgery, and then on days 1, 3, 7, and 14 post-surgery. At 2 weeks, ischemic reserve was significantly higher in the treatment group mice (0.50 ± 0.13 vs. 0.20 ± 0.06; p = 0.01). Treatment mice had higher functional scores and were able to walk better at two weeks. There was approximately three times less HIF1α found via western blotting and a small but statistically significant improvement of lectin perfusion in calf tissue of treatment mice. We conclude that low-altitude simulation improves blood perfusion in murine hindlimb ischemia. This approach may have therapeutic implications for humans with peripheral artery disease.

Low altitude simulation without hypoxia improves left ventricular function after myocardial infarction by reducing ventricular afterload.

Humans have a lower risk of death from myocardial infarction (MI) living at low elevations (<2500 m), which are not high enough to induce hypoxia. Both chronic hypoxia pre-MI, achieved by altitude simulation >5000 m, and intermittent hypobaric hypoxia post-MI can reduce MI size in rodents, and it is believed that hypoxia is the key stimulus. To explore mechanisms beyond hypoxia we studied whether altitude simulation <2500 m would also be associated with reduced infarct size. We performed left-anterior descending artery ligation on C57BL6 mice. Control mice (n = 12) recovered at 754 mmHg (atmospheric pressure, control), and treatment group mice (n = 13) were placed in a hypobaric chamber to recover 3-hours daily at 714 mmHg for 1 week. Echocardiographic evaluation of left ventricular function was performed on Day 0, Day 1 and Day 8. Intermittent hypobaric treatment was associated with a 14.2±5.3% improvement in ejection fraction for treatment group mice (p<0.01 vs. Day 1), with no change observed in control mice. Cardiac output, stroke volume, and infarct size were also improved in treated mice, but no changes were observed in HIF-1 activation or neovascularization. Next, we studied the acute hemodynamic effects of low altitude stimulation in intact mice breathing 100% oxygen using left ventricular catheterization and recording of pressure-volume loops. Acute reductions in barometric pressure from 754 mmHg to 714 mmHg and 674 mmHg were associated with reduced systemic vascular resistance, increased stroke volume and cardiac output, and no change in blood pressure or heart rate. Ex-vivo vascular function was studied using murine mesenteric artery segments. Acute reductions in barometric pressure were associated with greater vascular distensibility. We conclude that intermittent hypobaric treatment using simulated altitudes <2500 m reduces infarct size and increases ventricular function post-MI, and that these changes are related to altered arterial function and not hypoxia-associated neovascularization.

2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents.

Aortic Pressure Estimation Using Blind Identification Approach on Single Input Multiple Output Nonlinear Wiener Systems.

Aortic pressure () is important for diagnosis of cardiovascular diseases, but it cannot be directly measured by noninvasive means. We present a method for its estimation by modeling arterial system as multichannel Weiner system with linear finite impulse response filter accounting for larger arteries transmission channel and nonlinear memoryless function block accounting for all nonlinearities due to narrowing of arteries, branching and visco-elastic forces. With this structure when pressure waveforms are measured from two distinct peripheral locations, multichannel blind system identification (MBSI) technique can be used to estimate common input pressure signal or . Nonlinear MBSI method was employed on previously acquired human hemodynamic measurements (seven datasets); results show can be accurately derived. This method by nature is self-calibrating to account for any interpersonal, along with intrapersonal, vascular dynamics inconstancy. Besides Pa estimation, the proposed MBSI method also allows extraction of system dynamics for vascular channels.

Canadian Stroke Best Practice Recommendations: secondary prevention of stroke guidelines, update 2014.

Every year, approximately 62,000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2014 update of the Canadian Secondary Prevention of Stroke guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. Notable changes in this 5th edition include an emphasis on treating the highest risk patients who present within 48 h of symptom onset with transient or persistent motor or speech symptoms, who need to be transported to the closest emergency department with capacity for advanced stroke care; a recommendation for brain and vascular imaging (of the intra- and extracranial vessels) to be completed urgently using computed tomography/computed tomography angiography; prolonged cardiac monitoring for patients with suspective cardioembolic stroke but without evidence for atrial fibrillation on electrocardiogram or holter monitoring; and de-emphasizing the need for routine echocardiogram. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations using a standardized approach. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographical barriers to ensure equity in access within a universal health-care system.

Pyruvate dehydrogenase inhibition by the inflammatory cytokine TNFα contributes to the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMC). This apoptosis resistance is characterized by PASMC mitochondrial hyperpolarization [in part, due to decreased pyruvate dehydrogenase (PDH) activity], decreased mitochondrial reactive oxygen species (mROS), downregulation of Kv1.5, increased [Ca(++)](i), and activation of the transcription factor nuclear factor of activated T cells (NFAT). Inflammatory cells are present within and around the remodeled arteries and patients with PAH have elevated levels of inflammatory cytokines, including tumor necrosis factor-α (TNFα). We hypothesized that the inflammatory cytokine TNFα inhibits PASMC PDH activity, inducing a PAH phenotype in normal PASMC. We exposed normal human PASMC to recombinant human TNFα and measured PDH activity. In TNFα-treated cells, PDH activity was significantly decreased. Similar to exogenous TNFα, endogenous TNFα secreted from activated human CD8(+) T cells, but not quiescent T cells, caused mitochondrial hyperpolarization, decreased mROS, decreased K(+) current, increased [Ca(++)](i), and activated NFAT in normal human PASMC. A TNFα antibody completely prevented, while recombinant TNFα mimicked the T cell-induced effects. In vivo, the TNFα antagonist etanercept prevented and reversed monocrotaline (MCT)-induced PAH. In a separate model, T cell deficient rats developed less severe MCT-induced PAH compared to their controls. We show that TNFα can inhibit PASMC PDH activity and induce a PAH phenotype. Our work supports the use of anti-inflammatory therapies for PAH.