[Influence of chronic obstructive pulmonary disease on hospital outcomes of percutaneous coronary interventions in patients with acute coronary syndrome].

AIM: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on hospital outcomes of percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: A cohort prospective study of the COPD effect on mortality and coronary microvascular obstruction (CMVO, no-reflow) development after PCI in ACS was carried out. 626 patients admitted in 2019-2020 were included, 418 (67%) - men, 208 (33%) - women. Median age - 63 [56; 70] years. Myocardial infarction with ST elevation identified in 308 patients (49%), CMVO - in 59 (9%) patients (criteria: blood flow <3 grade according to TIMI flow grade; perfusion <2 points according to Myocardial blush grade; ST segment resolution <70%). 13 (2.1%) patients died. Based on the questionnaire "Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005", 2 groups of patients were identified: 197 (31%) with COPD (≥17 points) and 429 (69%) without COPD (<17 points). Groups were compared on unbalanced data (÷2 Pearson, Fisher exact test). The propensity score was calculated, and a two-way logistic regression analysis was performed. The data were balanced by the Kernel "weighting" method, logistic regression analysis was carried out using "weighting" coefficients. Results as odds ratio (OR) and 95% confidence interval. RESULTS: The conducted research allowed us to obtain the following results, depending on the type of analysis: 1) analysis of unbalanced data in patients with COPD: OR death 3.60 (1.16-11.12); p=0.03; OR CMVO 0.65 (0.35-1.22); p=0,18; 2) two-way analysis with propensity score: OR death 3.86 (1.09-13.74); p=0.04; OR CMVO 0.61 (0.31-1.19); p=0.15; 3) regression analysis with "weight" coefficients: OR death 12.49 (2.27-68.84); p=0.004; OR CMVO 0.63 (0.30-1.33); p=0.22. CONCLUSION: The presence of COPD in patients with ACS undergoing PCI increases mortality and does not affect the incidence of CMVO.

No robust reduction of infarct size and no-reflow by metoprolol pretreatment in adult Göttingen minipigs.

Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg-1 metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg-1 metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.).Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction.

Coronary microvascular dysfunction: an update.

Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy.

Direct comparison of coronary microvascular obstruction evaluation using CMR feature tracking and layer-specific speckle tracking echocardiography in STEMI patients.

PURPOSE: Layer-specific speckle tissue echocardiography (LS-STE) is a unique technique used to assess coronary microvascular obstruction (CMVO) that may offer more information on the myocardial anatomy of patients with ST-elevation myocardial infarction (STEMI). Cardiovascular magnetic resonance feature tracking (CMR-FT) has also been gaining popularity as a way to evaluate CMVO. The aim of the present study was to directly compare CMVO assessment in STEMI patients using CMR-FT and LS-STE. PATIENTS AND METHODS: A total of 105 STEMI patients with LS-STE, CMR-FT, and primary percutaneous coronary intervention (PPCI) were included in the study. Longitudinal peak systolic strain (LS), circumferential peak systolic strain (CS), and radial peak systolic strain (RS) were each used to evaluate CMVO using CMR-FT and LS-STE. RESULTS: Correlation coefficients were 0.56, 0.53, and 0.55 for CMR-FT CS vs. endocardial CS, midcardial CS, and epicardial CS comparisons, respectively, and 0.87, 0.51, and 0.32 for CMR-FT LS vs. endocardial LS, midcardial LS, and epicardial LS comparisons, respectively. Bland-Altman analysis revealed strong inter-modality agreement and little bias in endocardial LS, while the absolute of limited of agreement (LOA) value was 2.28 ± 4.48. The absolutes LOA values were 1.26 ± 11.16, -0.02 ± 12.21, and - 1.3 ± 10.27 for endocardial, midcardial, and epicardial respectively. Intraclass correlation coefficient value of 0.87 showed good reliability in endocardial LS, and moderate reliability with values of 0.71, 0.70, and 0.64 in endocardial, midcardial, and epicardial CS, respectively (all p < 0.001). CONCLUSIONS: CMR-FT is a viable technique for CMVO evaluation in STEMI patients. Endocardial LS showed good reliability for CMR-FT. STEMI patients can undergo LS-STE to assess the CMVO before PPCI.

Adenosine as adjunctive therapy in acute coronary syndrome: a meta-analysis of randomized controlled trials.

AIMS: Adenosine has been tested in several randomized controlled trials (RCTs) to minimize the incidence of coronary microvascular obstruction (CMVO). The aim of this study was to pool all the RCTs comparing intracoronary or intravenous adenosine versus placebo in patients with acute coronary syndrome (ACS) undergoing myocardial revascularization. METHODS AND RESULTS: PubMed and Scopus electronic databases were scanned for eligible studies up to 5th June 2022. A total of 26 RCTs with 5843 patients were included. Efficacy endpoints were major adverse cardiac events (MACE), all-cause death, non-fatal myocardial infarction, and heart failure. Atrioventricular blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were the safety endpoints. Myocardial blush grade, thrombolysis in myocardial infarction (TIMI) flow grade, left ventricular ejection fraction (LVEF), infarct size, and ST-segment resolution were also assessed. Adenosine administration was not associated with any clinical benefit in terms of MACE, all-cause death, non-fatal myocardial infarction, and heart failure. However, adenosine was associated with an increased rate of advanced atrioventricular blocks and of VF/SVT in studies with total mean ischaemic time >3 h, compared to placebo. Remarkably, among patients undergoing percutaneous coronary intervention, adenosine was associated with reduced myocardial blush grade 0-1 and TIMI flow grade 0-2, compared to placebo. Furthermore, adenosine did not show favourable effects on LVEF and infarct size. CONCLUSION: Adenosine infusion, as adjunctive therapy in ACS, was associated with an increased risk of advanced atrioventricular blocks and increased rates of adenosine-triggered ventricular arrhythmias in patients with long ischaemic time, without providing any clinical benefit compared to placebo.

Diazoxide is a powerful cardioprotectant but is not feasible in a realistic infarct scenario.

Introduction: Diazoxide is a powerful cardioprotective agent that activates mitochondrial ATP-dependent K-channels and stimulates mitochondrial respiration. Diazoxide reduced infarct size in isolated rodent heart preparations and upon pretreatment in juvenile pigs with coronary occlusion/reperfusion. We aimed to study the use of diazoxide in a more realistic adult pig model of reperfused acute myocardial infarction when diazoxide was administered just before reperfusion. Methods and results: In a first approach, we pretreated anaesthetised adult Göttingen minipigs with 7 mg kg-1 diazoxide (n = 5) or placebo (n = 5) intravenously over 10 min and subjected them to 60 min coronary occlusion and 180 min reperfusion; blood pressure was maintained by use of an aortic snare. The primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was the secondary endpoint. In a second approach, diazoxide (n = 5) was given from 50 to 60 min coronary occlusion, and blood pressure was not maintained. There was a significant reduction in infarct size (22% ± 11% of area at risk with diazoxide pretreatment vs. 47% ± 11% with placebo) and area of no-reflow (14% ± 14% of infarct size with diazoxide pretreatment vs. 46% ± 20% with placebo). With diazoxide from 50 to 60 min coronary occlusion, however, there was marked hypotension, and infarct size (44% ± 7%) and area of no-reflow were not reduced (35% ± 25%). Conclusions: Cardioprotection by diazoxide pretreatment was confirmed in adult pigs with reperfused acute myocardial infarction but is not feasible when diazoxide is administered in a more realistic scenario before reperfusion and causes hypotension.

Comparison of Diagnostic Value Between STE+LDDSE and CMR-FT for Evaluating Coronary Microvascular Obstruction in Post-PCI Patients for STEMI.

Background: Coronary microvascular obstruction (CMVO) is closely associated with poor prognosis of ST-segment elevation myocardial infarction (STEMI) patients. However, data showing the comparison between cardiac magnetic resonance feature tracking (CMR-FT) and speckle tracking echocardiography (STE) combined with low-dose dobutamine stress echocardiography (LDDSE) in evaluating CMVO was scarcely available. We aimed to explore and compare the predictive value between CMR-FT and STE+LDDSE in detecting CMVO. Methods: Sixty-one STEMI patients were executed cardiac magnetic resonance and echocardiography within the first 5-7 days after primary percutaneous coronary intervention (PCI). The myocardial strain analysis was performed in STE, STE+LDDSE, and CMR-FT, and strain parameters included radial strain (RS), circumferential strain (CS), and longitudinal strain (LS). ROC curves were performed to predict infarcted myocardium segments with CMVO. Results: Finally, 324 infarcted myocardium segments were analyzed, including 100 infarcted segments with CMVO and 224 segments without CMVO by the gold standard assessment of late gadolinium-enhancement cardiac magnetic resonance imaging (LGE-CMR). The results showed that CS was generally superior to RS and LS in identifying CMVO. CS in CMR-FT facilitated the detection of CMVO, with a sensitivity, specificity, and accuracy of 78.00%, 81.25%, and 80.25%, respectively. The sensitivity, specificity, and accuracy of CS in STE combined with LDDSE were better than STE alone (76.00% vs 60.00%, 79.91% vs 64.29%, and 78.70% vs 62.96%, P < 0.05). In addition, CMR-FT is not superior to STE+LDDSE for detection of CMVO (P > 0.05). Conclusion: Low-dose dobutamine can improve the clinical value of STE for evaluating CMVO in STEMI patients. Compared with CMR-FT, STE+LDDSE might be a better choice for STEMI patients because of its safety, convenience, and low-cost.

Reducing Cardiac Injury during ST-Elevation Myocardial Infarction: A Reasoned Approach to a Multitarget Therapeutic Strategy.

The significant reduction in 'ischemic time' through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

Using an Artificial Neural Network to Predict Coronary Microvascular Obstruction (No-Reflow Phenomenon) during Percutaneous Coronary Interventions in Patients with Myocardial Infarction.

The aim of the study was to develop, evaluate, and validate an artificial neural network to predict coronary microvascular obstruction (CMVO) during percutaneous coronary interventions (PCI) in patients with myocardial infarctions (MI) based on the parameters, which are routinely available in an operating room when choosing a surgical approach. Materials and Methods: 5621 patients with MI and emergency PCI were retrospectively selected from the database of the City Clinical Hospital No.13 (Nizhny Novgorod, Russia); among them, there were 3935 men (70%) and 1686 women (30%), their mean age was 61.5±10.8 years. CMVO was recorded in 201 (4%) patients (the blood flow in the infarction-related artery after PCI was less than 3 points according to TIMI flow grade). The following input parameters were assessed: age, gender, past history of coronary artery disease, previous revascularization, presence of ST-segment elevation, a class of acute heart failure, a fact of systemic thrombolytic therapy administration and its effectiveness, symptom-to-balloon time, severity of coronary thrombosis and atherosclerosis, the number of stents and the number of operated coronary arteries. The sampling was divided into a training group (n=4060), a testing group (n=717), and an independent validation group (n=844). Results: We developed an artificial neural network by a fully connected multilayer perception with forward signal propagation and two hidden layers (the area under the ROC curve - 0.69) to predict CMVO based on the subsampling for training and testing. The network model was tested on an independent subsampling (the area under the ROC curve - 0.64, negative predictive value - 97.4%, positive predictive value - 14.6%). Conclusion: The developed artificial neural network enables to use the parameters routinely available in an operating room when choosing a surgical approach and predict CMVO development during PCI in MI patients with accuracy sufficient for practical use.

Giant Left Ventricular (Pseudo?) Aneurysm Complicating Anterior Myocardial Infarction.

The differential diagnosis of true aneurysms and pseudoaneurysms is challenging, and multimodality cardiac imaging is often necessary. We report a case in which the limitations of these techniques are exposed, showing that post-operative evaluation of tissue layers remains the gold standard in establishing this diagnosis. (Level of Difficulty: Beginner.).

Non-infarct related artery microvascular obstruction is associated with worse persistent diastolic dysfunction in patients with revascularized ST elevation myocardial infarction.

BACKGROUND: Infarct-artery (IRA) microvascular obstruction (MVO) is associated with diastolic dysfunction (DD) in STEMI patients. However, association between nonIRA MVO and DD in STEMI patients remains unknown. We hypothesized that revascularized STEMI patients with IRA and nonIRA MVO (IRA + nonIRA+), compared to those without nonIRA MVO (IRA + nonIRA-), have worse DD at presentation and long-term follow-up. METHODS: 87 IRA-revascularized STEMI patients had cardiac magnetic resonance imaging (MRI) [to evaluate MVO] and TTE (to evaluate diastolic function) within 1 week of presentation. Diastolic function was re-assessed by TTE at 3.97 ± 3.24 years. Baseline and follow-up DD prevalence and grade were studied in IRA + nonIRA + vs. IRA + nonIRA- MVO patients. RESULTS: 54 (62%) patients were IRA + nonIRA+ and 33 (38%) IRA + nonIRA-at baseline. IRA + nonIRA + patients had higher DD frequency at baseline (40.7 vs. 6.1%, p = 0.006) and follow-up (50.0 vs. 13.0%, p = 0.05). Only IRA + nonIRA + patients had increase in mitral medial E/e' (20.0%, p = 0.043) and trend towards increase in mitral E/A (31.1%, p = 0.063) at follow-up. IRA + nonIRA + patients had greater left atrial volume index increase (23.7%, p = 0.032 vs. 15.5%, p = 0.029) and smaller prolongation in deceleration time (15.4%, p = 0.018 vs. 18.7%, p = 0.044) at follow-up compared to IRA + nonIRA-. Grade 1 DD increased (60.9-73.9%) and combined grades 2/3 decreased (30.4-13.0%) at follow-up in IRA + nonIRA-patients. In contrast, grade 1 DD decreased (77.8-61.1%) and combined grades 2/3 increased (8.3-22.2%) at follow-up in IRA + nonIRA + patients. CONCLUSION: Concurrent IRA and nonIRA MVO in revascularized STEMI patients is associated with higher DD prevalence and worse DD grade on long-term follow-up.

FGL2 prothrombinase contributes to the early stage of coronary microvascular obstruction through a fibrin-dependent pathway.

BACKGROUND: Membrane-associated fibrinogen-like protein 2 (FGL2 prothrombinase, pFGL2) is abundantly expressed in activated microvascular endothelial cells (MVECs) and plays a crucial role in microthrombus formation in microcirculatory vasculature. It has been widely reported that coronary microvascular obstruction (CMVO) contributes to adverse outcomes following myocardial ischemia/reperfusion. However, the role of pFGL2 in CMVO is poorly understood. METHODS AND RESULTS: We aimed to identify the effect of MVECs-pFGL2 in CMVO using FGL2 knockout mice. As results, the MVECs-pFGL2 expression progresses significantly over 3 days and then gradually decreases, which is positively correlated with the extent of CMVO as detected by HE staining in wild type mice. Furthermore, FGL2 deficiency is correlated with decreased areas of no-reflow and necrosis as detected by Evans Blue and TTC staining and that it ameliorates cardiac dysfunction detected by hemodynamics in the early stage of CMVO. Moreover, fibrin deposition in microvasculature is significantly reduced in FGL2-deficient mice as evidenced by immunohistochemistry, MSB and Carstairs staining, along with the down-regulation of leukocyte adhesion and infiltration. Additionally, we observed that the FGL2 deficiency decreases macrophage infiltration and shifts the macrophage phenotype from pro-inflammatory (M1,) to anti-inflammatory (M2,) pattern in the early stage of CMVO. CONCLUSION: These findings highlight the MVECs-pFGL2-fibrin pathway in the early stage of CMVO and provide insights into coagulation and inflammation for the coronary artery disease therapeutics.