Percutaneous Coronary Intervention Research Articles

Association of Neutrophil extracellular traps burden with clinical and angiographic characteristics in patients with ST-elevation myocardial infarction

Abstract Background The precise triggers for arterial plaque rupture and the underlying pathophysiology of thrombogenesis remain elusive. Polymorphonuclear neutrophils (PMN), particularly their formation of Neutrophil Extracellular Traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). Methods This study included 336 consecutive STEMI patients undergoing pPCI and TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. Results Manual TA was selectively performed in 72 cases with increased thrombotic burden and 60 thrombi were suitable for analysis. Most thrombi specimens displayed lytic features (63%) and almost three out of four specimens were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 minutes) OR=10.29 (95% CI 2.11-42.22, p=0.001) and stress-induced hyperglycemia (SIH) OR=6.58 (95% CI 1.23-52.63, p=0.04) after multivariate regression analysis. Additionally, distal embolization (DE), a predictor of adverse outcomes, was more frequent among patients with an elevated NETs burden OR=16.9 (95% CI 4.23-44.52, p<0.001). Conversely, no significant association between NETs burden and final TIMI flow=3 was observed. Conclusion Elevated NETs burden in STEMI thrombi is linked to delayed reperfusion, SIH and increased risk of DE. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

Effect of alirocumab on coronary plaque stratified by atherothrombotic risks

Abstract Background Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown. Purpose To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy. Methods This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks. Results A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P<0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009). Conclusions Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors

1-year outcomes of patients presenting with acute coronary syndromes in Western Cape, South Africa: findings from the PERFUSION ACS registry

Abstract Background Cardiovascular disease(CVD), particularly acute myocardial infarction(MI), has emerged as a public health challenge in South Africa(SA), however, there is a paucity of data regarding long-term clinical outcomes such as CVD mortality, heart failure, stroke and recurrence of MI in this region. Purpose To determine 1-year major adverse cardiac outcomes among individuals discharged alive following admission for troponin-positive Acute Coronary Syndromes(ACS) in Western Cape, SA. Methods Between February 2021 and May 2022, 838 adults(≥18 years) with a diagnosis of ACS were prospectively enrolled into the investigator-initiated, multi-center PrEsentation, Rationale, and impact of reperFUSION for Acute Coronary Syndromes (PERFUSION ACS) registry. Participants were enrolled at a tertiary-care referral center and four secondary-level healthcare facilities. Key data elements were measured at index admission, including baseline demographics, risk factors, clinical presentation, complications, laboratory tests, revascularization strategies, and discharge medication. Survivors at discharge provided consent for 30-day and 12-month telephonic evaluations for major adverse cardiovascular events(MACE), which were captured on a web-based system that was centrally managed and analyzed. Results Of 838 participants, 39% were female, one-third were <55 years of age, 76% had a history of smoking, 74% had hypertension, 58% had dyslipidemia, and 56% were obese. STEMI accounted for 51% of cases, with NSTEMI in 49%. Baseline data for the cohort, stratified into two categories of MI, are provided in Table 1. Median duration from symptom onset to hospital presentation was 10.42 (±15.26) hours, with a majority(80%) presenting first to a non-PCI-capable facility. Among STEMI cases, two-thirds received thrombolysis(65%), primarily with Streptokinase; 49% underwent angiography via a pharmacoinvasive strategy, and 3% received primary percutaneous coronary intervention(PCI). Overall, 57% of patients with NSTEMI were treated with an invasive approach. The one-year all-cause mortality was 21%, with 88% attributable to cardiovascular disease-related death. Cumulative MACE rate at one year was 57%. Event rates for the individual MACE components were 32% for heart failure, 19% for non-fatal MI, and 6% for non-fatal stroke. 6% of participants died in-hospital, while 30-day mortality was 9%. There were no significant differences in all-cause mortality between STEMI and NSTEMI at 1 year. Conclusion Troponin-positive ACS are associated with a high rate of 12-month mortality and non-fatal major adverse cardiac events in Western Cape, SA. The concerning registry findings emphasize the need to prioritize ischemic heart disease prevention and management, and highlight important gaps in care which can serve as targets for improvement throughout the country.PERFUSION: Table 1PERFUSION: All-cause mortality and MACE

Advancing prognostic insights in STEMI patients through microvascular resistance reserve evaluation

Abstract Background Coronary microvascular dysfunction (CMD) after ST-Elevation Myocardial Infarction (STEMI) is associated with persistent symptoms and poor outcomes. Microvascular Resistance Reserve (MRR) is an innovative metric for evaluating coronary microvasculature that is unaffected by epicardial stenoses or the hemodynamic impact of vasodilators. While MRR's prognostic ability is recognized in chronic coronary syndrome, its application in ACS remains unestablished. Purpose We sought to investigate the prognostic value of MRR in STEMI patients. Methods This is a prospective study of 210 STEMI patients with multivessel disease who had undergone successful primary percutaneous coronary intervention (PCI). At 3 months follow-up, they returned for complete revascularization and coronary physiology evaluations, including coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR), using bolus thermodilution. 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, respectively1. We utilized an MRR cutoff of 3.0 based on Boerhour et al. The association between MRR and major adverse cerebrocardiovascular events (MACCE) at 12-month follow-up, defined as the composite of stroke, revascularization, myocardial infarction (MI), heart failure hospitalization, and death, was investigated. Results The median age was 65 years, and 40.48% were female. At a 3-month follow-up, 27% (56 patients) exhibited MRR <3.0, who were predominantly female (62.50% vs 32.47%, p<0.001) with a higher incidence of diabetes (39.29% vs 18.83%, p = 0.004). No significant differences were observed in age, body mass index, or STEMI location (anterior or inferior) when comparing between MRR groups. The MACCE-free survival at 12 months was significantly lower in patients with an MRR < 3.0 (48.2%) compared to those with an MRR ≥ 3.0 (11.0%; log-rank p < 0.001, Fig1A). The MRR < 3.0 group showed higher rates of ischemic stroke (8.93% vs. 1.30%, p = 0.022) and hospitalization for heart failure (21.43% vs. 2.60%, p < 0.001), while the incidence of nonfatal myocardial infarction (MI) and cardiovascular death were similar between the two MRR groups (Figu1B). In multivariable Cox regression analysis, MRR was an independent predictor for 12-month MACCE (Hazard Ratio 0.45 per unit increase, 95% Confidence Interval 0.31-0.67, p<0.001). The areas under the receiver operating characteristic curves for predicting 12-month MACCE using FFR, CFR, IMR, and MRR yielded values of 0.609, 0.762, 0.781, and 0.743, respectively (Fig2). The prognostic performances of CFR, IMR, and MRR were similar and superior to that of FFR. Conclusion This study establishes the novel parameter MRR as a superior prognostic indicator in STEMI patients compared to FFR, and on par with CFR and IMR. MRR is a reliable predictor of MACCE, and various clinical incidents post-STEMI.

SGLT2-'eyes' on the reno-protection prize: reduction of post-PCI contrast-associated AKI in diabetic patients using SGLT2 inhibitors

Abstract Background Chronic therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) is associated with long term reno-protective benefits. There are limited data on the benefits of these agents against the risk of contrast-associated acute kidney injury (CA-AKI). Purpose The goal of our study was to assess the comparative efficacy of SGLT2i for the prevention of CA-AKI in diabetic patients undergoing PCI. Methods The study population included all diabetic patients enrolled in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Percutaneous Coronary Intervention (BMC2PCI) registry, a clinical registry of all PCI cases at non-federal hospitals in the state of Michigan, USA. Included patients underwent PCI between January 2022 and September 2023. Patients on dialysis were excluded. Predicted AKI risk was calculated using a previously validated and published machine learning BMC2 risk model. The primary outcome of CA-AKI was defined as an elevation in serum creatinine of ≥0.5 mg/dL following PCI. Risk-adjusted AKI rates were estimated by the product of event observed/expected ratio and overall collaborative AKI rate. Propensity matching on 23 covariates was used to adjust for the non-random use of SGLT2i. Results A total of 19,078 diabetic patients were included, of whom 3,087 (16.2%) were prescribed SGLT2i prior to PCI. Patients treated with SGLT2i were younger (66.1 vs 68.3 years), more likely to be men (73.3% vs 65.3%), have heart failure (50.4% vs 42.4%), have prior PCI (58.4% vs 48.8%), and have co-prescription of insulin (43.8% vs 37.3%) (p<0.001 for all). After propensity matching, no significant baseline difference between cohorts remained, with an absolute standardized difference less than 10% on all covariates. The pre-procedural use of SGLT2i was associated with a lower incidence of CA-AKI in unadjusted analysis (2.7% vs 3.8%, p=0.003) and after adjusting for the baseline predicted risk of CA-AKI (2.2% vs 2.8%, adjusted OR 0.69, 95% CI 0.54-0.89, p=0.0045). In a propensity-matched analysis, the use of SGLT2i was strongly associated with a reduced adjusted risk for CA-AKI (2.2 % vs 2.8%, adjusted OR 0.72, 95% CI 0.62-0.84, p=0.026). Conclusions Among patients with diabetes presenting for PCI, pre-procedural use of SGLT2i was associated with a significant reduction in the risk of CA-AKI. These results should compel further investigation into the beneficial effects of SGLT2 inhibitors in reducing the risk of CA-AKI.

Supersaturated oxygen therapy in patients with acute anterior myocardial infarction reduces infarct size

Abstract Background Myocardial final infarct size (FIS) is associated with heart failure hospitalizations and mortality in patients with ST-segment elevation myocardial infarction (STEMI). Interventional therapies beyond primary percutaneous coronary intervention (PCI) to reduce FIS are needed. Hyperoxemic supersaturated oxygen therapy (SSO2) has shown to reduce infarct size in previous clinical trials. Methods We performed routine SSO2 therapy in patients with acute anterior STEMI after successful primary PCI. Results from 22 SSO2 patients were compared with those from 22 pair-matched non-SSO2 acute anterior STEMI patients. Cardiac magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function, myocardial FIS (late gadolinium enhancement), area-at-risk (AAR, myocardial oedema), myocardial salvage index (MSI, proportion of non-necrotic inside oedematous myocardium), and microvascular obstruction (MVO, necrotic myocardium within the infarct zone). Results Both groups did not significantly differ regarding sex, age, weight, body mass index, hypertension, dyslipidaemia, smoking and diabetes status, prehospital cardiac arrest, door-to-balloon time, TIMI flow before and after PCI, numbers of stents placed, and renal function (p>0.1 each). SSO2 patients had significant lower maximum creatine kinase levels (2111 U/l) vs. non-SSO2 patients (4571 U/l, p=0.003). Cardiac MRI was performed 4 ± 2 days after PCI. LV ejection fraction (48% in SSO2 vs. 43% in non-SSO2, p=0.11) and AAR (42% of LV mass in SSO2 vs. 48% of LV mass in non-SSO2, p=0.096) did not significantly differ between the groups. SSO2 significantly reduced FIS by 38% (21% of LV mass vs. 34% of LV mass, p<0.001). MSI was significantly higher in SSO2 patients (46% vs. 18%, p<0.001). MVO occurred in 60% of SSO2 patients vs. 90% of non-SSO2 patients with a significant absolute difference (2.3% in SSO2 vs. 5.7% in non-SSO2, p=0.011). Conclusion While areas at risk were similar between both groups, SSO2 significantly reduced maximum creatine kinase levels, final infarct size and microvascular obstruction in patients with acute anterior STEMI.

Acute echocardiographic assessment of patients with ST-elevation myocardial infarction in detecting clinically hidden hemodynamic deterioration

Abstract Background Transthoracic echocardiography (TTE) offers an immediate non-invasive assessment of cardiac morphology and function that can be performed bedside. Acute TTE in the catheterization laboratory (cath.lab.) may be helpful to identify markers of subsequent development of cardiogenic shock (CS) in patients with ST-elevation myocardial infarction (STEMI) in addition to the previously validated ORBI risk score. This relationship has not been investigated thoroughly previously. Purpose To investigate the association between acute TTE estimates of left ventricular (LV) function prior to primary percutaneous coronary intervention (pPCI) in STEMI patients and pro-B-type natriuretic peptide (proBNP) as a proxy associated with of CS development. Method From September 2023 all non-CS STEMI patients at one tertiary heart center underwent acute bedside TTE in the cath.lab. and ORBI risk score assessing the risk of CS development aiming for inclusion of 500 patients. The 5 minutes TTE-protocol consisted of LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), mitral inflow (E and E/A), mitral deceleration time, and mitral annular early diastolic velocity é lateral. The primary endpoint was proBNP measured 24 hours (h) after pPCI (12-36h) stratified in quartiles (Q4 vs. Q1-3). The correlation between proBNP and TTE measurements and proBNP and ORBI risk score was examined using univariate linear regression models. Results Until now 153 STEMI patients (mean age 64 years, 25% female) were studied. Anterior STEMI was present in 36%, and median time from cath. lab. arrival to first wire over the culprit lesion was 28 minutes (IQR 24; 37). Patients with high proBNP level (Q4 vs. Q1-3) had significantly higher heart rate (median 84 bpm vs. 72 bpm) and Killip Class>1 (16% vs. 0%) at admission, but similar lactate levels (1.8mM vs. 1.5mM), systolic blood pressure (130 mmHg vs. 137 mmHg), and out-of-hospital cardiac arrest (11% vs. 12%). Patients with high proBNP levels (Q4 vs. Q1-3) had significantly lower LVEF (35% vs. 50%), higher E/é lateral (median 11.4 vs. 7.9), and higher ORBI risk score (median 8 vs. 4). LVEF, LVOT VTI, E/é lateral, and ORBI risk score were significantly associated with proBNP (Figure 1). Two patients developed CS after the pPCI; one with high proBNP level Q4, and one deceased prior to proBNP measurement. Conclusion Acute TTE is an easy tool for assessment of the acute hemodynamic status in STEMI patients bedside in the cath.lab., and it can be without delaying time to revascularization. LVEF, LVOT VTI, E/é lateral, and ORBI were all parameters associated with increased levels of the hemodynamic biomarker proBNP, and may together with the ORBI risk score improve the assessment and risk stratification of STEMI-patients at risk of CS-development.Figure 1.

Cost-effectiveness analysis of implementing the Nagasaki Acute Myocardial Infarction (AMI) secondary prevention clinical pathway

Abstract Background/Introduction Because of the poor prognosis associated with acute coronary syndromes (ACS), intensive low-density lipoprotein cholesterol (LDL-C) management therapy is recommended as early as possible after the onset of ACS, with the goal of lowering plasma LDL-C to <70 mg/dL. In Nagasaki City, a council was formed comprising all hospitals performing percutaneous coronary intervention along with general physicians, and an initiative to manage LDL-C using a region-wide LDL-C management clinical pathway (Figure 1) was launched in July 2022. The rate of intensive statin therapy at discharge increased from 34.5% to 79.8%, and the rate of patients achieving LDL-C <70 mg/dL at discharge increased from 37.2% to 54.6% following the implementation of the clinical pathway. However, the cost-effectiveness of implementing the clinical pathway remains to be determined. Purpose: The purpose of this study was to evaluate the cost-effectiveness of implementing the Nagasaki AMI Secondary Prevention Clinical Pathway. Methods: To evaluate the cost-effectiveness of implementing the clinical pathway compared with no implementation, a lifetime simulation was performed using mathematical models. The models consisted of a decision tree model to model the flow of the clinical pathway (Figure 2) and a Markov model to consider the risks of developing cardiovascular disease (CVD) events. The quality-adjusted life year (QALY) was used as the outcome. Drug costs and treatment costs for each CVD event were included. Drug costs were calculated from actual prescriptions. Treatment costs and utility scores for each event were based on the literature. The risk of each CVD event was calculated using baseline risks estimated using commercial claims data (DeSC Healthcare, Inc.) and patients' LDL-C levels at discharge and 1 month after discharge. LDL-C levels at each time point were set separately for the groups that achieved or did not achieve a discharge LDL-C < 70 mg/dL, for patients with and without implementing the clinical pathway. Results: Implementing the clinical pathway was evaluated as dominant, with an incremental gain of 0.079 QALYs per person and expected cost savings of JPY 103,124 per person. Implementing the clinical pathway was shown to not only provide additional health benefits by preventing CVD, but also to reduce future health care costs. In the analysis with a 10-year time horizon, the result remained dominant, and the same level of cost savings was expected. Conclusions: Implementing the Nagasaki AMI Secondary Prevention Clinical Pathway can be expected to reduce costs, in addition to increasing QALYs by preventing CVD. Further clinical and economic evaluation of long-term follow-up with a collaborative pathway to the general physician after discharge from the hospital is expected.

Effect of empagliflozin on no-reflow in patients with st elevation myocardial infarction undergoing primary percutaneous coronary intervention

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.

Multi-modality deep learning model for prediction of chronic obstructive coronary artery disease

Abstract Background/Introduction The incidence of coronary artery disease (CAD) is on the rise with an increasing burden of stable ischemic heart disease (SIHD) and high prevalence of obesity, diabetes, hyperlipidemia, and other cardiovascular risk factors. Pre-test probability estimation for CAD based on demographic features and characterization of chest pain is insufficient to accurately assess whether further evaluation for CAD is warranted. Purpose To develop and validate a deep learning (DL) algorithm utilizing electrocardiogram (ECG) waveforms and clinical features to predict obstructive CAD. Methods Clinical data from subjects undergoing invasive angiography over a 4-year period at a quaternary care center exclusive of subjects who had concern for acute coronary syndromes were used for model training. ECGs obtained up to 5 years prior to angiography were included; ECGs were partitioned 8:1:1 for training, validation, and test datasets. Obstructive CAD was defined as receiving percutaneous coronary intervention during elective angiography. Convolutional neural network models were developed for ECG waveforms alone (DL-ECG), clinical features from standard risk scores (DL-Clinical), and the combination of ECG waveforms and clinical features (DL-ECG+Clinical); a commonly used pre-test probability estimation tool derived from the CAD Consortium study was used as a comparison (PTP). The models were evaluated based on area under the curve receiver operating characteristics (AUC). Shapley additive explanations (SHAP) analysis was performed to understand feature importance in the DL models. Results A total of 40,602 ECGs and 8,361 coronary angiograms from 7,201 patients were included in the analysis. The median age was 66 (IQR 56-75), 71.9% were men, 34.9% had hypertension, 30.6% had diabetes mellitus, and 39.0% had dyslipidemia. The PTP model (AUC 0.733 [0.717-0.750]) had similar performance as the DL-Clinical model (AUC 0.762 [0.746-0.778]). The DL-ECG model (AUC 0.741 [0.726-0.758]) had similar performance as both the clinical feature models. The DL-ECG+Clinical model (AUC 0.807 [0.793-0.822]) trained on ECG waveforms and clinical features had a superior performance (Figure 1). SHAP analysis for the DL-ECG+Clinical model revealed that ECG waveforms had the largest influence on the model’s output followed by age and chest pain type (Figure 2). Conclusions Multi-modality DL model utilizing ECG and commonly used features can improve prediction of obstructive CAD in SIHD compared to traditional pre-test probability estimates. Prospective research is warranted to determine whether incorporation of DL methods to ECG analysis effectively improves diagnosis and outcomes in obstructive CAD.Figure 1.Figure 2.

Association of culprit lesions with in-hospital mortality in patients with acute coronary syndrome complicated by cardiogenic Shock

Abstract Background/Introduction The Society for Cardiovascular Angiography and Interventions (SCAI) shock stage is useful for stratifying short-term prognosis in patients with acute coronary syndrome (ACS). However, the impact of culprit lesion location for ACS on prognostic stratification by the SCAI shock stage remains insufficiently elucidated. Purpose This study aims to investigate the association between culprit lesion location for ACS and shock severity on in-hospital mortality. Methods We retrospectively investigated consecutive ACS patients who underwent percutaneous coronary intervention at a single center between January 2014 and October 2023. Patients were classified into five groups (No risk, Stage A, Stage B, Stage C, and Stage E) based on data at arrival in the emergency department using SCAI classification. The following culprit lesions were included in this analysis: left main coronary artery (LMCA), proximal right coronary artery (RCA), proximal left anterior descending artery (LAD), and proximal left circumflex artery (LCX). Results Of 1,665 patients included in the analysis, the mean age was 72±12 years, and females accounted for 26% overall. The distribution of SCAI shock stages by culprit lesions is shown in Figure 1. The proportion of stage B or higher in the LMCA, RCA, LAD, and LCX was 41%, 23%, 24%, and 24%, respectively. The corresponding in-hospital mortality was 20%, 3%, 5%, and 3%, respectively. The trend of in-hospital mortality stratified by shock severity and culprit lesions is demonstrated in Figure 2. LMCA and LAD showed increased in-hospital mortality with progressing shock severity. In contrast, this trend was not observed for RCA and LCX. Conclusions Except for LMCA, the proportion of shock stage B or higher was comparable. SCAI shock stage classification was useful in stratifying in-hospital mortality in patients where culprit lesions for ACS were LMCA and proximal LAD. Conversely, its validity in those with proximal RCA and LCX may be limited.

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

Cangrelor use in ticagrelor-loaded ST-elevation myocardial infarction patients with high residual platelet reactivity: a randomized controlled trial

Abstract Background Despite the use of potent P2Y12 inhibitor, many patients still present with high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI). HPR is associated with impaired myocardial reperfusion and the subsequent poor outcome. Purpose We sought to determine the impact of Cangrelor -a rapid and potent intravenous P2Y12 inhibitor- on myocardial reperfusion in patients with HPR admitted for primary PCI in a randomized trial. Methods Patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit (PRU) > 208) were randomly assigned in a 1:1 ratio to receive cangrelor (experimental group) or not (control group) just before PCI. The primary endpoint was optimal myocardial reperfusion defined as a final myocardial blush grade (MBG) 3 assessed by an independent core laboratory. Results After screening of 128 patients, a total of 60 patients were with HPR were enrolled and randomized. The ticagrelor loading dose to PRU measurement times were 83 ± 32 and 90 ± 47 minutes in the experimental and control groups, respectively. Baseline PRU were 245 ± 30 and 252 ± 35 in the experimental and standard group, respectively. A final MBG 3 was observed in 21/30 (55%) and 17/30 (45%) the experimental and standard groups (p=0.29). A final TIMI flow grade 3 was observed in 30/30 (100%) and 27/30 (90%) the experimental and standard groups (p=0.24). Peak troponin levels after PCI were 51381 ± 50047 and 51078 ± 63960 ng/L (p=0.98) in the experimental and standard group, respectively. At the end of the PCI, control PRU were 36 ± 57 and 198 ± 107 (p<0.0001) in the experimental and standard group, respectively. One patient of the experimental group presented an in-hospital major bleeding (BARC 3). Conclusion In ticagrelor-loaded STEMI patients with residual HPR at the time of PCI, cangrelor use was associated with a more effective platelet inhibition but failed to significantly improve the rates of optimal final myocardial blush grades.

Nomogram-based prediction of MACE in older adults with STEMI

Abstract Introduction Despite the significant progress made in diagnosing and treating patients with ST elevation myocardial infarction (STEMI), high-risk subgroups such as older adults (those over 65 years-old) still face considerable residual risk of major adverse cardiovascular events (MACE) following treatment for their index event. Thus, it is crucial to create accurate, validated, and actionable tools to stratify patients according to their risk of MACE after admission for STEMI. Purpose Utilizing clinical data obtained from a registry of patients diagnosed with STEMI, this study aims to develop a nomogram that can reliably predict the likelihood of MACE incidence. Methods Using a large electronic single-center registry, all consecutive patients with STEMI, undergoing primary percutaneous coronary intervention (PCI), and aged 65 and above were identified. Demographic, laboratory, clinical and intra-procedural variables were examined. Univariate and multivariate logistic regression analyses were utilized to identify those factors which were independently associated with MACE incidence in the post PCI follow-up period. A nomogram was developed in a training set, and performance metrics such as receiver operating curves (ROC), calibration plots, and decision curve analysis were used for validation in a testing set. Analyses were performed using tidyverse and rms packages in R programming language. Results 1946 patients were included in the study and split into 70% training and 30% testing sets. Both groups were similar in terms of baseline demographic and clinical characteristics. Mean follow-up period was 17 months. Total MACE incidence in the post PCI follow-up period was 18%. Thirty-eight factors with limited missing information (<5%) were examined for their relationship with MACE incidence and after performing univariate and multivariate analysis 8 were selected for construction of the nomogram: left-ventricular ejection fraction (LVEF), serum creatinine, hemoglobin and fasting blood glucose levels, presence of valvular heart disease, post PCI TIMI flow grade, diameter of the stent placed in the culprit lesion, and presence of shock in the post PCI setting. The area under the curve (AUC) for MACE prediction in post PCI follow-up period showed acceptable discrimination (c-statistic=73%, 95%CI 71.2% to 76.3%). Calibration plots demonstrated that the nomogram model was well-calibrated, and its predictions were closely aligned with observed outcomes. Additionally, decision curve analysis indicated that the model exhibited strong discriminatory ability in predicting MACE. Conclusions A nomogram developed using a combination of laboratory, clinical, and procedural parameters reliably predicts future risk for MACE in older adults following STEMI. Future implementation of this model may identify the highest risk individuals to target more aggressive preventive efforts in a vulnerable cohort of patients.Plot 1Plot 2

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.

Machine learning model using cardiovascular magnetic resonance to predict cardiovascular events in asymptomatic patients with known CAD

Abstract Background Despite declining rates, recurrent cardiovascular events continue to pose significant mortality and morbidity risks in patients with obstructive coronary artery disease (CAD). Traditional prognostic assessments in these patients rely on limited clinical and imaging data. Although several studies have shown the strong prognostic value of stress cardiovascular magnetic resonance (CMR) in asymptomatic patients with known CAD, no dedicated score using CMR was established. Machine learning (ML) methods present an opportunity to leverage a wider array of variables to address this gap. Purpose This study sought to investigate the feasibility and accuracy of ML using stress CMR and clinical data to predict major adverse cardiovascular events (MACE) over a 10-year period in patients with known obstructive CAD, comparing its performance with traditional statistical methods. Methods Between 2009 and 2011, consecutive asymptomatic patients with known obstructive CAD referred for vasodilator stress CMR in two independent centres were followed for the occurrence of MACE defined by cardiovascular mortality or recurrent non-fatal myocardial infarction (MI). Known obstructive CAD was defined by a history of percutaneous coronary intervention, coronary artery bypass surgery, or MI. The first center (N=866) was designated as the derivation cohort for variable selection and model building. The second center (N=224) was used as the validation cohort to evaluate the performance of the final ML-model. Various feature selection methods (Random Forest [RF], XGBoost, and Boruta) were employed to identify robust and informative variables. A final RF model was trained on the derivation cohort and evaluated on the validation cohort. Performance was compared with a standard generalized logistic regression model (GLM), utilizing the receiver operating characteristics (ROC) and the precision-recall (PR) curves as well as the area under the curves (AUC). Results In the derivation cohort (age 67±7 years, LVEF 43±8%, 81% male), 243 (28%) out of 866 patients encountered MACE during the 10-year follow-up period while in the validation cohort (age 67±7 years, LVEF 43±7%, 84% male), 53 (24%) out of 224 patients experienced MACE. Through feature selection method in the derivation cohort, one clinical and four CMR variables emerged as key predictors: number of ischemic segments, number of late gadolinium enhancement (LGE) segments, left ventricular ejection fraction, left ventricular end-diastolic diameter indexed, and age (Figure 1). Using those 5 variables, the RF model significantly outperformed the GLM, demonstrating superior predictive accuracy (AUROC: 0.89 vs. 0.73; PRAUC: 0.78 vs. 0.58, all p<0.001) in the validation cohort (Figure 2). Conclusions A supervised machine learning model using RF, integrating age and stress-CMR data, outperformed traditional statistical methods in predicting 10-year MACE for asymptomatic patients with known CAD.Figure1:Variable selectionFigure2:Models performance on validatio

Cardioprotection with transcoronary saline infusion during primary angioplasty for ST-elevation myocardial infarction: design and rationale of the STEMI-Cool pilot study

Abstract Background Prompt restoration of blood flow in ST-segment elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (pPCI) improves outcomes, but is associated with myocardial stunning, increased infarct size, and microvascular dysfunction. To date, there is no effective therapy to reduce this ischaemia-reperfusion injury (IRI). Mild systemic hypothermia has demonstrated potential but is difficult to achieve and poorly tolerated. Transcoronary hypothermia delivers rapid and effective myocardial cooling, is well tolerated, but not effective when commenced after flow restoration. Coronary haemodilution during reperfusion has shown cardioprotective effects in preclinical studies but has not been fully assessed. Purpose STEMI-Cool is a pragmatic, registry-based randomised clinical trial to assess recruitment rate, feasibility, and safety of a simple protocol which we have reported in a proof-of-concept study. The study has commenced recruitment and aims to overcome the limitations of previous negative studies by combining the beneficial effects of transcoronary cooling and dilution, initiating the infusion prior to wire insertion - therefore avoiding initial unprotected reperfusion (likely to be the critical time for IRI), and avoiding significant delays in reperfusion. Moreover, we will explore mechanistic endpoints and an original method to quantify the intracoronary dilution (with a thermodilution-derived "haemodilution constant ratio"). Lastly, we will investigate ways to "engineer out" the thermistor wire so that the method could be applied to routine pPCI with conventional equipment. Methods Pragmatic broad eligibility criteria allow potential recruitment of all STEMI cases clinically eligible for pPCI. Sixty patients will be randomised 1:1 to standard of care or protected reperfusion with continuous infusion of room temperature saline through the guiding catheter, to achieve intracoronary temperature reduction of 6-8°C. The infusion commences prior to crossing the occlusion with a thermistor wire, which is used as guidewire, and continues for 10 minutes after flow restoration (i.e., TIMI flow≥2). Invasive coronary physiology studies are undertaken after pPCI. Novel and established biomarkers of myocardial damage and inflammation (including dipeptidyl peptidase 3, tumor necrosis factor α, and interleukins 1β, 6, 10) are measured in the preprocedural arterial blood. Cardiac imaging and clinical outcomes are assessed at 48h and 6-12 months. Nesting STEMI-Cool in our local registry Heart-ACS facilitates blood sampling and follow-up. Conclusions STEMI-Cool will primarily investigate recruitment rate, feasibility and safety of an innovative, simple cooling and diluting strategy for cardioprotection during pPCI. Mechanistic outcomes will explore inflammatory, microvascular, structural and functional changes. Finally, we will aim to simplify further the protocol for future research and potential clinical use.STEMI-Cool method schematicSTEMI-Cool protocol timeline

Inhibition of fractalkine signalling in patients with acute myocardial infarction - First results from the FRACTAL trial

Abstract Background We have previously demonstrated a strong association between expression of the fractalkine receptor CX3CR1 on lymphocytes and microvascular obstruction (MVO) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. Our pre-clinical studies also found an improvement in infarct size, inflammation and intramyocardial haemorrhage (IMH) when rats were pre-treated with the fractalkine inhibitor KAND567. Purpose FRACTAL (FRACTalkine inhibition in Acute myocardial infarction) study was a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. Its primary aim was to assess the safety and tolerability of intravenous and oral administration of the fractalkine inhibitor KAND567 as well as reducing signs of reperfusion injury in STEMI patients undergoing PPCI. Methods Patients with a new diagnosis of anterior STEMI, who had index chest pain within 5 hours and angiographic occlusion of the LAD, were randomised on a 1:1 basis to receive either KAND567 or placebo over a period of 72 hours. All patients then underwent a baseline MRI scan at 3 days with a follow-up scan at 3 months, paralleled by longitudinal deep immuno­phenotyping over 9 time points. Results A total of 71 patients were enrolled into the study with 64 (90.1%) being male patients. The mean age of patients was 59.2 years. 37 patients received KAND567, whilst 34 received placebo over 72-hour period. Throughout the 3-month follow-up period, 23 (62%) patients from the KAND567 arm as compared to 24 (71%) patients in the placebo arm had reported adverse events. There was no statistical difference in serious adverse events (SAEs) between both arms with 9 documented in the placebo arm and 12 in the KAND567 arm. Safety bloods also demonstrated no significant differences between the two groups across all time points. There was a higher incidence of left ventricular (LV) thrombus in the placebo arm as compared to the KAND567 arm (17.6% vs. 2.7%; p=0.049). Additionally, the study also demonstrated a lower occurrence of IMH in the KAND567 arm compared to the placebo arm (35.5% vs. 55.2%; p=0.19). Deep immunephenotyping suggested clear target engagement in the KAND567 arm in natural killer cells as well as in cytotoxic T-lymphocytes. Conclusion This first in-man study demonstrates that inhibition of the fractalkine pathway in STEMI patients appears safe and well-tolerated, while demonstrating a promising potential in preventing LV thrombus and IMH. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase III study.LV thrombus and IMH

Impact of sex and age on culprit plaque type of acute coronary syndrome in Japanese patients from TACTICS registry

Abstract Background In acute coronary syndrome (ACS), plaque rupture (PR) is the most frequent etiology followed by plaque erosion (PE) while calcified nodule (CN) is the least etiology. These three are known as major etiologies of ACS. Traditionally, it has been believed that sex and age have impact on etiology of ACS. For example, plaque erosion was thought to often occur in young female while calcified nodule often occur in elderly patients. However, impact of sex and age have not been well described. Methods This is a sub-study from TACTICS registry which consist of 702 Japanese ACS patients who underwent primary percutaneous coronary intervention under optical coherence tomography (OCT) from multicenter. Based on the OCT findings, patients were divided into PR, PE, CN and others. These data were stratified by sex and ages (<50, 50s, 60s, 70s, 80 or over). In this sub-study, we mainly focused on 3 major etiologies of ACS (PR, PE, CN) and compared incidence and clinical characteristics based on sex and ages. Results Distribution of culprit plaque type in ACS patients are shown in figure 1A (male) and 1B (female). PR remained top etiology of ACS in any sex and any age category. However, trend of PE was different between male and female. In male, as patients get younger, incidence of PE increased. In male patients under 50, incidence of PE was almost similar as PR. On the other hand, in female, incidence of PE was greatest in 70s followed by 80 or over. Surprisingly, young female showed the least incidence of PE. CN was the least etiology of three but increased especially from 80. Clinical characteristics are shown in table 1A (male) and 1B (female). In male, most of the baseline characteristics differ between different ages while in female, most of the baseline characteristic did not differ between different ages. Conclusion In our data, PE was more distinct in younger male ACS patients while PE was not that distinct in younger female ACS patients. The impact of sex and age on culprit plaque type of ACS might be variable depending on population.

Fractalkine Inhibition in Acute Myocardial Infarction leads to reduced intramyocardial haemorrhage

Abstract Background The fractalkine receptor CX3CR1 has been linked to the development of microvascular obstruction (MVO) in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Pre-clinical studies have demonstrated a reduction in infarct size, inflammation and intramyocardial haemorrhage (IMH) with inhibition of CX3CR1. Purpose The FRACTAL study is a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. In addition to assessing the safety and tolerability of the fractalkine inhibitor KAND567 in STEMI patients, a subgroup exploratory analysis was performed. We investigated into the translation of MRI and blood samples characteristics between the two groups. Methods Patients with an anterior STEMI who had an occluded proximal to mid left anterior descending (LAD) artery were recruited. These patients had to present within 5 hours of the onset of their chest pain. They were subsequently randomised on a 1:1 basis to receive either KAND567 or placebo. Patients then underwent an MRI at day 3, and subsequently a comparator at 3 months. Additionally, throughout the period of their follow-up, patients would regularly undergo blood sampling to assess multiple parameters. Results Of the 71 patients recruited into the study, 29 patients in the KAND567 arm and 28 patients in the placebo arm received both MRIs. The KAND567 arm had shown a similar troponin rise at day 1 compared to placebo (4357 vs 4286). Baseline MRI demonstrated an identical infarct size between both arms. The presence and absence of IMH was then analysed defining IMH+ as presence of IMH and IMH- as IMH absence. The presence of IMH in patients showed a larger infarct size. The infarct size of IMH+ were the same between KAND567 and placebo, which was a similar finding in the IMH- arm too. However, when compared to day 90 MRI demonstrated a numerically smaller infarct size in the KAND567 group with a smaller percentage of IMH. This was consistent with a lower rate of IMH in the KAND567 arm too, when compared between the groups (35.5% vs 55.2%; p=0.15) (see table below). This seemed to be related to the smaller distribution IMH+, as the IMH+ infarcts were much larger in both arms, whilst overall infarct size in IMH subgroup were identical. Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn’t change infarct size in the respective subgroups of IMH+ or IMH-.MRI Comparator Table