777 Prehospital ECG in patients with acute myocardial infarction during the COVID-19 pandemic

Aims Primary percutaneous coronary intervention (PCI) represents the preferred revascularization strategy among patients with acute ST-segment elevation myocardial infarction (STEMI). A decline in the rates of primary PCI has been observed globally during the outbreak of coronavirus disease-19 (COVID-19). Fear of exposure to in-hospital infection has been hypothesized as the main mechanism of this phenomenon, also contributing to a delayed presentation of patients with STEMI. However, a formal assessment of initial electrocardiograms (ECGs) among STEMI patients during the COVID-19 pandemic is still lacking. We therefore compared pre-hospital ECGs of STEMI patients hospitalized in Italy after the first reported case of COVID-19 on 21 February 2020 with data from the same period in 2019 to identifying potential changes between the two periods. Methods and results Prehospital ECGs were obtained from the STEMI care network in the Campania region. Deidentified ECGs were analysed by two expert reviewers who were blinded to date of recording. Pathological Q-waves were defined as a Q-wave with a duration ≥40 ms and/or depth ≥25% of the R-wave in the same lead or the presence of a Q-wave equivalent. These criteria have been shown to be associated with final infarct size at cardiac magnetic resonance. For all conventional STEMI, the timing of STEMI onset was estimated with the Anderson-Wilkins (AW) acuteness score, ranging from 1 (least acute) to 4 (most acute). From 21 February 2020 to 16 April 2020, a total of 3239 pre-hospital ECGs were recorded by the emergency medical system and 167 (5.15%) were classified as STEMI. During the same period in 2019, 3505 pre-hospital ECGs were recorded, and 196 (5.59%) were classified as STEMI. There was no difference between the two study periods in terms of age, gender, type, and location of STEMI (Table 1). Pathological Q-waves were present in 54.5% of ECGs recorded during the COVID-19 period compared with 22.1% of ECGs recorded in the same period in 2019 (risk difference 32.3, 95% confidence intervals [CI]: 21.2–43.5 percentage points). There was also an increase in the mean number of Q-waves during the COVID-19 compared with the control period (1.4 vs. 0.9; P < 0.001). These findings remained similar when QS- and qR complexes were analysed separately. Consistently, the AW score was significantly lower during the COVID-19 period (2.4 vs. 2.8; P < 0.001). Conclusions Prehospital ECGs of STEMI patients during the COVID-19 pandemic presented more frequently with signs of late ischemia compared with the equivalent period in 2019. Approximately, one out of two patients had already pathological Q-waves in the initial ECG. The AW acuteness score is superior to patient history (historical timing) in predicting myocardial salvage and mortality after reperfusion in STEMI patients, thus explaining the higher mortality rate and the increased risk of infarct-related complications observed during the COVID-19 pandemic.

Increase in Plasma Oxidized Phosphatidylcholines (OxPCs) in Patients Presenting With ST-Elevation Myocardial Infarction (STEMI)

Objective: ST-segment Elevation Myocardial Infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using percutaneous coronary intervention (PCI), a large percentage of myocardial cells die after reperfusion which is recognized as ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPCs) are a group of oxidized lipids generated through non-enzymatic oxidation and have pro-inflammatory properties. This study aimed to examine the roles of OxPCs in a clinical setting of myocardial I/R.Methods: Blood samples were collected from STEMI patients at presentation prior to primary PCI (PPCI) (Isch) and at 4 time-points post-PPCI, including 2 h (R-2 h), 24 h (R-24 h), 48 h (R-48 h), and 30 days (R-30 d) post-PPCI. As controls, blood samples were collected from patients with non-obstructive coronary artery disease after diagnostic coronary angiography. Aspiration thrombectomy was also performed in selected STEMI patients. High-performance lipid chromatography-electrospray mass spectrometry (LC-MS/MS) was used for OxPCs analysis.Results: Twenty-two distinct OxPC species were identified and quantified in plasma samples in patients presenting with STEMI. These compounds were categorized as fragmented and non-fragmented species. Total levels of OxPCs did not significantly differ between Isch and control groups. However, total levels of fragmented OxPCs increased significantly in the ischemic period compared with controls (Isch: 4.79 ± 0.94, Control: 1.69 ± 0.19 ng/μl of plasma, P < 0.05). Concentrations of non-fragmented OxPCs had significant reductions during ischemia compared to the control group (Isch: 4.84 ± 0.30, Control: 6.6 ± 0.51 ng/μl, P < 0.05). Levels of total OxPCs in patients with STEMI were not significantly different during reperfusion periods. However, fragmented OxPCs levels were elevated at 48 h post-reperfusion and decreased at 30 days following MI, when compared to R-2 h and R-24 h time points (Isch: 4.79 ± 0.94, R-2 h: 5.33 ± 1.17, R-24 h: 5.20 ± 1.1, R-48 h: 4.18 ± 1.07, R-30 d: 1.87 ± 0.31 ng/μl, P < 0.05). Plasma levels of two fragmented OxPCs, namely, POVPC and PONPC were significantly correlated with peak creatine kinase (CK) levels (P < 0.05). As with plasma levels, the dominant OxPC species in coronary aspirated thrombus were fragmented OxPCs, which constituted 77% of total OxPC concentrations.Conclusion: Biologically active fragmented OxPC were elevated in patients presenting with STEMI when compared to controls. PONPC concentrations were subsequently increased after PPCI resulting in reperfusion. Moreover, levels of POVPC and PONPC were also associated with peak CK levels. Since these molecules are potent stimulators for cardiomyocyte cell death, therapeutics attenuating their activities can result in a novel therapeutic pathway for myocardial salvage for patients undergoing reperfusion therapy.

Prognostic value of the SYNTAX score on myocardial injury and salvage in STEMI patients after primary percutaneous coronary intervention: a single-center retrospective observational study

Background SYNTAX score (SS) was shown to positively correlate with postprocedural myocardial injury in patients after elective coronary artery intervention, but evidence about the association of SS with myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients is still needed. This study aimed to evaluate the prognostic value of SS for myocardial injury and salvage assessed by cardiac magnetic resonance (CMR) after primary percutaneous coronary intervention (PCI) in STEMI patients. Methods This single-center retrospective study consecutively enrolled STEMI patients who had undergone primary PCI within 12 h from symptom onset. Both angiography and CMR were performed during hospitalization, and patients were divided into low SS (SS ≤ 22), mediate-high SS (SS > 22) groups. Correlation and multivariable analyses were performed. Results A total of 149 STEMI patients (96 low SS, 53 mediate-high SS) were included. In terms of myocardial injury parameters, there was a positive correlation (p < 0.001, Spearman r = 0.292) between SS and infarct size (IS), and a negative correlation (p < 0.001, Spearman r = − 0.314) between SS and myocardial salvage index (MSI). In the multivariable model, SS (> 22 as categorical variable, OR = 2.245, 95% CI [1.002–5.053], p = 0.048; as continuous variable, OR = 1.053, 95% CI [1.014–1.095], p = 0.008) was significantly associated with high IS (≥ mean 35.43). The areas under the receiver operating characteristic (ROC) curves of SS for high IS and low MSI (≤ median 28.01) were 0.664 and 0.610. Conclusions In STEMI patients undergoing primary PCI, SYNTAX score positively correlated with infarct size and negatively with myocardial salvage, indicating an independent predictive value of the myocardial injury.

The role of IL-6 receptor trans-signalling in ischemia-reperfusion injury, infarct healing and future adverse events in patients with ST-Elevation Myocardial Infarction

Background Inflammation has emerged as a new treatment target in patients with coronary artery disease, and inflammation seems to play an important role in the ischemia/reperfusion injury in ST-elevation myocardial infarction (STEMI). The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to be associated with myocardial injury and poor prognosis in patients with STEMI. Purpose The aim of the study was to further elucidate possible associations between the IL-6 trans-signalling system and final infarct size, myocardial function, adverse remodelling, and future cardiovascular events in patients with STEMI. Methods A total of 272 patients with first-time STEMI included in the POSTEMI study on ischaemic postconditioning, with symptom duration &lt;6 hours and treated with percutaneous coronary intervention (PCI), were included. Blood samples for analysis of IL-6 and IL-6 receptor (IL-6R) were collected before PCI, immediately after PCI, at day 1 (median 18.3 hours after PCI), and at 4 months follow-up. Cardiac magnetic resonance imaging (CMR) was performed in the acute phase, median 2 days after admission, and repeated after 4 months. Clinical events and all-cause mortality were registered during 12 months' and 70 months' follow-up, respectively. Results There was a significant increase in IL-6 levels from admission to day 1 with a subsequent decline from day 1 to 4 months (Figure 1A). No significant change in IL-6R levels were found from admission to day 1 (Figure 1B). There was no difference between patients treated by postconditioning compared to routine PCI. High levels of IL-6 (&gt; median) at all sampling points were significantly associated with increased infarct size and reduced left ventricular ejection fraction (LVEF) measured by CMR. Additionally, high levels of IL-6 (&gt; median) at day 1 were associated with lower myocardial salvage, more presence of microvascular obstruction and larger increase in indexed LV end diastolic volume (LVEDVi). IL-6R measured during hospitalisation was significantly associated with change in LVEDVi, but did not associate with infarct size, LVEF or myocardial salvage. High levels of IL-6 (&gt;75th percentile) at all sampling points were associated with an increased risk of having an adverse clinical event during the first year and with long-term all-cause mortality (Figure 2), whereas there was no association between IL-6R and adverse clinical events. Conclusion Patients with high IL-6 levels during the acute phase of STEMI had larger infarct size, reduced myocardial salvage, reduced LV function and worse clinical outcome than patients with lower levels of IL-6. High levels of IL-6 measured after 4 months were associated with larger infarct size, reduced LVEF and increased all-cause mortality. IL-6R was significantly associated with increase in LVEDVi. The results add important information to the role of IL-6 in myocardial injury in acute STEMI and the IL-6 pathway as a potential treatment target. FUNDunding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Oslo, Norway. Figure 1 Figure 2

The de Winter Pattern as Pre-Anterior ST-Elevation-Myocardial-Infarction. “An Evolution Sequence”: A Case Report

Introduction: The de Winter pattern (dWP) was first described by de Winter and colleagues in 2008 as static pattern associated with anterior myocardial infarction. A recent study showed the evolution sequence of this pattern into typical ST-elevation myocardial infarction (STEMI). This case discussed dWP who present as pre-anterior STEMI. Case Illustration: A-56-year old Male arrived in the emergency room complained chest pain about 3 hours. The patient also complained of diaphoresis, nausea, and fatigue. The patient has a previous history of hypertension. The vital signs were stable with an unremarkable physical examination. The initial electrocardiogram (ECG) revealed sinus rhythm with j-point depression followed by prominent T wave in precordial leads, slight ST-segment elevation in aVR, and loss of precordial R-wave progression. The initial-troponin-T was 31 pg/mL. Follow-up 1-hour after initial ECG showed typical ST-segment-elevation in V1-V4. The patient undergoing thrombolytic, followed by angiography that showed subtotal occlusion in the proximal left anterior descending (LAD) artery, occlusion in the proximal circumflex artery and stenosis in proximal right coronary artery, echocardiography revealed regional wall motion abnormality in the septal and anterior segments and preserved ejection fraction 58%, the patient was discharged after 8-days treated in intensive cardiac care unit. Conclusion: dWP has been shown as static and dynamic pattern in some conditions and associated with acute LAD occlusion. In this case, we showed dWP as early anterior STEMI, recognition of this pattern lead to early reperfusion and better myocardial salvage as anterior STEMI has a poor outcome.

Assessment of Myocardial Salvage Index after Primary Percutaneous Intervention of ST Elevation Myocardial Infarction Patients Using Myocardial Magnetic Resonance Imaging Techniques

Objectives: The aim of this work was assessment of myocardial salvage using various magnetic resonance imaging techniques immediately after primary percutaneous coronary intervention of ST elevation myocardial infarction patients and at midterm follow up. Methods: The current study was conducted on 30 patients referred to Aswan heart center or Cardiology department, Tanta University hospital with a diagnosis of ST elevation myocardial infarction during the period from august2017 to December 2017. All patients were subjected to history taking ,clinical assessment ,12 lead ECG, Laboratory biomarkers including cardiac enzyme biomarkers, complete blood count, liver function test, renal function test and lipid profile primary then primary percutaneous coronary intervention was done then cardiac magnetic resonance imaging within 3 days and after 3 months including the following sequences: Steady-state free precession, T2 weighted triple inversion recovery sequence and Early and late gadolinium enhancement to measure the area at risk and myocardial salvage index. Results: Myocardial salvage index was found to improve with improving thrombolysis in myocardial infarction (TIMI) flow post intervention (p value=0.004), also the presence of microvascular obstruction (p value =0.034) and intramyocardial hemorrhage (p value=0.014) had a negative impact on myocardial salvage index. Peak cardiac enzyme biomarkers (troponin p value=0.001,CK p value=0.005,CKMB p value=0.002) were also associated with increased area at risk however did not affect the myocardial salvage index. Conclusion: Proper management of the occluded coronary artery is a corner stone in improving myocardial salvage index which can be properly assessed with cardiac MRI.

Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats

Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.

Surviving to Acute Myocardial Infarction: The Role of Psychological Factors and Alexithymia in Delayed Time to Searching Care: A Systematic Review

The time from symptom onset to reperfusion is a critical determinant of myocardial salvage and clinical outcomes in patients with acute myocardial infarction (AMI). This time period could be delayed if people do not seek help promptly and/or if the health system is not efficient in responding quickly and attending to these individuals. The aim of this study was to identify psychological factors associated with pre-hospital delay (PHD) or patients’ decisional delay (PDD) in people with an ongoing AMI. A search in PubMed/Medline from 1990 to 2021 with the keywords “pre-hospital delay” OR “prehospital delay” OR “patient delay” OR “decisional delay” OR “care seeking behavior” AND “psychological factors” OR “alexithymia” AND “myocardial infarction” was performed. Thirty-six studies were included, involving 10.389 patients. Wrong appraisal, interpretation and causal beliefs about symptoms, denial of the severity of the symptoms and high levels of alexithymia were found related to longer PHD or PDD. Alexithymia may be an overarching construct that explains the disparate findings of the studies exploring the role of psychological factors in PHD or PDD. Further studies are needed in order to analyse the role of alexithymia in patients with risk factors for AMI to prevent delay.

Hypothermia for Reduction of Myocardial Reperfusion Injury in Acute Myocardial Infarction: Closing the Translational Gap

Myocardial reperfusion injury—triggered by an inevitable inflammatory response after reperfusion—may undo a considerable part of the myocardial salvage achieved through timely percutaneous coronary intervention in patients with acute myocardial infarction. Because infarct size is strongly correlated to mortality and risk of heart failure, the importance of endeavors for cardioprotective therapies to attenuate myocardial reperfusion injury and decrease infarct size remains undisputed. Myocardial reperfusion injury is the result of several complex nonlinear phenomena, and for a therapy to be effective, it should act on multiple targets involved in this injury. In this regard, hypothermia remains a promising treatment despite a number of negative randomized controlled trials in humans with acute myocardial infarction so far. To turn the tide for hypothermia in patients with acute myocardial infarction, sophisticated solutions for important limitations of systemic hypothermia should continue to be developed. In this review, we provide a comprehensive overview of the pathophysiology and clinical expression of myocardial reperfusion injury and discuss the current status and possible future of hypothermia for cardioprotection in patients with acute myocardial infarction.