Larger Infarct Size Research Articles

Abstract Su306: Impact of Ventricular Fibrillation on Myocardial Infarct Size: A Clinical and Experimental Study

Background: Ventricular fibrillation (VF) - induced cardiac arrest is a frequent complication of ST-segment elevation myocardial infarction (STEMI). Although larger infarct sizes (IS) are associated with a higher risk of VF, there has been no investigation into the influence of VF itself on IS. To address this knowledge gap, we analyzed the impact of VF on IS in patients and 2 experimental models. Methods: From the prospective cohort HIBISCUS-STEMI, 30 STEMI patients with VF were matched on common determinants of IS in a 1:2 ratio with patients without VF. The primary endpoint was IS, assessed using the 48-hour area under the curve (AUC) for troponin. We compared IS in pigs with/without spontaneous VF during STEMI (n=15/group), and in an isolated rat heart model of acute myocardial infarction with/without electrically induced VF (n=7/group); IS was assessed using the ratio of the area of necrosis (AN) to the area at risk (AAR). Results: While patient characteristics were similar after matching (including AAR), IS was 33% lower in the VF group than in the control group (troponin AUC 1.6 [0.5-3.3] 10 6 vs. 2.4 [0.9-4.1] 10 6 arbitrary units; p=0.049). In pigs, IS was lower (p<0.01) in the VF group (24% [11-40]) than in controls (71% [48-75]). In the isolated heart model, IS was lower (p<0.05) in the VF group (9% [7-15]) than in controls (42% [38-44]). Conclusion: When common determinants of IS are comparable, the occurrence of VF prior to MI reperfusion is associated with significantly smaller IS.

Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction

Abstract Background Acute myocardial infarction is associated with high levels of cardiac sympathetic stimulation, which leads to the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and an association with increased risk for heart failure and microvascular dysfunction after acute ST-elevation myocardial infarction (STEMI) has been suggested. Purpose This study aims to comprehensively evaluate the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). Methods In this observational study, we included 260 STEMI patients treated with primary PCI. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging 4 days and 4 months after PCI. Results Median plasma concentrations of NPY were 70 [interquartile range (IQR): 35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48% vs. 52%, p=0.004), decreased GLS (-8.8% vs. -12.6%, p<0.001) and larger IS (17% vs. 13%, p=0.041) in the acute phase after infarction as well as in the chronic stage (LVEF: 50% vs. 52%, p=0.030, GLS: -10.5 vs. -12.9, p<0.001, IS: 13% vs. 10%, p=0.011). In addition, NPY levels were significantly related to presence of MVO (58% vs. 52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF: p<0.001, GLS: p<0.001, IS: p=0.003, MVO: p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. Conclusion High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a valuable biomarker for optimized risk stratification.

Clinical significance of 12-lead electrocardiogram QRS scores on admission in ST-segment elevation myocardial infarction

Abstract Background A QRS scoring system by 12-lead electrocardiography (ECG) is a quick and simple method to evaluate degree and extension of myocardial infarction. Previous studies have shown that high QRS scores (≥5) at hospitalization (before reperfusion) related to impaired myocardial reperfusion during percutaneous coronary intervention (PCI) and subsequent poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) (Figure 1). However, the pathogenesis and associated factors with high QRS scores remain poorly defined. Therefore, this study aimed to explore clinical and lesion characteristics associated with QRS scores at hospitalization in patients with STEMI. Methods This retrospective observational study enrolled 138 broad anterior-wall STEMI patients who underwent PCI in the proximal left anterior descending artery and achieved reperfusion within 3 hours of onset. Patients were divided by QRS scores at hospitalization into low (<5: n=97) and high (≥5: n=41) QRS-scores, and clinical and lesion characteristics were compared between the 2 groups. Lesion characteristics were evaluated by intravascular ultrasound (IVUS). Results Despite early phase of STEMI, QRS scores at hospitalization varied (3 [2-5] points). Clinical characteristics, including onset-to-door time (66 [41-101] min vs. 55 [42-76] min) and onset-to-reperfusion time (112 [88-145] min vs. 106 [81-120] min), were comparable between patients with low and high QRS-scores. In contrast, significantly higher percentages of lipid plaques, plaque rupture and large thrombus were seen at the culprit lesion sites in patients with high versus low QRS scores (Figure 2). As a result, patients with high QRS scores had higher incidence of no-reflow phenomenon during PCI (36.6% vs. 12.6%, p<0.05) and larger infarct size assessed by peak CK values (5333 [3307-7443] IU/l vs. 1941 [759-3559], p<0.05) compared with those with low QRS-scores. Conclusions High QRS scores at hospitalization were associated with vulnerable lesion characteristics, as well as impaired coronary reperfusion and large infarct size. Although the exact mechanisms of the associations require future studies, QRS scores may help risk stratification before reperfusion and prognostic prediction after reperfusion.Figure 1.Figure 2.

Long-term prognosis after ST-elevation myocardial infarction according to the Canadian Cardiovascular Society classification of tissue injury severity in acute myocardial infarction

Abstract Background The recently proposed Canadian Cardiovascular Society (CCS) classification of acute myocardial infarction (MI) describes 4 stages of tissue injury identified by cardiac magnetic resonance imaging (CMR); 1) oedema without late gadolinium enhancement (LGE); 2) LGE without microvascular obstruction (MVO); 3) MVO; and 4) intramyocardial haemorrhage (IMH). Prior studies examining the relationship between these characteristics and outcomes are limited by variations in imaging and measurement techniques, in particular the distinction between MVO and IMH. The relationship between the proposed CCS classification of MI and outcomes has not been described. Purpose To explore the prognostic significance of the CCS classification of MI tissue injury in patients with ST-elevation MI (STEMI). Methods The British Heart Foundation MR-MI study was a prospective single-centre CMR cohort study in patients with STEMI (July 2011-November 2012). CMR was performed on a single Siemens MAGNETOM Avanto 1.5-Tesla scanner at 2 days post-STEMI. The imaging protocol included LGE and T2* mapping, allowing for the identification of infarct, MVO, and IMH. Follow-up for the occurance of major adverse cardiovascular events (MACE) (recurrent MI, ischaemic stroke and cardiovascular death) and a composite outcome of heart failure hospitalization/ICD implantation (HFH) or all-cause death was performed via electronic case note review. Results 246 patients had complete data for this analysis. Of these, 6 (2%) were CCS Stage 1, 105 (43%) were Stage 2, 33 (13%) were Stage 3, and 102 (41%) were Stage 4. Due to the low number in CCS stage 1, these patients were pooled with Stage 2 for the purposes of this analysis (CCS Stage 1/2). Average age was 58 (SD 11) years and 188 (76%) were male. With higher CCS stage, more patients were Killip class III/IV at presentation, had the LAD as culprit artery and had TIMI flow 0/1 pre-PCI. Patients with higher CCS stage had higher peak troponin-I and NT-proBNP, lower left ventricular function, higher left ventricular volumes and larger infarct size (Table). Median follow-up was 11.8 years. HFH or all-cause death occurred in 80 (33%) patients (22 HFH and 58 all-cause deaths), and MACE occurred in 63 (26%) patients (41 recurrent MI, 11 ischaemic stroke events, and 11 cardiovascular deaths). There were no significant differences in outcomes between CCS Stage 3 and CCS Stage 1/2 (Figure). Patients with CCS Stage 4 had a higher risk of HFH or all-cause death (HR 1.73, 95%CI 1.08-2.77; p=0.022) and MACE (HR 1.88, 95%CI 1.10-3.20; p=0.021) as compared with those in CCS Stage 1/2 (Figure). Conclusion The novel CCS classification of MI tissue injury identifies patients at the highest risk of adverse outcomes following STEMI. The relationship between the presence of IMH (CCS Stage 4) and adverse outcomes highlights the importance of T2* imaging in post-MI CMR protocols in order to identify this prognostically important biomarker.

The distribution and mass index of epicardial adipose tissue were correlated with microvascular obstruction formation in patients with ST-segment elevation myocardial infarction

Abstract Introduction Epicardial adipose tissue (EAT), refers to a metabolically active fat depot between the visceral pericardium and the outer margin of the myocardium. EAT has gradually emerged as a novel target for risk stratification of coronary artery disease due to its distinctive location and multifaceted metabolic properties. Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction. However, the clinical implications of EAT in MVO formation in patients with ST-segment elevation myocardial infarction (STEMI) remain unclear. Recently, cardiac magnetic resonance (CMR) has emerged as the gold standard technique to detect the extent of MVO and evaluate EAT parameters. Purpose This study aimed to evaluate the correlation between EAT accumulation and MVO occurrence detected by CMR in STEMI patients. Methods A total of 129 STEMI patients who underwent pPCI successfully were enrolled. Clinical characteristics including demographic characteristics, cardiovascular risk factors, laboratory data and angiographic parameters were recorded from each patient by 1 trained physician. All patients underwent CMR within 1 week following pPCI to evaluate infarct size, MVO volume and EAT distribution. All CMR data were transferred to Q-MASS MR 8.1 imaging system (Medis, Leiden, The Netherlands) and interpreted twice by 2 expert radiologists who were blinded to the angiographic and clinical data of patients. Results Compared to STEMI patients without MVO, STEMI patients with MVO presented with higher peak troponin T levels, increase of neutrophil lymphocyte ratio (NLR) and C-reactive protein (CRP), larger infarct size and compromised left ventricular ejection fraction. Total EAT volume, EAT mass index, left atrioventricular EAT volume, left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were unanimously associated with the occurrence of MVO. The left atrioventricular EAT mass index in STEMI patients with MVO were significantly larger than that in STEMI patients without MVO (24.72±5.049 g/m2 vs 18.63±3.670 g/m2, P<0.001). Multivariate logistic regression analysis demonstrated that NLR, peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. LV EAT mass index showed a robust and independent relationship with MVO formation and a cutoff value >21.5192 g/m2 predicted the presence of MVO with a sensitivity and specificity of 79.5% and 80.4%, respectively. Conclusions Left atrioventricular EAT mass index is an independent predictor of MVO. Measurement of EAT using CMR could be used for risk stratification and might be a promising target in developing new therapies to reduce myocardial reperfusion injury in patients with STEMI.

Redefining Infarction Size for Small-Vessel Occlusion in Acute Ischemic Stroke: A Retrospective Case-Control Study.

Small-vessel occlusion, previously referred to as lacunar infarcts, accounts for approximately one-third of all ischemic strokes, using an axial diameter of less than 20 mm on diffusion-weighted imaging. However, this threshold may not adequately differentiate small-vessel occlusion from other pathologies, such as branch atheromatous disease (BAD) and embolism. This study aimed to assess the clinical significance and pathological implications of acute small subcortical infarctions (SSIs) based on infarct diameter. We conducted a retrospective case-control study using data from stroke patients recorded between 2016 and 2021 of the Stroke Registry in Chang Gung Healthcare System. Patients with acute SSIs in penetrating artery territories were included. Key variables such as patient demographics, stroke severity, and medical history were collected. Infarcts were categorized based on size, and the presence of early neurological deterioration (END) and favorable functional outcomes were assessed. Among the 855 patients with acute SSIs, the median age was 70 years and the median National Institutes of Health Stroke Scale (NIHSS) score at arrival was four. END occurred in 97 patients (11.3%). Those who experienced END were significantly less likely to achieve a favorable functional outcome compared to those who did not (18.6% vs. 59.9%, p < 0.001). The incidence of END increased progressively with infarct sizes of 15 mm or larger, with the optimal threshold for predicting END identified as 15.5 mm and for BAD, it was 12.1 mm. A multiple logistic regression analysis revealed that motor tract involvement [adjusted odds ratio (aOR) 2.3; 95% confidence interval (CI) 1.1-4.7], an initial heart rate greater than 90 beats per minute (aOR 2.3; 95% CI 1.2-4.3), and a larger infarct size (15 mm to less than 20 mm vs. 10 mm to less than 15 mm; aOR 3.0; 95% CI 1.4-6.3) were significantly associated with END. Our findings suggest that setting the upper limit for small-vessel occlusion at 15 mm would be more effective in distinguishing it from BAD. However, these findings should be interpreted in the context of the retrospective design and study population. Further multi-center research utilizing high-resolution vessel wall imaging is necessary to refine this threshold and enhance diagnostic accuracy.

Cardiac ultrasomics for acute myocardial infarction risk stratification and prediction of all-cause mortality: a feasibility study

BackgroundCurrent risk stratification tools for acute myocardial infarction (AMI) have limitations, particularly in predicting mortality. This study utilizes cardiac ultrasound radiomics (i.e., ultrasomics) to risk stratify AMI patients when predicting all-cause mortality.ResultsThe study included 197 patients: (a) retrospective internal cohort (n = 155) of non-ST-elevation myocardial infarction (n = 63) and ST-elevation myocardial infarction (n = 92) patients, and (b) external cohort from the multicenter Door-To-Unload in ST-segment–elevation myocardial infarction [DTU-STEMI] Pilot Trial (n = 42). Echocardiography images of apical 2, 3, and 4-chamber were processed through an automated deep-learning pipeline to extract ultrasomic features. Unsupervised machine learning (topological data analysis) generated AMI clusters followed by a supervised classifier to generate individual predicted probabilities. Validation included assessing the incremental value of predicted probabilities over the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 to predict 1-year all-cause mortality in the internal cohort and infarct size in the external cohort. Three phenogroups were identified: Cluster A (high-risk), Cluster B (intermediate-risk), and Cluster C (low-risk). Cluster A patients had decreased LV ejection fraction (P < 0.01) and global longitudinal strain (P = 0.03) and increased mortality at 1-year (log rank P = 0.05). Ultrasomics features alone (C-Index: 0.74 vs. 0.70, P = 0.04) and combined with global longitudinal strain (C-Index: 0.81 vs. 0.70, P < 0.01) increased prediction of mortality beyond the GRACE 2.0 score. In the DTU-STEMI clinical trial, Cluster A was associated with larger infarct size (> 10% LV mass, P < 0.01), compared to remaining clusters.ConclusionsUltrasomics-based phenogroup clustering, augmented by TDA and supervised machine learning, provides a novel approach for AMI risk stratification.

Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction

BackgroundIn acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into...

Right ventricular function and determining factors of dysfunction in ST-segment-elevation myocardial infarction: a cross-sectional study with cardiac magnetic resonance imaging (MRI).

Over the past few decades, left ventricular (LV) dysfunction in ST-segment elevation myocardial infarction (STEMI) patients has been the focus of research. Recently, co-occurring right ventricular (RV) dysfunction has received more attention in clinical practice. We aimed to assess RV function using cardiac magnetic resonance (CMR) imaging and identify factors that may contribute to RV dysfunction in STEMI patients. We retrospectively studied 189 patients with STEMI who underwent CMR 1-7 days after successful percutaneous coronary intervention (PCI). The ejection fraction (EF), wall thickening rate (WTR), peak radial strain (RS), circumferential strain (CS) and longitudinal strain (LS) of the LV, interventricular septum (IVS) and RV were measured with cine images. The location and extent of the infarct were determined using late gadolinium enhancement (LGE) imaging. The differences of function between STEMI patients with right ventricular ejection fraction (RVEF) <50% and those with RVEF ≥50% were compared using an independent-sample t-test. Linear regression analyses were used to determine independent predictors of RVEF. RVEF <50% was observed in 32.28%% STEMI patients, who also demonstrated significantly lower left ventricular ejection fraction (LVEF), WTR, RS, CS, LS and larger infarct sizes than those with RVEF ≥50%. Patients with RVEF <50% also demonstrated a higher incidence of RV infarction, higher RV end-systolic volume (ESV) index, and lower RV RS and CS. Multivariable linear regression analysis revealed LV EF, IVS WTR and IVS RS as significant predictors for RVEF, while male gender, the culprit lesion in the right coronary artery (RCA), peak troponin were negative predictors for RVEF. Notably, peak troponin, LV EF, LV RS, LV CS, LV WTR, and IVS WTR demonstrated higher area under the curve (AUC) values for predicting RV dysfunction. RV dysfunction was detected in 32.28% of STEMI patients. Patients with acute STEMI and RVEF <50% had impaired LV and IVS functions. Systolic function of the LV and IVS, peak troponin, and culprit lesions in the RCA were independent predictors of RV dysfunction in STEMI patients.

Association of Circulating PCSK9 With Ischemia-Reperfusion Injury in Acute ST-Elevation Myocardial Infarction.

Beyond therapeutic implications, PCSK9 (proprotein convertase subtilisin/kexin 9) has emerged as a promising cardiovascular biomarker. The exact role of PCSK9 in the setting of acute ST-elevation myocardial infarction (STEMI) is incompletely understood. We aimed to investigate the association of PCSK9 with ischemia-reperfusion injury, visualized by cardiac magnetic resonance imaging, in patients with STEMI revascularized by primary percutaneous coronary intervention (PCI). In this prespecified substudy from the prospective MARINA-STEMI (NCT04113356) registry, we included 205 patients with STEMI. PCSK9 concentrations were measured from venous blood samples by an immunoassay 24 and 48 hours after PCI. The primary end point was defined as presence of intramyocardial hemorrhage according to cardiac magnetic resonance T2* mapping. Secondary imaging end points were the presence of microvascular obstruction (MVO) and infarct size. The clinical end point was the occurrence of major adverse cardiac events. We observed a significant increase in PCSK9 levels from 24 to 48 hours (268-304 ng/mL; P<0.001) after PCI. PCSK9 24 hours after PCI did not show any relation to intramyocardial hemorrhage, MVO, and infarct size (all P>0.05). PCSK9 concentrations 48 hours post-STEMI were higher in patients with intramyocardial hemorrhage (333 versus 287 ng/mL; P=0.004), MVO (320 versus 292 ng/mL; P=0.020), and large infarct size (323 versus 296 ng/mL; P=0.013). Furthermore, patients with increased PCSK9 levels >361 ng/mL at 48 hours were more likely to experience major adverse cardiac events (15% versus 8%; P=0.002) during a median follow-up of 12 months. In patients with STEMI, a significant increase in PCSK9 was observed from 24 to 48 hours after PCI. While PCSK9 levels after 24 hours were not related to myocardial or microvascular injury, PCSK9 after 48 hours was significantly associated with intramyocardial hemorrhage, MVO, and infarct size as well as worse subsequent clinical outcomes. URL: https://www.clinicaltrials.gov; Unique identifier; NCT04113356.

Catastrophic Event Following Percutaneus Coronary Intervention Developing In-Stent Thrombosis Leading Massive Pericardial Effusion and Free Wall Rupture

BACKGROUND: One extremely unusual but serious side effect of an acute myocardial infarction is left ventricular free wall rupture. It was reported to happen either during the sub-acute phase with overt cardiac remodeling (type III, 45%) or early after the beginning of Myocardial Infarction (MI) (type I or II, about 55%). Large infarct sizes, female gender, and advanced age have all been linked to an increased risk of free wall rupture. Clinicians continue to face significant challenges in diagnosing and treating this condition because of the diverse clinical manifestations linked to elevated death rates. AIMS: This case report aims to highlight a rare occurrence of mechanical complication of acute myocardial infarction CASE: A 69-year-old male patient was referred because of chest pain and dyspneu. He had a primary Percutaneous Coronary Intervention (PCI) and was diagnosed with posterior ST-Evelation Myocardial Infarction (STEMI). The patient had a stent inserted into his ostial-distal Left Circumflex (LCx) artery. Three weeks later, a reangiography revealed a left ventricle (LV) aneurysm and stent thrombosis. Massive pericardial effusion with free wall rupture was seen on the echo. He was breathing heavily while in our emergency room. His blood pressure was 125/74 (94) heart rate was 94 bpm respiratory rate 24 times/minute, SpO2 was 98%, there were no rales, and his ankles had pitting edema. By the bedside, Echo revealed an LV aneurysm, a large, localized pericardial effusion without tamponade, and a possible free wall rupture. Later, he was taken to the intensive care unit and had heart surgery DISCUSSION: Complications from an acute myocardial infarction may be ischemic, mechanical, arrhythmic, embolic, or inflammatory. Significant short-term clinical improvement and long-term survival are linked to the emergence of mechanical problems following acute myocardial infarction. CONCLUSION: the fact that primary Percutaneous Coronary Intervention (PCI) has significantly reduced the prevalence of this deadly event. Our results indicate that one of the key predictors and primary causes of this problem is a longer symptom of angiography time.

Myocardial strain combined with clinical risk factors in the prediction of in-hospital heart failure among patients with ST-segment elevation myocardial infarction

To investigate the predictive value of myocardial strain derived from cardiac magnetic resonance (CMR) combined with clinical indicators for in-hospital heart failure (HF) in STEMI patients. In all, 139 STEMI patients were included, with 28 in the heart failure group and 111 in the non-HF group, and clinical and laboratory data were collected. Left ventricular (LV) global radial strain (GRS), global longitudinal strain (GLS), global circumferential strain (GCS), left ventricular ejection fraction (LVEF), stroke volume (SV), and infarct size (IS) were assessed by CMR. The HF group had worse GRS, GLS, GCS, LVEF, SV, larger IS, longer symptom to balloon time (SBT) and higher levels of high-sensitivity C-reactive protein (hs-CRP) and neutrophil percentage (N%) than the non-HF group (P<0.05). There was a strong correlation between GRS and LVEF (r=0.741, P<0.001). After adjustment for CMR and clinical risk factors, GRS<15.6%, LVEF<37.7%, SBT>350 min, hs-CRP>11.45 mg/L, and N%>74% were independently associated with HF. Clinical model (SBT>350 min+hs-CRP>11.45 mg/L+N%>74%) were associated with a lower diagnostic accuracy for predicting in-hospital HF than GRS+clinical co-model and LVEF+clinical co-model (P<0.05), respectively. There was no significant difference in the area under the curve (AUC) between GRS+clinical co-model and LVEF+clinical co-model (P=0.620): AUC for clinical model=0.824, AUC for GRS+clinical co-model=0.895, and AUC for LVEF+clinical co-model=0.907. GRS may be effective in predicting in-hospital heart failure after STEMI compared to LVEF, a classical cardiac function parameter, and its combination with clinical risk factors, especially SBT, hs-CRP, and N%, may provide further evidence for early prognostic assessment.

Inhibition of proline-rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes.

Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline-rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes. New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings. Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC. Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes.

Glucose Fluctuations in Acute Ischemic Stroke.

The Oxfordshire Community Stroke Project denotes four subtypes of ischemic stroke (total and partial anterior infarct, posterior, and lacunar). Hyperglycemia has been associated with a larger infarct size and poor prognosis. The purpose of the study was to investigate the correlation of glucose fluctuations with the Oxford sub-categories and patient outcomes using a blinded continuous glucose monitoring system. This is a non-interventional prospective observational study. Stroke patients with symptoms onset in the last 24h, participated in the study.A glucose sensor was placed for 72 hours. Disability was assessed using the modified Rankin Scale. Stroke subtypes were compared withtotal mean glucose and time in rangeusing ANOVA analysis. Multiple ordinal logistic regression was employed to analyze outcomes and survival. The sample consisted of 105 diabetic and non-diabetic patients. The overall mean glucose was 127.06 mg/dL and the time in range (70-140 mg/dL) was 70.98%. There was no significant difference between the stroke sub-categories and the total mean glucose. For every one-point increase in the time in range, we expect a 1.5%reduction in the odds of having a worse outcome. Patients with total anterior infarct are 2.31 times more likely to have a worse outcome than lacunar patients. The utilization of the Oxford classification may not be necessary for managing acute ischemic stroke glucose levels. Achieving glucose regulation and an increase in time in rangecan be attained through meticulous control, potentially extending life expectancy. Continuous glucose monitors may aid in achieving this objective.

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality.

We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac magnetic resonance (CMR) and mortality in patients with ST-elevation myocardial infarction (STEMI). The concentrations of six ECM-related proteins (periostin, osteopontin, syndecan-1, syndecan-4, bone morphogenetic protein 7, and growth differentiation factor (GDF)-15) were measured in serum samples from patients on Day 1 and Month 4 after STEMI (n = 239). Ischemic injury was assessed by myocardial salvage index, microvascular obstruction, infarct size, and left ventricular function measured by CMR conducted during the initial admission (median 2 days after admission) and after 4 months. All-cause mortality was recorded after a median follow-up time of 70 months. Levels of periostin increased from Day 1 to Month 4 after hospitalization, while the levels of GDF-15, osteopontin, syndecan-1, and syndecan-4 declined. At both time points, high levels of syndecan-1 were associated with microvascular obstruction, large infarct size, and reduced left ventricular ejection fraction, whereas high levels of syndecan-4 at Month 4 were associated with a higher myocardial salvage index and less dilatation of the left ventricle. Higher mortality rates were associated with periostin levels at both time points, low syndecan-4 levels at Month 4, or high GDF-15 levels at Month 4. In patients with STEMI, we found an association between serum levels of ECM biomarkers and ischemic injury and mortality. The results provide new insight into the role ECM components play in ischemic injury following STEMI and suggests a potential for these biomarkers in prognostication after STEMI.

Risk assessment by acute bedside echocardiography prior to acute coronary angiography in patients with ST-elevation myocardial infarction: a feasibility study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation. Background Early risk assessment by hemodynamic measurements in patients with ST-elevation myocardial infarction (STEMI) could be useful for early detection of patients at risk of developing hemodynamic instability after primary percutaneous coronary intervention (pPCI). Anterior STEMI patients have larger infarct size and may be of particular interest. Transthoracic echocardiography (TTE) is a quick, non-invasive, and available tool, however, evidence regarding the use of acute TTE prior to acute coronary angiography (CAG) is limited. Purpose To assess the feasibility of acute bedside hemodynamic assessment in the cath. lab. by TTE in addition to clinical examination, and blood samples in STEMI patients without CS at arrival in the cath. lab. Methods STEMI patients without CS at hospital arrival and treated with pPCI were included in the study during a five week period. Clinical examination (Killip class), blood sampling (lactate, troponin T (TNT), proB-type natriuretic peptide (proBNP), and focused bedside 2D TTE with Doppler were performed prior to the acute CAG. The TTE protocol was focused (approx. 5 minutes) on hemodynamic measurements, infarction related complications, and differential diagnoses e.g. aortic dissection. The TTE was performed during preparation for the acute CAG. Patients were stratified in anterior- vs. non-anterior STEMI based on the culprit artery and prehospital ECG. Feasibility was estimated by all of the following echocardiographic parameters; left ventricular ejection fraction (LVEF), left ventricular outflow tract (LVOT) velocity time integral (VTI), and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)). Results A total of 60 STEMI patients (aged mean 63 years, 18% female) were included, and 47% had an anterior STEMI. No differences in baseline characteristics between the two groups were found including comorbidities, clinical parameters, and time from cath. lab. arrival to first wire over the culprit lesion (median (IQR) 28 (23; 38) vs 32 (24; 40) minutes). Admission biomarkers of blood glucose, lactate, and proBNP plasma concentrations were similar between the two groups. Whereas admission TNT were higher for patients with anterior STEMI (median (IQR) 110 (37; 449) vs. 37 (20; 94) ng/L, p=0.01). The feasibility of TTE-study protocol was 93%. Patients with anterior STEMI had lower LVEF (mean: 36±11 vs. 48±9%, p=0.0003; missing: n=0), and a trend to lower LVOT VTI (19 (6.4) vs. 22 (5.0) cm, p=0.06; missing: n=4). No difference in parameters of diastolic function or TAPSE (missing: n=0) were found. None of the included patients had echocardiographic visible complications related to the infarction. Conclusion Acute TTE is to a high degree feasible and does not delay time to acute revascularization in STEMI patients. Patients with anterior STEMI have significantly higher admission TNT levels, lower LVEF, and a trend to lower LVOT VTI compared with non-anterior STEMI patients.

Hemorrhagic Transformation in Noncardioembolic Acute Ischemic Stroke: MRI Analysis From PACIFIC-STROKE.

In the phase 2 PACIFIC-STROKE trial (Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2433334 in Patients Following Acute Noncardioembolic Stroke), asundexian, an oral factor XIa inhibitor, did not increase the risk of hemorrhagic transformation (HT). In this secondary analysis, we aimed to investigate the frequency, types, and risk factors of HT on brain magnetic resonance imaging (MRI). This was a secondary analysis of the PACIFIC-STROKE trial. Patients with mild-to-moderate acute noncardioembolic ischemic stroke were randomly assigned to asundexian or placebo plus guideline-based antiplatelet therapy. Brain MRIs were required at baseline (≤120 hours after stroke onset) and at 26 weeks or end-of-study. HT was defined using the Heidelberg classification and classified as early HT (identified on baseline MRI) or late HT (new HT by 26 weeks) based on iron-sensitive sequences. Multivariable logistic regression models were used to test factors that are associated with early HT and late HT, respectively. Of 1745 patients with adequate baseline brain MRI (mean age, 67 years; mean National Institutes of Health Stroke Scale score, 2.8), early HT at baseline was detected in 497 (28.4%). Most were hemorrhagic infarctions (hemorrhagic infarction type 1: 15.2%; HI2: 12.7%) while a few were parenchymal hematomas (parenchymal hematoma type 1: 0.4%; parenchymal hematoma type 2: 0.2%). Early HT was more frequent with longer symptom onset-to-MRI interval. Male sex, diabetes, higher National Institutes of Health Stroke Scale large (>15 mm) infarct size, cortical involvement by infarct, higher number of acute infarcts, presence of chronic brain infarct, cerebral microbleed, and chronic cortical superficial siderosis were independently associated with early HT in the multivariable logistic regression model. Of 1507 with follow-up MRI, HT was seen in 642 (42.6%) overall, including 361 patients (23.9%) with late HT (new HT: 306; increased grade of baseline HT: 55). Higher National Institutes of Health Stroke Scale, large infarct size, cortical involvement of infarct, and higher number of acute infarcts predicted late HT. About 28% of patients with noncardioembolic stroke had early HT, and 24% had late HT detectable by MRI. Given the high frequency of HT on MRI, more research is needed on how it influences treatment decisions and outcomes.

Factors Contributing to Delayed Presentation In ST-Elevation Myocardial Infarction and Implication for In-Patient Outcomes

Introduction: ST-elevation myocardial infarction (STEMI) is a significant cause of mortality and morbidity among patients with ischemic heart disease. Early intervention, such as primary percutaneous coronary intervention (PPCI) or thrombolysis has been shown to improve patient outcomes. However, delayed presentation in STEMI results in larger infarct size and increased complications.Objectives: This retrospective descriptive study aimed to identify factors contributing to delayed presentation in STEMI and in-patient outcomes.Methodology: A retrospective descriptive study was conducted. All the STEMI patients who underwent primary percutaneous coronary intervention at National Hospital Kandy from February 2019 to December 2019 were studied.Results: A total of 243 STEMI patients who underwent PPCI at the National Hospital Kandy from February 2019 to December 2019 were studied. Among the study population, 31.27% were delayed presenters and 68.72% were non–delayed presenters. Atypical chest pain was identified as the main reason for a delayed presentation. Female gender was not associated with delayed presentation, contrary to the findings in other studies. Diabetes mellitus and the location of the culprit lesion did not significantly contribute to delayed presentation in this study group. Complications during hospital stay and average duration of hospital stay were not significantly different between delayed and non-delayed presenters. However, delayed presenters exhibited lower left ventricular ejection fraction on discharge, which is a critical predictor of short and long-term outcomes.Conclusions: Community awareness programs are essential to minimize pre-hospital delays in STEMI presentation. Early recognition of atypical symptoms, irrespective of gender, and timely intervention are vital for improving outcomes in STEMI patients. Further research is warranted to explore the impact of other risk factors and co-morbidities on the duration of presentation in STEMI patients.

Clinical and prognostic significance of baseline microRNA 223 in acute ischemic stroke

BackgroundAcute ischemic stroke (AIS) is the second leading cause of disability and death worldwide. Micro-RNA (miRNA)-223 was first identified as a regulator of hematopoietic lineage differentiation. Later, its diverse roles were discovered in a wide spectrum of pathological conditions. The present study aimed to assess the clinical and prognostic significance of miR-223 in patients with acute ischemic stroke (AIS). The study included 93 patients with AIS diagnosed on the basis of clinical and radiological findings. In addition, there were 50 healthy subjects who served as controls. Patients were classified into two categories: Those with favorable functional outcome (modified Rankin Scale (mRS): 0–2) and others with unfavorable functional outcome (mRS: 3–6) at 6 months post-stroke.ResultsThe present prospective longitudinal study included 93 patients with AIS. They included 60 males (64.5%) and 33 females (35.5%) with an age of 64.5 ± 12.4 years. At the end of 6-month follow up, 44 patients (47.3%) had favorable outcome while the remainder 49 patients (52.7%) had unfavorable outcome. Patients with favorable outcome had significantly lower baseline miR-223 levels [median (IQR): 4.4 (2.0–6.3) versus 8.4 (4.5–14.9), p < 0.001], lower HbA1c levels (5.6 ± 1.0 versus 6.2 ± 1.2, p = 0.006) and lower C-reactive protein (CRP) levels [median (IQR): 8.9 (5.1–26.7) versus 15.2 (6.2–39.3) mg/dL, p = 0.02]. Multivariate binary logistic regression analysis recognized high baseline miR-223 [OR (95% CI) 1.13 (1.06–1.24), p = 0.011], infarct size [OR (95% CI) 2.58 (1.66–4.77), p = 0.001] and National Institutes of Health Stroke Scale (NIHSS) [OR (95% CI) 2.11 (1.74–3.09), p = 0.004] as significant predictors of unfavorable outcome in the studied patients.ConclusionsElevated baseline miR-223 levels are associated with high NIHSS and larger infarct size at baseline and can effectively predict patients’ outcome at 6-months post-stroke.

Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction

BackgroundAcute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). MethodsIn this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging. ResultsMedian plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. ConclusionHigh plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI.