bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microdosing of alteplase leads to thrombolysis in an in vitro flow model of cardiac microvascular obstruction
Authors: Milusev A , Roesch Y , Wolint P , Kuster Y , Ulmer J , Raeber L , Weisskopf M , Cesarovic N , Obrist D 
Published: October 2024

Abstract

Background
Cardiac microvascular obstruction (MVO) is a frequent injury of the myocardial microcirculation after successful recanalisation of the occluded coronary artery in myocardial infarction. At least in part, MVO is caused by embolised microthrombi of less than 200 µm diameter [1]. MVO leads to hypoperfusion of the myocardium and negatively affects patient outcomes. However, there is no effective treatment for MVO [2, 3]. Thrombolytic drugs are a promising approach, but they are difficult to deliver to the MVO area, and an increased risk of bleeding limits their use. In a previous study using an in vitro fluidic multi-scale model for MVO [4, 5], it was shown that controlled flow infusion (CFI) with a novel drug-delivering catheter could be used to effectively deliver highly concentrated intracoronary microdoses of a thrombolytic drug to the MVO area [6]. We now aim to investigate how such locally administered drug microdoses can induce thrombolysis as a possible therapeutic approach for MVO treatment.

Methods
A microfluidic chip (Fig.1) was used to study thrombolysis under flow using different microdoses of the thrombolytic drug alteplase. The chip consists of a tapered straight channel, which traps injected porcine microthrombi without causing complete channel occlusion (Fig. 1A). To mimic intracoronary CFI (consisting of temporary balloon occlusion of a coronary vessel for 90 seconds while drug is injected distally through a catheter) in vitro, microthrombi were incubated (without flow) directly in the chip for 90 seconds with various microdoses of alteplase (Fig. 2A, C). The chip was subsequently perfused with porcine plasma for 25 min (matched for physiological shear stress of 30 dyn/cm²). Conventional intravenous (IV) drug infusion (10 mg dose) resulting in a low systemic alteplase concentration, was mimicked by perfusing microthrombi with porcine plasma containing 2 µg/ml alteplase (Fig. 2B, C).

Results
Thrombolysis after CFI was concentration dependent, with the lowest microdose (0.3 mg) achieving 24% lysis of the thrombus area and the highest microdose (1.5 mg) achieving 60% lysis. In contrast, conventional IV drug infusion (corresponding to 10 mg alteplase IV dose) only achieved 10% lysis and was not significantly higher than the control perfused with pure porcine plasma.

Conclusion
Our findings suggest that intracoronary CFI is more efficient at achieving porcine microthrombus lysis than the current standard of IV bolus infusion (2 µg/ml alteplase in the circulating blood). Intracoronary CFI microdosing of fibrinolytic drugs using a drug-delivering catheter is a promising therapeutic approach for treating embolising MVO with a reduced systemic drug burden. Importantly, our intracoronary CFI approach achieves locally 6–40 times higher drug concentrations than a conventional IV drug infusion while reducing the total drug dose 60–300 times (Fig. 2C).
Impact of coronary revascularization on clinical outcomes of post-acute myocardial infarction patients with left ventricular thrombus
Authors: Leow A S T , Seah A W J , Goh F Q , Tan B Y Q , Yeo L L L , Kong W K F , Poh K K , Yip J W L , Wong R C C , Chai P , Yeo T C , Chan M Y Y , Sia C H 
Published: October 2024

Abstract

Background
Left ventricular thrombus (LVT) is an uncommon, but dangerous complication seen in post-acute myocardial infarction (AMI). With advances in percutaneous coronary intervention (PCI) techniques, the incidence of post-AMI LVT has declined in the contemporary era. However, a minority of patients do not undergo coronary revascularisation due to medical contraindications or patient preference. This study aimed to evaluate the clinical characteristics and outcomes of post-AMI LVT patients treated with and without coronary revascularisation.

Methods
This was a retrospective study of 263 consecutive post-AMI patients diagnosed with LVT from November 2012 to January 2021, retrieved from a echocardiography database. Patients were stratified by the presence or absence of revascularisation treatment. Baseline clinical characteristics, treatment and outcomes data were collected and analysed.

Results
The median follow-up duration was 2.9 years (IQR: 0.9 – 4.7). A majority of post-AMI LVT patients underwent revascularisation via PCI (71.5%, n = 188), CABG (4.2%, n = 11) or thrombolysis (0.4%, n = 1). Unrevascularised patients (24.0%, n = 63) were older (p &lt;0.001), more likely to be female (p &lt;0.001), and had more co-morbidities such as previous stroke (p &lt;0.001), heart failure (p = 0.001), chronic kidney disease (p = 0.020), and malignancy (p = 0.021). More unrevascularised patient had NSTEMI (p &lt; 0.001), and significantly fewer were treated with triple therapy (p &lt; 0.001). Incidence of LVT resolution was lower (p &lt; 0.001) while all-cause mortality was higher (p &lt; 0.001) for unrevascularised patients on univariate survival analyses. On multivariable Cox regression, revascularisation status was not an independent predictor of LVT resolution, bleeding, stroke, or all-cause mortality outcomes.

Conclusion
While unrevascularised post-AMI LVT patients had poorer outcomes compared to revascularised patients overall, revascularisation status itself was not independently associated with poorer clinical outcomes. Optimising medical therapy such as triple therapy remains a key treatment goal for post-AMI LVT patients.
Effect of empagliflozin on no-reflow in patients with st elevation myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Nasef M A , Saber M , Gomaa Y , Kamal D 
Published: October 2024

Abstract

Background
Primary percutaneous coronary intervention (PPCI) restores myocardial tissue perfusion successfully in over 90 % of ST-elevation myocardial infarction (STEMI) patients .However there remains a small proportion of patients who exhibit no-reflow.(1) Empagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that acts as a powerful anti-oxidant and has beneficial effects on endothelial function and reducing burden of ischemia in-vitro.(2)
Aim and Objectives: To Assess the effect of Empagliflozin preloading in non-diabetic STEMI patients before PPCI on procedural, in-hospital outcomes and short-term Major Adverse Cardiovascular events (MACE) in a single tertiary center.
Patients and Methods: The study was carried out on 200 non-diabetic STEMI patients presenting to our university hospital within the first 8 hours of symptom onset. Patients were randomised into 2 groups , the intervention group received 10mg Empagliflozin before PPCI with the standard medical therapy while the control group received only the standard medical therapy. Patients were assessed for demographic data, risk factors, procedural outcomes, clinical and in-hospital outcomes, and short-term MACE up to 1 month.
Results: Our study found a significant difference between the intervention and control groups regarding contrast volume with a mean of 131 ml in the intervention group and 144 ml in control group with a p value of 0.009, incidence of no-reflow with 34.5% in the control group and only 18.2% in the intervention group and a p value of 0.014 and myocardial blush grade (MBG) were 84.1% of the patients in intervention group had MBG III after PCI while only 65.5% of the patients in the control group showed the same results with a p value of 0.019. Also, there was a significant difference in St-segment resolution post PCI as 59.1% of patients in the intervention group had complete ST segment resolution and only 39.1% of the patients in the control group had complete resolution with a p-value of 0.027, and total MACE in the first month which affected 44.8% of the patients in the control group and only 28.4% of those in the intervention group with a p-value of 0.024.

Conclusion
Our study showed that pre-loading of STEMI patients with Empagliflozin resulted in improvement in procedural outcomes, decreasing the incidence of coronary no-reflow, improvement in patient’s course during hospital stay and short-term MACE. Improvement in MACE was mainly due to reduced HF hospitalisations and anginal symptoms.
Symptoms and ASCVD score fail to identify majority of the patients at risk of first myocardial infarction
Authors: Mueller A , Konje S K , Barman N B , Argulian E A , Maslov P M , Namdarizandi V M , Leipsic J L , Tomey M T , Narula J N , Ahmadi A A 
Published: October 2024

Abstract

Background
Cardiovascular disease screening has long relied on the presence of symptoms like chest pain or on the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, which is typically initiated at age 40. However, current research suggests that the ASCVD risk score may not incorporate a comprehensive range of factors and should be started earlier. Furthermore, the absence of symptoms such as angina in some patients prior to acute coronary syndrome (ACS) casts doubt on the reliability of symptom-based screening methods.

Purpose
This study aimed to evaluate the effectiveness of the ASCVD risk score and chest pain as predictors for ACS.

Methods
We retrospectively analyzed the data of all patients of 65 or younger who presented with their first ACS event in a single US center from January 2020 to January 2024. We collected the demographic and clinical data, including age, sex, lipid panel, blood pressure, medical history, onset of symptoms, and calculated their individual ASCVD risk score. We explored whether these patients, if assessed one week before their ACS event, would have been identified as at risk and thus prescribed lipid lowering or recommended for further diagnostic tests.

Results
Among 166 patients presenting with ACS, 64 (39%) were considered low risk with an ASCVD risk score of &lt;5 or too low to calculate. 20 (12%) patients were assessed as borderline risk with an estimated risk score of 5-7.5%. In the intermediate risk category, 20 patients (12%) had a score of 7.5% -10% and 42 patients (25%) were estimated to have a score of &gt;10 to &lt;20%. 14 patients (8%) fell in the high-risk category, and lastly 6 patients had an LDL that was above 190 mg/dl.
Regarding symptoms of chest pain or shortness of breath, 14 patients (8%) did not experience any symptoms prior to their presentation, 98 (59%) patients experienced their first episode of symptoms within 48 hours, 19 patients (11%) within 2 days to a week, 10 patients (6%) had CP leading up to their event from a week to a month, 6 patients (4%) in the range of a month to 3 months and 19 patients (11%) had symptoms longer than 3 months prior to their presentation. To summarize if there were seen 1 week prior to their first ACS events, 51% of them were not recommended for statin therapy based on their ASCVD risk score and 67% of patients either had no chest pain until the event or chest pain within 48hrs of onset of their ACS and consequently would not have been routinely screened for coronary artery disease (CAD) by any anatomical or functional methods.

Conclusion(s)
ASCVD risk score and symptoms fail to identify majority of patient below 65 years of age with their first MI. Given high prevalence of CAD and associated mortality, improved screening tools, in addition to symptomatology or risk scores, would be more effective in identifying individuals at risk.
Circulating beta-hydroxybutyrate levels are associated with major adverse clinical events in patients with acute myocardial infarction
Authors: Dai Y , Xie L , Zhang Y , He Y , Liu H , Kong S , Chen W , Li H , Zhan Y , Tan N , Duan C , He P , Xue L , Liu Y 
Published: October 2024

Abstract

Background
Acute myocardial infarction (AMI) is associated with high mortality, and effective biomarkers are required for the risk stratification of patients with AMI. In cardiovascular diseases, circulating levels of ketone bodies (KB) such as beta-hydroxybutyrate (BHB) and acetoacetate are altered. However, the relationship between circulating KB levels and major adverse clinical events (MACE) in patients with ST-elevation myocardial infarction (STEMI) is unknown.

Methods
Patients with STEMI undergoing percutaneous coronary intervention (PCI) between January 2010 to June 2020 were enrolled, and divided into T1 (&lt; 0.09 mmol/L, n=219), T2 (0.09-0.28 mmol/L, n=202), and T3 (&gt; 0.28 mmol/L, n=211) tertiles according to the circulating BHB levels within 24 h of admission. The primary endpoint was in-hospital MACE, including all-cause mortality, stroke, recurrence of AMI, or target vessel revascularization.

Results
The incidence of in-hospital MACE in the T3 group (20.9%) was significantly higher than in the T1 group (10.5%) and T2 group (14.9%) (P=0.012). Multivariate logistic regression analysis showed that elevated circulating BHB levels were associated with an increased risk of all-cause mortality and MACE during hospitalization (OR = 1.41, 95% CI = 1.08-1.85, P = 0.012). During follow-up period, multivariate Cox regression analyses showed that elevated circulating BHB levels were associated with higher all-cause mortality and MACE (OR = 1.36, 95% CI = 1.19-1.56, P &lt; 0.001). The impact of BHB on MACE were similar for all the subgroups.

Conclusion
Elevated circulating BHB levels within 24 h of admission were associated with an increased risk of MACE in patients with STEMI undergoing PCI, and could be a promising prognosis biomarker.
To evaluate coronary microvascular obstruction by myocardial contrast echocardiography and its influence on prognosis in patients with ST-segment elevation myocardial infarction
Authors: Gao J , Dou J , Wang S F , Wang J X , Liu Y 
Published: October 2024

Abstract

Background
The goal of primary PCI (pPCI) is not only to restore epicardial coronary blood flow quickly but also to provide continuous myocardial tissue level reperfusion through coronary microcirculation. However, the incidence of coronary microvascular obstruction (MVO) after pPCI is as high as 50%-60%, which is closely related to the occurrence of heart failure and increased mortality of patients. Myocardial contrast echocardiography (MCE) is a new noninvasive technique for real-time observation of myocardial microcirculation perfusion in a specific imaging mode. At present, there are few studies on the application of MCE in the evaluation of coronary MVO in STEMI patients in China.

Purpose
To evaluate coronary MVO by MCE and its influencing factors and prognosis value after pPCI in patients with STEMI.

Methods
Patients with STEMI who received pPCI from October 2020 to June 2023 in the CCU were enrolled. MCE examination was performed on the 5th to 7th day after pPCI. The patients were divided into the MVO group and Non-MVO group. Major adverse cardiovascular events (MACE) were observed by 6-month follow-up after STEMI onset. Multiple Logistic regression analysis was used to analyze the risk factors for MVO, Multiple Cox regression analysis of the risk factors for MACE and Kaplan-Meier survival curve to compare the cumulative event-free survival of the two groups.

Results
A total of 98 patients were included in the analysis. The age was 59.88±11.71 years old, and 76(77.55%) were male. MCE examination showed 52 cases in the MVO group and 46 cases in the Non-MVO group. The incidence of MVO was 53.1% (52/98). There were 15 patients with MACE during follow-up. The results of stepwise Multivariate Logistic regression analysis showed that the peak value of cardiac troponin T (cTnT) (OR=1.354,95%CI 1.103-1.661, P=0.004) and without thrombus aspiration (TA) were independent risk factors for MVO (OR=5.588,95%CI 1.915-16.308, P=0.002). Multivariate Cox regression analysis indicated that female (HR=2.891, 95%CI 1.027-8.135, P=0.044), left ventricular ejection fraction (LVEF) &lt;40% (HR=9.960, 95%CI 3.370-29.435, P&lt;0.001) and MVO (HR=5.759,95%CI 1.279-25.935, P=0.023) were independent risk factors for MACE. Kaplan-Meier survival curve showed that the cumulative event-free survival rate in the Non-MVO group was higher than that in the MVO group, and the difference was statistically significant (P=0.0047).

Conclusion
The incidence of coronary MVO was higher in STEMI patients after pPCI, the peak value of cTnT and without TA were independent risk factors of MVO. The independent risk factors for MACE were female, LVEF &lt; 40%, and MVO.
Remote ischemic peri-conditioning suppressed cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction
Authors: Kondo T , Watanabe T , Yamada T , Morita T , Kawasaki M , Kikuchi A , Kawai T , Nishimoto Y , Seo M , Nakamura J , Fujita T , Taniichi M , Chang Y , Fukunami M 
Published: October 2024

Abstract

Background
Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). However, it remains to be elucidated whether RIPC affects the cardiac sympathetic nerve activity in patients with AMI.

Purpose
The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion respectively in patients with AMI.

Methods
We randomly assigned 157 patients with suspected AMI undergoing emergent PCI to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80). After excluding inappropriate patients such as those with other diagnosis than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). CSNA was assessed in the culprit and non-culprit lesion respectively by the cardiac MIBG SPECT imaging.

Results
Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. Patients in RIPC group tended to show higher late uptake only in the non-culprit lesion at discharge. At 1 year after discharge, patients in RIPC group demonstrated significantly higher late uptake (p=0.021) and lower washout rate (p=0.013) than those in control group in the non-culprit lesion. Regarding the culprit lesion, only washout rate tended to be lower in RIPC group at 1 year after discharge.
Conclusion(s): Remote ischemic peri-conditioning showed suppressive effect on cardiac sympathetic nerve activity especially in the non-culprit lesion in patients with acute myocardial infarction.SPECT parameters in RIPC and control
C-reactive protein after discharge and infarct size in patients with ST segment elevation myocardial infarction
Authors: Zhou Y , Madsen J M , Bo Kunkel J , Loenborg J T , Engstroem T 
Published: October 2024

Abstract

Background
C-reactive protein (CRP) peaks at 2 days in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and can predict final infarct size. It is, however, unknown whether CRP level after discharge, indicative of prolonged inflammation, plays a prognostic role in myocardial damage.

Purpose
To investigate the prevalence of high CRP level within 3 months after discharge in patients with STEMI and its association with myocardial damage.

Methods
In the current study, all patients were identified through the xx database and treated with timely PCI at xx hospital from 2011 to 2014. Blood samples were retrieved within 3 months after discharge. High CRP level was defined as CRP &gt;=3 mg/L. Only patients with a cardiac magnetic resonance (CMR) at baseline or follow-up were recruited. The primary outcome was final infarct size. Multiple regression was performed to adjust for potential confounders using any baseline variable with P&lt;0.10 for the difference between groups.

Results
Of the 1603 patients from xx, 273 patients had CRP measured following discharge and at least one CMR measured. Of them, 200 (73.3%) had high CRP level after discharge. There was no difference in period from PCI to CRP testing between patients with high CRP and those with low CRP [11 days, interquartile range (IQR) (4, 40) vs. 21 days, IQR (4, 42), P=0.31]. Patients with high CRP level showed larger final infarct size [12.5% left ventricle (LV) vs. 7.0% LV, P &lt;0.001] and larger acute infarct size [15.2% LV vs. 10.6% LV, p=0.004] compared with those with low CRP level. Patients with high CRP level also had lower final myocardial salvage index (MSI) (0.67 vs. 0.75, P=0.003) and lower acute MSI (0.47 vs. 0.61, P=0.006). The results persisted after adjusting for potential confounders in multiple regression.

Conclusions
A large proportion of patients with STEMI undergoing PCI persisted high CRP within 3 months after discharge. High CRP level after discharge was associated with larger acute and final infarct size as well as lower acute and final MSI level.
Clinical significance of 12-lead electrocardiogram QRS scores on admission in ST-segment elevation myocardial infarction
Authors: Tsutsumi K , Okada K , Hanajima Y , Kirigaya H , Horii M , Kirigaya J , Nakahashi H , Minamimoto Y , Gohbara M , Kimura Y , Matsushita K , Kosuge M , Ebina T , Sugano T , Hibi K 
Published: October 2024

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 (&lt;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&lt;0.05) and larger infarct size assessed by peak CK values (5333 [3307-7443] IU/l vs. 1941 [759-3559], p&lt;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.