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ST-segment elevation myocardial infarction (STEMI) is associated with high early mortality. However, it remains unclear if patients surviving the early phase have long-term excess mortality. This study aims to assess excess mortality in STEMI patients treated with primary percutaneous coronary intervention (PCI) compared with an age- and- sex-matched general population at landmark periods 0 to 30 days, 31 to 90 days, and 91 days to 10 years. Using the Western Denmark Heart Registry, we identified first-time PCI-treated patients who had primary PCI for STEMI from January 2003 to October 2018. Each patient was matched by age and sex to 5 individuals from the general population. We included 18,818 patients with first-time STEMI and 94,090 individuals from the general population. Baseline comorbidity burden was similar in STEMI patients and matched individuals. Compared with the matched individuals, STEMI was associated with a 5.9% excess mortality from 0 to 30 days (6.0% vs 0.2%; HR: 36.44; 95% CI: 30.86-43.04). An excess mortality remained present from 31 to 90 days (0.9% vs 0.4%; HR: 2.43; 95% CI: 2.02-2.93). However, in 90-day STEMI survivors, the absolute excess mortality was only 2.1 percentage points at 10-year follow-up (26.5% vs 24.5%; HR: 1.04; 95% CI: 1.01-1.08). Use of secondary preventive medications such as statins, antiplatelet therapy, and beta-blockers was very high in STEMI patients throughout 10-year follow-up. In primary PCI-treated STEMI patients with high use of guideline-recommended therapy, patients surviving the first 90 days had 10-year mortality that was only 2% higher than that of a matched general population. [Display omitted] [ABSTRACT FROM AUTHOR]

Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) are highly correlated measures of atherogenic lipoproteins. The study investigators hypothesized that excess apoB is associated with an increased risk of myocardial infarction (MI), atherosclerotic cardiovascular disease (ASCVD), and all-cause mortality. The study included 53,484 women and 41,624 men not taking statins from the Copenhagen General Population Study. Associations of excess apoB with the risk of MI, ASCVD, and all-cause mortality were estimated by Cox proportional hazards regressions with 95% CIs. Excess apoB was defined as measured levels of apoB minus expected levels of apoB from LDL-C alone; expected levels were defined by linear regressions of LDL-C levels vs apoB levels in individuals with triglycerides ≤1 mmol/L (89 mg/dL). During a median follow-up of 9.6 years, 2,048 MIs, 4,282 ASCVD events, and 8,873 deaths occurred. There was a dose-dependent association between excess apoB and the risk of MI and ASCVD in both women and men, as well as an association with the risk of all-cause mortality in women. For ASCVD in women compared with those with excess apoB <11 mg/dL, the multivariable adjusted HR was 1.08 (95% CI: 0.97-1.21) for excess apoB 11 to 25 mg/dL, 1.30 (95% CI: 1.14-1.48) for 26 to 45 mg/dL, 1.34 (95% CI: 1.14-1.58) for 46 to 100 mg/dL, and 1.75 (95% CI: 1.08-2.83) for excess apoB >100 mg/dL. Corresponding HRs in men were 1.14 (95% CI: 1.02-1.26), 1.41 (95% CI: 1.26-1.57), 1.41 (95% CI: 1.25-1.60), and 1.52 (95% CI: 1.13-2.05), respectively. Results were robust across the entire LDL-C spectrum. Excess apoB (ie, the value of apoB above that contributed by LDL-C levels alone) is associated dose-dependently with an increased risk of MI and ASCVD in women and men. This finding demonstrates that apoB provides important predictive value beyond LDL-C across the entire LDL-C spectrum. [Display omitted] [ABSTRACT FROM AUTHOR]

Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674) [Display omitted] [ABSTRACT FROM AUTHOR]

Telemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post–acute coronary syndrome (ACS). TELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS. Patients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat. A total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group. The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634) [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Despite impressive improvements in the care of patients with ST-segment elevation myocardial infarction, mortality remains high. Reperfusion is necessary for myocardial salvage, but the abrupt return of flow sets off a cascade of injurious processes that can lead to further necrosis. This has been termed myocardial ischemia-reperfusion injury and is the subject of this review. The pathologic and molecular bases for myocardial ischemia-reperfusion injury are increasingly understood and include injury from reactive oxygen species, inflammation, calcium overload, endothelial dysfunction, and impaired microvascular flow. A variety of pharmacologic strategies have been developed that have worked well in preclinical models and some have shown promise in the clinical setting. In addition, there are newer mechanical approaches including mechanical unloading of the heart prior to reperfusion that are in current clinical trials. [Display omitted] • MIRI exacerbates myocardial necrosis in patients with STEMI, contributing to mortality. • MIRI is mediated by varying combinations of ROS, inflammation, endothelial dysfunction, impaired microvascular flow, and other factors. • A variety of pharmacologic and mechanical strategies that mitigate MIRI in preclinical models have shown promise in clinical trials. [ABSTRACT FROM AUTHOR]

Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction. [Display omitted] [ABSTRACT FROM AUTHOR]

The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI. The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo. The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis–related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations. [Display omitted] [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Although clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing holds immense potential for genetic manipulation, its clinical application is hindered by the absence of an efficient heart-targeted drug delivery system. Herein, we developed CRISPR-Cas9 ribonucleoprotein (RNP)-loaded extracellular vesicles (EVs) conjugated with cardiac-targeting peptide (T) for precise cardiac-specific genome editing. RNP complexes containing Cas9 and single guide RNA targeting miR-34a, an MI-associated molecular target, were loaded into EVs (EV@RNP). Gene editing by EV@RNP attenuated hydrogen peroxide-induced apoptosis in cardiomyocytes via miR-34a inhibition, evidenced by increased B-cell lymphoma 2 levels, decreased Bcl-2-associated X protein levels, and the cleavage of caspase-3. Additionally, to improve cardiac targeting in vivo , we used click chemistry to form functional T-EV@RNP by conjugating T peptides to EV@RNP. Consequently, T-EV@RNP-mediated miR-34a genome editing might exert a protective effect against MI, reducing apoptosis, ameliorating MI injury, and facilitating the recovery of cardiac function. In conclusion, the genome editing delivery system established by loading CRISPR/Cas9 RNP with cardiac-targeting EVs is a powerful approach for precise and tissue-specific gene therapy for cardiovascular disease. [Display omitted] [ABSTRACT FROM AUTHOR]

The recent guidelines from the European Society of Cardiology recommends using high-sensitivity cardiac troponin (hs-cTn) in either 0/1-h or 0/2-h algorithms to identify or rule out acute myocardial infarction (AMI). Several studies have reported good diagnostic accuracy with both algorithms, but few have compared the algorithms directly. We aimed to compare the diagnostic accuracy of the algorithms head-to-head, in the same patients. This was a secondary analysis of data from a prospective observational study; 1167 consecutive patients presenting with chest pain to the emergency department at Skåne University Hospital (Lund, Sweden) were enrolled. Only patients with a hs-cTnT sample at presentation AND after 1 AND 2 h were included in the analysis. We compared sensitivity, specificity, and negative (NPV) and positive predictive value (PPV). The primary outcome was index visit AMI. A total of 710 patients were included, of whom 56 (7.9%) had AMI. Both algorithms had a sensitivity of 98.2% and an NPV of 99.8% for ruling out AMI, but the 0/2-h algorithm ruled out significantly more patients (69.3% vs. 66.2%, p < 0.001). For rule-in, the 0/2-h algorithm had higher PPV (73.4% vs. 65.2%) and slightly better specificity (97.4% vs. 96.3%, p = 0.016) than the 0/1-h algorithm. Both algorithms had good diagnostic accuracy, with a slight advantage for the 0/2-h algorithm. Which algorithm to implement may thus depend on practical issues such as the ability to exploit the theoretical time saved with the 0/1-h algorithm. Further studies comparing the algorithms in combination with electrocardiography, history, or risk scores are needed. [ABSTRACT FROM AUTHOR]

The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov , NCT00760656 , and is ongoing. 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0–31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9–19·5) compared with 0·9% (0·0–2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23–0·29) events per survivor compared with 0·009 (0·000–0·021) events per community control participant. Increasing cumulative burden of grade 1–4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1–6·0; p<0·0001; two conditions: 6·6, 4·6–9·5; p<0·0001; and three conditions: 7·7, 5·1–11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2–2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6–3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2–4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1–2 hypertriglyceridaemia, or grade 1–2 vascular stenosis. Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. The US National Cancer Institute and the American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94–1.12, P =0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83–1.18, P =0.90) for patients on beta-blockers. Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. NCT02573532. [ABSTRACT FROM AUTHOR]

There are strong associations between oxygen desaturations and cardiovascular outcomes. Additionally, oxygen resaturation rates are linked to excessive daytime sleepiness independent of oxygen desaturation severity. No studies have yet looked at the independent effects of comorbidities or medications on resaturation parameters. The Sleep Heart Health Study data was utilised to derive oxygen saturation parameters from 5804 participants. Participants with a history of comorbidities or medication usage were compared against healthy participants with no comorbidity/medication history. 4293 participants (50.4% female, median age 64 years) were included in the analysis. Females recorded significantly faster resaturation rates (mean 0.61%/s) than males (mean 0.57%/s, p < 0.001), regardless of comorbidities. After adjusting for demographics, sleep parameters, and desaturation parameters, resaturation rate was reduced with hypertension (-0.09 (95% CI -0.16, -0.03)), myocardial infarction (-0.13 (95% CI -0.21, -0.04)) and heart failure (-0.19 (95% CI -0.33, -0.05)), or when using anti-hypertensives (-0.10 (95% CI -0.17, -0.03)), mental health medications (-0.18 (95% CI -0.27, -0.08)) or anticoagulants (-0.41 (95% CI -0.56, -0.26)). Desaturation to Resaturation ratio for duration was decreased with mental health (-0.21 (95% CI -0.34, -0.08)) or diabetic medications (-0.24 (95% CI -0.41, -0.07)), and desaturation to resaturation ratio for area decreased with heart failure (-0.25 (95% CI -0.42, -0.08)). Comorbidities and medications significantly affect nocturnal resaturation parameters, independent of desaturation parameters. However, the causal relationship remains unclear. Further research can enhance our knowledge and develop more precise and safer interventions for individuals affected by certain comorbidities. • Oxygen resaturation rate is faster in females (0.61 %/s) than in males (0.57 %/s). • Oxygen resaturation rate is slowed with hypertension or myocardial infarction. • Mental health medications and anticoagulants significantly slowed resaturation rates. • Resaturation rate was not associated with ESS scores. [ABSTRACT FROM AUTHOR]

• Ezetimibe with statins during acute coronary syndrome associated with better outcomes. • An addition lowering of LDL-C by 19.55 mg/dl seen at 7-days. • Peak additional LDL-C lowering by 24.67 mg/dl seen by 1-month. • Durable additional LDL-C lowering by 18.0 mg/dl seen by 3-months therapy. • Durable additional LDL-C lowering by 16.90 mg/dl seen by 10–12-months therapy. Scant data is available on the efficacy and safety of adding ezetimibe to high-intensity statin therapy for early and rapid reduction of low-density lipoprotein cholesterol (LDL-C) within 4–12 weeks of an acute-event in acute coronary syndrome (ACS). We undertook this meta-analysis to address this knowledge-gap. Electronic databases were searched for RCTs involving patients with ACS receiving ezetimibe in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in LDL-C levels post-ACS. Secondary outcomes were to evaluate alterations in other lipid parameters and adverse events. From initially screened 4561 articles, data from 11 studies (20,291 patients) were analyzed. Compared to controls, patients receiving ezetimibe had significantly lower LDL-C at 7-days [MD -19.55 mg/dl(95 %CI:–36.46 to –2.63); P = 0.02; I 2 = 91 %], 1-month [MD-24.67 mg/dl (95 %CI:–34.59 to –14.76); P < 0.001; I 2 = 81 %], 3-months [MD -18.01 mg/dl(95 %CI:–24.11 to –11.90); P < 0.001; I 2 = 92 %] and 10–12 months [MD -16.90 mg/dl (95 % CI: –17.67 to –16.12); P < 0.001; I 2 = 0 %] of treatment. Compared to controls, patients receiving ezetimibe had significantly lower total cholesterol at 7-days [MD-21.05 mg/dl(95 %CI:–26.73 to –15.37); P < 0.001; I 2 = 0 %], 1-month [MD-25.56 mg/dl(95 %CI:–38.29 to –12.83); P < 0.001; I 2 = 85 %], 3-months [MD-22.54 mg/dl(95 %CI:–36.90 to –8.19); P = 0.002; I 2 = 22 %] and 12-months [MD-19.68 mg/dl(95 %CI:–20.78 to –18.59); P < 0.001; I 2 = 0 %] of treatment. Death from any cause, ACS and non-fatal stroke [OR0.89(95 %CI:0.83–0.96); P = 0.002; I 2 = 0 %], non-fatal myocardial infarction [OR0.86(95 %CI:0.79–0.94); P = 0.001; I 2 = 0 %] and ischemic stroke [OR0.80(95 %CI:0.68–0.94); P = 0.009; I 2 = 0 %] was significantly reduced in patients receiving ezetimibe. Addition of ezetimibe to high-intensity statin therapy at the time of ACS event is associated with significantly better cholesterol reduction at day-7,1-month, 3- months and 1-year of follow-up, which translates into a significantly lower recurrent cardiovascular events post an index event of ACS. Addition of ezetimibe to high-intensity statin therapy at the time of acute coronary syndrome (ACS) index event is associated with significantly better low density lipoprotein cholesterol and total cholesterol reduction at day-7, 1-month, 3-months and 1-year of follow-up, which translates into a significantly lower recurrent cardiovascular events (death from any cause, major ACS, non-fatal stroke, non-fatal myocardial infarction, and ischemic stroke) post an index event of ACS. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) is a powerful analytical technique in metabolomics, enabling the identification and quantification of metabolites. However, analyzing MS data poses challenges such as batch effects, outliers, and high-dimensional data. In this paper, we propose a comprehensive framework for MS data analysis. The framework integrates data calibration, outlier detection, and automatic classification modules. Data calibration is performed using a deep autoencoder to remove batch effects. Outlier detection combines multiple algorithms through ensemble learning to identify and remove outliers. Automatic classification utilizes a transformer model to handle high-dimensional data and capture global feature relationships. Experimental results on myocardial infarction (MI) and coronary heart disease (CHD) datasets demonstrate the effectiveness of the framework. It outperforms traditional classification models and achieves higher accuracy. The proposed framework provides a robust solution for MS data analysis, facilitating more accurate classification and enabling reliable biological insights in metabolomics research. [Display omitted] • Novel framework integrates three steps for MS data analysis. • Deep AE removes batch effects, while an ensemble approach removes outliers. • Transformer captures intrinsic relationships in MS data for accurate classification. • The framework provides a comprehensive solution to improve classification accuracy. • The framework also facilitates reliable biological insights. [ABSTRACT FROM AUTHOR]

While females have been found to have a higher rate of procedural complications with transcatheter aortic valve implantation (TAVI) than males, the effect of valve choice has not been fully elucidated. This study aimed to investigate the impact of gender and choice of balloon or self-expanding valve on TAVI complications. Data from patients who received a TAVI in our institution from January 2016 to September 2021 were retrospectively analyzed. A total of 971 patients were included and divided into self-expanding valve (n = 315) and balloon-expandable valve (n = 656) groups. The endpoints were 30-day mortality, need for a new pacemaker, and major adverse cardiovascular events (MACE) which is defined as cardiac arrest, stroke, myocardial infarction, major bleeding, and unplanned vascular surgery/intervention. There were more females in the self-expanding valve group than in the balloon-expandable valve group (64.1 % vs. 43.6 %: p < 0.0001). There is no significant difference in the prevalence of hypertension, diabetes mellitus, current smoker, hemodialysis, and the STS risk score between the 2 groups. Females had a higher rate of major adverse cardiovascular events (3.7 % in men vs. 6.8 % in women; p = 0.043), which was driven mostly by vascular complications. This difference was particularly observed in the self-expanding valve group (2.7 % in men vs. 9.4 % in women; p = 0.036). TAVI complications were more common in females than males, driven mostly by vascular complications. This difference was particularly observed in woman treated with a self-expanding valve. Particular attention should be given to access choices in females undergoing TAVI. • We investigated the impact of gender and type of TAVI valve on complications. • Vascular complication was more common in females than males. • This gender difference was mainly observed in patients with self-expanding valve. [ABSTRACT FROM AUTHOR]

Depression and anxiety may be significant prognostic factors after myocardial infarction (MI). Thus, we investigated depression and anxiety prevalence among older MI survivors and their impact on mortality, stroke, and recurrent MI. This population-based cohort study used the Korean National Health Insurance Service database for data concerning individuals aged 66 years who participated in the National Screening Program from 2009 to 2016. Overall, 11,721 individuals with MI history and 58,605 age- and sex-matched controls were included and followed up until 2019. The presence of depression and anxiety was assessed 2 years before and after participation in the program. Mortality and major adverse outcomes, defined as a composite outcome comprising mortality, stroke, and recurrent MI, were analyzed. Depression and anxiety prevalence among MI survivors was 20.4 % and 30.3 %, respectively. Crude odds ratios for depression and anxiety, compared with the control group, were 1.207 (1.148–1.269) and 1.078 (1.032–1.126), respectively. During the follow-up, individuals with depression, anxiety, or both showed increased hazard ratios (HRs) for mortality and major adverse outcomes; after adjustments, their HRs were 1.442 (1.182–1.759), 1.129 (0.960–1.328), and 1.498 (1.263–1.776), respectively, for mortality and 1.505 (1.289–1.758), 1.158 (1.021–1.314), and 1.530 (1.337–1.751), respectively, for major adverse outcomes. Although this was a nationwide cohort study, the MI, depression, and anxiety diagnoses were based on diagnostic codes. Higher depression and anxiety prevalence was observed among older MI survivors. Depression and anxiety occurrence correlated with increased adverse clinical outcomes after adjustments. [Display omitted] • A higher prevalence of depression and anxiety was observed in older myocardial infarction (MI) survivors. • The presence of depression and anxiety was associated with adverse clinical outcomes. • Cardiac rehabilitation models should prioritize the identification and management of depression and anxiety after MI. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required—moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health. [Display omitted] • Early-stage subclinical atherosclerosis can be identified in young individuals, but evidence-based strategies are needed to prevent progression of disease and clinical events. • Precision medicine using imaging and circulating biomarkers could facilitate early identification of atherosclerosis and the development of curative interventions. • A paradigm shift based on these principles could reduce the global burden of CVD with enormous implications for population health. [ABSTRACT FROM AUTHOR]

Little is known about the procedural characteristics, case volumes, and mortality rates for early- vs non–early-career interventional cardiologists in the United States. This study examined operator-level data for patients who underwent percutaneous coronary intervention (PCI) between April 2018 and June 2022. Data were collected from the National Cardiovascular Data Registry CathPCI Registry, American Board of Internal Medicine certification database, and National Plan and Provider Enumeration System database. Early-career operators were within 5 years of the end of training. Annual case volume, expected mortality and bleeding risk, and observed/predicted mortality and bleeding outcomes were evaluated. A total of 1,451 operators were early career; 1,011 changed their career status during the study; and 6,251 were non–early career. Overall, 514,540 patients were treated by early-career and 2,296,576 patients by non–early-career operators. The median annual case volume per operator was 59 (Q1-Q3: 31-97) for early-career and 57 (Q1-Q3: 28-100) for non–early-career operators. Early-career operators were more likely to treat patients presenting with ST-segment elevation myocardial infarction and urgent indications for PCI (both P < 0.001). The median predicted mortality risk was 2.0% (Q1-Q3: 1.5%-2.7%) for early-career and 1.8% (Q1-Q3: 1.2%-2.4%) for non–early-career operators. The median predicted bleeding risk was 4.9% (Q1-Q3: 4.2%-5.7%) for early-career and 4.4% (Q1-Q3: 3.7%-5.3%) for non–early-career operators. After adjustment, an increased risk of mortality (OR: 1.08; 95% CI: 1.05-1.17; P < 0.0001) and bleeding (OR: 1.08; 95% CI: 1.05-1.12; P < 0.0001) were associated with early-career status. Early-career operators are caring for patients with more acute presentations and higher predicted risk of mortality and bleeding compared with more experienced colleagues, with modestly worse outcomes. These data should inform institutional practices to support the development of early-career proceduralists. [Display omitted] [ABSTRACT FROM AUTHOR]

Ventricular septal rupture remains a dreadful complication of acute myocardial infarction. Although less commonly observed than during the prethrombolytic era, the condition remains complex and is often associated with refractory cardiogenic shock and death. Corrective surgery, although superior to medical treatment, has been associated with high perioperative morbidity and mortality. Transcatheter closure techniques are less invasive to surgery and offer a valuable alternative, particularly in patients with cardiogenic shock. In these patients, percutaneous mechanical circulatory support represents a novel opportunity for immediate stabilization and preserved end-organ function. Multimodality imaging can identify favorable septal anatomy for the most appropriate type of repair. The heart team approach will define optimal timing for surgery vs percutaneous repair. Emerging concepts are proposed for a deferred treatment approach, including orthotropic heart transplantation in ideal candidates. Finally, for futile situations, palliative care experts and a medical ethics team will provide the best options for end-of-life clinical decision making. [Display omitted] • The incidence of ventricular septal rupture after acute myocardial infarction has declined, yet there has been little improvement in clinical outcomes. • Corrective surgery and percutaneous septal closure are options for patients with severe hemodynamic derangement. • Collaboration among members of an interdisciplinary heart/shock team can help estimate the chances of viability vs futility, determine the role of mechanical circulatory support, and determine the timing of intervention. [ABSTRACT FROM AUTHOR]

Postinfarction ventricular free-wall rupture is a rare mechanical complication, accounting for <0.01% to 0.02% of cases. As an often-catastrophic event, death typically ensues within minutes due to sudden massive hemopericardium resulting in cardiac tamponade. Early recognition is pivotal, and may allow for pericardial drainage and open surgical repair as the only emergent life-saving procedure. In cases of contained rupture with pseudo-aneurysm (PSA) formation, hospitalization with subsequent early surgical intervention is warranted. Not uncommonly, PSA may go unrecognized in asymptomatic patients and diagnosed late during subsequent cardiac imaging. In these patients, the unsettling risk of complete rupture demands early surgical repair. Novel developments, in the field of transcatheter-based therapies and multimodality imaging, have enabled percutaneous PSA repair as a feasible alternate strategy for patients at high or prohibitive surgical risk. Contemporary advancements in the diagnosis and treatment of postmyocardial infarction ventricular free-wall rupture and PSA are provided in this review. [Display omitted] • Ventricular free-wall rupture is a rare, but potentially fatal, complication of acute myocardial infarction, requiring prompt surgical intervention. • Pseudoaneurysm formation results from contained rupture; characterization by multimodality imaging can enhance risk stratification and guide the surgical strategy. • Developments in transcatheter therapeutics have introduced percutaneous approaches for high-risk or inoperable patients with suitable pathoanatomy, but experience with these options is limited. [ABSTRACT FROM AUTHOR]

Ventricular aneurysm represents a rare complication of transmural acute myocardial infarction, although other cardiac, congenital, or metabolic diseases may also predispose to such condition. Ventricular expansion includes all the cardiac layers, usually with a large segment involved. Adverse events include recurrent angina, reduced ventricular stroke volume with congestive heart failure, mitral regurgitation, thromboembolism, and ventricular arrhythmias. Multimodality imaging is paramount to provide comprehensive assessment, allowing for appropriate therapeutic decision-making. When indicated, surgical intervention remains the gold standard, although additional therapy (heart failure, anticoagulation, and advanced antiarrhythmic treatment) might be required. However, the STICH (Surgical Treatment for Ischemic Heart Failure) trial did not show any advantage from adding surgical ventricular reconstruction to coronary artery bypass surgery in terms of survival, rehospitalization or symptoms, compared with revascularization alone. Finally, implantable cardiac defibrillator may reduce the risk of fatal arrhythmias. [Display omitted] • Acute myocardial infarction is the most frequent cause of left ventricular aneurysm formation, although genetic, metabolic, inflammatory, and traumatic conditions are additional etiologies. • Angina, heart failure, thromboembolism, and ventricular arrhythmias are potential complications requiring specific therapies, including surgical reconstruction, anticoagulation, ablation of arrhythmias, implantable devices, and pharmacological therapy. • In patients with ventricular aneurysm complicated by ventricular tachycardia, implanted cardioverter-defibrillators may reduce the risk of sudden death. Electrophysiological mapping is critical to determining whether to pursue surgical or percutaneous ablation. [ABSTRACT FROM AUTHOR]

Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear. The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds. The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold. In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk. Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited. [Display omitted] [ABSTRACT FROM AUTHOR]

Right ventricular infarction (RVI) complicates 50% of cases of acute inferior ST-segment elevation myocardial infarction, and is associated with high in-hospital morbidity and mortality. Ischemic right ventricular (RV) systolic dysfunction decreases left ventricular preload delivery, resulting in low-output hypotension with clear lungs, and disproportionate right heart failure. RV systolic performance is generated by left ventricular contractile contributions mediated by the septum. Augmented right atrial contraction optimizes RV performance, whereas very proximal occlusions induce right atrial ischemia exacerbating hemodynamic compromise. RVI is associated with vagal mediated bradyarrhythmias, both during acute occlusion and abruptly with reperfusion. The ischemic dilated RV is also prone to malignant ventricular arrhythmias. Nevertheless, RV is remarkably resistant to infarction. Reperfusion facilitates RV recovery, even after prolonged occlusion and in patients with severe shock. However, in some cases hemodynamic compromise persists, necessitating pharmacological and mechanical circulatory support with dedicated RV assist devices as a "bridge to recovery." [Display omitted] • RVI results from proximal RCA occlusion, occurs in approximately 50% of patients with inferior MI, and is associated with increased in-hospital morbidity and mortality due to shock and arrhythmias. • Augmented RA contraction optimizes RV performance. Reperfusion facilitates RV recovery and improves outcomes, even after prolonged occlusion and in patients with ventricular shock. • Shock in patients with RVI reduces LV preload, and involvement of the interventricular septum adversely affects LV function. Patients with persistent hemodynamic compromise may benefit from pharmacological and mechanical circulatory support. [ABSTRACT FROM AUTHOR]

Severe acute mitral regurgitation after myocardial infarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. This review focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patient management and eventually decrease mortality. [Display omitted] • Severe MR developing early after MI is associated with increased risks of heart failure and mortality. • Although surgical treatment can improve survival, the incidence of adverse events and mortality remain high. • Early mechanical cardiac support and transcatheter repair techniques can expand treatment options to a broader population and potentially improve outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (P interaction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence. [Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac rehabilitation programs are used as therapeutic and rehabilitation programs after myocardial infarction and angioplasty in order to reduce cardiovascular disease mortality since different training methods and gender differences have unique effects on the structural and functional responses of the cardiovascular system. Sixty men and women with coronary artery disease who underwent angioplasty were randomly divided into two groups of experiment (concurrent training and control group) in this prospective and semi-laboratory research with a pre- and post-test design. Forty minutes of aerobic training based on ACSM instructions (three sessions a week for eight weeks) and then twenty minutes of resistance training (two sessions a week) were performed in the training group in order to rehabilitate the patients. No significant difference was observed between the two genders in the effectiveness of concurrent training on the selected variables of blood and vascular biomechanics in the left femoral artery (especially on the resting lumen diameter in the systolic [ P = 0.22] and diastolic phases [ P = 0.43]). A global effect of concurrent training was observed, resulting in an increase in the resting lumen diameter in the systolic and diastolic phases (P < 0.001). No interaction effect was reported on artery compliance (P = 0.69), blood flow intensity (P = 0.85), and intima-media thickness to resting lumen diameter ratio (P = 0.56) and the decrease in the variables of blood flow velocity (P = 0.93, P = 0.73) and blood pressure (P = 0.78, P = 0.81) in the systolic and diastolic phases of the left femoral artery. Using the beneficial effects of concurrent training with appropriate intensity and duration is recommended in middle-aged (40–65 years old) male and female patients after coronary artery angioplasty in order to improve the variables of blood and vascular biomechanics. [ABSTRACT FROM AUTHOR]

Les patients atteints de polyarthrite rhumatoïde et d'autres rhumatismes inflammatoires chroniques ont un risque de maladie cardiovasculaire (CV) plus élevé que dans la population générale. Les mécanismes sous-jacents à cette association sont complexes. L'inflammation chronique est un facteur majeur d'athérosclérose accélérée, en association aux facteurs de risque CV traditionnels, conduisant à des lésions de la paroi artérielle, à la formation rapide de plaques d'athérome et à la thrombose. Les différents traitements symptomatiques et de fond exercent également une influence notable sur le risque CV. La gestion des différents facteurs de risque chez les patients atteints de rhumatismes inflammatoires chroniques devient donc cruciale pour prévenir les complications CV. Cela implique une approche multidisciplinaire incluant un contrôle efficace de l'inflammation, une surveillance attentive des facteurs de risque CV traditionnels, ainsi que des changements de mode de vie tels que l'arrêt du tabac, l'exercice régulier et une alimentation saine. Patients with rheumatoid arthritis and other rheumatic diseases have a higher risk of cardiovascular (CV) disease than the general population. The underlying mechanisms of this association are complex. Chronic inflammation is a major factor in accelerated atherosclerosis, in conjunction with traditional CV risk factors, leading to arterial wall damage, rapid atheroma plaque formation, and thrombosis. Various symptomatic and background treatments also exert a significant influence on CV risk. Therefore, managing different risk factors in patients with chronic rheumatic diseases becomes crucial to prevent CV complications. This involves a multidisciplinary approach, including effective inflammation control, careful monitoring of traditional CV risk factors, as well as lifestyle changes such as smoking cessation, regular exercise, and a healthy diet. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. Over a median follow-up of 3.4 years (2.8–4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79–8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87–9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment. [ABSTRACT FROM AUTHOR]

This review summarizes the current evidence regarding efficacy and safety of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the setting of cardiogenic shock. Currently, there is evidence from 4 randomized controlled trials which all do not support a mortality benefit and increased complication rates by VA-ECMO. Based on current evidence, possible subgroups will be discussed and indications in selected very small patient groups be discussed. [ABSTRACT FROM AUTHOR]

Myocardial ischemia-reperfusion injury (MIRI) is a complex process that occurs when blood flow is restored after myocardium infarction (MI) with exacerbated tissue damage. Macrophages, essential cell type of the immune response, play an important role in MIRI. Macrophage subpopulations, namely M1 and M2, are distinguished by distinct phenotypes and functions. In MIRI, macrophages infiltrate in infarcted area, shaping the inflammatory response and influencing tissue healing. Resident cardiac macrophages interact with monocyte-derived macrophages in MIRI, and influence injury progression. Key factors including chemokines, cytokines, and toll-like receptors modulate macrophage behavior in MIRI. This review aims to address recent findings on the classification and the roles of macrophages in the myocardium, spanning from MI to subsequent MIRI, and highlights various signaling pathways implicated in macrophage polarization underlining the complexity of MIRI. This article will shed light on developing advanced therapeutic strategies for MIRI management. • Modulation of macrophage polarization as a potential target for treating Myocardial Ischemia Reperfusion Injury (MIRI). • Summary for cell types of macrophages and their function. • Localization & phenotypes of macrophages in myocardial tissue. • Conclusion for recent researches of the potential mechanism of macrophages during myocardial infarction (MI) & MIRI. [ABSTRACT FROM AUTHOR]

Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac tissue impairment. Modified messenger RNA (modRNA) presents compelling properties that could allow new therapeutic strategies to tackle the underlying molecular pathways that ultimately lead to development of chronic heart failure. However, clinical application of modRNA for the heart is challenged by the lack of effective and safe delivery systems. Lipid nanoparticles (LNPs) represent a well characterized class of RNA delivery systems, which were recently approved for clinical usage in mRNA-based COVID-19 vaccines. In this study, we evaluated the potential of LNPs for cardiac delivery of modRNA. We tested how variations in C12–200 modRNA-LNP composition affect transfection levels and biodistribution after intramyocardial administration in both healthy and myocardial-infarcted mice, and determined the targeted cardiac cell types. Our data revealed that LNP-mediated modRNA delivery outperforms the current state of the art (modRNA in citrate buffer) upon intramyocardial administration in mice, with only minor differences among the formulations tested. Furthermore, we determined both in vitro and in vivo that the cardiac cells targeted by modRNA-LNPs include fibroblasts, endothelial cells and epicardial cells, suggesting that these cell types could represent targets for therapeutic interference with these LNP formulations. These outcomes may serve as a starting point for LNP development specifically for therapeutic mRNA cardiac delivery applications. [Display omitted] [ABSTRACT FROM AUTHOR]

• The definition of optimal blood pressure (BP) target for prevention of cardiovascular complications of hypertension remains uncertain. • Randomized strategy trials comparing lower (i.e., more intensive) versus higher (i.e., less intensive) BP targets should drive the definition, but these trials were extremely heterogeneous by testing different BP targets based on systolic BP, diastolic BP or combined systolic and diastolic BP goals. • The more intensive treatment targets reduced the risk of major cardiovascular complications of hypertension when compared with the less intensive targets, despite a higher incidence of unwanted effects. • Given the heterogeneity of available data in support to fixed BP targets, their definition should be personalized not only in frail patients, but in all patients and based on best trade-off between efficacy and safety, i.e., the lowest well tolerated BP. The optimal blood pressure (BP) target for prevention of cardiovascular complications of hypertension remains uncertain. Most Guidelines suggest different targets depending on age, comorbidities and treatment tolerability, but the underlying evidence is not strong. Results of randomized strategy trials comparing lower (i.e., more intensive) versus higher (i.e., less intensive) BP targets should drive the definition. However, these trials tested different BP targets based on systolic BP, diastolic BP or combined systolic and diastolic BP goals. Overall, the more intensive treatment targets reduced the risk of major cardiovascular complications of hypertension when compared with the less intensive targets, despite a higher incidence of unwanted effects including, but not limited to, hypotension, electrolyte abnormalities and renal dysfunction. Consequently, some Guidelines defined low BP thresholds (i.e., 120/70 mmHg) not to exceed downward because of the expectation that unwanted effects may outweigh the outcome benefits. The present review discusses the evidence underlying the choice of BP targets, which remains an important step in the management of hypertensive patients. We conclude that, on the ground of the heterogeneity of available data in support to fixed BP targets, their definition should be personalized in all patients and based on best trade-off between efficacy and safety, i.e., the lowest well tolerated BP. [ABSTRACT FROM AUTHOR]

This study aims to establish the significance of social determinants of health and prevalent co-morbidities on multiple indicators for quality of care in patients admitted to the Burn and Surgical Intensive Care Unit (ICU). We performed a retrospective analysis of population group data for patients admitted at the Burn and Surgical ICU from January 1, 2016, to November 18, 2019. The primary outcomes were length of hospital stay (LOS), mortality, 30-day readmission, and hospital charges. Pearson's chi-square test for categorical variables and t-test for continuous variables were used to compare population health groups. We analyzed a total of 487 burn and 510 surgical patients. When comparing ICU patients, we observed significantly higher mean hospital charges and length of stay (LOS) in BICU v. SICU patients with a history of mental health ($93,259.40 v. $50,503.36, p = 0.013 and 16.28 v. 9.16 days, p = 0.0085), end-stage-renal-disease (ESRD) ($653,871.05 v. $75,746.35, p = 0.0047 and 96.15 v. 17.53 days, p = 0.0104), sepsis ($267,979.60 v. $99,154.41, p = <0.001 and 39.1 v. 18.42 days, p = 0.0043), and venous thromboembolism (VTE) ($757,740.50 v. $117,816.40, p = <0.001 and 93.11 v. 20.21 days, p = 0.002). Also, higher mortality was observed in burn patients with ESRD, ST-Elevation Myocardial Infarction (STEMI), sepsis, VTE, and diabetes mellitus. 30-day-readmissions were greater among burn patients with a history of mental health, drug dependence, heart failure, and diabetes mellitus. Our study provides new insights into the variability of outcomes between burn patients treated in different critical care settings, underlining the influence of comorbidities on these outcomes. By comparing burn patients in the BICU with those in the SICU, we aim to highlight how differences in patient backgrounds, including the quality of care received, contribute to these outcomes. This comparison underscores the need for tailored healthcare strategies that consider the unique challenges faced by each patient group, aiming to mitigate disparities in health outcomes and healthcare spending. Further research to develop relevant and timely interventions that can improve these outcomes. • Social factors affect BICU and SICU patients differently. • BICU patients with mental health, renal disease, sepsis, and thrombosis face higher costs and LOS. • BICU patients with renal disease, heart attack, sepsis, thrombosis, and diabetes see higher death rates. • BICU patients with mental health, addiction, heart failure, and diabetes face more readmissions. [ABSTRACT FROM AUTHOR]

The beneficial role of dual anti-platelet therapy (DAPT) in coronary artery disease is well established. However, there is limited data describing the effects of DAPT in patients with atherosclerotic peripheral artery disease (PAD). The aim of this meta-analysis is to compare clinical outcomes associated with DAPT versus single anti-platelet therapy (SAPT) in patients with symptomatic PAD. We performed a literature search for studies assessing the risk of adverse cardiovascular and limb events in cohorts receiving either DAPT or SAPT. The primary endpoint was all cause mortality. The secondary endpoints included graft failure, amputation, total bleeding, severe bleeding and fatal bleeding. The search included the following databases: Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar. The search was not restricted to time or publication status. A total of 11 studies with 54,331 participants (24,449 on SAPT and 29,882 on DAPT) were included. Patients with PAD treated with SAPT had higher all-cause mortality compared to patients treated with DAPT (OR 1.37, 95 % CI 1.09–1.74; p < 0.01). There was no difference in risk of graft failure or amputation between patients treated with SAPT or DAPT (OR 0.9, 95 % CI 0.77–1.06; p = 0.19; OR 1.11, 95 % CI 0.88–1.41; p = 0.37). Patients treated with SAPT had lower total bleeds compared to patients treated with DAPT (OR 0.53, 95 % CI 0.36–0.77; p < 0.01). However, For SAPT plus AC vs SAPT, a total of 8 studies with 17,100 participants (3447 with SAPT plus AC and 8619 with only SAPT) were included. Patients on SAPT plus AC did not have a statistically significant difference in risk for all-cause mortality, (OR 0.91, 95 % CI 0.67–1.24; p = 0.56). SAPT plus AC had significantly lower risk of MI (OR 0.82, 95 % CI 0.69–0.97; p = 0.02), amputation (OR 0.72, 95 % CI 0.53–0.97; p = 0.03), and graft failure (OR 0.66, 95 % CI 0.48–0.93; p = 0.02). There was no significant different in risk of fatal bleeding be-tween the two groups (OR 1.60, 95 % CI 0.76–3.35; p = 0.22). In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events. • In patients with symptomatic PAD, a strategy of DAPT may confer a mortality benefit when compared to SAPT without significantly increasing the risk of serious bleeding events. • SAPT with AC maybe associated with lower risk of MI, amputation and graft failure without incraese risk of fatal bleeds. • Further randomised trials are needed to confirm such findings. [ABSTRACT FROM AUTHOR]

Contrast media (CM)-associated adverse effects including mainly acute kidney injury and hypersensitivity reactions still remain a significant treatment burden to vulnerable patients requiring percutaneous coronary intervention (PCI). The complete omission of CM administration accompanied by intravascular ultrasound (IVUS) guidance may offer an appropriate revascularization treatment. We hereby present a case series of four patients with challenging coronary lesions and relative/absolute contraindications to CM use [(hypersensitivity reaction owning to CM, history of contrast-induced acute kidney injury, solitary kidney, or advanced chronic kidney disease (CKD)] who underwent absolute zero-contrast IVUS-guided PCI following a predetermined protocol. The initial diagnostic angiography was reviewed for landmark identification, and multiple guidewires created a metallic road map providing additional landmarks and protected side branches. IVUS imaging was performed to determine lesion length, reference segments and landing zones, assess stent expansion/apposition and identify major complications. All procedures were successfully completed without any CM administration, renal function deterioration, pericardial effusion, or stent edge dissection. We demonstrated the feasibility of absolute zero-contrast IVUS-guided PCI in patients with complex coronary lesions susceptible to CM-associated adverse effects. Since the safety of this strategy is well-documented in patients with CKD and challenging lesions morphology even in acute settings, evidence-based validation of this approach is capable of changing the otherwise conservative treatment of vulnerable patients where even minimum doses of CM may have detrimental effects. Patients with vulnerable renal function as well as former hypersensitivity reaction to contrast media encounter a significant treatment burden regarding coronary artery disease. Zero-contrast IVUS-guided strategy based on a predetermined protocol provides a feasible alternative approach in patients susceptible to contrast media-associated adverse effects even in the presence of complex coronary lesions. • CM side effects (renal function impairment and hypersensitivity reactions) are a treatment burden to vulnerable patients. • The complete omission of CM during PCI with the advent of IVUS may be the answer to CM-associated adverse effects. • Zero-contrast IVUS-guided strategy based on a predetermined protocol is a feasible approach even in complex coronary lesions. • A randomized multicenter control trial will examine the effectiveness of this technique and its clinical significance. [ABSTRACT FROM AUTHOR]

The clinical benefits of transcatheter edge to edge mitral valve repair have been well established in patients with heart failure and severe mitral regurgitation (MR) who have prohibitive surgical risk. In March of 2019, the FDA approved the MitraClip for treatment of selected patients with HF and severe secondary MR. However, the relative outcomes of patients with HFrEF and HFpEF treated with MitraClip are largely unknown. We therefore sought to investigate the incidence and characteristics of in-hospital mortality in patients with HFpEF and HFrEF following MitraClip. The study sample analyzed was originated from the National Inpatient Sample (NIS) registry which includes data from hospitalized patients in the United States (US) between January 1, 2012 and December 31, 2020. Data were extracted from the entire NIS registry using ICD-9 codes. Patients with the primary or secondary diagnosis of MitraClip were identified. Hospitalizations for HFpEF and HFrEF were identified based on ICD-9-CM and ICD-10-CM codes. Demographics, conventional risk factors, and in-hospital outcomes were evaluated. 23,260 hospitalizations for MitraClip implantation between 2016 and 2020 were analyzed. The HFrEF group had higher absolute rates of complications as well as a higher observed in-hospital mortality (2.4 % vs 1.7 %; OR 0.75 95 % CI 0.44–1.26; p 0.28) which did not meet statistical significance. Absolute rates of acute myocardial infarction (AMI), acute kidney injury (AKI) and respiratory failure necessitating invasive mechanical ventilation were observed to be higher among HFrEF patients. Post-procedural shock was significantly more common in patients with HFrEF (9.0 % vs 2.8 %: OR 0.34 95 % CI 0.25–0.48 p < 0.001). Significantly longer hospitalizations were observed in the HFrEF cohort (5.3 ± 11.2 days vs 4.2 ± 7.3 days; p < 0.001) as well as a higher total hospitalization cost (61,723 ± 56,728 USD vs 57,278 ± 46,143). In the present study of US patients, those with HFrEF were observed to have statistically higher risk of in-hospital post-procedural shock and longer hospitalization length of stay when compared with patients with HFpEF who underwent MitraClip implantation. Additionally, patients with HFrEF undergoing MitraClip procedure were observed to have higher absolute rates of certain post-procedural complications, however these observations did not reach statistical significance. Understanding of the aforementioned differences after MitraClip implantation may be useful in-patient selection, prognostic guidance, and hypothesis generation to propel future large clinical studies. • Patients with HFrEF were associated with higher risk of in-hospital post-MitraClip shock and longer hospitalization length of stay when compared with patients with HFpEF. • Patients with HFrEF undergoing MitraClip procedure were observed to have higher absolute rates of certain post-procedural complications. • Understanding of the aforementioned differences after MitraClip implantation may be useful in-patient selection and prognostic guidance. [ABSTRACT FROM AUTHOR]

To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD). The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke. The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups. The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group. • Depression is a well-known risk factor for atherosclerotic cardiovascular disease. • We examined the risk of ASCVD in depression patients with/without antidepressants. • Depression patients with antidepressants showed an increased risk of ASCVD. • Depression patients without antidepressants showed a decreased risk of ASCVD. • The use of antidepressants, rather than depression, is the risk factor for ASCVD. [ABSTRACT FROM AUTHOR]

Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. This study sought to determine the effect of ticagrelor on limb events. Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P interaction = 0.40) or TIMI major bleeding (P interaction = 0.3239). Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795) [Display omitted] [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) is a causal genetic risk factor for atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large U.S. population cohorts. This study examined the relationship of Lp(a) with ASCVD outcomes in a large, pooled, multi-ethnic U.S. cohort. The study included data on Lp(a) and ASCVD outcomes from 5 U.S. prospective studies: MESA (Multi-Ethnic Study of Atherosclerosis), CARDIA (Coronary Artery Risk Development in Young Adults), JHS (Jackson Heart Study), FHS-OS (Framingham Heart Study-Offspring), and ARIC (Atherosclerosis Risk In Communities). Lp(a) levels were classified on the basis of cohort-specific percentiles. Multivariable Cox regression related Lp(a) with composite incident ASCVD events by risk group and diabetes status. The study included 27,756 persons without previous ASCVD who were aged 20 to 79 years, including 55.0% women, 35.6% Black participants, and 7.6% patients with diabetes, with mean follow-up of 21.1 years. Compared with Lp(a) levels <50th percentile, Lp(a) levels in the 50th to <75th, 75th to <90th, and ≥90th percentiles had adjusted HRs of 1.06 (95% CI: 0.99-1.14), 1.18 (95% CI: 1.09-1.28), and 1.46 (95% CI: 1.33-1.59), respectively for ASCVD events. Elevated Lp(a) predicted incident ASCVD events similarly by risk group, sex, and race or ethnic groups, but more strongly in patients with vs without diabetes (interaction P = 0.0056), with HRs for Lp(a) levels ≥90th percentile of 1.92 (95% CI: 1.50-2.45) and 1.41 (95% CI: 1.28-1.55), respectively. Lp(a) also individually predicted myocardial infarction, revascularization, stroke, and coronary heart disease death, but not total mortality. The study shows, in a large U.S. pooled cohort, that higher Lp(a) levels are associated with an increased ASCVD risk, including in patients with diabetes. [Display omitted] [ABSTRACT FROM AUTHOR]

The natural history of moderate/severe atrial functional mitral regurgitation (AFMR) is unknown. The authors sought to study the incidence of left ventricular (LV) systolic dysfunction (LVSD), progression or regression of ≥mild-moderate AFMR, and impact on mortality. Adults with left atrial (LA) volume index ≥40 mL/m2, ≥mild-moderate AFMR, and follow-up echocardiogram were followed for incident LVSD (ejection fraction <50% and ≥10% lower than baseline), progression of mild-moderate/moderate AFMR to severe, and persistent regression of AFMR to no/trivial. Relation of AFMR progression or regression as time-dependent covariates with all-cause mortality was studied. Incidence of LVSD was compared with patients with no/mild AFMR matched on age, sex, comorbidities and ejection fraction. Patients were followed until mitral intervention, myocardial infarction, or last follow-up. A total of 635 patients (median age 75 years, 51% female, 96% mild-moderate/moderate AFMR, 4% severe AFMR) were included. Over a median 2.2 years (Q1-Q3: 1.0-4.3 years), incidence rates per 100 person-years were 3.2 for LVSD (P = 0.52 vs patients with no/mild AFMR), 1.9 for progression of AFMR, and 3.9 for regression. Female sex and larger LA volume index were independently associated with progression, whereas younger age, male sex, absent atrial fibrillation, and higher LA emptying fraction were independently associated with regression. Neither AFMR progression nor regression was independently associated with mortality. Instead, independent risk factors for mortality included older age, concentric LV geometry, and higher estimated LV filling and pulmonary pressures. In patients with predominantly mild-moderate/moderate AFMR, regression of MR was more common than progression, but neither was associated with mortality. Instead, diastolic function abnormalities were more important. Over a median 2-year follow-up, LVSD risk was not increased. [Display omitted] [ABSTRACT FROM AUTHOR]

Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis. • Following an ACS, 10-15% of patients experience further ischaemic events within 1-year. Impaired endogenous fibrinolysis is a strong independent risk factor that may drive this "residual risk" and is unaffected by dual antiplatelet therapy (DAPT). • In a prospective trial, we assessed whether very low dose rivaroxaban (VLDR, 2.5mg b.i.d.), on top of DAPT, can improve fibrinolysis. Endogenous fibrinolysis was assessed with the Global Thrombosis Test and Thromboelastography. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75mg daily; clopidogrel 75mg daily plus VLDR; or ticagrelor 90mg b.i.d., in addition to aspirin. At 30-days, there was no difference in fibrinolysis or clot lysis times between the groups, nor compared to baseline. • Addition of VLDR fails to enhance lysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic strategies can improve fibrinolysis. [ABSTRACT FROM AUTHOR]

The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69–0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72–0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32–0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50–0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60–0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59–0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27–0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users. • Statins possess antithrombotic and profibrinolytic properties • We compare the 3 months all-cause mortality in patients with DVT according to the use of statins • Statin users with isolated DVT were at lower adjusted risk for death at 3 months • Randomized trials are needed to confirm these data [ABSTRACT FROM AUTHOR]

The American College of Cardiology (ACC) recently published an Expert Consensus Decision Pathway for chest pain. The purpose of this study was to validate the ACC Pathway in a multisite U.S. cohort. An observational cohort study of adults with possible acute coronary syndrome was conducted. Patients were accrued from 5 U.S. Emergency Departments (November 1, 2020, to July 31, 2022). ECGs and 0- and 2-hour high-sensitivity troponin (Beckman Coulter) measures were used to stratify patients according to the ACC Pathway. The primary safety outcome was 30-day all-cause death or myocardial infarction (MI). Efficacy was defined as the proportion stratified to the rule-out zone. Negative predictive value for 30-day death or MI was assessed among the whole cohort and in a subgroup of patients with coronary artery disease (CAD) (prior MI, revascularization, or ≥70% coronary stenosis). ACC Pathway assessments were complete in 14,395 patients, of whom 51.7% (7,437 of 14,395) were women with a median age of 56 years (Q1-Q3: 44-68 years). Known CAD was present in 23.5% (3,386 of 14,395) and 30-day death or MI occurred in 8.1% (1,168 of 14,395). The ACC Pathway had an efficacy of 48.1% (95% CI: 47.3%-49.0%). Among patients in the rule-out zone, 0.3% (22 of 6,930) had death or MI at 30 days, yielding a negative predictive value of 99.7% (95% CI: 99.5%-99.8%). In patients with known CAD, 20.0% (676 of 3,386) were classified to the rule-out zone, of whom 1.5% (10 of 676) had death or MI. The ACC expert consensus decision pathway was safe and efficacious. However, it may not be safe for use among patients with known CAD. [Display omitted] [ABSTRACT FROM AUTHOR]

Clinical presentation of postoperative myocardial infarction (POMI) is often silent. Several international guidelines recommend routine troponin surveillance in patients at risk. We compared how these different guidelines select patients for surveillance after noncardiac surgery with our established risk stratification model. We used outcome data from two prospective studies: Measurement of Exercise Tolerance before Surgery (METS) and Troponin Elevation After Major non-cardiac Surgery (TEAMS). We compared the major American, Canadian, and European guideline recommendations for troponin surveillance with our established risk stratification model. For each guideline and model, we quantified the number of patients requiring monitoring, % POMI detected, sensitivity, specificity, diagnostic odds ratio, and number needed to screen (NNS). METS and TEAMS contributed 2350 patients, of whom 319 (14%) had myocardial injury, 61 (2.5%) developed POMI, and 14 (0.6%) died. Our risk stratification model selected fewer patients for troponin monitoring (20%), compared with the Canadian (78%) and European (79%) guidelines. The sensitivity to detect POMI was highest with the Canadian and European guidelines (0.85; 95% confidence interval [CI] 0.74–0.92). Specificity was highest using the American guidelines (0.91; 95% CI 0.90–0.92). Our risk stratification model had the best diagnostic odds ratio (2.5; 95% CI 1.4–4.2) and a lower NNS (21 vs 35) compared with the guidelines. Most postoperative myocardial infarctions were detected by the Canadian and European guidelines but at the cost of low specificity and a higher number of patients undergoing screening. Patient selection based on our risk stratification model was optimal. [ABSTRACT FROM AUTHOR]

The management of adult patients with anomalous aortic origin of the right coronary artery (ARCA) from the left aortic sinus poses important challenges. The presence of symptoms or documented ischaemia, the anatomical characteristics of the ostium, and the course of the coronary determine decision-making. A retrospective review was performed of all cases of surgical management of ARCA at a single centre. The primary endpoints were mortality and myocardial infarction at 30 days. Secondary endpoints included recurrence of symptoms, freedom from re-intervention, and mortality during long-term follow-up. From October 2019 to August 2023, 15 adult patients underwent surgery for ARCA; 13 patients were included in this study (mean age 53.9±11.1 years; 10 female). A slit-like orifice, a long intramural segment, and an interarterial course were found in all patients. Twelve (12) patients (92.3%) were symptomatic: nine with angina, combined with dyspnoea on exertion in seven. One (1) patient had history of pre-syncope. One (1) patient presented with out-of-hospital cardiac arrest. All patients underwent formal unroofing of the orifice and intramural portion of the ARCA; five patients had a concomitant procedure. No 30-day mortality nor myocardial infarction was recorded. At a mean follow-up of 20.1±12.8 months, all patients were alive. One (1) patient (7.6%) developed recurrent dyspnoea; investigations showed no ischaemia. No repeated interventions were required. Surgical unroofing of anomalous coronary artery in the adult is safe and effective; correction of both the slit-like orifice and intramural portion of the anomaly provides a durable result in patients with ARCA. [ABSTRACT FROM AUTHOR]