Culprit Lesion Research Articles

Trend in culprit plaque phenotype in ACS patients over the past 10 years

Abstract Background Although the incidence of acute myocardial infarction has been declining over the past decade, the etiology of this trend is unknown. One possible explanation could be changes in coronary plaque phenotype. Purpose The aim of this study was to investigate the changes in plaque characteristics over the last 10 years. Methods Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography (OCT) imaging from 2008 to 2018 were included. Patients were divided into 4 periods: (P1) 2008-2010, (P2) 2011-2013, (P3) 2014-2015, and (P4) 2016-2018. Plaque characteristics at culprit lesion in each period were compared. Results Among 1144 patients, 594 (51.9%) presented with ST-segment–elevation myocardial infarction (STEMI). The prevalence of thin-cap fibroatheroma decreased from P1 to P4 in both STEMI group (57.4% to 24.6%, P<0.001) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) group (40.4% to 17.0%, P<0.001) (Figure). Conclusions The prevalence of OCT features of plaque vulnerability has decreased over the past 10 years. A decrease in plaque vulnerability may explain the favorable trend in cardiovascular events.Prevalence of thin-cap fibroatheroma

Complete vs culprit-lesion-only myocardial revascularization in patients with out-of-hospital cardiac arrest: insights from the multicentric "Lombardia CARe" registry

Abstract Background Out-of-hospital Cardiac Arrest (OHCA) is a potentially devastating complication of patients with Myocardial Infarction (MI). Multivessel Disease (MVD) is a frequent occurrence in this setting, being present in nearly half patients undergoing Coronary Angiography (CAG). We previously reported that, in case of MI complicated by OHCA and evidence of MVD, a complete myocardial revascularization, as compared to culprit-lesion-only revascularization, was associated with an improved 1-year survival and favorable neurological outcomes. We aimed to validate and confirm these results on a multicentric scale with a larger patient cohort. Methods This is a multicentric, prospective, observational study. We considered all the consecutive patients with OHCA and MI enrolled in the Lombardia CARe Registry from January 1st 2015 to December 31st 2022 who underwent CAG in 6 centers in Northen Italy. Results A total of 623 patients were included; of these, 403 underwent CAG. Median age was 64 years, and about 80% had no previous history of ischemic heart disease. Median ejection fraction (EF) at presentation was 40%. MVD was present in 186 (46.1%) patients and was subsequently treated with either complete (32.3%) or incomplete (67.7%) coronary revascularization. Left anterior descendent (LAD) artery was the culprit lesion in almost 1/3 of patients. The 1-year survival rate was 78.3% in the complete revascularization group and 42.9% in the culprit-lesion-only revascularization group (p-value < 0.001). After correction for factors that were predictors on univariate analysis, complete revascularization strategy was independently associated with a reduced risk of death [HR: 0.27 (95% CI: 0.01 to 0.739; p = 0.01] and death or unfavorable neurological outcome [HR: 0.23 (95% CI: 0.08 to 0.67); p = 0.007]. Conclusions Complete revascularization strategy was confirmed to be associated with an improvement of 1-year survival and with a good neurological outcome in patients resuscitated from OHCA. These results highlight the independent impact on survival of a complete coronary intervention strategy in patients with OHCA plus MVD.

The impact of SYNTAX score on culprit lesion morphology of acute coronary syndrome

Abstract Background The SYNTAX score quantifies the complexity of coronary artery morphology and is useful in determining the indication for CABG (Coronary Artery Bypass Grafting) or PCI (Percutaneous Coronary Intervention), which often reflect coronary artery disease severity. However, how SYNTAX score affects etiology of ACS (Acute Coronary Syndrome) patients observed by OCT (Optical Coherence Tomography) has been unclear. Methods This is a sub study of TACTICS OCT registry (n=702) which include ACS patients who underwent OCT guided PCI. Based on SYNTAX score, patients were divided into low-SYNTAX-group (1-22 points) and high-SYNTAX-group (23 points or higher). ACS culprit lesions were classified into plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN). We compared patient characteristics and culprit lesions in low-group and high-group. Results High-SYNTAX-group was significantly younger with relatively greater prevalence of diabetes and lower body mass index. Peak CK, LVEF, Multi vessel and TIMI grade were also significantly greater in high-SYNTAX-group than low-SYNTAX-group. Although PR and PE were 2 most common etiologies of ACS in both groups, proportion of CN was much greater in high-SYNTAX-group than low-SYNTAX-group. Conclusion High-SYNTAX score was likely to have impact on ACS etiology increasing proportion of CN.

Clinical impact of perfusion balloon for ST-segment elevated myocardial infarction: RYUSEI study

Abstract Background Drug-eluting stents have significantly contributed to reducing mortality in patients with ST-segment elevation myocardial infarctions (STEMIs), but slow flow/no-reflow phenomenon and in-stent restenosis are still clinical problems. On the other hand, perfusion balloons (PBs) can compress thrombi and ruptured plaque for long inflation without ischemia and can be used as a delivery device for infusion of nitroprusside to distal risk area during ballooning. Purpose We conducted RYUSEI (Reduction of risk bY perfUsion balloon for ST-segment Elevated myocardial Infarction) study to evaluate whether PBs before stenting are more effective than conventional stenting for STEMIs. Methods We divided consecutive patients with STEMIs who underwent optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) into PB group who were treated with PBs before stenting and the conventional PCI (CP) group. In PB group, we inflated PB at the culprit lesion for five minutes to compress thrombi and ruptured plaque as a pre-stent lesion modification. In addition, an intra-coronary injection of nitroprusside (total dose: 120 µg; slow bolus injection of 24 µg/5mL every minute [5 times]) into the distal vascular bed to the culprit lesion through the PB was performed during a 5-minute PB ballooning. We compared clinical results including slow flow/no-reflow phenomenon, OCT findings, and one-year clinical events including cardiac death, target vessel-related myocardial infarctions, target lesion revascularization and stent thromboses between the two groups. Results We finally analyzed 34 patients in PB group and 90 in CP group. After propensity score matching, PB and CP groups consisted of 23 patients, respectively. In the propensity score-matched cohort, there were no significant differences of the patients’ backgrounds and lesion and procedural characteristics between the two groups. In the cohort, regarding post PCI angiographic and OCT findings, the incidence of slow flow/no-reflow phenomenon and maximum protrusion area detected by OCT were significantly lower (P=0.047 and P=0.019, respectively) and TIMI flow grade 3 was significantly higher (P=0.022) in the PB group than CP group while the other parameters were similar (Table). Kaplan-Meier analysis revealed a significantly better one-year clinical outcome in PB group than CP group (p=0.038) (Figure). Conclusions The RYUSEI study revealed a pre-stent lesion modification in addition to nitroprusside infusion using PB is useful to achieve better clinical course in STEMI patients.Post PCI Angiographic and OCT FindingsComparison of One-year Clinical Outcome

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.

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

MELD-albumin score is strongly associated with all-cause mortality in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Kidney and liver injury are frequent complications in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) because of hypoperfusion and venous congestion. Model of End-Stage Liver Disease replacing INR with albumin (MELD-Albumin) score quantifies liver and kidney function and has been associated with mortality in acute heart failure. Higher MELD-albumin score indicates particularly more severe hepatic dysfunction. The predictive value of MELD-albumin score has yet to be assessed in AMICS. Methods This is a retrospective, multicenter observational cohort study of 1,716 patients admitted with AMICS at two tertiary facilities in Denmark between 2010 and 2017. MELD-albumin was calculated for each patient individually from 0–72-hour peak s-albumin, s-creatinine and s-bilirubin values in patients alive beyond day 2. Patients were stratified into groups according to score (Low: 1-10, Intermediate: 11-25, High: >25). Using national health registries, we performed follow-up until a maximum of 5 years (median 3.4 years). The primary outcome was all-cause mortality. Results Of 1716 patients in the cohort, 1284 (75%) were alive beyond admission day 2. Albumin, creatinine, and bilirubin measurements were available in 764 patients (60%). The median MELD-albumin score was 17. In the comparison across high vs. intermediate vs. low score groups, the high score group revealed a significantly higher prevalence of hypertension (61 vs. 49 vs. 39%, p=0.038), diabetes mellitus (33 vs. 18 vs. 13%, p=0.003), and history of acute myocardial infarction (24 vs. 13 vs. 17%, p=0.026). Fewer had suffered out-of-hospital cardiac arrest (34 vs. 52 vs. 48%, p=0.014) and revascularization attempts (82 vs. 93 vs. 92%, p=0.007) in the high score group. No significant differences were observed in the initial hemodynamic pressures, lactate levels, left ventricular ejection fraction (LVEF), number of diseased vessels and culprit lesions between the three groups. Patients in the high score group had a 30-day mortality rate of 58%, which was higher compared to 40% in the medium- and 17% in the low score group (Figure 1, p<0.001, using the log-rank test). These findings were still significant when excluding s-creatinine from the calculations. In a Cox Regression analysis, a MELD-albumin score of >25 was associated with a hazard ratio (HR) of 4.34 for 5-year mortality (p < 0.001), whereas a score of 11-25 was associated with a HR of 2.52 (p < 0.001). When adjusting for age, diabetes, hypertension, dyslipidemia, peripheral arterial disease, STEMI, left ventricular ejection fraction and baseline lactate, scores of >25 and 11-25 were still associated with similar 4- to 2.5-fold increases in 5-year mortality risks. Conclusions This study revealed a strong association between MELD-albumin score and all-cause mortality among patients with AMICS, supporting kidney and liver function inclusion in future risk stratification models.

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.

Association of polarimetric signatures with coronary plaque composition in patients with acute and chronic coronary syndrome: an intravascular polarization-sensitive optical coherence tomography study

Abstract Background Intravascular polarimetry with polarization-sensitive (PS-) optical coherence tomography (OCT) measures polarization properties, birefringence and depolarization, in parallel with structural features available with conventional OCT (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, which imparts mechanical integrity to fibrous caps. Depolarization is elevated in the presence of macrophages and lipid/necrotic core. Purpose This study aimed to investigate polarimetric signatures of coronary lesions in patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions. Methods This was the first-in-human study of intracoronary PS-OCT in Japan, consisting of 17 patients with ACS (n = 5) or CCS (n = 12) who underwent intravascular PS-OCT. ACS culprit lesions (ACS-lesions) and CCS target lesions (CCS-lesions) were included in the analysis, resulting in a total of 862 cross-sections. In the cross-sectional images, lumen segmentation and guidewire artifact were automatically segmented. The median value of birefringence and depolarization were automatically analyzed using depolarization cut-off value (cross-sectional level). Birefringence and depolarization of ACS- and CCS-lesions were compared by using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic performance of polarimetric signatures for the identification of ACS-lesions. Results Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05) (Figure 2). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025). Conclusions Intravascular PS-OCT provides quantitative compositional assessment of coronary lesions. Decreased birefringence and pronounced depolarization within the ACS-lesions indicate increased collagenolytic activity and the presence of macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing natural history of coronary atherosclerosis.

Circulating nucleases degrade high-molecular-weight cell-free DNA in coronary vessels during acute myocardial infarction

Abstract Introduction Extracellular cell-free DNA (cfDNA) originates from various biological processes, including cell turnover, apoptosis, necrosis, NETosis, and other forms of cell death. In healthy individuals, highly fragmented cfDNA is elevated in the bloodstream due to infection, cancer, inflammation and thrombosis. In thrombotic vascular diseases, neutrophils release elongated, high-molecular-weight DNA with bioactive and prothrombotic properties in a process termed NETosis. Circulating nucleases are thought to counteract pathogenic properties of NETs. However, attempts to connect total cfDNA concentration to nuclease activity have failed. Purpose We aimed to elucidate the in vivo connection between extracellular DNA and circulating nucleases in thrombotic vascular diseases by investigating DNA length as a potential novel biomarker in cardiovascular disease. Methods Citrated plasma from healthy volunteers (n=363) and from ST-elevation myocardial infarction (MI) coronary aspirates (n=59) and peripheral arterial sites (n=96) were analyzed for DNA concentration, length, and nuclease activity. Total DNA concentration was measured with a fluorescent DNA binding dye, and elongated DNA assessed using qPCR and Agilent bioanalyzer high-sensitivity DNA chip. Nuclease activity was measured by single radial enzyme-diffusion (SRED) assay. Cardiac MRI assessed infarct size acutely and six months after the event. Results Coronary aspirates exhibited an elevation in total DNA, with a significant rise in high-molecular weight cell-free DNA in addition to an increase in sub-nucleosome fragmentation (Figure 1). Peripheral and coronary plasma samples from individuals with myocardial infarction (MI) showed elevated levels of total and elongated cfDNA. When compared to healthy individuals, the integrity of cfDNA was lower in peripheral samples and higher in coronary aspirates. During myocardial infarction, circulating nuclease activity was elevated systemically but low at the coronary culprit lesion site. Elongated high-molecular-weight cfDNA accumulates primarily in coronary vessels but is also elevated systemically. In coronary aspirates, nuclease activity negatively correlated with elongated DNA and DNA integrity (rs=0.6255, p<0.0001). Conclusions Elongated DNA accumulates during MI at the culprit lesion site. Its inverse correlation with nuclease activity underscores the role of nucleases in cleaving elongated DNA to shorter, soluble fragments. This study establishes DNA length and integrity as novel biomarkers in thrombotic cardiovascular disease.Figure 1:Coronary cfDNA lengthFigure 2:Nuclease activity and cfDNA

Functional improvement of non-infarct related coronary artery stenosis by extensive LDL-C reduction with a PCSK9 antibody: the FITTER trial, microvascular function analysis

Abstract Background Atherosclerosis and microvascular dysfunction are closely linked. Moreover, impaired microvascular function is strongly associated with increased risk on major adverse cardiac events. In patients presenting with acute coronary syndrome (ACS), microvascular function is reduced. PCSK9-inhibitors have shown to reduce plaque burden and lipid load in epicardial vessels and might exhibit similar results on microvascular vessels, thereby improving microvascular function. The FITTER trial offers the unique opportunity to test this hypothesis. Methods The FITTER trial is a multi-center, randomized, double blind, placebo controlled clinical trial for patients presenting with ACS and multi-vessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) measurement of non-infarct related artery (non-IRA) lesions was performed. Patients with intermediate, non-critical lesions (FFR: 0.67-0.85) were included in this trial. For exploratory purpose, additional physiological assessment of the non-IRA included coronary flow reserve (CFR) and microvascular resistance index (IMR) measurements. Microvascular function was evaluated using a pressure- and temperature-sensitive guidewire and a bolus thermodilution method. Participants were randomized and treated for 12 weeks with either evolocumab or placebo in addition to high-intensity statin therapy. Staged reevaluation was done at 12 weeks. After repeated physiology testing, PCI was performed if deemed necessary. Pre-defined exploratory analysis includes the absolute and relative difference in change between CFR and IMR from baseline to follow up in the non-IRA. PCSK9 inhibition might result in a relatively larger increase of CFR and larger decrease of IMR. Results Between March 2020 and August 2023, a total of 150 patients were included in the trial. In 61 patients (88.5% male, age 65.3 ± 9.1 years, 23.0% STEMI, 70.5% non-STEMI, 6.6% UAP) successful baseline and follow-up measurements of microvascular function were performed. Complete results will be available at the beginning of March 2024. The primary- and secondary endpoints will be submitted for late-breaking clinical trials selection. The results of this abstract will include a per vessel analysis of coronary artery microvascular function. Conclusion The FITTER trial will provide new insights on the potential of extensive LDL-C reduction with a PCSK9 antibody on microvascular coronary artery function in patients presenting with ACS and MVD.

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

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

Microvascular functional assessment using microvascular resistance reserve in patients undergoing elective fractional flow reserve-guided percutaneous coronary intervention

Abstract Background Microvascular resistance reserve (MRR) has been proposed as an index for coronary microvascular function. However, the determinants of MRR and the prevalence of coexistent coronary microvascular dysfunction (CMD) in patients with obstructive coronary disease remains elusive. We sought to assess the prevalence of CMD and determinants for MRR. Methods We retrospectively investigated 703 physiologically significant (FFR≤0.80) chronic lesions in our institutional physiological registry. All patients underwent pre-PCI physiological assessment including FFR, CFR and MRR. CMD was defined with MRR<2.1. The characteristics and physiological findings were compared between CMD and non-CMD. The predicting factors for CMD were investigated. Results In a total cohort, FFR, CFR and MRR were 0.70(0.6-0.75), 1.82 (1.27-2.80) and 3.20 (2.22-4.30), respectively. CMD was observed in 142 (20.2%) vessels. Older age (71[65-77] vs 69[62-75], p=0.007), female patients (24.6% vs 14.4%, p=0.005) and non-LAD culprit lesions (42.3% vs 32.4%, p=0.014) were significantly more frequent in CMD. Furthermore, CMD group was significantly associated with the history of hemodialysis and heart failure (10.6% vs 3.6%, p=0.001, 38.0% vs 31.0%, p=0.015 respectively). FFR and CFR were lower in CMD than non-CMD (0.67[0.60-0.73] vs 0.70[0.61-0.76], p<0.001, 1.03[0.82-1.21] vs 2.16[1.56-3.00], p<0.001, respectively). In multiple linear regression analysis, low FFR, non-LAD lesion, older age, female and history of hemodialysis were significant predictors for the presence of CMD. Conclusion The prevalence of coexistent CMD in patients undergoing PCI was 20.2%, when defined as MRR≤2.1. Non-LAD lesion location, older age, women, history of hemodialysis, and FFR were significantly associated with the presence of CMD.

Drug-coated balloon versus drug-eluting stent for de novo culprit lesion in acute coronary syndromes: a report from nationwide registry in japan

Abstract Background Randomized trials have demonstrated the non-inferiority of DCB strategy compared to DES strategy for ACS [1-3]. However, generalizability in clinical settings remains unclear. Purpose This study aims to compare the outcomes between drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) within a nationwide procedure-based registry. Methods This is a retrospective analysis of a cohort study from a prospective, nationwide registry from January 2017 to December 2020 in Japan, focusing on ACS patients who underwent DCB or DES strategy for a single de novo lesion. One-year incidence of all-cause death, cardiovascular death, non-cardiovascular death, non-fatal ACS, stroke, and major bleeding events were compared. Subgroup analysis included lesion-based and ST-elevation myocardial infarction/non-ST-elevation ACS stratification. Results Among 5,212 propensity-matched ACS patients, DCB and DES strategies showed no significant differences in one-year incidence of all-cause death (4.5% vs. 4.6%, hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.72-1.19), cardiovascular death (2.5% vs. 2.5%, HR: 0.90, 95% CI: 0.64-1.26), non-cardiovascular death (2.0% vs. 2.1%, HR: 0.96, 95% CI: 0.65-1.42), and non-fatal ACS (1.7% vs. 2.0%, HR: 1.04, 95% CI: 0.70-1.54). DCB showed higher stroke occurrence (0.8% vs. 0.3%, HR: 2.33, 95% CI: 1.06-5.08) but lower major bleeding events (1.4% vs. 2.3%, HR: 0.65, 95% CI: 0.43-0.99) (Figure 1). Subgroup analyses did not reproduce these findings (Figure 2). Conclusions ACS patients using the DCB strategy demonstrated clinical outcomes equivalent to those undergoing the DES strategy at one year. Further investigation with an extended follow-up is necessary to confirm these findings.

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.

Remote ischemic periconditioning suppresses cardiac sympathetic activation in acute myocardial infarction: a randomized controlled trial.

Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions.

Management of Acute Coronary Syndrome in Elderly Patients: A Narrative Review through Decisional Crossroads.

Diagnosis and treatment of acute coronary syndrome (ACS) pose particular challenges in elderly patients. When high troponin levels are detected, the distinction between non-ischemic myocardial injury (NIMI), type 1, and type 2 myocardial infarction (MI) is the necessary first step to guide further care. However, the assessment of signs of ischemia is hindered in older patients, and no simple clinical or laboratory tool proved useful in this discrimination task. Current evidence suggests a benefit of an invasive vs. conservative approach in terms of recurrence of MI, with no significant impact on mortality. In patients with multivessel disease in which the culprit lesion has been treated, a physiology-guided complete percutaneous revascularization significantly reduced major events. The management of ACS in elderly patients is an example of the actual need for a multimodal, thorough clinical approach, coupled with shared decision-making, in order to ensure the best treatment and avoid futility. Such a need will likely grow throughout the next decades, with the aging of the world population. In this narrative review, we address pivotal yet common questions arising in clinical practice while caring for elderly patients with ACS.

8282 A Diagnostically Challenging Case of Ectopic ACTH Secreting Pancreatic Neuroendocrine Tumor Presenting with Cushing’s Syndrome

Abstract Disclosure: O.A. Aluko: None. S. Patel: None. S.V. Silparshetty: None. T. Gallagher: None. Introduction: Ectopic ACTH mediated Cushing’s syndrome is an uncommon but treatable condition that poses time constrained diagnostic and therapeutic challenge due to severe morbidity as illustrated by our case below. Clinical case:A 65-year-old male was admitted with profound generalized weakness. He became restricted to wheelchair from being able to hike a trail at Yosemite national park 8 weeks prior. Recent history included hospitalization with uncontrolled diabetes and hypertension, new vertebral compression fractures, AKI, hypokalemia, proximal myopathy, anasarca, upper GI bleed and acute upper extremity DVT. Initial testing there revealed hypercortisolemia, elevated ACTH and a normal pituitary MRI. Further workup at our center revealed elevated 24hr urinary cortisol 2598 (n = 5 - 64 μg/24hr), random cortisol 55 (n= 4.2 -22.4 μg/dL) with elevated ACTH 194 (n= 7.2 - 63.3 pg/mL) consistent with ACTH dependent hypercortisolism. IPSS deferred due to AKI, underlying comorbidities and severe cervical stenosis with myelopathy. ACTH and cortisol remained elevated with an 8mg dexamethasone suppression test suggesting ectopic source ACTH. CT with contrast of chest, abdomen and pelvis showed 5mm right lower lobe lung nodule and bilateral adrenal nodularity. Bronchoscopic FNAC was negative for NET.Ketoconazole 400 mg twice daily was started pending localization of culprit lesion with improvement in 24 hr urinary cortisol to 554μg/24 hr however this was stopped within 4 weeks due to acute transaminasemia. Repeat imaging with Gallium-68 dotatate PET CT showed a 1.8 X 2.4 X 1.7 cm pancreatic mass. He underwent distal pancreatectomy with splenectomy. Pathology confirmed a 2.2cm well differentiated neuroendocrine tumor limited to the pancreas with immunohistochemistry strongly for ACTH and weakly for Gastrin. Postoperatively, patient was given hydrocortisone replacement. ACTH was 14.3 pg/mL and cortisol 6.2μg/dL a few weeks later. His diabetes, hypertension, hypokalemia, transaminasemia and proximal myopathy improved. Discussion:Ectopic ACTH mediated Cushing’s syndrome is responsible for about 5 - 20% of all Cushing’s syndrome cases. Pancreatic neuroendocrine tumor secreting Ectopic ACTH is rarer but can be aggressive. Clinical presentation can be confounding due to secretion of >1 neurohormone i.e ACTH and Gastrin in our patient. Gallium-DOTATATE PET/CT tracer has a very high sensitivity and specificity. Early use of this imaging may prevent comorbidity and mortality as surgical resection of ectopic ACTH secreting neuroendocrine tumor is first line therapy. Other diagnostic principles to consider are that severely elevated ACTH levels correlate only with a pituitary macroadenoma, IPSS is invasive and has relative contraindication in sick patients and Desmopressin stimulation test is not widely available. Presentation: 6/1/2024

Predictive models for cholesterol crystals and plaque vulnerability in acute myocardial infarction: Insights from an optical coherence tomography study

BackgroundCholesterol crystals (CCs) are recognized as a risk factor for vulnerable atherosclerotic plaque rupture (PR) and major adverse cardiovascular events. However, their predictive factors and association with plaque vulnerability in patients with acute myocardial infarction (AMI) remain insufficiently explored. Therefore, This study aims to investigate the association between CCs and plaque vulnerability in culprit lesions of AMI patients, identify the factors influencing CCs formation, and develop a predictive model for CCs. MethodsA total of 431 culprit lesions from AMI patients who underwent pre-intervention optical coherence tomography (OCT) imaging were analyzed. Patients were divided into groups based on the presence or absence of CCs and PR. The relationship between CCs and plaque vulnerability was evaluated. A risk nomogram for predicting CCs was developed using the least absolute shrinkage and selection operator and logistic regression analysis. ResultsCCs were identified in 64.5 % of patients with AMI. The presence of CCs was associated with a higher prevalence of vulnerable plaque features, such as thin-cap fibroatheroma (TCFA), PR, macrophage infiltration, neovascularization, calcification, and thrombus, compared to patients without CCs. The CCs model demonstrated an area under the curve (AUC) of 0.676 for predicting PR. Incorporating CCs into the TCFA model (AUC = 0.656) significantly enhanced predictive accuracy, with a net reclassification improvement index of 0.462 (95 % confidence interval [CI]: 0.263–0.661, p < 0.001) and an integrated discrimination improvement index of 0.031 (95 % CI: 0.013–0.048, p = 0.001). Multivariate regression analysis identified the atherogenic index of plasma (odds ratio [OR] = 2.417), TCFA (OR = 1.759), macrophage infiltration (OR = 3.863), neovascularization (OR = 2.697), calcification (OR = 1.860), and thrombus (OR = 2.430) as independent risk factors for CCs formation. The comprehensive model incorporating these factors exhibited reasonable discriminatory ability, with an AUC of 0.766 (95 % CI: 0.717–0.815) in the training set and 0.753 (95 % CI: 0.704–0.802) in the internal validation set, reflecting good calibration. Decision curve analysis suggested that the model has potential clinical utility within a threshold probability range of approximately 18 % to 85 %. ConclusionsCCs were associated with plaque vulnerability in the culprit lesions of AMI patients. Additionally, this study identified key factors influencing CCs formation and developed a predictive model with potential clinical applicability.

Impact of serum cholinesterase on calcified nodules in patients with stable coronary artery disease.

Calcified nodules (CNs) are an advanced stage of coronary calcification that can have significant clinical implications. We investigated factors associated with CNs, the etiology of which is not fully understood. We retrospectively evaluated 619 patients with stable coronary artery disease who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI). CNs in the culprit lesion were evaluated via IVUS, and all-cause mortality and major cardiovascular and cerebrovascular events (MACCEs) were compared between the CN and non-CN groups. The CN group (n = 40 patients) had a significantly lower survival rate and a higher incidence of MACCE than the non-CN group (P = 0.020 and P < 0.001, respectively). Multivariate logistic regression analysis models revealed that chronic kidney disease and serum cholinesterase (ChE) level were associated with CN formation [odds ratio (OR): 3.15, 95% confidence interval (CI): 1.30-7.69, P = 0.001 and OR: 0.94, 95% CI: 0.88-0.99, P = 0.042]. The optimal cutoff of serum ChE level as per the receiver operating characteristic curve was 309 units/l (Area under the curve = 0.67, sensitivity = 93%, specificity = 40%, P = 0.001). The low-ChE group divided according to the optimal cutoff value showed significantly higher cumulative incidence of MACCEs after PCI than the high-ChE group as per Kaplan-Meier analysis. The presence of CNs is significantly associated with a poor prognosis and MACCE after PCI among patients with stable coronary artery disease. Serum ChE levels may affect CN formation.