bluuebunny/crossref_metadata_2025 huggingface dataset:
Myeloid differentiation factor 2 inhibitor and N-acetyl cysteine synergistically reduced left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury
Authors: Apaijai N , Vongsfak J , Singhanat K , Arunsak B , Samneong N , Maneechote C , Chunchai T , Chattipakorn S , Chattipakorn N
Published: October 2022

Background

Myeloid differentiation factor 2 inhibitor (MD2i) is a novel anti-inflammatory agent that exerts favorable outcomes in various diseases including cardiac ischemia/reperfusion (I/R) injury. However, whether a potent antioxidant N-acetyl cysteine (NAC) can augment the beneficial effects of MD2i in rats with cardiac I/R injury have never been investigated.

Purpose

We tested the hypothesis that NAC increases the beneficial effects of MD2i against cardiac I/R injury in rats.

Methods

Rats were divided into either a sham (n=6) or cardiac I/R group (n=72). Rats in the I/R group received one of the following 6 treatments (n=12 each) at the onset of reperfusion: vehicle, MD2i at 20 and 40 mg/kg, NAC at 75 and 150 mg/kg, and combined MD2i 20 mg/kg with NAC 150 mg/kg. Left ventricular (LV) function, infarct size, arrhythmia score, and cardiac mitochondrial function and dynamics were determined.

Results

Myocardial infarction, LV dysfunction, and cardiac arrhythmias were observed in rats with cardiac I/R injury, along with mitochondrial dysfunction (Fig. 1). Treatment with MD2i at either 20 or 40 mg/kg effectively reduced LV dysfunction but failed to reduce the infarct size (Fig. 1). NAC at 150 mg/kg, but not at 75 mg/kg, significantly decreased both LV dysfunction and infarct size following cardiac I/R injury (Fig. 1). However, combined treatment exerted even greater efficacy in reducing cardiac I/R injury than monotherapy, through a greater reduction of cardiac mitochondrial dysfunction and mitochondrial fission (Fig. 1). However, no benefit on reducing the arrhythmia score in all groups.

Conclusion

Combined MD2i and NAC treatment exerted a superior cardioprotective effect against cardiac I/R injury than either monotherapy regimen via an improved cardiac mitochondrial function.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. NSTDA Research Chair Grant from the National Science and Technology Development Agency Thailand2. National Research Council of Thailand
Ticagrelor or prasugrel in patients with acute coronary syndrome and high bleeding risk
Authors: Lahu S , Presch A , Ndrepepa G , Bernlochner I , Joner M , Xhepa E , Kufner S , Sager H B , Mayer K , Kessler T , Laugwitz K L , Schunkert H , Neumann F J , Kastrati A , Cassese S
Published: October 2022

Background

The relative efficacy and safety of more potent P2Y12 inhibitors in patients with acute coronary syndrome (ACS) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI) remains unclear.

Purpose

To study the treatment effect of ticagrelor and prasugrel in PCI patients presenting with ACS and HBR.

Methods

This post-hoc analysis of the ISAR-REACT 5 trial included patients with ACS undergoing PCI, randomized to ticagrelor or prasugrel, in whom HBR was defined as per Academic Research Consortium criteria. The primary (efficacy) endpoint was the composite of all-cause death, myocardial infarction, or stroke. The secondary (safety) endpoint was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Outcomes were assessed 12 months after randomisation.

Results

Out of the 3,239 patients included in this analysis, 486 fulfilled the criteria for ARC-HBR definition (HBR group; ticagrelor, n=230 and prasugrel, n=256), whilst 2,753 did not (non-HBR group; ticagrelor, n=1,375 and prasugrel, n=1,378). Compared to the non-HBR group, the HBR group had a higher risk for the primary (hazard ratio [HR]=3.57, 95% confidence interval [CI], 2.79–4.57, p<0.001), and secondary endpoint (HR=2.94 [2.17–3.99], p<0.001). In the HBR group, the primary (HR=1.09; [0.73–1.62]) and secondary (HR=1.18 [0.67–2.08]) endpoints were not statistically different between patients assigned to ticagrelor and prasugrel. In the non-HBR group, the primary endpoint (HR=1.62 [1.19–2.20]) occurred more frequently in patients assigned to ticagrelor as compared to patients assigned to prasugrel, without difference in safety (HR=1.08 [0.74–1.58]). There was no treatment allocation-by-HBR status interaction with respect to the primary (p for interaction = 0.123), or secondary (p for interaction = 0.803) endpoints.

Conclusions

In patients with ACS undergoing PCI, HBR status increased both ischemic and bleeding risks without significant impact on the relative efficacy or safety of ticagrelor versus prasugrel. These results warrant confirmation in larger cohorts.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Center for Cardiovascular Research (DZHK)Deutsches Herzzentrum München
Lipoprotein(a) and the effect of alirocumab on coronary and non-coronary revascularization following acute coronary syndrome
Authors: Steg P , Szarek M , Valgimigli M , Islam S , Zeiher A M , Bhatt D L , Bittner V A , Diaz R , Goodman S G , Harrington R A , Jukema J W , Pordy R , Scemama M , White H D , Schwartz G G
Published: October 2022

Background

Many patients require arterial revascularization after an index ACS. Lipoprotein(a) is thought to play a pathogenic role in atherothrombosis. In the ODYSSEY OUTCOMES trial, the PCSK9 inhibitor alirocumab reduced major adverse cardiovascular events after ACS, with greater reduction among those with higher lipoprotein(a).

Objectives

We determined whether the risk of first coronary or any (coronary, peripheral artery or carotid) revascularization after ACS was modified by the level of lipoprotein(a) and treatment with alirocumab or placebo.

Methods

The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with ACS and elevated atherogenic lipoproteins despite optimized statin treatment. Treatment effects were summarized by competing-risks proportional hazard models.

Results

A total of 1559 (8.2%) patients had coronary, 204 (1.1%) peripheral artery, and 40 (0.2%) carotid revascularization after randomization. Alirocumab reduced first coronary revascularization (9.6% vs. 11.3% at 4 years; hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.80–0.97; p=0.01) and any first revascularization (10.8% vs. 13.0%; HR 0.85, 95% CI 0.78–0.94; p=0.001). Baseline lipoprotein(a) quartile was directly associated with risk of coronary or any revascularization in the placebo arm (ptrend <0.0001) and inversely related to treatment HRs (ptrend <0.001). The greatest benefits of alirocumab on coronary or any revascularization were observed in patients with baseline lipoprotein(a) in the top quartile (≥59.6 mg/dL) (figures).

Conclusions

Alirocumab reduced revascularization after ACS. The risk of revascularization and reduction in that risk with alirocumab were greatest in patients with elevated lipoprotein(a) at baseline.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): SanofiRegeneron Pharmaceuticals
Comparison between ticagrelor and clopidogrel in high bleeding risk patients with acute coronary syndrome
Authors: Tjerkaski J , Jernberg T , Alfredsson J , Erlinge D , James S , Lindahl B , Mohammad M A , Omerovic E , Venetsanos D , Szummer K
Published: October 2022

Background

Potent antiplatelet agents such as ticagrelor are associated with a lower risk of ischemic events than clopidogrel in patients with acute coronary syndrome (ACS). However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in individuals who have a high bleeding risk (HBR). This study aimed to assess treatment outcomes following dual antiplatelet therapy (DAPT) using either ticagrelor or clopidogrel in ACS patients with HBR.

Methods

All HBR patients enrolled in the SWEDEHEART registry who were discharged with DAPT using ticagrelor or clopidogrel following ACS between 2010 and 2017 were included in this study. Bleeding risk was assessed using the 4-item PRECISE-DAPT score, which consists of age, prior bleeding, haemoglobin concentration and creatinine clearance. HBR was defined as a PRECISE-DAPT score ≥25. Inverse-probability of treatment weighting was used to adjust for baseline differences between the treatment groups. The main analysis consisted of a doubly robust estimation of causal effect using Cox proportional hazards models. Data on major bleeding, recurrent myocardial infarction (MI), ischemic stroke and all-cause mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, ischemic stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and major bleeding.

Results

Of all ACS patients, 36% (n=25,042) had a PRECISE-DAPT score ≥25. Approximately half of the study participants were treated with ticagrelor (n=11,848). Ticagrelor reduced the risk of MI (hazard ratio [HR], 0.82 [95% CI 0.74–0.91]), ischemic stroke (HR, 0.73 [95% CI 0.60–0.88]) and MACE (HR, 0.90 [95% CI 0.84–0.97]), while also increasing the risk of major bleeding compared to clopidogrel (HR, 1.30 [95% CI 1.16–1.47]). We found no significant differences in all-cause mortality (HR 1.02 [95% CI 0.92–1.12]) and NACE (HR 0.98 [95% CI 0.92–1.05]).

Conclusions

Ticagrelor was associated with a lower risk of recurrent ischemic events, but a higher risk of major bleeding compared to clopidogrel. There were no significant differences in all-cause mortality and NACE between the treatment groups. These results suggest that more potent antiplatelet agents might not be superior to clopidogrel in ACS patients with HBR.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Stockholm county council
Effect of alirocumab added to high-Intensity statin therapy on endothelial function in patients with acute myocardial infarction: a sub-study of the randomized placebo-controlled PACMAN-AMI trial
Authors: Rexhaj E , Soria R , Baer S , Kavaliauskaite R , Yasushi U , Tatsuhiko O , Temperli F , Shibutani H , Siontis Cm G , Haener D J , Stortecky S , Windecker S , Koskinas C K , Losdat S , Raeber L
Published: October 2022

Background

Endothelial dysfunction is involved early in the development of vascular dysfunction leading to atherosclerosis and cardiovascular diseases. Statins have shown to improve endothelial function. The role of the protein convertase subtilisin/kexin type 9-inhibitor (PCSK9) alirocumab on endothelial function among patients with acute myocardial infarction (AMI) remains unknown.

Purpose

We investigated the effect of alirocumab on endothelial function among AMI patients receiving PCSK9i alirocumab in addition to high intensity statin therapy.

Methods

This is a pre-specified, sub-study nested within the PACMAN-AMI (effects of the PCSK9 antibody AliroCuMab on coronary Atherosclerosis in patieNts with Acute Myocardial Infarction) trial, a randomized trial that compared the effects of biweekly PCSK9-inhibitor alirocumab 150 mg vs. placebo, initiated within 24h of presentation in patients with AMI on top of high-intensity statin. Patients recruited at Bern University Hospital and adherent to the study drug (alirocumab or placebo) were analysed for the current study. Endothelial function was assessed by flow mediated dilation (FMD) of the brachial artery at week 4 and 52 after treatment initiation.

Results

Among 139 patients (68 alirocumab, 71 placebo) completing the sub-study, baseline characteristics were well balanced between groups (alirocumab vs. placebo: mean age 57.5±10.1 years vs. 58.7±8.4 years, p=0.45; mean LDL-C 4.03±0.93 mmol/L vs. 4.05±0.74 mmol/L, p=NS). At week 52 LDL-C levels decreased to 0.65±0.71 mmol/L in the alirocumab group and to 1.98±0.71 mmol/L in the placebo group (p<0.001). There was no difference in FMD at 52 weeks in the alirocumab (5.44±2.24%) versus placebo (5.45±2.19%) group (between groups difference FMD, −0.21% (95% CI −077 to 0.35), p=0.47). Compared to baseline, follow-up FMD was improved in both groups (from 4.52±1.87 to 5.44±2.24%, p<0.001 in the alirocumab group and from 4.32±1.62 to 5.45±2.19%, p<0.001 in the placebo group).

Conclusion

Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy did not result in additional improvement of endothelial function after 52 weeks of treatment.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): The PACMAN-AMI study was supported by a research grant from Sanofi, Regeneron and Infraredx. This substudy was funded by the University of Bern.
Efficacy and safety of proprotein covertase subtilisin/kexin type 9 inhibitors among patients with acute coronary syndrome: a meta-analysis of randomized controlled trials
Authors: Delgado S , Tiongco R H
Published: October 2022

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have formed part of the armamentarium of lipid-lowering therapy, most especially low-density lipoprotein-cholesterol (LDL-C) reduction, which in turn decreases the risk of atherosclerotic cardiovascular diseases and adverse cardiovascular events. However, studies are sparse on the benefit of initiating PCSK9 inhibitors during the early phase of an acute coronary sydrome (ACS).

Purpose

The objective of this meta-analysis is to investigate the efficacy and safety of the PCSK9 inhibitors evolocumab and alirocumab in the acute setting of an ACS.

Methods

A systematic search for randomized controlled trials (RCTs) that involve the use of PCSK9 inhibitors in ACS was done using MEDLINE/PubMed and Cochrane Library.

Results

Three RCTs (n=385 participants) were included in this meta-analysis comparing PCSK9 inhibitors versus placebo in patients hospitalized for ACS. Among patients being managed for ACS, PCSK9 inhibitors demonstrated a greater reduction in LDL-C compared to placebo as early as day 3 (WMD −41.65%, 95% CI [−60.09, −23.21], p<0.00001), and was maintained until week 4 (WMD −45.67%, 95% CI [−64.82, −26.53], p<0.00001). The occurrence of adverse events did not significantly differ between the two groups in terms of hospitalization for recurrent ACS (OR 0.99, 95% CI 0.10–9.98, p=1.0), hospitalization for heart failure (OR 6.18, 95% CI 0.26–146.78, p=0.26), or cerebrovascular events (OR 3.12, 95% CI 0.31–31.30, p=0.33).

Conclusion

In patients admitted for ACS, the early administration of PCSK9 inhibitors such as evolocumab and alirocumab during the first 24 hours of hospitalization resulted in a rapid and significant reduction of LDL-C without any significant adverse event as compared to placebo. Further validation of the role of PCSK9 inhibitors in the setting of ACS is needed to robustly investigate its contribution in improving hard cardiovascular outcomes.

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): St. Luke's Medical Center Global City
Infarct size, inflammatory burden and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry
Authors: Sansonetti A , Paolisso P , Bergamaschi L , Santulli G , Gallinoro E , Cesaro A , Gragnano F , Sardu C , Mileva N , Mauro C , Vassilev D , Marfella R , Calabro' P , Barbato E , Pizzi C
Published: October 2022

Background

Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) with pleiotropic beneficial effects. Nowadays, the inflammation response in the setting of acute myocardial infarction (AMI) has been proposed as a potential pharmacological intervention target. In this setting, we tested the hypothesis that the SGLT2-I displays anti-inflammatory effect along with glucose-lowering properties. We investigated the relationship between stress hyperglycemia, inflammation burden and infarct size in a cohort of type 2 diabetic AMI patients treated with SGLT2-I versus other oral anti-diabetic (OAD) agents alone.

Methods

In this multicenter international registry, all diabetic patients with AMI treated with percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, patients were divided into those receiving SGLT2-I versus other OAD agents alone. Patients on insulin therapy alone or combined with OAD agents were excluded from the study. The following inflammatory markers were evaluated at different time points: total white blood cell, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR), C-reactive protein. Infarct size was assessed by peak troponin levels and echocardiographic parameters.

Results

The final study population consisted of 583 patients hospitalized for AMI (both STEMI and NSTEMI) classified as SGLT2-I users (n=98) versus other OAD agents alone (n=485). Admission hyperglycemia was more prevalent among the other OAD agents group. Reduced infarct size was detected in patients treated with SGLT2-I compared to those treated with other OAD agents alone. Both at admission, and after 24 hours, inflammatory indices were significantly higher in patients treated with other OAD agents alone, with a significant increase in neutrophils levels at 24 hours, compared to the SGLT2-I group. In multivariate analysis, SGLT2-I emerged as a significant predictor of reduced inflammatory response (OR 0.45, 95% CI 0.27–0.75, p=0.002), together with peak troponin values, independently of age, admission creatinine values and admission glycemia.

Conclusions

Type 2 Diabetic patients hospitalized for AMI and receiving SGLT2-I exhibited modest inflammatory response and myocardial damage/infarct size compared to other OAD agents alone, independently of glucose-metabolic control. Our findings pave the way for new pathophysiological and therapeutic insights regarding the cardioprotective effect of SGLT2-I in the setting of coronary artery disease.

Funding Acknowledgement

Type of funding sources: None.
Long-term assessment and target achievement of LDL-C and systolic blood pressure in primary care after acute coronary syndrome
Authors: Schubert J , Svensson M , Denstedt G , Johnston N , Cars T , Gustafsson S , Schalin L , Hagstrom E
Published: October 2022

Background

Hospital-based cardiac rehabilitation and risk factor control decreases the risk of recurrent events after acute coronary syndrome (ACS). Little is known on long-term assessment and target achievement after referral to primary care. Patients with diabetes, regardless of ACS, have yearly follow-up visits in primary care, whereas there is no structured follow-up after ACS for patients without diabetes.

Purpose

To describe long-term assessment and target achievement of LDL-C and systolic blood pressure (SBP) in ACS patients after referral to primary care. Further, to compare patients with and without diabetes at the time of index ACS.

Methods

A non-interventional population-based observational study of patients with first ever ACS in a Swedish region with 390,000 inhabitants. Data on clinical measurements after ACS were collected from the electronic medical records between 2012 and 2020. Patients were followed until new ACS event, death, moving out of the county, or end of study. Target levels studied were LDL-C <1.8 mmol/L and SBP <140 mmHg. The same assessments with the addition of target levels of HbA1c ≤70 mmol/mol were evaluated in patients with diabetes.

Results

Median follow-up was 2.9 years (inter quartile range [IQR]: 1.0–5.4) and 4,733 patients were detected. Median age was 72 years (IQR 63–80) and 34% were female. Follow-up data were available for 3,579 (76%) patients any time during the first, 2,891 (61%) during the second, and 2,308 (49%) during the third year after the index ACS event. The number of patients with diabetes was 1311 (28%), and of these 921, 723, and 562 could be followed for the first, second, and third year. During the first three years, 898 (19%) of all patients with available follow-up died.

The proportion of patients with assessments of LDL-C and SBP declined for each year of follow-up and target achievement was low (Table). Among patients with diabetes a larger proportion had measurements for LDL-C and SBP, while the target achievement was similar to that of the whole study population. HbA1c was measured equally frequently as SBP and was at target in 81% of patients with diabetes during the three years of follow-up (Table).

Conclusion

The proportion of patients with follow-up assessment and measurements in primary care declined each year after the index ACS event. Patients with diabetes had more frequent LDL-C and SBP measurements but the same low target achievement after an ACS compared with patients without diabetes. This could potentially be due to an increased focus on glycaemic control at these visits. A structured long-term follow-up for ACS patients in primary care might improve both assessment and target achievement and prevent recurrent ACS events.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AmgenSwedish Heart Lung Foundation
Prevalence of reaching target low-density lipoprotein cholesterol (LDL-C) in very high-risk patients using high intensity lipid-modifying therapy
Authors: Omar Khader A , Van Der Brug S , Liem A , Hamer B , Groenemeijer B , Martens F , Alings M
Published: October 2022

Background

Hyperlipidemia is an important risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease: the longer LDL-C remains low, the better. We studied the effect of implementing a guideline based, stepwise approach of lipid-modifying therapy to achieve target LDL-C levels in very high-risk patients in daily clinical practice in the Netherlands.

Methods

Nine hundred and ninety-nine (999) patients with a type I (N)STEMI and a history of Atherosclerotic Cardiovascular Disease and/or Diabetes mellitus II were included. Patients with LDL-C >1.8 mmol/L were treated with high-intensity statin (HIST) monotherapy. If target LDL-C level was not reached, first ezetimibe and subsequently a PCSK9i was added. The primary objective was to assess the prevalence of reaching LDL-C ≤1.8mmol/L with HIST and/or ezetimibe.

Results

Nine hundred and thirty-nine (939) patients were treated with HIST and/or ezetimibe, of whom 89% reached LDL-C ≤1.8 mmol/L. Yet thirty four (34) of the 40 patients (85%) who received additional treatment with PCSK9i, reached the target LDL. After treatment with HIST, HIST plus ezetimibe, and HIST plus ezetimibe and PCSK9i in the per protocol population the cumulative prevalence of reaching target LDL-C was 71%, 89% and 99% respectively.

Conclusion

Using an ESC guideline-based flowchart with stepwise intensification of lipid-lowering drugs, using HIST and/or ezetimibe, 89% of the very high-risk patients reached an LDL-C ≤1.8 mmol/L in 57 days ± 38 (mean ± SD). Including patients in whom additional PCSK9i was started, success rate of meeting target LDL-C rose to 99%.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Sanofi-Aventis Netherlands B.V.
Association of malnutrition with in-hospital and long-term outcomes among ST-elevation myocardial infarction patients receiving primary PCI
Authors: Hosseini F , Pitcher I , Kang M , MacKay M , Singer J , Lee T , Madden K , Cairns J , Wong G , Fordyce C
Published: October 2022

Background

The impact of malnutrition on outcomes in a contemporary ST-segment-elevation myocardial infarction (STEMI) population is unclear. We hypothesized that malnutrition severity amongst STEMI patients undergoing primary percutaneous coronary intervention (pPCI) is associated with worse long-term outcomes.

Purpose

The aim of this study was 2-fold: 1) to establish the prevalence of malnutrition among STEMI patients undergoing pPCI; 2) to determine the association of malnutrition severity on in-hospital and 1-year outcomes in STEMI patients receiving pPCI

Methods

We retrospectively identified 1,169 STEMI patients of age ≥65 years who had received pPCI (2013–2020). Patients who had presented with out-of-hospital cardiac arrest or those who received fibrinolytic therapy were excluded. The Controlling Nutritional Status (CONUT) score, based on serum albumin, total cholesterol and lymphocyte count, was used as a tool to assess the nutritional status of included patients. Malnourished patients were defined as those with a CONUT score of 5 to 12. To account for the impact of frailty, a frailty index (FI) was determined using the health deficit accumulation model (Table 1). The primary outcome was 1-year all-cause mortality. The secondary outcome was a composite of in-hospital heart failure, cardiogenic shock, re-infarction, major bleeding, stroke, and all-cause mortality. A multivariable model adjusting for baseline covariates, including frailty index score, was performed (Figure 1).

Results

Among 1,169 STEMI patients receiving pPCI, 315 (26.9%) were classified as malnourished. Malnourished patients were older (mean 77.4 vs. 76.0 years, p=0.009) and had a higher comorbidity burden. After multivariable adjustment, worsening malnutrition was associated with increased 1-year all-cause mortality (odds ratio [OR] = 1.29, p<0.001). Worsening malnutrition was also associated with a higher incidence of the in-hospital composite adverse outcome (OR = 1.12, p=0.003) and increased in-hospital all-cause mortality (OR=1.41, p<0.001).

Conclusion

Among STEMI patients receiving pPCI, 1 in 4 were malnourished. Malnutrition was associated with increased rate of in-hospital composite adverse outcome and worse long-term outcomes, even when accounting for frailty. Efforts to routinely identify malnourished STEMI patients and to implement best practices to reduce the risk of adverse events in this vulnerable population are warranted.

Funding Acknowledgement

Type of funding sources: None.
Specific characteristics of STEMI in COVID-19 patients and their practical implications: a systematic review
Authors: Gitto M , Novelli L , Cozzi O , Reimers B , Condorelli G , Stefanini G G
Published: October 2022

Introduction

STEMI is one of the cardiac emergencies whose management has been mostly challenged by the COVID-19 pandemic. Patients presenting with the “lethal combo” of STEMI and concomitant SARS-CoV-2 infection have faced dramatic issues related to need for self-isolation, systemic inflammation with multi-organ disease, and difficulties to obtain timely diagnosis and treatment.

Methods

We performed a systematic search of three electronic databases from February 1st 2020 to January 31st 2022. We included all studies reporting crude rates of in-hospital outcomes of STEMI patients with concomitant COVID-19.

Results

A total of 9 observational studies were identified, mainly conducted during the first wave of the pandemic. STEMI patients with COVID −19 were more likely Afro-American and displayed higher rates of hypertension and diabetes with lower smoking prevalence. Associated comorbidities, including coronary artery disease, prior stroke and chronic kidney disease were also more common in those with SARS-CoV-2 infection.

At coronary angiography, a higher thrombus burden in COVID-19 positive STEMI patients was highlighted, with up to 10-fold higher rates of stent thrombosis and greater need for glycoprotein IIb/IIa inhibitors and aspiration thrombectomy; this was not always associated with prolonged times from symptom onset to hospital admission and door-to-balloon. COVID-19 positive STEMI patients were less likely to receive coronary angiography and primary PCI, and more likely to be treated with fibrinolytics only. At the same time, patients with Covid-19 were more prone to present MINOCA.

In-hospital mortality ranged from 15% to 40%, with consistent variability across different studies and subjects who tested positive for SARS-CoV-2 did also present higher rates of cardiogenic shock, cardiac arrest, prolonged ICU stay, mechanical ventilation, major bleeding, and stroke.

Conclusion

The coexistence of STEMI and COVID-19 was associated with increased in-hospital mortality and poor short-term prognosis. This was not entirely attributable to logistic issues determining delayed coronary revascularization, since patients' specific clinical and angiographic characteristics, including higher burden of cardiovascular risk factors and greater coronary thrombogenicity might have substantially contributed to this trend.

Funding Acknowledgement

Type of funding sources: None.
Differential electrocardiographic changes related to the culprit coronary artery in patients with acute myocardial infarction and left bundle branch block
Authors: Sole Gonzalez E , Soriano Amores M , Di Marco A , Barrabes J A , Torres Sanchez L M , Gonzalez Calle D , Tomas Querol C , Garcia Garcia C , Cinca J
Published: October 2022

Background

The electrocardiographic (ECG) recognition of acute myocardial infarction (AMI) in patients with concurrent left bundle branch block (LBBB) is hampered by background changes in QRS complex duration and ST segment, potential directly caused by LBBB. Currently available ECG algorithms were constructed to suspect the presence of AMI but they not take into a count the culprit coronary artery and this fact could explain their low sensitivity.

Objectives

To analyze the influence of the culprit coronary artery on the ECG changes and on the diagnostic yielding of ECG algorithms in patients with acute myocardial infarction and LBBB.

Methods

We analyzed the index ECG of 240 patients with acute chest pain and LBBB referred to emergent coronary angiography. Patients were classified in 3 groups according their coronary anatomy: a) acute coronary occlusion (n=48); b) critical non occlusive lesion (n=45); and c) absence of coronary lesions (n=76). In all ECGs we measured the ST-segment shifts and QRS duration and compared the pattern of changes in relation to the culprit coronary artery.

Results

Location of the culprit coronary artery induced differential ECG patterns: a) mean ST segment elevation ≥3mm in leads V2-V3 in patients with LAD occlusion (n=27); b) absence of ST segment depression in leads V5-V6 in LCX occlusion (n=11); and c) mean ST segment elevation ≥1.5 mm in leads III-aVF and attenuation of the ST elevation in leads V1-V2 (mean <1mm) in cases of RCA occlusion (n=10). Patients with critical non occlusive lesions (n=45) did not show particular ECG changes. QRS complex duration was longer in patients with LCX occlusion. Sensitivity of the Sgarbossa score was around 50%, sensitivity of the Smith score was >70% in all coronary groups and sensitivity of Barcelona score was really good for LCX and RCA occlusion. The combination of the three algorithms increased the sensitivity in all groups (>74%) but more markedly in patients with LCX occlusion (90.9%) and RCA occlusion (90%). All the ECG algorithms lose sensitivity for the critical non occlusive lesions group.

Conclusions

Patients with acute myocardial infarction and LBBB present distinct patterns of QRS and ST segment changes and different diagnostic yielding of ECG algorithms in relation to the location of the occluded coronary artery. Data suggest that ECG prediction of the culprit coronary artery in patients with AMI and LBBB might be possible using artificial intelligence systems in larger series of patients.

Funding Acknowledgement

Type of funding sources: None.
First medical contact facility type as a determinant of prognosis in a regional ST elevation myocardial infarction network
Authors: De Diego Soler O , Garcia-Garcia C , Rueda F , Carrillo X , Andrea R , Regueiro A , Mauri F , Lidon R M , Tizon H , Garcia-Pitarch J , Bayes-Genis A
Published: October 2022

Background

Delay in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infartion (STEMI) is associated with worse prognosis. In our regional STEMI network, the first medical contact (FMC) facility type defines 4 different assistance pathways (i.e. emergency medical services'diagnosis on the field and direct transfer to the catheterization laboratory (cath. lab) of a PCI hospital (EMS group); direct admission to a PCI hospital (PCI-H group); admission to community hospital and transfer to the cath lab of the PCI-H (CH group); diagnosis in a primary care centre and transfer to the cath lab of the PCI-H (PCC group). Each different FMC has been associated with different degrees in reperfusion delay.

Objective

To determine the influence of FMC facility type on 1-year mortality in patients with STEMI in our regional STEMI network.

Methods

This is a retrospective study based on the STEMI network registry, a mandatory registry conducted since its implantation and supervised by the regional health authorities. We included STEMI patients treated with PPCI from January 2010 to December 2020. We analyzed differences in clinical variables, reprefusion times and 1-year all-cause mortality regarding the FMC facility type.

Results

We included 18332 patients (EMS 34.25%, PCI-H 12.28%, CH 33.47%, PCC 20.01%). Initial Killip classes III–IV: EMS 8.43%, PCI-H 7.51%, CH 5.54%, PCC 3.76%; p<0.001. All comorbidities and complications in first medical assistance were more frequent in EMS and PCI-H groups (p<0.05). PCC group had the lowest risk profile regarding comorbidities and first medical assistance complications (p<0.05 for most of variables). The PCI-H group had the shortest system delay (median 82 min, p<0.001), the EMS group had the shortest total ischemic time (median 151 min, p<0.001). Crude 1-year mortality was EMS 8.6%, PCI-H 9.11%, CH 8.25%, and PCC 4.77% (p<0.001). After adjusting for several covariables with a logistic regression model, PCI-H and CH groups were associated with higher 1-year mortality compared to EMS group (OR 1.23 (IC95% 1.01–1.49; p=0.04) and OR 1.16 (IC95% 1.01–1.34; p=0.04) respectively), while PCC group was associated with lower 1-year mortality (OR 0.69 (IC95% 0.57–0.84; p<0.01)).

Conclusions

First medical contact with EMS and direct transfer to the cath lab was associated with lower adjusted 1-year mortality compared to first medical contact with a PCI hospital or a community hospital.

Funding Acknowledgement

Type of funding sources: None.
Association of accompanying dyspnea with diagnoses and outcome of patients presenting with suspected acute coronary syndromes
Authors: Boeddinghaus J , Nestelberger T , Koechlin L , Lopez-Ayala P , Wildi K , Rubini Gimenez M , Miro O , Martin-Sanchez J , Keller D , Christ M , Twerenbold R , Mueller C
Published: October 2022

Background

The presence of accompanying dyspnea is routinely assessed and common in chest pain patients with suspected acute coronary syndromes (ACS), but its impact on differential diagnoses, diagnostic work-up and outcome is incompletely understood.

Purpose

To determine the association of accompanying dyspnea with diagnoses, diagnostic work-up, and outcome of patients presenting with suspected ACS to the emergency department (ED).

Methods

We prospectively enrolled unselected patients presenting to the ED with chest pain as the main symptom suggestive of ACS in an international multicenter study. Final diagnoses were adjudicated by two independent cardiologists using all information including cardiac imaging. Patients were stratified by the presence or absence of self-reported dyspnea. The primary diagnostic endpoint was the differential diagnosis. The secondary diagnostic endpoint was the performance of high-sensitivity cardiac troponin (hs-cTn) and the European Society of Cardiology (ESC) 0/1h-algorithms for the diagnosis of myocardial infarction (MI). The primary prognostic endpoint was all-cause mortality at two years.

Results

Among 6045 patients, 2892/6045 (48%) had accompanying dyspnea. Final diagnoses in patients with versus without dyspnea were different (overall p<0.001), but prevalence of ACS was comparable (MI 22.4% vs. 21.9%, p=0.602, unstable angina 8.7% vs. 7.9%, p=0.291). In contrast, patients with dyspnea more often had cardiac, non-coronary disease (15.3% vs. 10.2%, p<0.001). Diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn)T/I concentrations at presentation for the diagnosis of MI was high and not affected by the presence of dyspnea (area under the curve 0.89–0.91 in both groups). The ESC 0/1h-algorithms performed excellent in both groups with negative predictive values >99.4%. The presence of dyspnea was associated with all-cause death at two years (hazard ratio [HR] 2.487 [95% CI, 2.001–3.091, p<0.001) and remained an independent predictor after adjustment for covariates at baseline (HR 1.813 [95% CI, 1.453–2.261, p=0.001]). Overall mortality rates were higher in patients with dyspnea at two years (9.0% vs. 3.7%, p<0.001).

Conclusion

Accompanying dyspnea was not associated with a higher prevalence of ACS but with cardiac, non-coronary disease such as heart failure. While the safety of the diagnostic work-up was not affected, accompanying dyspnea was associated with and an independent predictor for two-year all-cause mortality.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Swiss Heart Foundation, University of Basel.
Extending the no objective testing rules to patients triaged by the ESC 0/1-hour algorithms
Authors: Boeddinghaus J , Ratmann P D , Nestelberger T , Lopez-Ayala P , Koechlin L , Wildi K , Miro O , Martin-Sanchez J , Christ M , Gualandro D , Rubini Gimenez M , Keller D , Buser A , Mueller C
Published: October 2022

Background

It is unclear which patients, after rule-out of non-ST elevation myocardial infarction (NSTEMI) with the European Society of Cardiology (ESC) 0/1h-algorithms, require further objective anatomical or functional cardiac testing and which do not.

Purpose

To test the safety and efficacy of the no-objective-testing (NOT)-rules after NSTEMI rule-out by the well-validated ESC 0/1h-algorithms.

Methods

We prospectively enrolled adult patients presenting with acute chest pain to 12 emergency departments (ED) in five European countries in an international, prospective, diagnostic multicenter study. The final diagnosis of major adverse cardiovascular events (MACE), defined as nonfatal acute coronary syndromes (NSTEMI or unstable angina) or cardiovascular death was centrally adjudicated by two independent cardiologists applying the 4th Universal Definition of myocardial infarction using all information including cardiac imaging and serial measurements of high-sensitivity cardiac troponin (hs-cTn) T/I. The primary endpoints were the safety and efficacy of the NOT-rules for the rule-out of MACE within 30-days follow-up including index events. Secondary endpoints included MACE within 365 and 730 days.

Results

Among 4804 and 4569 eligible patients with available 0h and 1h hs-cTnT-Elecsys or hs-cTnI-Architect concentrations, 2783 (58%) and 2252 (49%) patients were eligible for application of the NOT-rules after rule-out of NSTEMI by the respective ESC hs-cTnT/I-0/1h-algorithm. The first rule (weighted score including age, sex, cardiovascular risk factors, previous MI or known coronary artery disease (CAD), nitrate use) identified 26% of patients, had a sensitivity of 100% (95% CI 98.3–100%), a negative predictive value (NPV) of 100% (95% CI, n.c.) for hs-cTnT-Elecsys and 99.4% (95% CI 96.7–99.9%) and 99.8% (95% CI 98.8–99.9%) for hs-cTnI-Architect, respectively. The dichotomized second (age <50y, no previous MI or known CAD, <3 risk factors, no nitrate use) and even simpler third rule (nitrate use omitted) both identified 31% of patients with 99.5% (95% CI 97.4–99.9%) sensitivity and a NPV of 99.9% (95% CI 99.2–99.9%) for hs-cTnT-Elecsys. Sensitivities were 98.8% (95% CI 95.7–99.9%) and NPV 99.7% (95% CI 98.9–99.9%) for hs-cTnI-Architect. High safety was confirmed with consistently very high sensitivities and NPV for 365-day and 2-year MACE.

Conclusion

All three NOT-rules performed very well for rule-out of MACE. The third NOT-rule best balanced feasibility, safety and efficacy by identifying nearly one out of three patients as low-risk, who may not require further cardiac testing.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Swiss Heart Foundation, University of Basel.
Bleeding risk in patients hospitalized for non-ST-segment elevation acute coronary syndromes in Switzerland: performance of the CRUSADE score
Authors: Wenzl F , Kraler S , Raeber L , Staehli B E , Roffi M , Muller O , Rodondi N , Camici G G , Puhan M A , Rickli H , Radovanovic D , Luescher T F
Published: October 2022

Background

Evaluation of bleeding risk is critical to the management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). The CRUSADE score is the most established tool to estimate major bleeding events following the index NSTE-ACS.

Purpose

We aimed to assess the performance of the CRUSADE score and the predictive utility of the individual score variables in contemporary European populations.

Methods

The CRUSADE score was studied in prospectively recruited Swiss patients with NSTE-ACS included in the multicentre SPUM-ACS study (n=4'787) and main findings were validated in the nation-wide AMIS Plus registry (n=46'939). Major bleeding during hospitalization was defined as Bleeding Academic Research Consortium (BARC) class IIIB, IIIC, IV, or V. Discrimination was evaluated by the area under the receiver operating characteristic curve (AUC). Multivariable-adjusted risk ratios (adj RR) were estimated for each of the 8 score variables. Hematocrit estimates were based on hemoglobin concentrations in AMIS Plus. Analyses were performed on complete and imputed data (multiple imputation using chained equations).

Results

CRUSADE showed poor discriminatory performance (SPUM-ACS: AUC, 0.65; 95% CI 0.57 to 0.72) and low balanced accuracy (SPUM-ACS: 0.50). Risk predicted by CRUSADE exceeded the observed risk across all predefined risk categories (very low, low, moderate, high, and very high). Decision curve analyses suggested little to no net benefit from using the score. Adjusting for other score variables, signs of heart failure (adj RR, 3.83; 95% CI, 1.93 to 7.37), low hematocrit (adj RR, 2.16; 95% CI, 0.55 to 7.70; <31% vs. >40%), and low systolic blood pressure (adj RR, 2.70; 95% CI, 1.14 to 6.16; <100 mmHg vs. >121 mmHg) were the strongest predictors of major in-hospital bleeds in SPUM-ACS. These findings were similarly observed in AMIS Plus.

Conclusion

The CRUSADE score overestimates bleeding risk in NSTE-ACS. Among all 8 score variables, signs of heart failure, low hematocrit, and low systolic blood pressure are the strongest predictors of major in-hospital bleeds in contemporary patients with NSTE-ACS.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation
Prognostic impact of plasma glucose on cardiogenic shock patients with or without diabetes ellitus: smart rescue trial
Authors: Choi S H , Park S D , Lee M J , Ko Y G , Yu C W , Chun W J , Jang W J , Kim H J , Bae J W , Kwon S U , Kim J S , Lee W S , Jeong J O , Lim S H , Yang J H
Published: October 2022

Background

Even though the presence of hyperglycemia has shown to affect the clinical outcome of cardiogenic shock patients, the extent of hyperglycemia and its association with prognosis have not been fully addressed in large population

Purpose

Investigate the clinical relationship between hyperglycemic status and in-hospital mortality in cardiogenic shock patients

Method

A total of 1,177 consecutive cardiogenic shock patients were enrolled from January 2014 to December of 2018 at 12 hospitals in South Korea. The primary outcome was in-hospital mortality. Patients were divided into four groups according to their initial plasma glucose level in each of diabetes patients (n=752) and non-diabetes patients (n=425); group 1 (≤8 mmol/L), group 2 (8–12 mmol/L), group 3 (12–16 mmol/L) and group 4 (≥16 mmol/L).

Results

The groups with higher admission plasma glucose were associated with lower systolic blood pressure and higher lactic acid level in both diabetic and non-diabetic patients. In-hospital mortality increased in groups with higher admission plasma glucose level in non-diabetic patients (group-1:24.2%, group-2: 28.6%, group-3: 38.1%, group-4: 49.0%, p<0.01) whereas in diabetic patients, mortality and admission plasma glucose level showed no significant association (group-1: 45%, group-2: 35.4%, group-3: 33.3%, group-4: 43.1%, p=0.26). Even after Multivariate analysis, high plasma glucose was an independent predictor of in-hospital mortality in non-diabetic patients

Conclusion

In cardiogenic shock patients, plasma glucose obtained at admission was associated with in-hospital mortality in non-diabetic patients

Funding Acknowledgement

Type of funding sources: Private hospital(s). Main funding source(s): Inha University hospital
Impact of COVID-19 on mechanical complications in ST elevation myocardial infarction
Authors: El Ouaddi N , Escabia C , Rueda F , Oliveras T , Montero S , Labata C , Ferrer M , Garcia-Garcia C , Bayes-Genis A
Published: October 2022

Background

Mechanical complications (MC) give a poor prognosis for ST elevation myocardial infarction (STEMI). Its prevalence had decreased in the era of primary angioplasty, at the expense of free wall rupture (FWR).

Purpose

To analyse the prevalence of post-STEMI MC for two periods, before and after the COVID-19 pandemic.

Methods

Unicentric prospective registration of patients with STEMI admitted between January-2018 and December-2021. They are classified into two groups according to the onset of the pandemic by COVID-19: Pre-COVID: January-2018 to December-2019, and Post-COVID: January-2020 to December-2021. The prevalence of post-STEMI MC is analysed, including ventricular septal rupture (VSR), papillary muscle rupture (PMR) and FWR, and 30-day mortality.

Results

1507 consecutive patients with STEMI (Pre-COVID n=775, Post-COVID n=732) are included. Age 62.9 years vs 63.3 years (p=0.5097). Men 78.1% Vs 79.5% (p=0.493). No differences in cardiovascular risk factors, previous heart infarction or anterior wall STEMI. Primary angioplasty was similar in both groups (92%). The Post-COVID group has a higher prevalence of Killip>I (21.7% vs 17.2% p=0.025) and LVEF ≤40% (27.2% vs 20% p=0.001), and longer symptom onset to balloon dilatation interval (316 min vs 257 min p=0.0004). MC are most developed in Post-COVID (2.6% vs 1.2% p=0.039), at the expense of FWR (1.91% vs 0.3% p=0.001). No significant changes in VSR and PMR prevalence or 30-day mortality. Multivariate analysis identifies the independent predictors of FWR: Age (OR 1.05, p=0.024), Primary angioplasty (OR 0.09, p<0.001), and Post-COVID (OR 6.8, p=0.013).

Conclusions

The COVID-19 pandemic is independently associated with a higher prevalence of FWR, probably due to delayed reperfusion.

Funding Acknowledgement

Type of funding sources: None.