Early coronary angiography in patients after out‐of‐hospital cardiac arrest without ST‐segment elevation: Meta‐analysis of randomized controlled trials

Objectives: To compare early coronary angiography to a delayed or selective approach in out‐of‐hospital cardiac arrest (OHCA) without ST‐segment elevation of possible cardiac cause by means of meta‐analysis of available randomized controlled trials (RCTs). Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for RCTs comparing early with delayed or selective coronary angiography in OHCA patients of possible cardiac origin without ST‐segment elevation. The primary endpoint was all‐cause short‐term mortality (PROSPERO CRD42021271484). Results: The search strategy identified three RCTs enrolling a total of 1167 patients. An early invasive approach was not associated with improved short‐term mortality (odds ratio 1.19, 95% confidence interval 0.94–1.52; p = 0.15). Further, no significant differences were shown with respect to the risk of severe neurological deficit, the composite of all‐cause mortality or severe neurological deficit, need for renal replacement therapy due to acute renal failure, and significant bleeding at short‐term follow‐up. Conclusion: Early coronary angiography in OHCA without ST‐segment elevation is not superior compared to a delayed/selective approach

Impact of Morphine Treatment on Infarct Size and Reperfusion Injury in Acute Reperfused ST-Elevation Myocardial Infarction

Current evidence regarding the effect of intravenous morphine administration on reperfusion injury and/or cardioprotection in patients with myocardial infarction is conflicting. The aim of this study was to evaluate the impact of morphine administration, on infarct size and reperfusion injury assessed by cardiac magnetic resonance imaging (CMR) in a large multicenter ST-elevation myocardial infarction (STEMI) population. In total, 734 STEMI patients reperfused by primary percutaneous coronary intervention <12 h after symptom onset underwent CMR imaging at eight centers for assessment of myocardial damage. Intravenous morphine administration was recorded in all patients. CMR was completed within one week after infarction using a standardized protocol. The clinical endpoint of the study was the occurrence of major adverse cardiac events (MACE) within 12 months after infarction. Intravenous morphine was administered in 61.8% (n = 454) of all patients. There were no differences in infarct size (17%LV, interquartile range [IQR] 8–25%LV versus 16%LV, IQR 8–26%LV, p = 0.67) and microvascular obstruction (p = 0.92) in patients with versus without morphine administration. In the subgroup of patients with early reperfusion within 120 min and reduced flow of the infarcted vessel (TIMI-flow ≤2 before PCI) morphine administration resulted in significantly smaller infarcts (12%LV, IQR 12–19 versus 19%LV, IQR 10–29, p = 0.035) and reduced microvascular obstruction (p = 0.003). Morphine administration had no effect on hard clinical endpoints (log-rank test p = 0.74) and was not an independent predictor of clinical outcome in Cox regression analysis. In our large multicenter CMR study, morphine administration did not have a negative effect on myocardial damage or clinical prognosis in acute reperfused STEMI. In patients, presenting early ( ≤120 min) morphine may have a cardioprotective effect as reflected by smaller infarcts; but this finding has to be assessed in further well-designed clinical studie

Optimal timing of invasive angiography in non-ST-segment elevation acute coronary syndromes—do we need more data?

International audienc

Revascularization Strategy in Myocardial Infarction with Multivessel Disease

The proportion of patients with multivessel coronary artery disease in individuals experiencing acute coronary syndrome (ACS) varies based on age and ACS subtype. In patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock, the prognostic benefit of complete revascularization has been demonstrated by several randomized trials and meta-analyses, leading to a strong guideline recommendation. However, similar data are lacking for ACS without ST-segment elevation (NSTE-ACS). Non-randomized data suggesting a benefit from complete revascularization in non-ST-segment elevation myocardial infarction (NSTEMI) are prone to selection bias and should be interpreted with caution. A series of large randomized controlled trials have been initiated recently to address these open questions

Connexin45 is expressed in vascular smooth muscle but its function remains elusive.

Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear although its expression has been suggested in vascular smooth muscle (VSM). Therefore, we studied expression and function of Cx45 in vessels using different mice models allowing to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced green fluorescence protein (EGFP) in these mice. Conduction of vasomotor responses was studied in cremasteric arterioles using intravital microscopy and arterial pressure was measured telemetrically. Cx45 is transcriptionally expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre). Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations evoked by the endothelium-dependent agonist acetylcholine were not different between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated endothelium-independent constrictions (K(+)) and dilations (adenosine) declined similarly with distance in both genotypes indicating an intact VSM conduction pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during day or night. We conclude that Cx45 is physiologically expressed in VSM, but not in EC in murine arterioles. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other Cx functionally replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion does not seem to alter arterial pressure in freely moving mice

Early coronary angiography in patients after out‐of‐hospital cardiac arrest without ST‐segment elevation: Meta‐analysis of randomized controlled trials

Objectives: To compare early coronary angiography to a delayed or selective approach in out‐of‐hospital cardiac arrest (OHCA) without ST‐segment elevation of possible cardiac cause by means of meta‐analysis of available randomized controlled trials (RCTs). Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for RCTs comparing early with delayed or selective coronary angiography in OHCA patients of possible cardiac origin without ST‐segment elevation. The primary endpoint was all‐cause short‐term mortality (PROSPERO CRD42021271484). Results: The search strategy identified three RCTs enrolling a total of 1167 patients. An early invasive approach was not associated with improved short‐term mortality (odds ratio 1.19, 95% confidence interval 0.94–1.52; p = 0.15). Further, no significant differences were shown with respect to the risk of severe neurological deficit, the composite of all‐cause mortality or severe neurological deficit, need for renal replacement therapy due to acute renal failure, and significant bleeding at short‐term follow‐up. Conclusion: Early coronary angiography in OHCA without ST‐segment elevation is not superior compared to a delayed/selective approach

Connexin45 Is Expressed in Vascular Smooth Muscle but Its Function Remains Elusive

Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear although its expression has been suggested in vascular smooth muscle (VSM). Therefore, we studied expression and function of Cx45 in vessels using different mice models allowing to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced green fluorescence protein (EGFP) in these mice. Conduction of vasomotor responses was studied in cremasteric arterioles using intravital microscopy and arterial pressure was measured telemetrically. Cx45 is transcriptionally expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre). Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations evoked by the endothelium-dependent agonist acetylcholine were not different between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated endothelium-independent constrictions (K(+)) and dilations (adenosine) declined similarly with distance in both genotypes indicating an intact VSM conduction pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during day or night. We conclude that Cx45 is physiologically expressed in VSM, but not in EC in murine arterioles. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other Cx functionally replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion does not seem to alter arterial pressure in freely moving mice

Early coronary angiography in patients after out‐of‐hospital cardiac arrest without ST‐segment elevation: Meta‐analysis of randomized controlled trials

Objectives: To compare early coronary angiography to a delayed or selective approach in out‐of‐hospital cardiac arrest (OHCA) without ST‐segment elevation of possible cardiac cause by means of meta‐analysis of available randomized controlled trials (RCTs). Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for RCTs comparing early with delayed or selective coronary angiography in OHCA patients of possible cardiac origin without ST‐segment elevation. The primary endpoint was all‐cause short‐term mortality (PROSPERO CRD42021271484). Results: The search strategy identified three RCTs enrolling a total of 1167 patients. An early invasive approach was not associated with improved short‐term mortality (odds ratio 1.19, 95% confidence interval 0.94–1.52; p = 0.15). Further, no significant differences were shown with respect to the risk of severe neurological deficit, the composite of all‐cause mortality or severe neurological deficit, need for renal replacement therapy due to acute renal failure, and significant bleeding at short‐term follow‐up. Conclusion: Early coronary angiography in OHCA without ST‐segment elevation is not superior compared to a delayed/selective approach