The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

Inflammation, lipid peroxidation and chronic activation of the rennin – angiotensin system (RAS) are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2)-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by pro-inflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL). Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang) II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation

Cardiac troponin T and echocardiographic dimensions after repeated sprint vs. moderate intensity continuous exercise in healthy young males

Regular physical exercise can positively influence cardiac function; however, investigations have shown an increase of myocardial damage biomarkers after acute prolonged endurance exercises. We investigated the effect of repeated sprint vs. moderate long duration exercise on markers of myocardial necrosis, as well as cardiac dimensions and functions. Thirteen healthy males performed two different running sessions (randomized, single blinded cross-over design): 60 minutes moderate intensity continuous training (MCT, at 70% of peak heart rate (HRpeak)) and two series of 12 × 30-second sprints with set recovery periods in-between (RST, at 90% HRpeak). Venous blood samples for cardiac troponin T (cTnT), creatine kinase (CK) and MB isoenzyme (CK-MB) were taken 1 and 4 hours after exercise sessions. After each session electrocardiographic (ECG) and transthoracic echocardiographic (TTE) data were recorded. Results showed that all variables - average heart rate, serum lactate concentration during RST, subjective exertion and cTnT after RST - were significantly higher compared to MCT. CK and CK-MB significantly increased regardless of exercise protocol, while ECG and TTE indicated normal cardiac function. Our results provide evidence that RST contributes significantly to cTnT and CK release. This biomarker increase seems to reflect a physiological rather than a pathological phenomenon in healthy, exercising subjects

Treatment of Stable Angina with a New Fixed-Dose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40119-017-0099-1">https://link.springer.com/article/10.1007/s40119-017-0099-1</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Comparison of Mortality Risk Models in Patients with Postcardiac Arrest Cardiogenic Shock and Percutaneous Mechanical Circulatory Support

Background. Although scoring systems are widely used to predict outcomes in postcardiac arrest cardiogenic shock (CS) after out-of-hospital cardiac arrest (OHCA) complicating acute myocardial infarction (AMI), data concerning the accuracy of these scores to predict mortality of patients treated with Impella in this setting are lacking. Thus, we aimed to evaluate as well as to compare the prognostic accuracy of acute physiology and chronic health II (APACHE II), simplified acute physiology score II (SAPS II), sepsis-related organ failure assessment (SOFA), the intra-aortic balloon pump (IABP), CardShock, the prediction of cardiogenic shock outcome for AMI patients salvaged by VA-ECMO (ENCOURAGE), and the survival after venoarterial extracorporeal membrane oxygenation (SAVE) score in patients with OHCA refractory CS due to an AMI treated with Impella 2.5 or CP. Methods. Retrospective study of 65 consecutive Impella 2.5 and 32 CP patients treated in our cardiac arrest center from September 2015 until June 2020. Results. Overall survival to discharge was 44.3%. The expected mortality according to scores was SOFA 70%, SAPS II 90%, IABP shock 55%, CardShock 80%, APACHE II 85%, ENCOURAGE 50%, and SAVE score 70% in the 2.5 group; SOFA 70%, SAPS II 85%, IABP shock 55%, CardShock 80%, APACHE II 85%, ENCOURAGE 75%, and SAVE score 70% in the CP group. The ENCOURAGE score was the most effective predictive model of mortality outcome presenting a moderate area under the curve (AUC) of 0.79, followed by the CardShock, APACHE II, IABP, and SAPS score. These derived an AUC between 0.71 and 0.78. The SOFA and the SAVE scores failed to predict the outcome in this particular setting of refractory CS after OHCA due to an AMI. Conclusion. The available intensive care and newly developed CS scores offered only a moderate prognostic accuracy for outcomes in OHCA patients with refractory CS due to an AMI treated with Impella. A new score is needed in order to guide the therapy in these patients

Comparison of mechanical circulatory support with venoarterial extracorporeal membrane oxygenation or Impella for patients with cardiogenic shock: a propensity-matched analysis

Background!#!Percutaneous mechanical circulatory devices are increasingly used in patients with cardiogenic shock (CS). As evidence from randomized studies comparing these devices are lacking, optimal choice of the device type is unclear. Here we aim to compare outcomes of patients with CS supported with either Impella or vaECMO.!##!Methods!#!Retrospective single-center analysis of patients with CS, from September 2014 to September 2019. Patients were assisted with either Impella 2.5/CP or vaECMO. Patients supported ultimately with both devices were analyzed according to the first device implanted. Primary outcomes were hospital and 6-month survival. Secondary endpoints were complications. Survival outcomes were compared using propensity-matched analysis to account for differences in baseline characteristics between both groups.!##!Results!#!A total of 423 patients were included (Impella, n = 300 and vaECMO, n = 123). Survival rates were similar in both groups (hospital survival: Impella 47.7% and vaECMO 37.3%, p = 0.07; 6-month survival Impella 45.7% and vaECMO 35.8%, p = 0.07). There was no significant difference in survival rates, even after adjustment for baseline differences (hospital survival: Impella 50.6% and vaECMO 38.6%, p = 0.16; 6-month survival Impella 45.8% and vaECMO 38.6%, p = 0.43). Access-site bleeding and leg ischemia occurred more frequently in patients with vaECMO (17% versus 7.3%, p = 0.004; 17% versus 7.7%, p = 0.008).!##!Conclusions!#!In this retrospective analysis of patients with CS, treatment with Impella 2.5/CP or vaECMO was associated with similar hospital and 6-month survival rates. Device-related access-site vascular complications occurred more frequently in the vaECMO group. A randomized trial is warranted to examine the effects of these devices on outcomes and to determine the optimal device choice in patients with CS

Biventricular Unloading with Impella and Venoarterial Extracorporeal Membrane Oxygenation in Severe Refractory Cardiogenic Shock: Implications from the Combined Use of the Devices and Prognostic Risk Factors of Survival

Since mechanical circulatory support (MCS) devices have become integral component in the therapy of refractory cardiogenic shock (RCS), we identified 67 patients in biventricular support with Impella and venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) for RCS between February 2013 and December 2019 and evaluated the risk factors of mortality in this setting. Mean age was 61.07 ± 10.7 and 54 (80.6%) patients were male. Main cause of RCS was acute myocardial infarction (AMI) (74.6%), while 44 (65.7%) were resuscitated prior to admission. The mean Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment Score (SOFA) score on admission was 73.54 ± 16.03 and 12.25 ± 2.71, respectively, corresponding to an expected mortality of higher than 80%. Vasopressor doses and lactate levels were significantly decreased within 72 h on biventricular support (p 6 mmol/L, vasoactive score > 100 and pH 3 and prior resuscitation were independent predictors of survival. In conclusion, biventricular support with Impella and VA-ECMO in patients with RCS is feasible and efficient leading to a better survival than predicted through traditional risk scores, mainly via significant hemodynamic improvement and reduction in lactate levels

Left Ventricle Architecture and Valvular Integrity Following Microaxial Mechanical Support: A Two-Year Follow-Up Study

Although the use of microaxilar mechanical circulatory support systems may improve the outcome of patients with cardiogenic shock (CS), little is known about its effect on the long-term structural integrity of left ventricular (LV) valves as well as on the development of LV-architecture. Therefore, we aimed to study the integrity of the LV valves and architecture and function after Impella support. Thus, 84 consecutive patients were monitored over two years having received ImpellaTM CP (n = 24) or 2.5 (n = 60) for refractory CS (n = 62) or for high-risk percutaneous coronary interventions (n = 22) followed by optimal medical treatment. Beside a significant increase in LV ejection fraction after two years (p ≤ 0.03 vs. pre-implantation), we observed a statistically significant decrease in LV dilation (p &lt; 0.001) and severity of mitral valve regurgitation (p = 0.007) in the two-year follow-up period, suggesting an improved LV architecture. Neither the duration of support, nor the size of the Impella device or the indication for its use revealed any devastating impact on aortic or mitral valve integrity. These findings indicate that Impella device is a safe means of support of LV-function without detrimental long-term effects on the structural integrity of LV valves regardless of the size of the device or the indication of support

Analysis of Atrial Fibrillation Treatment Regimes in a Multicenter Cohort of Transcatheter Edge-to-Edge Mitral Valve Repair Patients

Background. Atrial fibrillation (AF) is a highly prevalent comorbidity in patients with severe mitral valve regurgitation (MR). Recent studies show a deleterious outcome of patients with concomitant AF after transcatheter mitral valve repair (TMVR). This underlines the essential need for additional strategies that ameliorate the prognosis of these patients. Fundamental data on AF characteristics and treatment regimes in this special cohort of patients are lacking. Methods. We retrospectively analyzed the data of 542 consecutive patients with severe MR undergoing TMVR in three tertiary heart centers with special focus on AF type and underlying treatment strategies. Results. The prevalence of concomitant AF was 73.3%, and AF did not affect the procedural success or the incidence of major adverse cardiac and cerebrovascular events. The patients with AF were more frequently >75 years, had more tricuspid regurgitation, and less coronary artery disease than non-AF patients. The distribution of AF types was 32% paroxysmal AF, 27% persistent AF, and 41% permanent AF. Except for a higher degree in severe tricuspid regurgitation and a higher likelihood of male sex, no substantial differences were observed while comparing permanent and nonpermanent AF patients. The predominant treatment regime was rate control (57%), with only beta blockers (BB) in the majority of persistent and permanent AF patients, while additional digitalis or a pacemaker was used infrequently. Rhythm control was mainly achieved with BB alone in paroxysmal AF patients and with additional antiarrhythmic drugs in the majority of persistent AF patients. Interventional rhythm control therapy was performed in 2.5% and 30.9% of paroxysmal and persistent AF patients, respectively. The guideline-adherent use of oral anticoagulants was comparable and high in both groups (91.9% in nonpermanent vs. 90.1% in permanent AF). Conclusion. This is the first study to provide necessary information for the understanding of the current clinical practice in dealing with TMVR patients. Since evidence suggests that AF is not a benign concomitant disease, further investigations are needed to assess the prognostic impact of these different AF treatment strategies