Choice of new oral anticoagulant agents versus vitamin K antagonists in atrial fibrillation: FANTASIIA study

[Abstract] Introduction: Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Many patients with AF receive chronic anticoagulation, either with vitamin K antagonists (VKAs) or with non-VKA oral anticoagulants (NOACs). We sought to analyze variables associated with prescription of NOAC. Methods: Patients with AF under anticoagulation treatment were prospectively recruited in this observational registry. The sample comprised 1290 patients under chronic anticoagulation for AF, 994 received VKA (77.1%) and 296 NOAC (22.9%). Univariate and multivariate analyses were performed to identify variables associated with use of NOAC. Results: Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. The CHA2DS2-VASc score was 0 in 4.9% of the population, 1 in 24.1%, and ≥2 in 71% (median = 4, interquartile range = 2). Variables associated with NOAC treatment were major bleeding (odds ratio [OR] = 3.36; confidence interval [CI] 95%: 1.73-6.51; P < .001), hemorrhagic stroke (OR = 3.19; CI 95% 1.00-10.15, P = .049), university education (OR = 2.44; CI 95%: 1.55-3.84; P < .001), high diastolic blood pressure (OR = 1.02; CI 95%: 1.00-1.03; P = .006), and higher glomerular filtration rate (OR 1.01, CI 95% 1.00-1.01; P = .01). And variables associated with VKA use were history of cancer (OR = 0.46; CI 95%: 0.25-0.85; P = .013) and bradyarrhythmia (OR = 0.40; CI 95% 0.19-0.85; P = .020). Conclusion: Medical and social variables were associated with prescription of NOAC. Major bleeding, hemorrhagic stroke, university education, and higher glomerular filtration rate were more frequent among patients under NOAC. On the contrary, patients with history of cancer or bradyarrhythmias more frequently received VKA.Instituto de Salud Carlos III; RD12/0042/0068Instituto de Salud Carlos III; RD12/0042/0063Instituto de Salud Carlos III; RD12/0042/0010Instituto de Salud Carlos III; RD12/0042/0069Instituto de Salud Carlos III; RD12/0042/004

New Electrocardiographic Algorithm for the Diagnosis of Acute Myocardial Infarction in Patients With Left Bundle Branch Block

Background Current electrocardiographic algorithms lack sensitivity to diagnose acute myocardial infarction (AMI) in the presence of left bundle branch block. Methods and Results A multicenter retrospective cohort study including consecutive patients with suspected AMI and left bundle branch block, referred for primary percutaneous coronary intervention between 2009 and 2018. Pre-2015 patients formed the derivation cohort (n=163, 61 with AMI); patients between 2015 and 2018 formed the validation cohort (n=107, 40 with AMI). A control group of patients without suspected AMI was also studied (n=214). Different electrocardiographic criteria were tested. A total of 484 patients were studied. A new electrocardiographic algorithm (BARCELONA algorithm) was derived and validated. The algorithm is positive in the presence of ST deviation ≥1 mm (0.1 mV) concordant with QRS polarity, in any lead, or ST deviation ≥1 mm (0.1 mV) discordant with the QRS, in leads with max (R|S) voltage (the voltage of the largest deflection of the QRS, ie, R or S wave) ≤6 mm (0.6 mV). In both the derivation and the validation cohort, the BARCELONA algorithm achieved the highest sensitivity (93%-95%), negative predictive value (96%-97%), efficiency (91%-94%) and area under the receiver operating characteristic curve (0.92-0.93), significantly higher than previous electrocardiographic rules (P<0.01); the specificity was good in both groups (89%-94%) as well as the control group (90%). Conclusions In patients with left bundle branch block referred for primary percutaneous coronary intervention, the BARCELONA algorithm was specific and highly sensitive for the diagnosis of AMI, leading to a diagnostic accuracy comparable to that obtained by ECG in patients without left bundle branch block

Mashing with unmalted sorghum using a novel low temperature enzyme system: impacts of sorghum grain composition and microstructure

Brewing lager beers from unmalted sorghum traditionally requires the use of high temperature mashing and exogenous enzymes to ensure adequate starch conversion. Here, a novel low-temperature mashing system is compared to a more traditional mash in terms of the wort quality produced (laboratory scale) from five unmalted sorghums (2 brewing and 3 non-brewing varieties). The low temperature mash generated worts of comparable quality to those resulting from a traditional energy intensive mash protocol. Furthermore, its performance was less dependent on sorghum raw material quality, such that it may facilitate the use of what were previously considered non-brewing varieties. Whilst brewing sorghums were of lower protein content, protein per se did not correlate with mashing performance. Rather, it was the way in which protein was structured (particularly the strength of protein starch interactions) which most influenced brewing performance. RVA profile was the easiest way of identifying this characteristic as potentially problematic

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Maximized PUFA measurements improve insight in changes in fatty acid composition in response to temperature

A general mechanism underlying the response of ectotherms to environmental changes often involves changes in fatty acid composition. Theory predicts that a decrease in temperature causes an increase in unsaturation of fatty acids, with an important role for long-chain poly-unsaturated fatty acids (PUFAs). However, PUFAs are particularly unstable and susceptible to peroxidation, hence subtle differences in fatty acid composition can be challenging to detect. We determined the fatty acid composition in springtail (Collembola) in response to two temperatures (5°C and 25°C). First, we tested different sample preparation methods to maximize PUFAs. Treatments consisted of different solvents for primary lipid extraction, mixing with antioxidant, flushing with inert gas, and using different temperature exposures during saponification. Especially slow saponification at low temperature (90 min at 70°C) in combination with replacement of headspace air with nitrogen during saponification and methylation maximized PUFAs for GC analysis. Applying these methods to measure thermal responses in fatty acid composition, the data showed that the (maximized) proportion of C20 PUFAs increased at low acclimation temperature. However, C18 PUFAs increased at high acclimation temperature, which is contrary to expectations. Our study illustrates that PUFA levels in lipids may often be underestimated and this may hamper a correct interpretation of differential responses of fatty acid composition.