Ischemic Events Research Articles

Association of ticagrelor vs clopidogrel with net adverse clinical events in patients with mild thrombocytopenia undergoing PCI

Abstract Backgrounds Current guidelines recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for managing ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L, undergoing percutaneous coronary intervention (PCI). Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events for patients with mild thrombocytopenia undergoing PCI. Methods A retrospective cohort study of patients with mild thrombocytopenia undergoing PCI who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (includinig clopidogrel or ticagrelor) was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023. All patients meeting the criteria were included in the analysis, with a follow-up of at least one year. Propensity Score Matching (PSM) was performed to equalize the effects of following characteristics: age, sex, hypertension, diabetes, dyslipidemia, stroke, atrial fibrillation, Killip class, percutaneous coronary intervention (PCI), beta-blockers, statins, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB), angiotensin receptor-neprilysin inhibitor (ARNI), diuretic, organic nitrates, and oral anticoagulation. The primary endpoint was net adverse clinical events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included the components of NACE. Results A total of 3647 patients met the inclusion criteria, with 2684 receiving aspirin plus clopidogrel and 963 receiving aspirin plus ticagrelor, matched by a 1:3 ratio using the PSM method. Demographic characteristics were well balanced between the clopidogrel and ticagrelor groups. The 1-year risk of NACE did not significantly differ between ticagrelor and clopidogrel (11.1% vs. 8.4%, p=0.370). Similarly, there was no significant difference in the risk of cardiac death (7.3% vs. 4.2%, p=0.720), recurrent myocardial infarction (9.3% vs. 5.8%, p=0.550), ischemic stroke (8.8% vs. 6.7%, p=0.055), or BARC type ≥ 3 bleeding (7.9% vs. 4.5%, p=0.990). Conclusion In routine clinical practice, among patients with a platelet count of 100~150×109/L undergoing PCI, ticagrelor compared with clopidogrel was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this setting, considering potential unmeasured confounders.

Respective impact of bleeding and ischemic complications of mortality after percutaneous coronary interventions: substudy from the FRANCE-PCI registry

Abstract Background Patients undergoing percutaneous coronary interventions (PCI) remain at high risk of both bleeding and ischemic events, both burdened with high morbimortality. The respective impact of both type of complications in contemporary PCI, however, remains unclear. Purpose To evaluate and compare the respective impact of ischemic and bleeding complications on mortality after PCI Methods The FRANCE PCI is an ongoing registry of consecutive French patients undergoing PCI and monitored for one year thereafter. Patients presenting with complications after the index PCI were categorized as ischemic complications in case of stent thrombosis, myocardial infarction, stroke or unplanned revascularization, as hemorrhagic complications in case of bleeding BARC ≥3 or as ischemic and hemorrhagic when both types of events occurred in the same patients. The impact of ischemic and hemorrhagic complications on mortality was evaluated separately for the index hospitalization and the 12-months follow-up after hospital discharge, using multivariate logistic model and Cox proportional hazards model, respectively. The multivariate Cox model was developed using complications as time-dependent variables and estimating the hazard ratios (HRs) over 3 periods of time (0 to 8 weeks, 8 to 24 weeks, and 24 to 52 weeks). Consequently, the proportional hazard assumption, tested using the Schoenfeld test, was met for each period. Multiple imputations were performed for missing data on covariates. Results A total of 54,599 patients, with a median age of 69 [60.0-78.0] years, 75.0% male, underwent PCI in 30 centers between 2014 and 2020, in an elective setting for 47% of the cases. During the index hospitalization, an ischemic and hemorrhagic complications occurred in 610 (1.1% 95%CI 1.0-1.2) and 531 (1.0% 95%CI 0.9-1.1) patients, respectively, while the mortality rate was 2.1% 95%CI 2.0-2.2. The association between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality was aOR 8.4 95%CI 6.4-10.9, aOR 10.3 95%CI 8.1-13.2 and aOR 13.2 95%CI 7.0-24.7, respectively. Among the 51,738 patients alive and not lost-to-follow-up after discharge, an ischemic and hemorrhagic complications occurred in 2,727 (5.3% 95%CI 5.1-5.5) and 1,022 (2.0% 95%CI 1.9-2.1) patients, respectively, while the mortality incidence was 3.8% 95%CI 3.6-4.0. The associations between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality according to the periods of time are detailed in Table 1 and Figure 1. Conclusion Both ischemic and hemorrhagic complications after PCI are associated with increased risk of mortality. The risk is particularly increased during the early period after the index PCI and diminishes over time, albeit faster after ischemic complications alone, compared to hemorrhagic events alone or the association of ischemic and hemorrhagic complications.

Impact of left atrial appendage occlusion in atrial flow evaluated through 4D flow cardiac magnetic resonance

Abstract Introduction Device-related thrombus (DRT) and peri-device leak constitute significant complications following left atrial appendage occlusion (LAAO), primarily due to its association with strokes and thromboembolic events. Patient-specific fluid simulations have been employed to explore this hypothesis(1). However, these simulations require detailed anatomical and physiological data, rely on certain assumptions when defining boundary conditions, and involve long computational times. Recently, there has been growing interest in the use of 4D flow cardiac magnetic resonance (CMR) imaging for various cardiovascular diseases, owing to its capability to reproduce blood flow. While its role in the LAAO scenario has been evaluated in silico(2), there are no reported cases of its application in patients undergoing LAAO. Purpose Our objective was to evaluate the impact of LAAO in atrial flow through 4D flow CMR. Methods Five patients undergone LAAO were included in the pilot study. A pre- and 90-days post-procedure 4D flow CMR scans were performed. One of the patients was excluded due to suboptimal image quality. To assess the impact of LAAO on atrial flow dynamics, three parameters were evaluated: a) mean velocity, b) stasis velocity ratio, and c) endothelial cell activation potential (ECAP) index — all associated with an elevated risk of thrombus formation(3,4). Results Baseline and procedural characteristics, along with imaging results, are presented in Table 1. Preprocedural 4D flow CMR for all patients revealed low velocities (Figure 1A) and a high ECAP index (Figure 2A) in the left atrial appendage, indicating flow stasis and an elevated risk of thrombus formation. Successful device implantation was performed in all cases, and no periprocedural complications were detected. Postprocedural 4D flow CMR was feasible in all cases, and no artifacts were detected despite the presence of the LAAO device. An objective increase in velocities and a decrease in the ECAP index were observed in all cases following LAAO. No DRT or ischemic events were reported during follow-up. Conclusions Our preliminary study demonstrates that 4D flow CMR provides valuable information on left atrial flow dynamics following the LAAO procedure. Further studies are warranted to evaluate this promising technique.Table 1.Patient characteristicsFigure 1 and 2.Representative example

Real-world implementation of a genotype-guided p2y12-inhibitor de-escalation strategy in acute coronary syndrome patients

Abstract Background CYP2C19 genotype-guided de-escalation from ticagrelor or prasugrel to clopidogrel, may optimize the balance between ischemic and bleeding risk in ACS patients. Purpose Compare bleeding and ischemic event rates in genotyped patients versus standard care. Methods Since 2015, ACS patients in the FORCE-ACS registry received standard dual antiplatelet therapy (DAPT). Since 2021, immediate genotype-guided P2Y12-inhibitor de-escalation was applied, switching non-carriers of the loss-of-function allele CYP2C19*3 or CYP2C19*2 from ticagrelor or prasugrel to clopidogrel, while loss-of-function carriers, carrying at least one loss-of-function allele, remained on ticagrelor or prasugrel. The primary ischemic endpoint, a composite of cardiovascular mortality, myocardial infarction (MI) or stroke and the primary bleeding endpoint, BARC 2, 3, or 5 bleeding, were compared between genotyped those on standard DAPT after one year. Results Among 5,321 enrolled ACS patients, 406 underwent genotyping, compared with 4,915 non-genotyped ACS patients on standard DAPT. In the genotyped cohort, 65.3% (n=265) were non-carriers, whereas 34.7% (n=141) were loss-of-function carriers. The primary ischemic endpoint occurred in 5.2% of patients in the genotyped cohort compared to 6.9% in the standard care cohort (adjHR 0.88, 95% CI 0.56–1.38). The rate of the primary bleeding endpoint was lower in the genotyped cohort compared to the standard care cohort (4.7% vs. 9.8%; adjHR 0.50, 95% CI 0.31-0.78). Conclusion These results demonstrate the feasibility of a CYP2C19 genotype-guided P2Y12-inhibitor de-escalation strategy in a real-world ACS population. This strategy reduced bleeding events, while ischemic events were not increased as compared to a standard DAPT regime.Primary ischemic endpointBARC 2, 3 or 5 bleeding

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Association of ticagrelor vs clopidogrel with net adverse clinical events in STEMI patients with mild thrombocytopenia

Abstract Backgrounds Current guidelines advocate for aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing STEMI patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L. Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events in STEMI patients with a platelet count of 100~150×109/L. Methods A retrospective cohort study was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023.The study included STEMI-patients with a platelet count of 100~150×109/L who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (either clopidogrel or ticagrelor) All STEMI patients with a platelet count of 100~150×109/L were included in the analysis with a follow-up of at least one year. The inverse probability of treatment weighting (IPTW) approach based on propensity score was utilized to balance observed confounders between treatments. The primary endpoint was net adverse events (NACE) at 1 year, including ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes were cardiac death, recurrent myocardial infarction, and ischaemic stroke. Results The study cohort consisted 2941 participants with median age of 69 years, and 21.0% were female. Following adjustment using the inverse probability of treatment weighting, ticagrelor and clopidogrel demonstrated similar NACE (aHR, 0.86; 95%CI, 0.60-1.23). Cardiac death (aHR, 0.69; 95%CI, 0.36-1.31), recurrent myocardial infarction (aHR, 0.94; 95%CI, 0.50-1.78), and ischaemic stroke (aHR, 0.62; 95%CI, 0.34-1.14) did not significantly differ between the two groups. Conclusion In routine clinical practice, among STEMI patients with a platelet count of 100~150×109/L ticagrelor compared with clopidogrel, was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this particular patient population.

Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2

Beyond secondary prevention drugs: added benefit in survival and events of a healthy lifestyle in patients after an acute coronary syndrome

Abstract Background Despite advances in drug treatment and secondary prevention programs, cardiovascular disease remains the leading cause of death. The full extent and independent benefit of a healthy lifestyle, particularly after optimal medical therapy in secondary prevention, has not been widely reported. Purpose To quantify the added benefit on survival and events of a healthy lifestyle following an acute coronary syndrome (ACS). Our study seeks to answer the question: Is adherence to medical therapy sufficient or a healthy lifestyle provides additional improvement?. Methods This a prospective observational multi-center study of 685 patients included during admission for ACS. At 6 months patients were asked about their post-ACS lifestyle and were given a score (range: 0-7) with the following items: Intake of ≥3 fruits and vegetables/day, ≥2 fish servings/week, ≤7 alcohol beverages/week, feeling stress RESULTS: After adjusting for demographic variables, cardiovascular risk factors, characteristics of the index event, high-sensitivity C-reactive protein (hs-CRP), and drug therapy, multivariate Cox regression showed that the lifestyle SCORE was independently and inversely associated with both the incidence of the primary outcome (ischemic events [any ACS, stroke, or Transient Ischemic Attack] or death) (HR 0.65 (CI95% 0.44-0.96); p=0.029) and death (HR 0.41 [95%CI 0.18-0.91]; p=0.029). Statin therapy was also independently and inversely associated with both the incidence of the primary outcome. Kaplan-Meier curves showed a higher event-free survival for both outcomes in patients with SCORE≥4 than in those with SCORE<4 (p=0.03 and p<0.001, respectively). Additionally, patients with a SCORE≥4 had a significantly greater decrease of total cholesterol (-52 [-16.5, -79] vs -38 [-7.5, -68] mg/dl; p=0.040) and hs-CRP (-1.1 [-0.1, 2.5] vs -0.5 [0.7, -1.9] mg/L; p=0.001) at six months. Conclusions Among patients with ACS and similar medical therapy, a healthy lifestyle is an independent and added marker of a lower incidence of ischemic events and death. It is also associated with a better lipid profile and lower inflammation.

Association of P2Y12 inhibitor pretreatment strategy with short and long term ischemic and bleeding outcomes in NSTE-ACS patients

Abstract Background and Aims Oral P2Y12 inhibitors form the basis of both short and long term antiplatelet therapy in NSTE-ACS patients. While reducing thrombogenic activity and ischemic risk is the basis of routine P2Y12 inhibitor pretreatment in NSTE-ACS patients, timing of treatment became controversial as a result of studies showing routine P2Y12 inhibitor pretreatment is associated with an increased risk of bleeding. Even though routine pretreatment is no longer recommended in the ESC guidelines, the inadequacies in RCTs combining all treatment modalities have been noted. Our study aims to determine the relationship between P2Y12 inhibitor pretreatment strategy and short and long-term ischemic and bleeding events. Methods The study was designed as a single-center, prospective and observational study. 2602 patients, aged between 18 and 85, diagnosed with NSTE-ACS in accordance with ESC guidelines were included in the study. 2189 patients were administered with P2Y12 inhibitor pretreatment while 413 patients weren't. Demographic data, CVD risk factors, ECG, echocardiography and laboratory findings at the time of admission, interventional procedural details, type of antiplatelet and anticoagulant treatment and application time were recorded. Patients were divided into two groups as pretreatment and no-pretreatment according to the time of administration of P2Y12 inhibitor loading dose. In the no-pretreatment group choice of P2Y12 inhibitor was left to operator in the cath lab before proceeding to PCI. Post-procedural in-hospital and long term follow up (1 year) were obtained through hospital and national registry systems and patient survey. Results In the no-pretreatment group 91.3% of patients underwent coronary angiography and PCI was performed in 51.8%. In patients proceeding to PCI, 58.5% were given clopidogrel and 41.5% were given a potent P2Y12 inhibitor. In the pretreatment group, clopidogrel was the drug of choice in 93.8% of patients. In the pretreatment group, the primary composite endpoint (MACE and bleeding events) were more common during in-hospital follow-up and this difference was due to a significant increase in both BARC class I & II and class III, IV & V bleedings (Table 1). In the long-term follow up, statistically significant difference was only seen in BARC class I & II bleedings in the pretreatment group. There were no difference in MACE rates in neither in-hospital or long-term follow up (Table 2). Also in multivariate regression analysis, pretreatment with a P2Y12 inhibitor was found to be an independent predictor of short term primary composite endpoints and long-term all-cause mortality. Conclusion The results of our study investigating the effects of the P2Y12 inhibitor pretreatment strategy on ischemic and bleeding endpoints in NSTE-ACS patients showed that the pretreatment strategy did not lead to an improvement in MACE rates in in-hospital and long-term follow-up but caused on overall increase in bleeding events.Kaplan-Meier Survival Analysis

Advanced biologic therapies are associated with fewer adverse cardiovascular events in patients with inflammatory bowel diseases

Abstract Background Chronic inflammation is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD) and associated events. Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions, and meta-analyses of cohort studies demonstrate an increased risk of ASCVD events in IBD patients. Advanced biologic therapies (ABT) targeting the immune system revolutionized treatment of IBD patients but the impact of these therapies on ASCVD events is not known. Purpose To investigate the impact of ABT on ASVCD events in IBD patients. Methods A retrospective cohort study was performed using the TriNetX Diamond Network, a multi-institutional database providing real-time access to de-identified electronic health records, with data updated on 02/14/2024. ABT were defined as one or more the following: infliximab, adalimumab, golimumab, certolizumab pegol, ustekinumab, risankizumab, vedolizumab, or natalizumab. ASCVD events were based on ICD codes for ischemic heart, cerebrovascular, and peripheral vascular diseases. Individuals >40 years with IBD were included. ASCVD events in (1) patients on ABT and (2) patients not on ABT (NABT) were compared. Propensity score matching was performed on sex, aspirin use, and the following ASCVD risk factors: age, hypertension, hyperlipidemia, tobacco use, and type 2 diabetes mellitus. Results This study includes 72,650 individuals in each of the two matched cohorts. There were no differences in baseline characteristics between the two propensity-score matched cohorts (Table). The probabilities of experiencing any ASCVD event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (8.3% vs. 12.4%, OR 0.64; 13% vs. 18.6%, OR 0.66; and 15% vs. 21.2%, OR 0.65; respectively, all p<0.01). Similarly, the probability of experiencing an ischemic heart disease event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (5.2% vs. 7.9%, OR 0.64; 8% vs. 11.7%, OR 0.66; and 9.2% vs. 13.4% OR 0.66; respectively, all p<0.01). The probability of cerebrovascular disease events at one, three, and five years in the ABT group were all significantly lower than in the NABT group (2% vs. 3.3%, OR 0.59; 3.5% vs. 5.7%, OR 0.59; and 4.2% vs. 6.8% OR 0.60; respectively, all p<0.01) and the probability of a peripheral artery disease event at one, three, and five years in the ABT group were also all significantly lower than in the NABT group event (2.8% vs. 4.5%, OR 0.62; 5.1% vs. 7.6%, OR 0.65; and 6.2% vs. 9.3% OR 0.65; respectively, all p<0.01). Conclusions ABT are associated with significantly fewer ASCVD events in the IBD patient population. Future studies examining the differential benefit of drug subclasses on ASCVD outcomes and mechanisms responsible for the ABT benefit, as well as prospective study designs have the potential to identify new therapeutic targets in IBD patients and with applicability beyond IBD patients.Table

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

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

The gut-microbiome derived phenylacetylglutamine predicts adverse events in patients with acute coronary syndromes

Abstract Background and Introduction The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is associated with incident cardiovascular events(1). Acute coronary syndromes (ACS) present a major health challenge, especially as population ages(2). Data from our group show increased PAG levels during aging in humans. However, the predictive potential of PAG for mortality and major adverse cardiovascular events (MACE) in patients (pts) with ACS is unknown. Purpose Here, we investigated the potential of PAG to predict ischemic and fatal events in pts with acute coronary syndromes (ACS). We also compared the predictive potential of PAG to another relevant gut-microbiota derived metabolite involved in CVD, namely Trimethylaminoxyde, (TMAO), and we evaluated their cumulative risk potential. Methods A total of 1’848 patients were enrolled in Cohort I of the SPUM-ACS study – a multi-center prospective ACS cohort study from Switzerland. Overall survival and incident MACE after 1 year follow-up were analyzed using Kaplan-Meier (KM) estimates and compared by log-rank test after patient stratification into PAG tertiles. Uni- and multivariable Cox-regression models were fit to calculate the hazard ratios for 1-year MACE in a crude model and adjusted model (adjusted for established confounders). Healthy controls served as additional controls. PAG plasma levels were quantified using LC-HRMS. Results The median PAG plasma level in the healthy control group was 1.76µM, whereas for the whole ACS patient population it was 1.92µM (Table 1). Pts in the third PAG tertile had a two times higher MACE rate and a four times higher mortality rate compared to pts in the first PAG tertile (p<0.001). (Table 2). PAG levels were significantly higher in pts who presented with MACE (2.63µM) or died (3.1µM) within the 1-year follow-up compared to the healthy control subjects (p<0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p<0.0001), while a negative association with eGFR was observed (r=-0.51, p<0.0001) (Figure 1B). KM estimates indicated that pts in the highest PAG tertile had significantly higher 1-year MACE risk relative to those with low levels (Figure 1C; p<0.001 log rank). Following multivariable adjustment, PAG remained an independent predictor for MACE at 1-year follow-up with a hazard ratio (HR) of 1.8 (95% CI, 1.1–3.2, p=0.048) (Figure 1D). KM estimates of both, high levels of PAG and high levels of TMAO together, indicate that the combination of these two detrimental metabolites leads to an even higher risk of 1-year MACE relative to lower levels (Figure 1E). Conclusion PAG is a novel and independent predictor of adverse outcomes in patients with ACS. This study indicates the role of the gut-microbiome and its metabolites in predicting ischemic and fatal outcomes of pts with established CVD.

Low chronotropic response in post-myocardial infarction exercise test predicts worse prognosis in patients with preserved or mildly reduced left ventricular ejection fraction

Abstract Background Chronotropic incompetence is common in post-myocardial infarction (MI) patients and is associated with reduced exercise capacity. However, its prognostic significance and a determination of threshold values for prognosis remain unclear. Methods & Results We assessed 96 post-MI patients 4 weeks after their initial event with left ventricular ejection fraction (LVEF) ≥ 40%. All patients underwent combined stress echocardiography and cardiopulmonary exercise tests. The chronotropic response was measured as a percent of the maximal predicted heart rate at peak exercise (%MPHR). Exclusion criteria included patients with exercise limitations for pulmonary or peripheral reasons and those who declined to complete the study. Follow-up was conducted in 86 patients. The primary outcome measured was a composite of all-cause mortality or hospitalization for ischemic heart disease events (acute MI, unstable angina, or revascularization procedures) or heart failure exacerbation. The median follow-up duration was 4.0 (IQR 2, 5.6) years. The median patient age was 60 (IQR 53, 65) years, 64% of patients were males, and 84% were on beta-blockers. Median LVEF was 57 (IQR 51, 62)%, and median peak VO2 was 19 (IQR 15, 22) mL/kg/min. There were 15 composite end-point events, including 3 deaths, during the follow-up period. The %MPHR threshold of 67% had the best predictive value with an area under the curve (AUC) of 77% for predicting the primary outcome (PPV 31%, NPV 97%, sensitivity 93%, specificity 55%). A significant difference (p = 0.0022) in the occurrence of the composite end-point was noted between patients with a %MPHR below versus above this threshold (Figure. Kaplan-Meier curves for survival free of primary outcome). In the multivariate Cox regression analysis adjusting for demographic, clinical variables, and beta-blocker doses, only chronotropic response and current smoking correlated with the primary end-point (Table. The Cox proportional hazards regression model for prediction of the primary outcome). Conclusions A low chronotropic response to exercise is a negative prognostic marker in post-myocardial infarction patients with either preserved or mildly reduced left ventricular ejection fraction.Figure.Table.

Risk score guided dual antiplatelet therapy duration in patients with acute coronary syndrome: insights from the FORCE-ACS registry

Abstract Background The use of risk scores to guide the duration of dual antiplatelet therapy(DAPT) in patients with acute coronary syndrome(ACS) is recommended in current guidelines, however clinical data on the impact of its prospective use is lacking. Purpose To compare risk-score guided DAPT duration to standard of care in ACS patients. Methods Since 2015, patients with ACS are enrolled in the prospective FORCE-ACS registry. In 2018, we implemented a risk score-guided approach for DAPT duration. In this analysis, we compared patients in which DAPT duration was guided by bleeding and ischemic risk assessment using PRECISE-DAPT-scores and DAPT-scores to a standard treatment group in a 1:4 ratio. In risk score-guided patients, high bleeding risk patients(HBR) were advised short DAPT(≤6 months); patients without HBR or high ischemic risk(HIR) were advised 12 months DAPT; and patients without HBR but with HIR were advised prolonged DAPT(≥30 months). In the standard treatment group DAPT duration was left at the discretion of the treating physician. Exclusion criteria included no DAPT or oral anticoagulation at discharge or implanted bio-vascular stents. Primary outcome was a composite of all-cause mortality, myocardial infarction(MI), stent thrombosis(ST), stroke and Bleeding Academic Research Consortium(BARC) 3 or 5 bleeding; a secondary composite ischemic outcome consisted of cardiovascular mortality, MI, ST and ischemic stroke. Kaplan-Meier plots with log-rank testing and Cox proportional hazard regression after adjustment of potential confounders were performed for the primary outcome. Sensitivity analyses were performed for patients included after implementation of the risk score-guided approach and for censoring events within the first six months. Results Between 2015 and 2020 8,009 patients were enrolled in the FORCE-ACS registry, of which 5,518 patients were included for analysis. The risk-score guided group(n=1,200) more often presented with ST-elevation MI, percutaneous coronary intervention or optimal medical therapy, while standard treatment patients(n=4,318) were older, more often had prior MI, prior revascularization, received coronary artery bypass grafting or conservative management. In the risk-score guided group, 15.7% had HBR, 46.4% were without HBR or HIR, and 37.9% showed HIR without HBR. The primary outcome was 6.3%(n=75) in risk score-guided patients versus 14.8%(n=637) in the standard treatment group (adjusted hazard ratio(HR) 0.47 [95%CI 0.36–0.61], p<0.001). These results remained consistent after sensitivity analyses (fig 1B). Both the composite ischemic outcome(HR 0.54 [95%CI 0.41–0.72] p<0.001) and BARC 3 or 5 bleeding (HR 0.23 [95%CI 0.08-0.63], p=0.004) were significantly lower in risk score-guided patients compared to the standard treatment group. Conclusion In this prospective analysis, risk-score guided DAPT duration showed a significant reduction of both ischemic and bleeding events compared to standard treatment.

Cardiac amyloidosis and left atrial appendage closure: a multicenter retrospective study

Abstract Background Thromboembolic stroke risk remains a clinical challenge in cardiac amyloidosis (CA) patients with atrial fibrillation because of the increased prevalence of left atrial appendage thrombi irrespective of CHA2DS2-VASc score and a higher prevalence of factors that increase the risk of bleeding with anticoagulation. Left atrial appendage closure (LAAC) is an effective option in patients with atrial fibrillation and high bleeding risk; however, data describing a LAAC strategy for stroke prevention in patients with CA is limited. Among non-CA patients, procedural success and serious complication rates are around 98% and 3% respectively. Purpose In this multicenter retrospective study, we aimed to investigate whether left atrial appendage closure (LAAC) could reduce the risk of bleeding complications and ischemic cerebrovascular events in patients with CA. Methods In an international multi-center retrospective study, patients with CA that underwent LAAC were included. The diagnosis of CA was established on the basis of histologic confirmation or advanced multimodality cardiac imaging as per current consensus statements. Results A total of 28 patients (93% male; 87% ATTR-CA; 13% AL-CA; mean age 80 years) met inclusion criteria. At baseline, mean CHA2DS2-VASc and HAS-BLED scores were 4 and 3 respectively, mean left ventricular ejection fraction was 50%, and mean indexed left atrial volume was 58 mL/m2. 21% of patients had a prior history of ischemic stroke, 14% prior history of hemorrhagic stroke, 7% prior transient ischemic attack, and 54% had a prior history of major or minor bleeding. Procedural success was achieved in 26 patients (93%) with procedural complications occurring in 2 patients (vascular access site bleeding and cardiac tamponade). Regarding in-hospital and follow-up complications, 0% ischemic stroke, 0% hemorrhagic stroke, and major or minor bleeding in 4% of patients. During follow up, device thrombosis occurred in only 1 patient. Conclusion LAAC is a feasible and effective alternative to anticoagulation in patients with CA and excessive bleeding risk, with procedural success and complication rates similar to reported studies of non-CA patients.

Thirty days clinical outcomes following stent implantation with aspirin-free prasugrel monotherapy in non-ST segment elevation myocardial infarction. Interim report from ASET-Japan pilot study

Abstract Background Dual antiplatelet therapy with a P2Y12 inhibitor, in addition to aspirin, is the standard therapy after percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) to prevent ischemic cardiovascular events. The Acetyl-Salicylic Elimination Trial (ASET) pilot studies conducted in Japan in patients with NSTE-ACS investigated the safety and feasibility of a low-dose prasugrel monotherapy after PCI. Purpose To ensure the safety of the patients, enrolment in the study was implemented only after confirmation of a successful procedure. The abstract reports our interim analysis, aimed at evaluating preliminary safety and feasibility. Methods The ASET-Japan pilot study was designed to explore the feasibility and safety of a low dose of prasugrel monotherapy (3.75mg/day), without adjunctive aspirin, after optimal PCI using Everolimus eluting stent (EES) in Japanese patients with non-ST-segment elevation acute coronary syndromes. The primary endpoint in the ASET-Japan NSTE-ACS (Phase 2) is a 12-month clinical outcome. The study is currently in the follow-up phase. All the target lesions were treated with a platinum-chromium everolimus-eluting stent. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis, and the primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding up to 12-month. If more than 3 events occurred, trial enrollment would have to be terminated by the data and safety monitoring board. Results One hundred one patients were enrolled after successful index PCI and completed a 30 days follow-up. The mean age was 69.1±12.3 years and 75.2% was male. The mean anatomical SYNTAX score was 7.9±4.7. Unstable angina (UAP) and NSTEMI were seen in 24.8% (25/101) and 75.2% (75/101) patients, respectively. According to the Braunwald classification, 8 percent of the patients were categorised as Class IA UAP, 48% as Class IB, 20% as Class IIB, 4% as Class IIIA and 20% as Class IIIB. In NSTEMI patients, the median (IQR) pre-procedural troponin value (cardiac Troponin T or I) was 2.79 (1.12 – 22.27) times the Upper Limit of Normal. According to the PRECISE DAPT score, 36.6% of patients were categorised as High Bleeding Risk (HBR) with scores above 25. At one month, the primary ischemic endpoints of cardiac death, target-vessel spontaneous MI or definite Stent thrombosis did not occur. Two patients (2.0%) had BARC type 3a bleeding. Conclusion Prasugrel monotherapy in the first 30 days following platinum-chromium everolimus-eluting stent deployment is a feasible and safe strategy in NSTE-ACS patients with simple anatomy and successful PCI.

Short versus conventional DAPT in patients undergoing PCI with ultra-thin DES by renal function: an analysis from the HOST-IDEA trial

Abstract Background Patients with impaired renal function are known to have an elevated risk of both ischemic and bleeding events following percutaneous coronary intervention (PCI). However, there is insufficient data available on the optimal duration of dual antiplatelet therapy (DAPT), especially with the latest generation of drug-eluting stent (DES)s. Objective We investigated to assess the efficacy and safety of abbreviated duration of DAPT in patients undergoing PCI with 3rd generation DESs based on their renal function. Methods In this prespecified subgroup analysis of the HOST-IDEA trial, a total of randomized 1997 patients with available baseline estimated glomerular filtration rate (eGFR) were categorized into three groups: high eGFR (>90 mL/min), intermediate eGFR (60 to 90 mL/min), and low eGFR (<60 mL/min). The primary outcome assessed during the 1-year follow-up period was net adverse clinical events (NACE). Ischemic and bleeding endpoints were also evaluated. Results Compared to intermediate or high eGFR groups, the low eGFR group resulted in significantly worse outcomes (P < 0.001). 3-6 month DAPT was associated with similar risk of NACE across all eGFR groups (High eGFR: HR: 0.91; 95% CI: 0.38-2.20; Intermediate eGFR: HR: 0.76; CI: 0.33-1.73; Low eGFR: HR: 0.99; CI: 0.51-1.92). There was also no significant difference in target lesion failure (HR: 0.95; CI: 0.32-2.83, HR: 0.77; CI: 0.29-2.06, and HR: 1.14; CI: 0.47-2.75) and major bleeding (HR: 0.84; CI: 0.19-3.74, HR: 0.59 CI: 0.14-2.48; and HR 0.83 CI: 0.34-2.05) among all stratified eGFR groups. This effect was also consistent in patients of end stage of renal disease (eGFR <15 mL/min). Conclusions In patients undergoing PCI with third generation DESs, short DAPT was comparable to conventional DAPT regardless of their baseline renal function.

Real-world analysis exploring the association between anti-hypertensive therapy with perindopril-based single-pill combinations (SPC) and cardiovascular outcomes and all-cause mortality in Italy

Abstract Background/Introduction A combination of blood pressure (BP)-lowering medications is recommended by guidelines as an effective strategy to obtain rapid and optimal BP control in hypertensive patients. However, the prescription of multiple BP-lowering medications increases the pill burden, potentially reducing medication adherence. Guidelines also recommend using single pill combinations(SPCs) containing ≥2 anti-hypertensive medications as a practical approach to simplify treatment schedules and possibly improve adherence. Yet, real-world evidence on the association between SPC or free combination of BP-lowering medications and hyperthensive patient outcome remains limited. Purpose We compared the association of SPC versus free-pill combination(free) on cardiovascular outcomes and all-cause mortality in hypertensive patients treated with perindopril(PER)-based therapies in real clinical practice in Italy. Methods A retrospective analysis was conducted using administrative databases covering 6.7 million health-assisted Italian residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, the study included patients prescribed with a combination of PER with amlodipine(AML) and/or indapamide(IND), either as SPC or free or mixed (SPC plus separate pill) combinations. Results The analysis included 24,476 hypertensive subjects receiving a PER-based therapy, 22,663 (93%) of them using SPC, 1458 (6%) free and 355 (1.4%) mixed. The last cohort was not included in the analysis due to the small sample size (N=355). The patients in the free cohort were significantly older than those in the SPC cohort (69.5±12.3 vs. 64.3±12.2 years, p<0.001), showed a higher number of pre-existing comorbidities (0.5±0.8 vs. 0.4±0.7, p<0.001), and received a larger number of different medications (pill burden: 1.2±1.7 vs. 0.7±1.3, p<0.001). To minimize selection bias, the groups were balanced with propensity score and inverse probability weighting (IPW), adjusting for baseline covariates, including comorbidity profile and pill burden. The IPW-adjusted Kaplan-Meier plots and Cox’s proportional hazard model (Table 1) revealed that, compared with SPC users, patients on free regimens had a significantly increased risk of all-cause mortality (36%, p<0.001), all cardiovascular events (45%, p<0.001), ischemic heart disease (29%, p<0.05), cerebrovascular events (84%, p<0.001), and occurrence of the composite outcome cardiovascular events/all-cause mortality (40%, p<0.001). Conclusions This real-world data from a large Italian administrative dataset suggested that PER-based anti-hypertensive therapy with SPC results in significant clinical benefits in terms of lowered risk of cardiovascular/cerebrovascular events and all-cause mortality. Reducing pill burden and simplifying therapeutic schedules is of crucial importance to maximize the potential benefits derived from the prescription of anti-hypertensive treatment.

The comparison of short-term dual antiplatelet therapy versus standard dual antiplatelet therapy in elderly patients with coronary artery disease who underwent percutaneous coronary intervention

Abstract Introduction Elderly patients are likely to have more underlying risk factors for bleeding and the bleeding risk increases with age although dual anti-platelet therapy (DAPT) is mandatory for patients who underwent percutaneous coronary intervention (PCI) for prevention of ischemic events. Therefore, elderly patients aged 75 or older are included as minor criteria for high bleeding risk, as defined by the Academic Research Consortium for High Bleeding Risk criteria. However, only limited data have been investigated of optimal duration of DAPT for patients aged 75 or older. Purpose The aim of this study is to evaluate optimal DAPT duration for elderly patients aged 75 and older. Methods We selected 1,571 patients aged 75 and older with coronary artery disease (CAD) from the pooled database among the 5 randomized controlled trials related to DAPT duration after PCI. DAPT was consisted of clopidogrel or ticagrelor in addition to aspirin. Short-term DAPT duration was defined as 1 to 3months, and standard DAPT duration was defined as 6 to 12months after PCI. Primary outcomes were net clinical adverse outcomes (NACE), composite of major cardiovascular and cerebrovascular adverse outcomes (MACCE) and TIMI major bleeding at 1 year. The inversed probability of treatment weighting (IPTW) analysis was performed to minimize selection bias effects of pooled database. Results The NACE was not significantly different between the short-term DAPT group (3.9%) and standard DAPT group (7.6%) (HR: 0.69, 95% CI: 0.46-1.04; p=0.076) (Figure A). Moreover, MACCE was not different in both groups. However, the significant reduction of bleeding risk was observed in short-term DAPT group (1.4%) than standard DAPT group (3.4%) (hazard ratio (HR): 0.40, 95% confidential interval (CI): 0.19-0.83; p=0.015) (Figure B). These results were consistent after multivariable Cox regression analysis and IPTW analysis. Conclusions Short-term DAPT duration (1 to 3months) was found to be superior to standard DAPT duration (6 to 12months) in terms of bleeding outcomes without the increased ischemic outcomes in patients aged 75 or older with CAD who underwent PCI.

The association of steatotic liver disease with recurrent ischemic events in patients with chronic coronary syndrome: a multicenter cohort study

Abstract Background/introduction A panel of multi-society experts has proposed new subcategories under the term steatotic liver disease (SLD), replacing the exclusive term non-alcoholic fatty liver disease with the new nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). However, the prognostic impact of SLD subtypes in patients with chronic coronary syndrome (CCS) remains unknown. Purpose We aimed to investigate the associations between SLD subtypes and recurrent event risks in CCS patients. Methods Our analysis included a total of 9,448 patients with CCS from a large multicenter nationwide cohort. Hepatic steatosis was defined as hepatic steatosis index ≥36 and ultrasound evidence. Patients were categorized into four groups based on the evidence of steatosis, cardiometabolic risk factors and alcohol intake: 1) no SLD; 2) MASLD; 3) MASLD with increased alcohol intake (MetALD) and 4) SLD with other causes. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, stroke and unplanned revascularization. Results The prevalence of no SLD, MASLD, MetALD and SLD with other causes in our population was 37.3%, 47.7%, 14.7% and 0.3%, respectively. During a median follow-up of 2.0 years, 759 (8.0%) MACCE events occurred. After multivariable adjustment, MASLD (HR 1.25, 95%CI 1.06-1.48), MetALD (HR 1.31, 95%CI 1.04-1.65) and SLD with other causes (HR 2.81, 95%CI 1.04-7.57) were all significantly associated with higher MACCE risks compared to no SLD. Conclusions A significant proportion of SLD was observed in CCS patients. Patients with various SLD subcategories all had higher risks of recurrent events.