2023 European Society of Cardiology guidelines for the management of acute coronary syndromes : Statement of endorsement by the NVVC.

This review discusses the new recommendations in the 2023 European Society of Cardiology guidelines on the management of acute coronary syndrome and provides a perspective on topics specific to clinical practice in the Netherlands, including pre-treatment, antiplatelet agent strategies, the use of risk scores and logistical considerations with regard to the timing of coronary angiography.

A novel risk score to identify the need for triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a post hoc analysis of the RE-DUAL PCI trial.

BACKGROUND: Current guidelines recommend treating atrial fibrillation (AF) patients who undergo percutaneous coronary intervention (PCI) with triple antithrombotic therapy (TAT) for up to one month in patients at high thrombotic risk. It is unclear how to select these high-risk patients. AIMS: The aim of this study was to identify patients at high thrombotic risk who might benefit from TAT over double antithrombotic therapy (DAT). METHODS: This study was a post hoc subanalysis of the RE-DUAL PCI trial. A Cox proportional hazards model was built by stepwise selection of plausible predictor variables for a composite ischaemic endpoint, defined as cardiovascular death, myocardial infarction (MI), stent thrombosis (ST) or ischaemic stroke. The effect of TAT versus DAT was calculated for those patients with the highest proportion of predicted thrombotic risk. A simplified risk score was constructed based on beta-coefficients. RESULTS: For 209 patients (7.7%) the composite ischaemic endpoint occurred during the first year. The simplified risk score contained six variables. In patients with a score ≥5 (n=154, 5.7%), a significant reduction in the composite of MI and ST was observed with TAT versus DAT (6.3% vs 21.0%, p=0.041), without a penalty in terms of bleeding. In patients at low thrombotic risk, a significant increase in bleeding was observed without a reduction of ischaemic events. CONCLUSIONS: Our findings support the use of DAT in the majority of patients. A small subgroup of patients might benefit from TAT and we propose a novel clinical risk score to select these patients.

Safety of Selective Intracoronary Hypothermia During Primary Percutaneous Coronary Intervention in Patients With Anterior STEMI.

OBJECTIVES: The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. METHODS: The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. RESULTS: In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50). CONCLUSIONS: Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial.

New Antithrombotic Drugs in Acute Coronary Syndrome.

In recent years, much progress has been made in the field of antithrombotic drugs in acute coronary syndrome (ACS) treatment, as reflected by the introduction of the more potent P2Y12-inhibitors prasugrel and ticagrelor, and novel forms of concomitant anticoagulation, such as fondaparinux and bivalirudin. However, despite substantial improvements in contemporary ACS treatment, there remains residual ischemic risk in this group and hence the need for even more effective antithrombotic drugs, while balancing antithrombotic efficacy against bleeding risk. This review discusses recently introduced and currently developed antiplatelet and anticoagulant drugs in ACS treatment.

Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction.

Morphine can delay absorption of P2Y12-inhibitors in ST-elevation myocardial infarction (STEMI) patients, which has the potential to expose these patients to increased stent thrombosis risk after primary percutaneous coronary intervention (PPCI). Limited evidence exists for pharmacotherapeutic strategies aiming to mitigate this risk. We evaluated the impact of guideline-driven 'routine' glycoprotein IIb/IIIa antagonist (GPI) use in morphine-treated patients undergoing PPCI. A total of 3224 consecutive STEMI patients undergoing PPCI at a large tertiary cardiac center between 2012 and 2017 were evaluated. GPI use and outcomes before and after introduction of a local guideline were compared, and rates of definite stent thrombosis were identified at 24 h and 30 days. GPI use increased from 42.4% to 69.9% after the introduction of the new guideline. Stent thrombosis occurred in 1.3% (26/1947) pre-guideline and 0.6% (7/1244) post-guideline (P = .037). Of the 33 stent thrombosis cases, 90% (27/30) had received morphine, of whom 85.2% (23/27) had not received adjunctive GPI. Complete records for assessing 30-day bleeding rates were only available in 374 patients and, in this subset, there was no significant difference in rates of GUSTO moderate or severe bleeding before vs. after introduction of the local guideline (1.7% vs 2.8%; P = .47) although, in both cohorts combined, any GUSTO bleeding was observed more frequently in GPI-treated patients (21.8%) compared to those not receiving a GPI (10.0%; P = .002). In conclusion, routine GPI use in morphine-treated STEMI patients undergoing PPCI appears to protect against stent thrombosis. Large-scale studies are needed to establish the overall risk-benefit of GPI therapy in morphine-treated PPCI patients and to assess alternative strategies for preventing acute stent thrombosis in these patients.

Measuring high on-treatment platelet reactivity in clinical practice; should we use a panel of platelet function tests?

: High on-treatment platelet reactivity (HPR) on P2Y12-inhibitors in patients treated with dual antiplatelet therapy is strongly associated with adverse ischaemic events. Studies have shown conflicting results with regard to the correlation and agreement between the different tests. Several assays are available to establish HPR. A composite advice based on more than one test might be a better way to identify HPR patients. To compare HPR rates and agreement between individual platelet function tests and a panel of three tests In our large percutaneous coronary intervention centre, all patients who suffered a stent thrombosis were invited back to a dedicated clinic. Platelet function testing was performed in all patients and matched control patients. HPR rates were compared between individual tests and with a composite comprised of three tests. A total of 242 patients were included, of whom in 193 patients all tests were available. HPR rates ranged from 14.6% [VerifyNow cut-off >235 platelet reactivity units (PRU)] to 49.7% (Vasodilator-Stimulated Phosphoprotein Assay). HPR according to the composite advice (≥2 out of 3 tests indicating HPR) was present in 29.8% of patients. The best correlation with the composite advice was observed with light transmittance aggregometry (kappa = 0.78) and VerifyNow (lower cut-off >208 PRU; kappa = 0.68). VerifyNow with cut-off more than 235 PRU identified the smallest proportion of patients with HPR, whereas Vasodilator-Stimulated Phosphoprotein Assay seemed to 'over-identify' HPR. In this real life patient cohort, a large variability was observed between four different platelet function tests. The use of a composite advice based on three tests is a promising alternative.

High risk of stent thrombosis in the first 6 months after coronary stenting: Do not discontinue clopidogrel early after ACS.

OBJECTIVES: To estimate the incidence of stent thrombosis (ST) after early discontinuation of clopidogrel. BACKGROUND: Premature discontinuation of clopidogrel is the strongest risk factor for ST. In contrast, recent studies suggest that shorter dual antiplatelet therapy (DAPT) can be discontinued as soon as 3 months after stenting. However, these studies included very few ACS patients and were not powered for ST. Hence, little is known about the occurrence of ST in high-risk populations when DAPT is discontinued early. METHODS: This is a subanalysis of The Dutch ST Registry 437 ST cases (mainly first-generation DES and BMS). Acute coronary syndrome was the indication for index-PCI in 74% of the patients. Clopidogrel discontinuation rates in ST patients and matched controls were used to calculate the absolute incidence of ST after early clopidogrel discontinuation. RESULTS: The overall rate of ST after cessation of clopidogrel was 4.6% (95%CI: 3.9-5.4%), as compared to 1.7% (95%CI: 1.5-1.9%) in patients who did not discontinue clopidogrel. The incidence of ST was 35.4% when clopidogrel was discontinued in the first 30 days after index-PCI declining to 11.7% when clopidogrel was discontinued in the first 180 days. CONCLUSIONS: This dedicated ST registry shows that ST rates were very high when clopidogrel was discontinued before 6 months after index-PCI and therefore suggests that clopidogrel discontinuation in the first 6 months after ACS should be avoided.

Effect of Tailored Antiplatelet Therapy to Reduce Recurrent Stent Thrombosis and Cardiac Death After a First Episode of Stent Thrombosis.

The recurrence rate of coronary stent thrombosis (ST) is high. Patients with ST often demonstrate high on-treatment platelet reactivity (HPR). It is suggested that patients at high risk of atherothrombotic events, that is patients with ST, could benefit from tailored antiplatelet therapy (APT). This study evaluated whether tailored APT, based on platelet function testing, reduced the rate of cardiac death and/or recurrent ST at 1 year after ST, compared with a historical cohort of patients with ST without tailored APT. Patients with definite ST visited our ST outpatient clinic for platelet function testing and tailored APT. These patients were evenly matched to a historical cohort of patients with ST treated with aspirin and clopidogrel, which was the standard of care at that time. The primary end point was a composite of cardiac death and/or recurrent definite ST after 1 year. In total, 113 patients who visited the outpatient clinic were included. HPR was observed in 46%, 6.7%, and 0% of the patients on clopidogrel, prasugrel, and ticagrelor, respectively. After tailored APT, 93% of the patients with HPR demonstrated normal platelet reactivity. The primary end point was observed in 4 patients who had visited the outpatient clinic and in 23 patients of the historical cohort. The odds ratio of tailored APT on the primary end point was 0.26 (95% confidence interval 0.11 to 0.64, p = 0.003), independent from the possible confounders prior myocardial infarction and stent type. In conclusion, the outpatient ST clinic was associated with lower HPR rates in patients with ST after tailored APT. Patients who visited the ST outpatient clinic had a lower risk for cardiac death and/or recurrent ST compared with a historical cohort of patients with ST without tailored APT. Regarding the high HPR rate in patients with ST on clopidogrel, these patients might benefit in particular from the strategy of tailored APT.

Triggering mechanisms of stent thrombosis.

AIMS: The aim of this study was to determine the role of potential triggers of stent thrombosis. METHODS AND RESULTS: Patients (n = 437) with "definite" ST were recruited consecutively in the setting of a large multicentre observational cohort study. Patients were interviewed with validated questionnaires to identify one of the following triggers: i) timing of onset of ST, ii) performance of vigorous ( ≥ 6 MET) physical activity in the two hours preceding ST, iii) presence of emotional stress (experiencing a serious life event in the 14 days preceding the ST or feelings of anger in the 12 hours of ST) and iv) presence of a documented active infection at the time of ST. A total of 363 patients (83.1%) were able to supply adequate information. A significant trigger was identified in 83 patients (22.9%). Analysis of the different categories according to timing of ST revealed a higher prevalence of triggers with an increasing time-interval between index PCI and ST. Analysis of circadian variation showed a steep peak incidence from 7 am-12 pm. CONCLUSIONS: Triggering mechanisms such as time of the day, physical exertion, emotional stress and infection may play an important role in a considerable number of patients presenting with ST, in particular in patients with (very) late ST.

Coronary stent thrombosis in the current era: challenges and opportunities for treatment.

OPINION STATEMENT: The introduction of the drug-eluting stent has raised concerns regarding the occurrence of stent thrombosis (ST), particularly late (and very late) thrombosis. This renewed attention shows that ST remains a major concern after implantation of both bare metal and drug-eluting stents. Cardiologists should be aware of this dreadful complication, because it is associated with substantial morbidity and mortality. Numerous clinical, procedural, and angiographic risk factors have been identified. Moreover, the influence of novel determinants, such as high on-treatment reactivity, genetic predisposition, and the stent's direct effects on the (healing of the) vessel wall, now are recognized. Consequently, the pathophysiology of ST has evolved into a complex multifactorial model. This broader understanding of the pathophysiology of ST enables cardiologists to perform extensive risk stratification to identify patients at higher risk and provides clues to important treatment options. The core of primary prevention after stent implantation, as well as secondary prevention after ST, should consist of a) the prevention of modifiable risk factors and b) optimal individualized treatment for each patient. Future developments, such as genetic bedside testing, point-of-care platelet testing, and sophisticated imaging modalities, might aid in this approach.

CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study.

AIMS: despite treatment with clopidogrel on top of aspirin, stent thrombosis (ST) still occurs being the most serious complication after percutaneous coronary interventions (PCIs). In this study, we aimed to determine the effect of variations in genes involved in the absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C19*2 and *3, CYP2C9*2 and *3, CYP3A4*1B and CYP3A5*3), and pharmacodynamics (P2Y1 A1622G) of clopidogrel on the occurrence of ST. METHODS AND RESULTS: the selected genetic variants were assessed in 176 subjects who developed ST while on dual antiplatelet therapy with aspirin and clopidogrel and in 420 control subjects who did not develop adverse cardiovascular events, including ST, within 1 year after stenting. The timing of the definite ST was acute in 66, subacute in 87, and late in 23 cases. The presence of the CYP2C19*2 and CYP2C9*3 variant alleles was significantly associated with ST (OR(adj): 1.7, 95% CI: 1.0-2.6, P = 0.018 and OR(adj): 2.4, 95% CI: 1.0-5.5, P = 0.043, respectively). The influence of CYP2C19*2 (OR(adj): 2.5, 95% CI: 1.1-5.5, P = 0.026) and CYP2C9*3 (OR(adj): 3.3, 95% CI: 1.1-9.9, P = 0.031) was most strongly associated with subacute ST. No significant associations of the other genetic variations and the occurrence of ST were found. CONCLUSION: carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk on ST after PCI.

Vigorous exercise as a triggering mechanism for late stent thrombosis: A description of three cases.

Although (very) late coronary stent thrombosis is a rare complication after percutaneous coronary interventions (PCI), its consequences are devastating with a high morbidity and mortality. Previous studies have identified several clinical, procedural and angiographic characteristics that are associated with stent thrombosis but little is known about the underlying mechanisms that induce, provoke or trigger the of stent thrombosis. In the present paper, we describe three patients who suffered from a stent thrombosis immediately after vigorous exercise. Patient 1 suffered a stent thrombosis (ST) after performing an in-hospital bicycle ergometer test, 6 weeks after an acute coronary syndrome. Patient 2 suffered from ST immediately following his first excessive endurance cycling tour, more than 2 years after myocardial infarction. Patient 3 suffered ST while performing vigorous exercise on a bicycle ergometer in a fitness centre. These findings implicate that ST might be triggered by vigorous exercise, especially in untrained patients. Further research after triggering mechanisms of ST is urgently warranted.

Time does not heal every wound: coronary stent thrombosis of a bare-metal stent more than one decade after its implantation.

In the present report, we describe a unique case of very late stent thrombosis with a bare-metal stent that occurred more than a decade after stent implantation. Potential explanations for the late stent thrombosis are non-compliance to aspirin, late acquired malapposition of the stent, progression of atherosclerosis or in-stent restenosis. In our patient, none of these explanations seems to have played a role. Although the occurrence of (very) late stent thrombosis is not uncommon with drug-eluting stent (DES), it is rather unusual with bare-metal stent (BMS). Nevertheless, cardiologists should be aware of the potential complication of late stent thrombosis, even with bare-metal stents.

Long-term clinical outcome after a first angiographically confirmed coronary stent thrombosis: an analysis of 431 cases.

BACKGROUND: There are limited data on the long-term clinical outcome after an angiographically confirmed (definite) stent thrombosis (ST). METHODS AND RESULTS: Four hundred thirty-one consecutive patients with a definite ST were enrolled in this multicenter registry. The primary end point was the composite of cardiac death and definite recurrent ST. Secondary end points were all-cause death, cardiac death, definite recurrent ST, definite and probable recurrent ST, any myocardial infarction, and any target-vessel revascularization. The primary end point occurred in 111 patients after a median follow-up of 27.1 months. The estimated cumulative event rates at 30 days and 1, 2, and 3 years were 18.0%, 23.6%, 25.2%, and 27.9%, respectively. The cumulative incidence rates of definite recurrent ST, definite or probable recurrent ST, any myocardial infarction, and any target-vessel revascularization were 18.8%, 20.1%, 21.3%, and 32.0%, respectively, at the longest available follow-up. Independent predictors for the primary end point were diabetes mellitus, total stent length, severe calcification, American College of Cardiology/American Heart Association B2-C lesions, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after percutaneous coronary intervention, and left ventricular ejection fraction <45%. The implantation of an additional coronary stent during the first ST was also associated with unfavorable outcome. Clinical outcome was not affected by the type of previously implanted stent (drug-eluting or bare-metal stent) or the category of ST (early versus late). CONCLUSIONS: The long-term clinical outcome after a first definite ST is unfavorable, with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction <45%, long total stent length, complex coronary lesions, TIMI flow grade <3 after percutaneous coronary intervention, and implantation of an additional coronary stent during the emergent percutaneous coronary intervention for the ST were associated with this unfavorable outcome.

Extended-spectrum-beta-lactamase production in a Salmonella enterica serotype Typhi strain from the Philippines.

A Salmonella enterica serotype Typhi strain was cultured from blood and fecal samples from a 54-year-old man with fever and diarrhea. He had returned from travel to the Philippines a few days earlier. Phenotypic and genotypic analysis confirmed the production of the SHV-12 extended-spectrum beta-lactamase.