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In this study, fractional flow reserve was used to identify patients with high-risk coronary stenoses, who received either PCI or medical therapy alone; patients with lower-risk lesions were entered in a registry. The PCI group had better outcomes than the medical-therapy group. The benefit of percutaneous coronary intervention (PCI) as an initial treatment strategy in patients with stable coronary artery disease remains controversial. 1 – 3 The potential result from revascularization depends on the extent and the degree of myocardial ischemia. 4 , 5 A fractional flow reserve (FFR) value of 0.80 or less (i.e., a drop in maximal blood flow of 20% or more caused by stenosis), as measured with the use of a coronary pressure wire during catheterization, indicates the potential of a stenosis to induce myocardial ischemia. 6 – 8 In such cases, robust clinical-outcome data favor FFR-guided revascularization, as compared with revascularization guided by . . .

Brown bears ( Ursus arctos ) hibernate for 5–6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9–107.9) vs 782.3, IQR (422.8–1586.0; p < 0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis.

In this trial, fractional flow reserve was used to assess the functional significance of coronary stenoses in patients with clinically stable coronary artery disease. The clinical outcomes were better when this technique was used to direct the use of coronary stenting. Percutaneous coronary intervention (PCI) improves the outcome in patients with acute coronary syndromes. 1 In contrast, for the treatment of patients with stable coronary artery disease, controversy persists regarding the extent of the benefit from PCI, as compared with the best available medical therapy, as an initial management strategy. 2 – 5 The potential benefit of revascularization depends on the presence and extent of myocardial ischemia. 6 – 8 Performing PCI on nonischemic stenoses is not beneficial 9 and is probably harmful. 10 Thus, careful selection of ischemia-inducing stenoses is essential for deriving the greatest benefit from revascularization in patients with stable coronary artery disease. Fractional flow . . .

AbstractObjectivesTo study circadian rhythm aspects, national holidays, and major sports events as triggers of myocardial infarction.DesignRetrospective observational study using the nationwide coronary care unit registry, SWEDEHEART.SettingSweden.Participants283 014 cases of myocardial infarction reported to SWEDEHEART between 1998 and 2013. Symptom onset date was documented for all cases, and time to the nearest minute for 88%.InterventionsMyocardial infarctions with symptom onset on Christmas/New Year, Easter, and Midsummer holiday were identified. Similarly, myocardial infarctions that occurred during a FIFA World Cup, UEFA European Championship, and winter and summer Olympic Games were identified. The two weeks before and after a holiday were set as a control period, and for sports events the control period was set to the same time one year before and after the tournament. Circadian and circaseptan analyses were performed with Sunday and 24:00 as the reference day and hour with which all other days and hours were compared. Incidence rate ratios were calculated using a count regression model.Main outcome measuresDaily count of myocardial infarction.ResultsChristmas and Midsummer holidays were associated with a higher risk of myocardial infarction (incidence rate ratio 1.15, 95% confidence interval 1.12 to 1.19, P<0.001, and 1.12, 1.07 to 1.18, P<0.001, respectively). The highest associated risk was observed for Christmas Eve (1.37, 1.29 to 1.46, P<0.001). No increased risk was observed during Easter holiday or sports events. A circaseptan and circadian variation in the risk of myocardial infarction was observed, with higher risk during early mornings and on Mondays. Results were more pronounced in patients aged over 75 and those with diabetes and a history of coronary artery disease.ConclusionsIn this nationwide real world study covering 16 years of hospital admissions for myocardial infarction with symptom onset documented to the nearest minute, Christmas, and Midsummer holidays were associated with higher risk of myocardial infarction, particularly in older and sicker patients, suggesting a role of external triggers in vulnerable individuals.

Long-term outcomes of percutaneous coronary intervention (PCI) for bifurcation lesions are underexplored. We investigated long-term PCI outcomes for proximal LAD bifurcation lesions involving D1. Using Swedish registries, we included all patients undergoing LAD-D1 bifurcation PCI with drug-eluting stents between 2010 and 2020. Patients were stratified into two groups: simple PCI and complex PCI. The simple PCI group included those with stents in the proximal LAD only, while complex PCI involved the kissing balloon technique or a 2-stent approach for the proximal LAD and D1. A multivariable Cox regression model was used to estimate event rates of major adverse clinical events (MACE), defined as all-cause death or a new myocardial infarction. Secondary outcomes included target segment revascularization or coronary artery by-pass graft surgery (CABG) and definite stent thrombosis. A total of 6,796 individuals were analyzed: 2,007 underwent complex PCI and 4,789 simple PCI. Baseline characteristics were comparable between groups. The complex PCI group was slightly younger, more often male, and more frequently taking statins. At 1-year, MACE rates were lower in the complex PCI group (6.2% vs 7.9%; adjusted HR 0.74, 95% CI 0.59-0.93, p = 0.010). The result was driven by lower all-cause mortality (3.6% vs. 5.0%; adjusted HR 0.73, 95% CI 0.54-0.98, p = 0.036). No significant differences in myocardial infarction, target segment revascularization, CABG, stent thrombosis, stroke, or bleeding were observed between groups, persisting at five years. Over a five-year period, complex PCI of LAD/D1 bifurcation lesions was associated with better outcome than simple PCI in a routine clinical setting.

The infrastructure of an established PCI registry was used to conduct a randomized trial comparing manual thrombus aspiration before PCI with PCI alone in patients with STEMI. There was no significant difference between the two groups in mortality at 30 days. One of the most important therapeutic challenges in the management of ST-segment elevation myocardial infarction (STEMI) is the establishment of normal coronary blood flow after percutaneous coronary intervention (PCI). Reduced flow is closely associated with reperfusion injury, 1 which can lead to arrhythmias, contractile dysfunction, microvascular impairment, and irreversible myocardial damage. 2 Reduced myocardial perfusion is also associated with heart failure and death. 3 , 4 Coronary-artery thrombus aspiration, a simple, rapidly performed, and relatively inexpensive adjunct to PCI, may improve blood flow and resolution of ST-segment elevation, 5 – 9 although this is not a universal finding. 10 – 12 Previous studies of thrombus aspiration have not . . .

ST-elevation myocardial infarction (STEMI) triggers a significant inflammatory response. Sweat may offer a novel, non-invasive medium for monitoring inflammation. In this prospective study, we characterized the inflammatory signatures in plasma and sweat collected from the skin surface of two patient groups: (1) 18 STEMI patients immediately following percutaneous coronary intervention (exposure) and (2) six patients who underwent outpatient angiography without subsequent intervention (control). Levels of 92 biomarkers were measured using a high-throughput proteomic assay and reassessed after 4–6 weeks in STEMI patients. Adjusting for patient group, sweat biomarkers did not show significant changes over time. In plasma, hepatocyte growth factor and interleukin-6 showed a significant decrease from the acute phase to follow-up, adjusted for patient group. STAM binding protein was significantly higher in the sweat of STEMI patients compared to controls, adjusted for time effects. While sweat was less sensitive than plasma for detecting biomarker levels in the setting of STEMI, its longitudinal analysis via wearable sensors holds promise for detecting specific markers. Trial registration : The trial is registered on www.clinicaltrials.gov with the trial registration number NCT05843006.

Brown bears (Ursus arctos) prepare for winter by overeating and increasing adipose stores, before hibernating for up to six months without eating, drinking, and with minimal movement. In spring, the bears exit the den without any damage to organs or physiology. Recent clinical research has shown that specific lipids and lipid profiles are of special interest for diseases such as diabetes type 1 and 2. Furthermore, rodent experiments show that lipids such as sulfatide protects rodents against diabetes. As free-ranging bears experience fat accumulation and month-long physical inactivity without developing diabetes, they could possibly be affected by similar protective measures. In this study, we investigated whether lipid profiles of brown bears are related to protection against hibernation-induced damage. We sampled plasma from 10 free-ranging Scandinavian brown bears during winter hibernation and repeated sampling during active state in the summer period. With quantitative shotgun lipidomics and liquid chromatography-mass spectrometry, we profiled 314 lipid species from 26 lipid classes. A principal component analysis revealed that active and hibernation samples could be distinguished from each other based on their lipid profiles. Six lipid classes were significantly altered when comparing plasma from active state and hibernation: Hexosylceramide, phosphatidylglycerol, and lysophosphatidylglycerol were higher during hibernation, while phosphatidylcholine ether, phosphatidylethanolamine ether, and phosphatidylinositol were lower. Additionally, sulfatide species with shorter chain lengths were lower, while longer chain length sulfatides were higher during hibernation. Lipids that are altered in bears are described by others as relevant for and associated with diabetes, which strengthens their position as potential effectors during hibernation. From this analysis, a range of lipids are suggested as potential protectors of bear physiology, and of potential importance in diabetes.

In a randomized trial, over 7000 patients with ST-segment elevation MI were assigned to undergo thrombus aspiration followed by percutaneous coronary intervention or PCI alone. At 1 year, there was no significant between-group difference in the rate of death from any cause. Acute ST-segment elevation myocardial infarction (STEMI) is often caused by intracoronary thrombus formation with blockage of antegrade coronary flow leading to myocardial ischemia and cell death. 1 Thrombus burden, reduced coronary flow, and reduced myocardial perfusion are important predictors of a poor clinical outcome, including recurrence of myocardial infarction, stent thrombosis, and death. 2 Prompt initiation of antithrombotic therapy in combination with percutaneous coronary intervention (PCI) is the preferred approach to optimize myocardial perfusion and clinical outcomes. 3 Coronary-artery thrombus aspiration before PCI reduces the thrombus burden and improves ST-segment resolution and coronary flow. 4 , 5 To our knowledge, however, no adequately powered randomized . . .

Hibernation is a period of metabolic suppression utilized by many small and large mammal species to survive during winter periods. As the underlying cellular and molecular mechanisms remain incompletely understood, our study aimed to determine whether skeletal muscle myosin and its metabolic efficiency undergo alterations during hibernation to optimize energy utilization. We isolated muscle fibers from small hibernators, Ictidomys tridecemlineatus and Eliomys quercinus and larger hibernators, Ursus arctos and Ursus americanus . We then conducted loaded Mant-ATP chase experiments alongside X-ray diffraction to measure resting myosin dynamics and its ATP demand. In parallel, we performed multiple proteomics analyses. Our results showed a preservation of myosin structure in U. arctos and U. americanus during hibernation, whilst in I. tridecemlineatus and E. quercinus , changes in myosin metabolic states during torpor unexpectedly led to higher levels in energy expenditure of type II, fast-twitch muscle fibers at ambient lab temperatures (20 °C). Upon repeating loaded Mant-ATP chase experiments at 8 °C (near the body temperature of torpid animals), we found that myosin ATP consumption in type II muscle fibers was reduced by 77–107% during torpor compared to active periods. Additionally, we observed Myh2 hyper-phosphorylation during torpor in I. tridecemilineatus , which was predicted to stabilize the myosin molecule. This may act as a potential molecular mechanism mitigating myosin-associated increases in skeletal muscle energy expenditure during periods of torpor in response to cold exposure. Altogether, we demonstrate that resting myosin is altered in hibernating mammals, contributing to significant changes to the ATP consumption of skeletal muscle. Additionally, we observe that it is further altered in response to cold exposure and highlight myosin as a potentially contributor to skeletal muscle non-shivering thermogenesis. Many animals use hibernation as a tactic to survive harsh winters. During this dormant, inactive state, animals reduce or limit body processes, such as heart rate and body temperature, to minimise their energy use. To conserve energy during hibernation, animals can use different approaches. For example, garden dormice undergo periodic states of extremely low core temperatures (down to 4–8 o C); whereas Eurasian brown bears see milder temperature drops (down to 23–25 o C). An important organ that changes during hibernation is skeletal muscle. Skeletal muscle typically uses large amounts of energy, making up around 50% of body mass. To survive, hibernating animals must change how their skeletal muscle uses energy. Traditionally, active myosin – a protein found in muscles that helps muscles to contract – was thought to be responsible for most of the energy use by skeletal muscle. But, more recently, resting myosin has also been found to use energy when muscles are relaxed. Lewis et al. studied myosin and skeletal muscle energy use changes during hibernation and whether they could impact the metabolism of hibernating animals. Lewis et al. assessed myosin changes in muscle samples from squirrels, dormice and bears during hibernation and during activity. Experiments showed changes in resting myosin in squirrels and dormice (whose temperature drops to 4–8 o C during hibernation) but not in bears. Further analysis revealed that cooling samples from non-hibernating muscle to 4–8 o C increased energy use in resting myosin, thereby generating heat. However, no increase in energy use was found after cooling hibernating muscle samples to 4–8 o C. This suggest that resting myosin generates heat at cool temperatures – a mechanism that is switched off in hibernating animals to allow them to cool their body temperature. These findings reveal key insights into how animals conserve energy during hibernation. In addition, the results show that myosin regulates energy use in skeletal muscles, which indicates myosin may be a potential drug target in metabolic diseases, such as obesity.