Primary Percutaneous Coronary Intervention Research Articles

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.

Trends in major cardiac events after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention from 2003 to 2017: the western Denmark heart registry

Abstract Background In Denmark, primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003. We recently reported a gradual decline in 1-year mortality in patients treated with pPCI-treated STEMI from 2003 to 2017. To elucidate potential causes of this observation, we examined temporal trends in the 1-year risk of major adverse cardiovascular events (MACE). Purpose To examine trends in 1-year risks of MACE following STEMI treated with pPCI from 2003 to 2017. Methods Using the Western Denmark Heart Registry, we identified STEMI patients undergoing first-time pPCI from 2003 to 2017 and divided the patients into four time periods. The main outcome was 1-year risk of MACE, defined as recurrent myocardial infarction, ischaemic stroke, or cardiovascular death. Cause-specific adjusted hazard ratios (HR) were used to assess temporal trends using the first period (2003-2006) as reference. Further, temporal trends were compared to an age-, sex-, and calendar-year matched general population. Results From 2003 to 2017, 18,540 pPCI-treated STEMI patients were identified (median [Q1-Q3] age, 64 [55-74] years); 13,639 men [74%]). Trends in 1-year risk of MACE showed a gradual reduction over time from 13.0% in 2003-2006, 11.8% in 2007-2010, 9.7% in 2011-2014, to 8.7% in 2015-2017 (Figure). The adjusted relative risk reduction was 33% when comparing 2015-2017 with 2003-2006 (adjusted HR 0.67, 95% CI 0.58-0.76). Comparable relative risk reductions were observed for all three individual components of MACE of 33-35%. Compared to the matched general population, the 1-year risk difference in MACE decreased from 11% in 2003-2006 to 7% in 2015-2017. Conclusions In a high-income European country with a fully implemented pPCI strategy, 1-year risk of MACE declined by approximately one-third after first-time STEMI between 2003 to 2017. This MACE reduction was substantially larger than observed in the matched general population, i.e., confirming an important reduction in the excess risk associated with STEMI.

Survival in STEMI in resource limited settings - obstacles and potential solutions. Critical lesson learnt thorough a prospective observational study

Abstract Background Early revascularization in ST segment elevation myocardial infarction(STEMI) by Primary Percutaneous coronary Intervention (PPCI) or fibrinolysis, reduces mortality. In the absence of a well-functioning STEMI care system, patients may not get guideline directed revascularisation (GDR). Objective We sought to determine the prevalent mode of revascularisation for STEMI in the community, to discern the factors contributing to lack of GDR during their initial medical encounter, and to investigate the consequences of not getting GDR. Methods Consecutive patients within 24 hours of STEMI from October 2021 to December 2021 in a public hospital from a developing nation, were enrolled. In addition to baseline data, the details of the first medical contact (FMC) and second medical contacts (SMC) before reaching the study site were collected. The hospitals where patients sought care earlier, could be lysis capable hospitals (LCH), PCI/lysis capable hospitals (PLCH) and non-lysis-capable hospitals (NLCH). Medical records related to these visits were scrutinised and in-depth interviews were conducted with patients and their care givers. Details of GDR offered / received during FMC/SMC and the reasons for not receiving GDR were collected. Results 300 patients were enrolled during the study period. 19 reported directly to the study site, while others had visited 1-3 hospitals en route(Figure-1). The 159 who received fibrinolysis in at least one of their medical contacts, had a significantly lower incidence of cardiogenic shock and in-hospital mortality, compared to the rest(Figure-2). 162(54%) patients had had FMC in NLCH and had to be referred to SMC for GDR. Of the 157 visits by a patient with STEMI in a LCH / PLCH within 6 hours’ time window (6HTW), GDR was provided only 44 visits(28%) (Figure-1). The common reason for not receiving GDR was financial. This revascularisation solutions offered were not affordable. These include, PPCI only or pharmaco-invasive package only in PLCH and high cost bolus lytic only in LCH. Of the 132 patients, who had FMC ≤ 12 hours in LCH, only 33 had lysis. Patients who did not receive revascularisation, despite reaching within 6HTW, had adverse in-hospital outcome. (Figure-2) Conclusion The public awareness of the need for early revascularisation in STEMI and the revascularisation solutions available in the neighbourhood hospitals is low. Most patients with STEMI do not receive GDR despite reaching revascularisation capable hospitals within 6HTW. The common reasons for this include, non-availability of low cost fibrinolytics and lack of financial resources. Hospitals should offer fibrinolysis when patients cannot afford PPCI, and low-cost infusion lytics, when patients cannot afford high cost bolus lytics. Provision of GDR in STEMI at the first medical contact, is a social responsibility. Governmental and non-governmental organisations should work in tandem, to ensure 100% GDR at first medical contact.

Clinical characteristics and outcomes of patients with acute coronary syndrome without standard metabolic cardiovascular risk factors

Abstract Background/Introduction Patients with acute coronary syndrome (ACS) commonly present with hypertension, diabetes mellitus (DM), and dyslipidaemia as standard modifiable metabolic risk factors. However, little is known about patients with ACS who do not have these risk factors. Purpose This study investigated the clinical characteristics and outcomes of patients with ACS without these risk factors who underwent primary percutaneous coronary intervention (PCI). Methods This retrospective, single-centre observational study included 1131 consecutive patients with ACS who were admitted to a hospital between January 2013 and May 2021. After excluding patients who did not undergo revascularization or who underwent emergency coronary artery bypass surgery, 947 patients who underwent primary PCI were included in the analysis. Patients were classified into two groups: those with one or more of the following: hypertension, DM, or dyslipidaemia (risk group) and those without any of these factors (non-risk group). Major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), stroke, and heart failure requiring rehospitalisation, were assessed at the 1-year follow-up. Results This study classified 78 patients (8.2%) in the non-risk group, who exhibited a significantly lower body mass index (BMI) [23.0 (interquartile range: 21.8–24.7) vs. 23.8 (interquartile range: 21.8–26.2) kg/m2, p = 0.016], compared to the risk group. There were no significant differences in smoking history between the two groups (51.2% vs. 48.9%, p = 0.39). Within 1 year after PCI, MACE occurred in 146 (15.4%) patients (88 [9.2%] with all-cause death, 13 [1.3%] with MI, 23 [2.4%] with stroke, and 27 [2.8%] with heart failure requiring rehospitalisation), with a significantly higher incidence in the non-risk group compared to the risk group (24.4% vs. 14.6%, p = 0.027). Multivariate analysis revealed that both being in the non-risk group and having a low BMI (< 21.5) were independent determinants for the incidence of MACE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.01–2.29; p = 0.042 and HR: 3.08; 95% CI: 1.30–7.27; p = 0.010, respectively). Kaplan–Meier survival analysis showed a higher MACE rate in the non-risk group than in the risk group (p = 0.009). Conclusions Patients with ACS without hypertension, DM, or dyslipidaemia have a poorer prognosis than those with these risk factors, independent of the presence of a lower BMI, and the underlying pathophysiology in this subset of patients needs to be clarified.figure

Reduction of thrombus burden by cangrelor in ticagrelor-loaded st-elevation myocardial infarction patients with high residual platelet reactivity: the imaging sub-study of the ERMIT randomized trial

Abstract Background Residual high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with higher residual thrombus burden and the subsequent suboptimal reperfusion. Purpose We sought to determine the impact of intravenous Cangrelor on the residual post-PCI thrombus burden in patients with HPR admitted for primary PCI in a prespecified intracoronary optical coherence tomography (OCT) sub-study of the ERMIT randomized trial. Methods In the ERMIT trial patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit >208) were randomly assigned in a 1:1 ratio to receive cangrelor on top of standard therapy or standard therapy alone prior to PCI. The primary endpoint of the sub-study was the relative thrombus volume quantified on OCT. Other OCT quantified parameters were predefined as secondary endpoints. Results After screening of 128 patients, a total of 60 patients with HPR were enrolled and randomized. The OCT sub-study included 53 patients, 29 in the cangrelor and 24 in the control group. As reported in the table, baseline characteristics were similar between the groups. The post-PCI PRU was dramatically lower in the cangrelor as compared to the standard group (p<0.001). The primary endpoint was 4.5% [3.4;7.2] versus 6.9% [5.2;8.5], (p=0.03) in the cangrelor and control groups respectively. All other imaging parameters confirmed the significantly lower thrombus burden in patients receiving cangrelor (Table). Conclusion The imaging sub-study of the randomized ERMIT trial shows that cangrelor use is associated with a more effective platelet inhibition and lower post-PCI residual thrombus burden in ticagrelor-loaded STEMI patients with residual HPR. The clinical implications of such finding warrant larger size trials.Table

Comprehensive remote myocardium characterisation using T1 mapping in patients with ST-segment elevation myocardial infarction

Abstract Background Myocardial tissue injury due to acute myocardial infarction (AMI) does not only occur in the myocardium that is supplied by the culprit lesion, but can also extend to the remote, non-infarcted myocardium. The prognostic implications of remote myocardium changes assessed by cardiac magnetic resonance (CMR) are not fully understood. The aim was to investigate the prognostic relevance of remote myocardium alterations assessed by CMR T1 mapping (native T1 and extracellular volume (ECV)) in patients after ST-segment elevation myocardial infarction (STEMI). Methods This study analyzed 491 STEMI patients treated with primary percutaneous coronary intervention (PCI) that were included in the prospective MARINA-STEMI study (NCT04113356). CMR imaging was performed 4 (Interquartile range [IQR]: 3-5) days after PCI. CMR images were analyzed for left ventricular (LV) function, standard infarct characteristics as well as native remote T1 and remote ECV. The primary clinical endpoint was the composite of all-cause mortality, re-infarction and new congestive heart failure (Major adverse cardiovascular events, MACE). Results Remote native T1 (median: 1009 [IQR: 979-1044] ms) was associated with female sex, peak NT-pro-BNP levels, peak hs-cTnT elevations, TIMI-risk score, admission Killip class, anterior infarct location, post-interventional TIMI-flow, LV ejection fraction and microvascular injury. Remote ECV (median: 26.37 [IQR: 24.28-29.27] %) was associated with age, female sex, peak NT-pro-BNP levels, diabetes, TIMI-risk score, admission Killip class, anterior infarct location, LV ejection fraction and microvascular injury. Over a median follow-up of 12 months (IQR: 12-13) after STEMI, 42 MACE outcomes occurred. Higher native remote T1-times (1018.5 [IQR: 997.0-1064.0] ms vs. 1007.0 [IQR: 977.0-1041.5] ms, p=0.033) as well as a higher remote ECV-values (28.07 vs. 26.27 %, p=0.009) were observed in patients with MACE. Multivariable Cox regression analysis demonstrated that remote ECV (hazard ratio (HR): 1.53 [confidence interval (CI): 1.07-2.19], p=0.020) but not native remote T1 associated with MACE. Conclusions A comprehensive assessment of the remote myocardium with native T1 and ECV provides prognostic information in a contemporary cohort of low risk STEMI patients. Remote ECV, but not remote native T1, was found to be an independent predictor of MACE.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

Effect of primary pci in asymptomatic stemi patients presenting 12 to 48 hours of symptom onset, on myocardial viability assessed by spect tc 99m sestamibi scan epitome99

Abstract Background Guidelines on revascularization of asymptomatic stable STEMI patients presenting 12-48 hours of symptom onset are limited. We utilized TC-99mSestaMIBI scan to study the impact of primary PCI on myocardial viability by deriving myocardial salvage index (MSI) from area at risk (AAR), prior to revascularization and final infarct size (FIS) at follow up, in asymptomatic stable STEMI patients presenting between 12-48 hours of symptom onset to PCI. Purpose Evidence contributing lack of symptoms to a non-viable myocardium is lacking and it would be unethical to randomize patients with myocardial infarction (< 48 hours old) to a control arm or a non-intervention arm without evaluating the possibility of salvageable myocardium. Our study aims to inculcate evidence based management of late presenting stable asymptomatic STEMI patients. Methods We enrolled 141 patients presenting with STEMI (12-48 hours), from January 2021 to December 2023, who then underwent TC-99mSestaMIBI scan, followed by revascularization of IRA with 138 patients completing the designed study with follow-up scan at 3 months. Subjects were subcategorised into cohort A(12-24 hrs.), B(25-36 hrs.), and C(37-48 hrs.) according to the duration of symptom onset. Results A substantial MSI of > 0.50 was achieved by 36 %, 8% and 5 % of patients from cohort A, cohort B, and cohort C respectively. Although the AAR was comparable throughout cohorts, on post HOC analysis a statistically significant reduction in the final infarct size was seen among patients in cohort A vs C [Q = 4.72 (p = .00309)], while a reduction of FIS in cohort B and cohort C were obvious but statistically insignificant. Myocardial salvage index was smaller in late presenters, with no statistically significant difference among cohort B & cohort C [Q = 0.96 (p = .77697)]. Delaying the timing of Primary PCI from symptom onset was associated with larger AAR (R= - 0.01) & FIS (R= 0.35) although with a lower correlation coefficient. While evaluating MSI against timing of Primary PCI, a moderately negative (R= - 0.41) relation exists, indicating a linear correlation to reduced myocardial salvage Index with delay in the timing of primary PCI to symptom onset. Conclusion Asymptomatic stable STEMI patients presenting 12-24 hours of symptom onset to PCI, benefited from primary PCI with lesser final infarct size and larger MSI. Despite a comparable AAR across cohorts, MSI fell sharply among patients undergoing primary PCI 24-48 hours of symptom onset with a larger final infarct size, warranting viability guided revascularization. Although primary PCI improved final LVEF and MSI in patients with ischemic heart failure, parameter gain alone was insufficient in endeavoring a positive clinical impact.

Impact of microvascular resistance reserve on post-STEMI cardiac remodelling and diastolic function

Abstract Background Coronary microvascular dysfunction (CMD) is a common sequelae of ST-segment elevation myocardial infarction (STEMI), preventing adequate recovery of left ventricular (LV) perfusion. The interferences of con-commitment epicardial stenosis or hyperemic hemodynamic alterations limit traditional physiologic metrics. The microvascular resistance reserve (MRR) was developed to overcome these shortcomings. Purpose We aim to investigate the association between post-STEMI MRR, and the ensuing left ventricle (LV) diastolic dysfunction, and functional remodeling. Methods In this prospective, observational study, we enrolled STEMI patients with multivessel disease who successfully underwent primary percutaneous coronary intervention (PCI). At three months post-PCI, all patients received complete revascularization followed by coronary physiology assessment using the bolus thermodilution method to measure the fractional flow reserve (FFR), coronary flow reserve (CFR), and the index of microcirculatory resistance (IMR). MRR was calculated using the formula: MRR = (CFR/FFR) × (Pa rest/Pa hyper), where Pa rest and Pa hyper represent resting and hyperemic aortic pressure, respectively(1). CMD was defined as an MRR < 3.0 based on Boerhout et al(2). Diastolic dysfunction was defined according to the ASE 2016 guidelines. Functional LV remodelling (FLVR) was categorized according to Chimed et al(3). The relationship between CMD and the stages of FLVR and diastolic dysfunction was scrutinized over a 12-month follow-up period. Results We enrolled 210 patients, of whom 125 (59.5%) were men with a median age of 65 (IQR: 58–76). At the 3-month follow-up, the MRR was 3.46 (IQR 3.00, 3.92), with 56 (26.7%) patients having CMD (MRR<3.0). MRR is significantly correlated with the change of LVEF between primary PCI and 12 months (r=0.48, p<0.001, Fig1A). CMD patients have lower LVEF at 12 months (50.00% vs. 40.00%; p < 0.001) and demonstrated significantly less recovery in LV systolic function (-10.00% vs. 8.00%; p < 0.001, Fig 1B, 1C). CMD patients had a higher prevalence of grade 2 or 3 LV diastolic dysfunction (65.38% vs. 3.95%; p < 0.001, Fig 2A) and a higher incidence of advanced FLVR (Groups 3 and 4) compared to those without CMD (30.77% vs. vs. 10.53%; p < 0.001, Fig 2B). In multivariable logistic regression analysis, MRR was independently associated with LV diastolic dysfunction (0.17, 95%CI 0.08-0.33, p<0.001). Conclusions The novel parameter MRR is significantly related to LVEF recovery in STEMI patients and is an independent predictor for advanced LV diastolic dysfunction and FLVR. CMD patients, as diagnosed with MRR, showed a higher prevalence of advanced FLVR and diastolic dysfunction. These results suggest that MRR is a useful parameter for the identification and management of CMD in STEMI patients.

Temporal trends in major bleeding after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction from 2003 to 2017: the Western Denmark Heart Registry

Abstract Background Management of patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has changed during the last two decades. Introduction of more potent platelet inhibitors may carry an increased risk of bleeding complications, while other therapeutic options, such as use of radial artery access and proton pump inhibitors may reduce bleeding risk. The combined impact of these treatment changes on bleeding risk in patients with STEMI remains unknown. Purpose To examine temporal trends in 1-year risk of major bleeding after STEMI treated with primary PCI from 2003 to 2017. Methods We used the Western Denmark Heart Registry to identify first-time PCI-treated patients undergoing primary PCI for STEMI from 2003 to 2017. Patients were divided into 4 calendar periods based on the time of STEMI. The main outcome was 1-year risk of major bleeding defined as a hospital admission for bleeding using a validated definition with high accuracy. Additionally, the 1-year risk of major bleeding in STEMI patients was compared with the risk in an age- and sex-matched general population cohort without prior coronary artery disease. Results From 2003 to 2017, we identified 18,540 patients treated with primary PCI for STEMI (median age 64 years, 75% men)and 92,700 age- and sex-matched individuals. The 1-year risk of major bleeding after STEMI was similar across the different time periods; 4.1% in 2003-2006, 3.8% in 2007-2010, 3.8% in 2011-2014, and 4.5% in 2015-2017. The adjusted HR for bleeding in STEMI patients was 1.03 (95% CI 0.83-1.26) when comparing the latest period with the earliest period. The age- and sex-matched general population exhibited a 1-year risk of major bleeding of around 1% in all time periods (Figure 1). Conclusions Despite changes in management, the 1-year risk of major bleeding remained stable around 4% after primary PCI-treated STEMI from 2003 to 2017. This risk was approximately 4 times higher than the bleeding risk observed in an age- and sex-matched general population.

Baseline heart rate as a key prognostic indicator in AMI patients with cardiogenic shock undergoing successful primary PCI

Abstract Background Cardiogenic shock presents as a critical condition in patients experiencing acute myocardial infarction (AMI). Even that primary percutaneous coronary intervention (PCI) has become widespread, the mortality rate of AMI complicated with cardiogenic shock remains high. However, comprehensive prognostic stratification remains elusive. Objective Our study sought to elucidate the relationship between baseline parameters and prognostic outcomes in AMI patients with cardiogenic shock. Methods From the GETBACK-AMI multicenter retrospective registry encompassing 935 AMI patients who underwent primary PCI and attained TIMI 3 flow upon final angiography. There were 73 patients diagnosed with cardiogenic shock were ultimately analyzed. The primary endpoint of our study was all-cause mortality. Results Over a median follow-up duration of 425 days, 17 patients (23%) succumbed, of which 14 were in-hospital fatalities. Employing the Cox regression model, we identified that heart rate (HR) at the time of admission bore a potent and independent correlation with the primary endpoint (hazard ratio: 1.04 [95% CI: 1.01-1.06], p=0.002), even post-adjustment for various covariates. ROC analysis pinpointed an admission HR of 82 bpm as the threshold for the primary endpoint. Kaplan-Meier curves further highlighted a pronounced elevation in the primary endpoint occurrence rate for patients with HR > 82 bpm compared to those with HR < 82 bpm (53% vs. 13%, p=0.0002). Conclusions Within our multicenter study cohort, a heightened admission HR was demonstrably linked to increased mortality in AMI patients with cardiogenic shock who reached a final TIMI 3 flow. This readily accessible and impactful prognostic marker may guide clinicians in identifying high-risk patients, subsequently allowing for enhanced support and interventions to optimize patient outcomes.

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) < 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p < 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

Trimethylamine N-oxide as a Novel Biomarker for Left Ventricular Diastolic Dysfunction and Functional Remodeling in ST-Elevation Myocardial Infarction Patients

Abstract Background Over the last three decades, the mortality from ST-elevation myocardial infarction (STEMI) has halved. However, the incidence of heart failure or persistent angina remains high after STEMI, and the post-STEMI left ventricular (LV) systolic and diastolic function remains unpredictable. Thus, there is an unmet need to identify patients at risk of LV diastolic dysfunction or adverse remodeling. Purpose This study aims to investigate the potential of Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite associated with heart failure, and atherosclerosis, as a biomarker for adverse LV remodeling and diastolic dysfunction following STEMI. Methods In this prospective, observational cohort study, 210 STEMI patients with multivessel coronary artery disease (CAD) were enrolled after primary PCI. At 3 months follow-up, all patients underwent complete revascularization with FFR-guided PCI. Plasma TMAO, C-reactive protein (CRP), and brain natriuretic peptide (BNP) levels at 3 months follow-up and peak troponin level at primary PCI were collected. Echocardiographies were performed within 24 hours of STEMI and at 12-month follow-ups. Diastolic dysfunction was defined according to the ASE 2016 guidelines.(1) Functional LV remodeling (FLVR) was categorized into 4 categories according to Chimed et al.(2) Receiver operating characteristic (ROC) curve analysis, including the Delong test and Youden index, was performed to compare the biomarkers' diagnostic value and determine the optimal cutoffs for predicting diastolic dysfunction and FLVR, respectively. Results Of the 210 patients enrolled, 85 (40.48%) were female, with a median age of 65 years [interquartile range (IQR): 58.00, 76.00] and a median body mass index (BMI) of 27.39 kg/m² (IQR: [24.56, 30.69]). The area under the ROC curve for predicting post-PCI LV diastolic dysfunction ≥ grade II was 0.72 (95% CI 0.63–0.81; p<0.001) for TMAO (Figure 1). The optimal TMAO cutoff value of 3.80 yielded a sensitivity of 0.75 (95% CI 0.63–0.86) and a specificity of 0.82 (95% CI 0.76–0.88). For FLVR grade 3 or 4, the area under the ROC curve was 0.62 (95% CI 0.50–0.74) and 0.72 (95% CI 0.62 -0.83) for TMAO and BNP, respectively (Figure 2), but the AUC was not significantly different (p= 0.191). In multivariable logistic regression analysis, TMAO was independently associated with FLVR grade 3 or 4 (OR 1.18, 95% CI 1.00-1.38, p = 0.046) and diastolic dysfunction ≥grade 2 (OR 1.30, 95% CI 1.12-1.50, p < 0.001). Conclusion The novel parameter of TMAO is a useful predictor for LV diastolic dysfunction after STEMI. TMAO is independently associated with an increased risk of LV diastolic dysfunction and worse FLVR. These results suggest that monitoring plasma TMAO levels could be an effective and cost-efficient strategy for monitoring patients with an elevated risk of LV diastolic dysfunction or adverse LV remodeling.Figure 1Figure 2

Microcirculatory resistance after primary percutaneous coronary intervention predicts residual myocardial damage: a post hoc analysis from the CLEVER-ACS trial

Abstract Introduction Coronary microvascular dysfunction has been associated with adverse cardiovascular events following acute myocardial infarction. This study evaluates the role of the angiography-derived index of microcirculatory resistance (angio-IMR) in predicting myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and Methods In this post hoc analysis of the Controlled Level Everolimus in Acute Coronary Syndromes (CLEVER-ACS) trial, the associations between post-PCI angio-IMR of infarct-related coronary arteries (IRAs) and infarct size, microvascular obstruction (MVO), and left ventricle ejection fraction (LVEF) at 30 days as assessed with cardiac magnetic resonance (CMR) imaging were investigated. High post-PCI angio-IMR value was defined as a value >40 U. In non-IRAs angio-IMR was measured before the IRA-PCI. Results A total of 52 IRAs and 94 non-IRAs of 52 patients were included in the analysis. Post-PCI Angio-IMR was 41.5 (IQR 28.5–55.7) U in IRAs and pre-PCI Angio-IMR was 43.7 (31.7–54.0) U in non-IRAs (p = 0.70). Patients with high post-PCI angio-IMR (52%) exhibited a larger myocardial infarct size (36.0 [23.0–52.5] g vs. 14.5 [6.50–26.5] g, p < 0.001) and a lower LVEF (46.5 [39.5–49.5] % vs. 55.0 [48.0–61.4] %, p = 0.002) at 30 days as compared to those with low post-PCI angio-IMR values. Post-PCI angio-IMR correlated with myocardial infarct size (r = 0.45, p = 0.001) and extent of MVO (r = 0.40, p = 0.004) at 30 days. Post-PCI angio-IMR predicted myocardial infarct size (AUC = 0.78 [0.65–0.92], p = 0.001) and extent of MVO (AUC = 0.74 [0.60–0.89], p = 0.009) at 30 days. Conclusion In patients with STEMI undergoing PCI, post-PCI angio-IMR was identified as independent predictor of myocardial infarct size and extent of MVO at 30 days. The assessment of post-PCI angio-IMR values may represent a novel tool for early risk stratification of patients with STEMI.Central illustration

Malondialdehyde-specific natural IgM inhibit toll-like receptor 4 and peptidyl-arginine deiminase 4-dependent NETosis triggered by coronary extracellular vesicles of myocardial infarction patients

Abstract Background Neutrophil extracellular traps (NETs) are critical mediators of thromboinflammation during acute myocardial infarction (AMI). However, triggers and signalling pathways of NETosis in AMI remain incompletely understood. Levels of extracellular vesicles (EV) carrying oxidation-specific epitopes (OSE) originating from lipid peroxidation are increased at the culprit site in AMI. Importantly, natural IgM antibodies with specificity for OSE, such as malondialdehyde (MDA), have been shown to modulate functional effects of EV, and are associated with reduced cardiovascular risk. Purpose We investigated the stimulatory capacity of EV on neutrophil effector functions and specifically targeted key mediators of NET formation using pharmacological inhibitors and atheroprotective natural IgM to inhibit this process. Methods Patients were included after diagnosis of ST-segment elevation myocardial infarction and blood was aspirated from the culprit site and peripheral arterial site (n=28) during primary percutaneous coronary intervention (pPCI). Myocardial function was documented by cardiac magnetic resonance imaging 4±2 days and 195±15 days after pPCI. EV were isolated from cell culture supernatants and culprit site plasma for neutrophil stimulation in vitro. Pharmacological inhibitors were used to map NET signalling pathways of EV. Isolated EV were used for neutrophil stimulation in a murine injection model in the presence of the MDA-specific IgM LR04 or an isotype control. NET formation and other neutrophil functions were assessed by flow cytometry, ELISA and fluorescence microscopy. Results Levels of NET surrogate markers and CD45+ MDA+ EV were higher at the culprit site than in the peripheral circulation. EV generated by LPS-activated THP-1 monocytic cells induced in vitro NET formation, release of neutrophil elastase and IL-8, and degranulation of MPO and NGAL in primary human neutrophils, but not reactive oxygen species. Toll-like receptor 4 (TLR4) and peptidyl-arginine deiminase 4 (PAD4) were identified as key mediators of NET formation induced by in vitro-generated EV and EV isolated from the culprit site of AMI patients. Functionally, the MDA-specific monoclonal IgM antibody LR04, but not an isotype control, inhibited the ability of patient-derived and in vitro-generated EV to trigger release of NETs in primary human neutrophils and in mice. Titres of MDA-specific IgM antibodies were inversely associated with the NET marker citH3 in blood of AMI patients. Finally, we found that the concentration of CD45+ MDA+ EV per protective MDA-specific IgM at the culprit site showed an inverse association with left ventricular ejection fraction 72 hours and 6 months after AMI. Conclusions We show that EV can trigger several neutrophil effector functions. EV-induced NET formation is TLR4- and PAD4-dependent and can be inhibited by OSE-specific natural IgM potentially influencing cardiovascular outcomes after an acute event.

Negative long-term prognostic value of stress echocardiography in patients with incomplete revascularization after successful primary PCI

Abstract Background The role of stress echocardiography (SECHO) in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) has not been extensively documented. The Aim The aim of our study was to assess the negative long-term prognostic value of SECHO after successful pPCI and incomplete revascularization of non-culprit lesions. Methods Our study consisted of 194 patients (mean age 59±10years, male 136; 70.1%) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion other than treated vessel. Lesion severity of non-culprit coronary arteries was assessed by quantitative coronary angiography. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), chronotropic incompetence, heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were calculated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow up of the patients was 96 ± 32.5 months for the occurrence of all-cause mortality and non-fatal myocardial infarction (MI). Results Out of 194 patients, 38 (19.6%) had positive SECHO test, and 7 patients (3.6%) were lost to follow up so they were excluded from further analysis. During the follow-up period 29 out of 149 patients (18.8%) had an adverse event (20 deaths and 9 non-fatal MI). Negative predictive value of SECHO test was 81.2%. Median time from MI to SECHO test was 8 months. Using the Cox regression analysis, univariate predictors of adverse events were slow HRR (HR 3.750 [95% CI 1.620-8.679], p=0.002), Duke score (HR 0.866 [95% CI 0.755-0.994], p=0.040) and chronotropic incompetence (HR 0.310 [95% CI 0.107-0.895], p=0.030). In the multivariate analysis only the slow HRR remained an independent predictor of adverse events (HR 3.329 [95% CI 1.417-7.825], p=0.006). Using the Kaplan-Meier survival curve we see that the patients with slow HRR had much shorter event-free time (slow HRR 117.2 ± 13.4 months vs normal HRR test 139.4 ± 4.2 months, Log Rank 4.988, p=0.026). (Figure 1.) Conclusion SECHO test has excellent negative long-term prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI while patients with slow HRR have more pronounced risk for the occurrence of adverse events.Figure 1.Kaplan-Meier survival curve

Comparison of 600 mg VS 300 mg clopidogrel loading dose for patients with ischemic heart disease: a meta-analysis of randomized controlled trials

Abstract Background While a 600-mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300-mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether a higher clopidogrel LD regimen in primary percutaneous coronary intervention outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease. Purpose The objective of this meta-analysis is to validate current randomized trials that investigate the efficacy and safety of two clopidogrel loading regimens (600 mg vs 300 mg) in patients with ischemic heart disease treated with primary percutaneous coronary intervention. Method A systematic literature search for randomized controlled trials was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects. Result Nine randomized control studies involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only 8 studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced incidence of overall MACE (OR:0.82, 95% CI:0.74-0.91, p=0.0002), nonfatal myocardial infarction (OR:0.56; 95% CI:0.32-0.99, p = 0.15) and target vessel revascularization (OR 0.63; 95% CI 0.41 to 0.95, p = 0.03 ), without significant difference in terms of cardiac death (OR:0.89; 95% CI:0.76-1.04, p=0.15) and stroke (OR 0.92; 95% CI 0.67 to 1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR:1.27; 95% CI:1.08-1.49, p=0.005] without significant difference in minor bleeding (OR:1.05; 95% CI:0.94-1.17, p=0.35). Conclusion The administration of 600 mg of clopidogrel LD reduces the overall risk of MACE with an associated increased risk of major bleeding in patients with ischemic heart disease undergoing primary percutaneous coronary intervention.MACE OUTCOMES

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.

Comparing predictive accuracy: systolic blood pressure to left ventricular end-diastolic pressure ratio versus TIMI score for short-term mortality after primary percutaneous coronary intervention

Abstract Objective Aim of this study was to evaluate the predictive performance of systolic blood pressure (SBP) to left ventricular end-diastolic pressure (LVEDP) ratio for the prediction of in-hospital and short-term mortality in a contemporary cohort of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) at a tertiary care cardiac center. Methods This study included a consecutive series of patients diagnosed with STEMI who underwent primary PCI. The SBP/LVEDP ratio and TIMI (Thrombolysis in Myocardial Infarction) score were calculated, and their ability to predict in-hospital and short-term mortality was evaluated by analyzing the area under the curve (AUC) on the receiver operating characteristics (ROC) curve. Results This study involved 977 patients, with 780 (79.8%) being male and a mean age of 55.6±11.5 years. Among them, 191 (19.5%) had an SBP/LVEDP ≤5.4. The in-hospital mortality rate was 4.3% (42), and the short-term all-cause mortality rate after a mean follow-up of 5.9±2.4 months was 15% (140). Patients with SBP/LVEDP ≤5.4 had higher in-hospital mortality rates (14.1% vs. 1.9%; p<0.001) and short-term mortality rates (35.1% vs. 9.8%; p<0.001) compared to those with SBP/LVEDP >5.4. The AUCs of SBP/LVEDP and TIMI for predicting in-hospital mortality were 0.766 [0.681-0.851] and 0.787 [0.713-0.861], respectively. For short-term mortality, the AUCs of SBP/LVEDP and TIMI were 0.731 [0.682-0.780] and 0.736 [0.690-0.782], respectively. Conclusion In conclusion, SBP/LVEDP showed sufficiently high predictive power comparable to the TIMI risk score. SBP/LVEDP is a readily available ratio that can rapidly provide valuable prognostic information during primary PCI.operating characteristics curveComparative distribution

Mortality rate of percutaneous coronary interventions in st-segment elevation myocardial infarction patients under the public health insurance schemes of thailand

Abstract Background ST-elevation myocardial infarction (STEMI) presents a critical public health challenge internationally, including in Thailand. Currently, standard therapeutic interventions, particularly primary percutaneous coronary interventions (pPCI), are administered to Thai citizens. However, selected healthcare systems restrict access to specific pharmaceuticals and medical devices, causing inequalities in the quality of medical care amongst different healthcare systems. Such inequalities have the potential to significantly impact the quality of life of patients, particularly in the long term. Purpose The primary objective is to compare mortality rates within one year of STEMI patients after treatment with pPCI among the public health insurance schemes of Thailand. The secondary objective is to study prognostic determinants for one-year mortality rates among patients diagnosed with STEMI who have undergone pPCI. Methodology This study is a single-centre retrospective analysis of patients with STEMI treated with pPCI. It involves patients utilising various state health insurance schemes in Thailand from 1 January 2010 to 31 December 2020. Data collection occurred through the hospital's computerised management system and the registration administration office of the Department of Provincial Administration. The data analysis employed the Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards regression modelling method. Results The study involved 1,077 patients, categorised into three groups based on their state health insurance: Universal Health Coverage (UC) (546 patients, 50.7%), Social Security System (SS) (199 patients, 18.5%), and Civil Service Reimbursement (CS) (332 patients, 62.6%). The one-year mortality rates in these groups were 10.57%, 4.21%, and 6.47%, respectively (p=0.010). In the unadjusted model, the SS group showed a lower risk of one-year mortality rate (HR 0.38, 95% CI 0.18-0.80, p=0.011), and the CS group also demonstrated a lower risk (HR 0.59, 95% CI 0.35-0.99, p=0.047) compared to the UC group. In the adjusted model, only the CS group significantly reduced the risk of one-year mortality. Other factors that affected one-year mortality were age ≥65 years, a Killip score of 3-4, pre-discharge prescription of angiotensin-converting enzyme inhibitors, occlusion in the left anterior descending artery, and pericardial effusion. Conclusion Healthcare schemes play a significant role in influencing one-year mortality rates among STEMI patients treated with pPCI. The use of civil service reimbursement is a protective factor for the one-year mortality rate in STEMI patients. This information would be crucial for developing strategies and programs to aid healthcare policymakers at both regional and international levels in reducing morbidity and mortality.