Long-term Adverse Events Research Articles

Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis.

Statins are the gold standard in the treatment of dyslipidemia, significantly reducing the risk of cardiovascular disease. To systematically review the efficacy and safety of Moderate-intensity Rosuvastatin Plus Ezetimibe compared with High-intensity Rosuvastatin in treating Composite Cardiovascular Events. PubMed, Embase, Cochrane Library, CINAHL, Web of Science, China Knowledge Network, China Biological Literature Database, Wan Fang Database, and Weipu Database were searched to retrieve randomized controlled trials assessing the safety and efficacy of the two therapies from the time of construction to December 2023. The Jadad scale assessment tool was used to evaluate the quality of the included literature, and Review Manager 5.4 software was used for meta-analysis. The heterogeneity of outcomes was estimated by the I2 test, where we applied risk ratios (RR) and 95% confidence intervals (CI) to assess dichotomous outcomes and mean difference (MD) and 95% CI to present continuous outcomes. We used funnel plots to assess study publication bias and sensitivity analysis was used to address significant clinical heterogeneity. The meta-analysis described 21 RCTs involving 24592 participants. The findings indicated that moderate-intensity statin combination therapy improved low-density lipoprotein cholesterol (LDL-C) (MD -8.06, 95% CI [-9.48, -6.64] p < 0.05), total cholesterol (TG) (MD -5.66, 95% CI [-8.51, -2.82] p < 0.05), and non-high-density lipoprotein cholesterol (non-HDL-C) (MD -17.04, 95% CI [-29.55, -4.54] p < 0.05) to a greater extent and superior in achieving LDL-C <70 (RR1.26, 95% CI [1.22, 1.29] p < 0.05) and LDL-C <55 (RR1.66, 95% CI [1.56, 1.77] p < 0.05) ratios and in the incidence of adverse events than the high-intensity Rosuvastatin monotherapy group. However, there was no statistical difference between the two in improving HDL-C, total cholesterol (TC), and preventing long-term composite adverse cardiovascular events (ACE). Funnel plots indicated publication bias. Sensitivity analysis suggested instability in long-term composite cardiovascular events, HDL-C, and TC results. Moderate-intensity statin plus ezetimibe with combination therapy had better efficacy and safety than high-intensity statins. Future validation is needed with more long-term high-quality large samples.

Intraoperative Methadone in Spine Surgery ERAS Protocols: A Systematic Review of the Literature.

Systematic review. To systematically review the use of intraoperative methadone in spine surgery and examine its effects on postoperative opioid use, pain, length of stay, and operative time. Spine surgery patients commonly have a history of chronic pain and opioid use, and as a result, they are at an increased risk of severe postoperative pain. While pure mu opioids remain the standard for acute surgical pain management, they are associated with significant short-term and long-term adverse events. Methadone presents an alternative to pure mu opioids which may improve postoperative management of pain following intraoperative use. A systematic review of MEDLINE, Embase, and Web of Science databases was conducted to review existing literature detailing operating time, postoperative pain, opioid usage, and hospital length of stay (LOS) following intraoperative methadone administration in spine surgery. Following screening of 994 articles and application of inclusion criteria, 8 articles were included, 4 of which were retrospective. Conventional spine surgery intraoperative analgesic strategies used as comparators for intraoperative methadone included hydromorphone, ketamine, and sufentanil. Considering patient outcomes, included studies observed that patients treated with intraoperative methadone had statistically similar or significantly reduced pain scores, opioid usage, and LOS compared with comparator analgesics. However, one study observed that intraoperative methadone used in a multimodal analgesia regimen strategy with ketamine resulted in a shortened LOS compared with the use of intraoperative methadone alone. Differences in operating time between cases that used intraoperative methadone and cases that used comparator analgesics were not statistically significant among included studies. Methadone may present an alternative option for both intraoperative and postoperative analgesia in spine surgery recovery protocols and may reduce postoperative pain, opioid use, and LOS while maintaining consistent operating time and reduced side effects of pure mu opioids. Level II.

Long-Term Efficacy and Safety of Bimekizumab and Other Biologics in Moderate to Severe Plaque Psoriasis: Updated Systematic Literature Review and Network Meta-analysis.

Biologic treatments have made complete skin clearance in moderate to severe plaque psoriasis a real possibility. Although clinical trials demonstrated the superiority of bimekizumab over secukinumab, adalimumab, and ustekinumab, direct comparisons with other biologics are not available. This systematic literature review (SLR) and network meta-analysis (NMA) aimed to evaluate the 1-year efficacy and safety of bimekizumab versus other biologic systemic therapies for moderate to severe plaque psoriasis. We conducted an SLR to retrieve published randomised controlled trials (RCTs) in patients with moderate to severe plaque psoriasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews and PsycINFO on 13 January 2022. Two NMA types were used to analyse the long-term achievement of 100% improvement from baseline in Psoriasis Area and Severity Index (PASI100): (1) NMA of cumulative clinical benefits, based on the area under the curve, from week0 to 52; (2) multinomial NMA at weeks44‒60. Binomial NMA was used to evaluate long-term serious adverse events (SAEs). The SLR identified 38 RCTs, of which 19 were included in the NMA. Bimekizumab 320mg administered every 4weeks to week16 then every 8weeks (Q4W/Q8W) showed a greater cumulative average number of days of PASI100 response compared with all other biologics. These differences were statistically significant versus all biologics, except risankizumab 150mg. The multinomial NMA demonstrated that interleukin (IL)-17 and IL-23 inhibitors were the most efficacious treatments. No significant differences were found in long-term occurrence of SAEs. Bimekizumab 320mg Q4W/Q8W was superior to most other treatments in maintaining complete skin clearance during the first year of treatment. It demonstrated a greater cumulative average number of days with completely clear skin while displaying a comparable safety profile compared with all other biologics.

Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors

The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms. We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts). The ICI benefit group was enriched for propionate (P=0.01) and butyrate/isobutyrate (P=0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P<0.001, butyrate/isobutyrate P=0.002). The acetyl-CoA pathway (P=0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P=0.07), which was validated in the Routy cohort (P=0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P=0.03), propionic acid (P=0.09), and butyric acid (P=0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P<0.05). Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088). This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).

Incidence and outcomes of transient new-onset atrial fibrillation complicating acute coronary syndromes: results from a systematic review and meta-analysis

Abstract Background The overall risk of long-term adverse events of a transient episode of new-onset atrial fibrillation (AF) in patients with acute coronary syndrome (ACS) remains uncertain. This meta-analysis aimed to assess the prognostic impact of transient new-onset AF complicating ACS. Methods and results Cohort studies examining the risk of adverse events in patients with transient new-onset AF compared to those in sinus rhythm after ACS were identified through a comprehensive search of MEDLINE, Scopus, Cochrane, and Google Scholar Library. Studies reporting the incidence of ischaemic stroke events, recurrent AF, or all-cause mortality at the longest follow-up were included. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CI) were synthesized using inverse variance-weighted random-effects meta-analysis. In the seven observational studies included, comprising 151 735 patients, 6 597 (4.3%) experienced transient new-onset AF, which was associated with an increased risk of ischaemic stroke, recurrent AF, or all-cause mortality (HR: 2.24, 95% CI: 1.75–2.85; P &amp;lt; 0.0001; I2 = 30.76%; seven studies). The results remained consistent across each individual endpoint, including ischaemic stroke (HR 2.38, 95% CI: 1.64–3.44; P &amp;lt; 0.01; I2 = 50.2%; five studies), recurrent AF (HR 4.68, 95% CI: 2.07–10.59; P = 0.0002; I2 = 50.2%; four studies), and all-cause mortality (HR 1.36, 95% CI: 1.08–1.71; P = 0.0089; I2 = 53.25%; four studies). Meta-regression analyses revealed a significant increase in these adverse events associated with ST-elevation myocardial infarction (P = 0.001), while there was a tendency for their decrease associated with oral anticoagulant prescription at discharge (P = 0.07). Conclusions The occurrence of transient new-onset AF is associated with an elevated long-term risk of stroke, recurrent AF, and all-cause mortality in patients with ACS. Consequently, these data urge randomized clinical trials to assess the best antithrombotic regimen while potentially helping the current treatment decision-making process for these patients.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

Novel role of human epicardial adipocyte-derived SPARCL1 in suppression of postoperative atrial fibrillation in patients undergoing cardiovascular surgery

Abstract Background Postoperative atrial fibrillation (POAF) occurs in 20-50% after cardiovascular surgery and is associated with the short and long-term morbidity/mortality. The epicardial adipose tissue (EAT) may have a potential role to regulate the incidence of POAF. Purpose We explored the possible role of human epicardial adipocyte-derived adipokines in the regulation of the myocardial redox state and POAF. Methods We prospectively evaluated 149 patients without known AF who underwent scheduled open-heart cardiovascular surgery between May 2020 and November 2022. They were divided into POAF or Non-POAF group and followed up after discharge (476.6 ± 290.0 days). POAF was defined as AF lasting more than 30 seconds after the surgery. Human EAT samples were obtained from these patients during surgery and the preadipocytes were isolated. Preadipocytes were terminally differentiated to mature adipocytes and mRNAs were extracted. Genome-wide expression profiling of 6 vs. 6 matched samples of the POAF and Non-POAF groups was performed using Microarray analysis, and the results were validated with qPCR in all the cohort samples. The effects of secreted adipokines on the cardiomyocytes were assessed in terms of oxidative stress. Superoxide and whole reactive oxygen species (ROS) were evaluated with luminometry and live-cell fluorescent probes respectively. As the oxidative stress associated signalling, the phosphorylation of ERK and p38-MAPK were evaluated with western blotting. Angiotensin II (Ang-II) was used to induce oxidative stress and phosphorylation of MAPK. Results POAF was observed in 53 patients (36%). Microarray analysis (n = 6) revealed that there were 132 down- or up-regulated cording genes in epicardial adipocytes of the POAF group compared to the Non-POAF group. Of these genes, 11 genes cording secretable molecules were validated by qPCR (n = 69), showing that only SPARCL1 had significantly downregulated in the POAF group compared to the Non-POAF group (P = 0.005). Superoxide and ROS were induced by Ang II (P &amp;lt; 0.01) and attenuated by SPARCL1 dose-dependent manner (P &amp;lt; 0.01) in neonatal rat cardiomyocytes. The phosphorylation of ERK and p38-MAPK were induced by Ang II (P &amp;lt; 0.01) and attenuated by SPARCL1 (P &amp;lt; 0.01) dose-dependently. Co-culture of human induced pluripotent stem cell-derived atrial cardiomyocytes (iPS-ACM) and human epicardial adipocytes revealed that the adipocytes derived from Non-POAF group suppressed the superoxide (P = 0.002) and ROS (P = 0.02) in iPS-ACM compared to POAF group. Kaplan-Meier survival analysis revealed that the POAF group (P = 0.01) and low SPARCL1 expression in epicardial adipocytes (P = 0.018) were associated with a higher incidence of long-term adverse cardiovascular events after surgery. Conclusion: SPARCL1 derived from epicardial adipocytes may play an important role in the suppression of POAF and long-term cardiovascular events via improving the myocardial redox state.

Stroke-Heart syndrome: a population-based cohort study and cluster analysis

Abstract Background The onset of acute cardiovascular complications following a stroke, also known as "Stroke-Heart Syndrome", can occur in up to 20% of patients following a stroke. The syndrome remains under-investigated and limited data exists related to the occurrence and impact of the Stroke-Heart Syndrome in an Asian population. Objectives We aimed to investigate the potential impact of the Stroke-Heart Syndrome and its associations in a retrospective population based-cohort study. Methods The analysis included patients with new-onset ischaemic stroke (IS) June 2006 and May 2022 with 5 years’ follow-up. Patients who developed acute cardiovascular complications within 28 days of their index stroke were compared to patients who did not. The association between acute cardiovascular complications and longer term outcomes were evaluated using multivariate Fine-Grey analyses to adjust for competing risk of mortality, and a Cox regression model for all-cause mortality. Inverse probability of treatment weighting was applied prior to analysis. Furthermore, a hierarchical cluster analysis was performed in the cohort of stroke patients with "Stroke-Heart Syndrome", to further evaluate associations between the identified clusters and (i) longer term outcomes, as well as (ii) the development of acute cardiovascular complications. Results A total of 141,118 patients (median age 72.4 (IQR 62.6 to80.8) years; 45.4% female) were included in the analysis, 6,457 of who developed acute cardiovascular complications, and 134,661 of whom did not. At 5 years follow-up, acute cardiovascular complications were associated with a higher risk of developing recurrent ischaemic stroke (Sub-distribution Hazard Ratio [SHR]: 1.20, 95% Confidence Interval [CI]: 0. 1.12-1.28, p= &amp;lt;0.001), haemorrhagic stroke (SHR: 1.15, 95%CI: 1.03-1.28, p=0.014), myocardial infarction (SHR: 1.53, 95%CI: 1.39-1.69, p=&amp;lt;0.001), and cardiovascular death (SHR: 1.57, 95%CI: 1.45-1.71, p=&amp;lt;0.001) as well as all-cause mortality (HR: 1.07, 95%CI: 1.07-1.07, p=&amp;lt;0.001). A total of 4 clusters were identified in the cluster analysis. Compared to Cluster 3, the other Clusters were associated with increased 5-year risk of myocardial infarction, cardiovascular death and all-cause mortality (p=&amp;lt;0.001). In this cohort, compared to Cluster 2, the other clusters had an increased risk of developing acute cardiovascular complications, in particular acute ischaemic heart disease and acute heart failure (p=&amp;lt;0.001). Cluster 3 tended to be younger with fewer comorbidities and prescribed medications. Over 90% of the patients in Cluster 2 were aged over 75 (with 43% aged 85 years or over). Conclusion Stroke-Heart Syndrome was associated with long-term adverse cardiovascular events in this Asian cohort of ischaemic stroke patients.

A novel marker of cardiovascular risk stratification: the role of total cardiovascular calcium score using cardiac CT

Abstract Introduction It is widely accepted that coronary and valve calcification measured by cardiac CT, individually, are associated with cardiovascular events and mortality. However, the role of an encompassing marker of cardiovascular atherosclerosis could be more representative of the real cardiovascular risk. Objectives To determine the prognostic value of a combined coronary, valvular and aortic calcium score to predict long-term major adverse cardiac and cerebrovascular events (MACCE). Methods We conducted a single center study on 316 consecutive patients who underwent cardiac CT scan between January 2018 and December 2019. We excluded patients with poor imaging quality, constrictive pericarditis, prosthetic valves and/or devices. The calcium score of coronary arteries (CA), mitral valve (MV), aortic valve (AoV), ascending aorta (AAo) and aortic arch (AAc) were calculated from non-contrast ECG-gated CT using the Agatston method and were combined to derive a valvular (VA=MV+AoV), total cardiac (TC=CA+VA) and total cardiovascular (TCV=TC+AAo+AAc) calcium scores (Fig.1A). The primary endpoint was a composite of MACCE, defined as all-cause death, stroke, myocardial infarction and hospital admission for heart failure. Results A total of 275 CT scans were suitable for analysis. Mean age was 59.6±12.3 years, 48.4% were female. A total of 183 (66.7%) patients presented calcification in at least one location. Patients with calcification on any of the prespecified locations had higher prevalence of hypertension, dyslipidemia and type 2 diabetes mellitus (DM) than those without any calcium (p&amp;lt;0.05). After a median follow-up of 3.18 [IQR 2.84-3.69] years, 40 (14.5%) patients had met the primary endpoint. Regression analyses demonstrated that all CA, VA, TC and TCV scores were independent predictors of MACCE (p&amp;lt;0.05 for all). The best prediction models included calcium score (all combinations), age, sex, type 2 DM and smoking status (Fig.1B). The model with TCV score was the most powerful predictor of MACCE (χ2 47.8), followed by TC score (χ2 43.1). Of interest, the model with CA score had the poorest performance (χ2 35.4). Conclusion Coronary calcium score is a quick way to stratify risk in clinical practice, but its performance is too focused on coronary events. Total cardiovascular calcium score, however, is more encompassing, also quick to measure, and a more truthful depiction of the patient’s cardiac and cerebrovascular risk, potentially allowing a more tailored and timely approach to risk factors in clinical practice.

Hs-CRP modifies the impact of stress hyperglycemia ratio on long-term outcomes in patients with acute coronary syndrome

Abstract Background In recent years, studies have demonstrated the promising predictive value of stress hyperglycemia ratio (SHR) for adverse outcomes in patients with acute coronary syndrome (ACS). Nevertheless, knowledge regarding the effects of inflammation on the risks associated with SHR remains limited. Considering the potential interplay, we hypothesize that the well-recognized biomarker reflecting residual inflammation, high-sensitivity C-reactive protein (hs-CRP), may exert an influence on SHR-related cardiovascular risks. Purpose The objective of this study was to investigate the association between hs-CRP level and SHR-related long-term adverse events in ACS patients. Methods Among 10,724 consecutive patients who underwent percutaneous intervention treatment throughout the year 2013, 6149 ACS patients were eventually enrolled. SHR was calculated employing the formula: SHR = admission blood glucose (ABG) / [1.59 x HbA1c (%) – 2.59]. Based on their levels of hs-CRP, patients were stratified into two groups, with the cut-off set at 2 mg/L. The primary endpoint was defined as all-cause mortality, and the secondary endpoint was the major adverse cardiac and cerebrovascular events (MACCE), consisting of all-cause death, non-fatal myocardial infarction, coronary revascularization, and ischemic stroke. Results 238 (3.7%) all-cause mortality and 1275 (20.0%) MACCE occurred during the 5-year follow-up. The average age of the overall cohort was 58.39 ± 10.38 years, and 4723 (76.8%) were male. After adjusting for the potential confounders, multivariable Cox regression revealed a significant correlation between hs-CRP level and SHR for all-cause mortality (P for interaction = 0.009), and there were diverse associations between SHR and long-term risks depending on the levels of hs-CRP: With hs-CRP &amp;lt; 2mg/L, there was no significant risk of all-cause mortality at any SHR quantiles, while the lowest SHR quantile showed a 1.321-fold increased risk of MACCE [Hazard Ratio (HR): 1.321, 95% confidence interval (CI) 1.034-1.688, P = 0.026]. Conversely, with hs-CRP ≥ 2mg/L, significant association was observed between SHR and all-cause mortality (all P &amp;lt; 0.05). Notably, the highest SHR quantile exhibited the greatest risk for both all-cause mortality (HR: 4.030, 95% CI 1.778-9.134, P &amp;lt; 0.001) and MACCE (HR: 1.299, 95% CI 1.010-1.672, P = 0.042). Conclusions This large-scale real-world study was the first to report that the pattern of SHR-associated long-term cardiovascular risks in ACS patients was modified by the levels of hs-CRP, suggesting a potential interaction between inflammation and stress hyperglycemia that contributes to poor prognosis. When applying risk stratification, both factors should be comprehensively considered, and patients exhibiting high SHR along with concomitantly elevated hs-CRP may merit more rigorous risk management.Figure 1.Multivariable COX regression

Predictive role of peak VO2 for short- and long-term major adverse cardiac events in patients with high cardiovascular risk.

The objective of this study was to assess the accuracy of VO2 measurements in predicting long-term major adverse cardiac events (MACEs) in patients with high cardiovascular risk. Based on a10-year atherosclerotic cardiovascular disease risk score, 333 patients with high cardiovascular risk were included in this retrospective analysis. The study endpoint was MACEs, comprising all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction or stroke, and coronary revascularization. The study cohort was divided into two groups according to the frequency of MACE occurrence. Measurements of VO2 were assessed for the prediction of MACEs. The best predictive accuracy for 1‑year MACEs was determined to be aVO2 max value of ≥ 20.3 mL/kg/min, with 60% specificity and 60% sensitivity (area under the curve [AUC]: 0.61; 95% confidence interval [CI]: 0.51-0.71; p < 0.001), and for 5‑year MACEs it was ≥ 19.9 mL/kg/min, with 69% specificity and 64% sensitivity (AUC: 0.69; 95% CI: 0.62-0.76; p < 0.001). Multivariable Cox regression analysis, after adjusting for univariable factors, showed that VO2 max was independently associated with both short- and long-term MACEs in patients at high cardiovascular risk (hazard ratio [HR]: 0.900, 95% CI: 0.858-0.943, p < 0.001). According to the results of this pilot study, VO2 max can predict both short- and long-term MACEs in patients at high cardiovascular risk.

Arterial Stiffness Associated with Long-Term Major Adverse Cardiac Events in Patients of Primary Aldosteronism.

As a novel parameter for risk prediction, artery stifiness may hold promise in refining risk assessment strategies, guiding therapeutic interventions, and ultimately improving cardiovascular outcomes in patients with primary aldosteronism (PA). To investigate the correlation between brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, and the occurrence of major adverse cardiovascular events (MACEs) in patients with PA under a primary prevention design. Among the 830 patients included in the final analysis, 113 (13.6%) developed inciden t MACEs over a median follow-up period of 5.8 years, with a crude rate of 23.2 per 1000 person-years. Multivariable Cox proportional hazards analyses revealed that baPWV was an independent risk factor for incident MACEs, with an adjusted hazard ratio of 1.01 (P = 0.028). The generalized additive model identified a cut-off value of 2000 cm/s for baPWV, which was independently associated with incident MACEs, with a hazard ratio of 1.72 (P = 0.045). Subgroup analyses revealed that PA patients who were mineralocorticoid receptor antagonist (MRA) users and had high baPWV had a significantly higher risk of incident MACEs (HR = 3.34; P < 0.001), while the risk was not significant in patients who underwent adrenalectomy (P = 0.062). Furthermore, the addition of baPWV to the cardiovascular Framingham risk score significantly improved the category-free net reclassification index (0.308, P < 0.001). Our study found that 13.6% of patients with PA developed MACEs after a median follow-up of 5.8 years. Our findings highlight the potential utility of baPWV as a tool for risk stratification in PA patients in primary prevention, whereas adrenalectomy appears to mitigate this risk irrespective of baPWV. The measurement of baPWV could be a valuable addition to hypertension screening programs for primary prevention, providing additional predictive information for the potential occurrence of MACEs.

Safety and efficacy of high thoracic epidural analgesia for chest wall surgery in young adolescents: A retrospective cohort analysis and a new standardised definition for success rate.

Chest wall surgery for the correction of pectus excavatum or pectus carinatum has gained increased interest in recent years. Adequate pain treatment, respiratory physiotherapy and early ambulation are key to improving the outcomes. Although thoracic epidural analgesia is highly effective, its safety is controversial, leading to extensive scrutiny and questioning of its role. We hypothesise that thoracic epidural analgesia is effective and well tolerated to use in adolescents, with a high success rate and low pain scores. Observational retrospective cohort study. All adolescent cases in a high-volume academic tertiary chest wall surgery centre between March 1993 and December 2017 were included. A total of 1117 patients aged from 12 to 19 years of age and receiving either Ravvitch, Nuss or Abramson chest wall reconstruction for pectus excavatum were identified in our institutional chest wall surgery database. After applying selection and exclusion criteria, 532 patients were included in the current analysis. The primary endpoint of this study was the safety of epidural analgesia, assessed by the incidence of acute adverse events. Secondary endpoints were block success rates using a specific novel definition, and analgesic efficacy using recorded postoperative pain scores. More than 60% of patients experienced one or more adverse events. However, all events were minor and without consequences. No serious or long-term adverse events were detected. The success rate of thoracic epidural placement was 81%. Low postoperative pain scores were observed. Thoracic epidural analgesia is an extremely effective pain control technique, with a surprisingly high number of minor adverse events but safe with regard to serious adverse events. The local research ethics committee approved and registered this study on 16 May 2022 (registration number: S66594).

TCT-173 Contemporary Risk Prediction and Stratification of Long-Term Major Adverse Cardiac and Cerebrovascular Events After Percutaneous Coronary Intervention: The REMEDY Score

TCT-173 Contemporary Risk Prediction and Stratification of Long-Term Major Adverse Cardiac and Cerebrovascular Events After Percutaneous Coronary Intervention: The REMEDY Score

Association between haemoglobin decline and long-term outcomes in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention.

To explore the association between in-hospital haemoglobin decline and long-term mortality and major adverse cardiovascular and cerebrovascular events (MACCE) among ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). This retrospective analysis included adult patients who underwent primary PCI for STEMI. Haemoglobin levels were recorded at admission and 48-72 h later. Patients were divided into two groups based on the extent of haemoglobin decline: low (<3 g/dl or no decline) and high (≥3 g/dl). The primary endpoint was all-cause mortality at long-term follow-up. The secondary endpoint was MACCE. Patients were divided into two groups: low group (n = 665) and high group (n = 111). The mortality rate was significantly higher in the high group (72 of 111 patients; 65%) than in the low group (185 of 655 patients; 28%). Propensity score matching confirmed this association, with higher mortality (41 of 79 patients [52%] versus 25 of 79 patients [32%]) and MACCE rates (56 of 79 patients [71%] versus 41 of 79 patients [52%]) in the high group compared with the low group, respectively. There was a significant association between in-hospital haemoglobin decline, even without visible bleeding, and increased long-term mortality and MACCE in STEMI patients undergoing primary PCI.

Long-Term Adverse Limb Events After Femoral Artery Endovascular Revascularization: The Boston FAROUT Study

Background: Patient, lesion, and procedural characteristics may impact the long-term risks of adverse limb outcomes differently after successful endovascular revascularization for lower extremity peripheral artery disease. The study objective was to assess the relationships of patient, lesion, and procedural characteristics to the subsequent risk of major and minor adverse limb events over the decade after successful endovascular revascularization of the superficial femoral artery for chronic limb-threatening ischemia (CLTI) or lifestyle-limiting claudication. MethodsA retrospective cohort of patients who underwent endovascular revascularization between 2003-2011 were followed for a median of 9.3 (IQR, 6.8-11.1) years. Hazard ratios (HR) and 95% CI from Cox proportional hazards models assessed the risk of major adverse limb events (MALE) (major amputation, bypass, or thrombolysis) or minor revascularization, MALE alone, and minor revascularization alone. ResultsThere were 232 index limb revascularizations in 185 patients. Longer lesion length was associated with a higher risk of MALE or minor revascularization (HR, 2.09; 95% CI, 1.22-3.60) and minor revascularization alone (HR, 2.53; 95% CI, 1.39-4.61). Current smoking was linked with minor revascularization (HR, 3.83; 95% CI, 1.54-9.56). CLTI was associated with MALE or minor revascularization (HR, 1.89; 95% CI, 1.09-3.29), and MALE alone (HR, 7.43; 95% CI, 3.11-17.79). Black race/ethnicity (HR, 4.74; 95% CI, 1.51-14.9) and low-density lipoprotein >100 mg/dL (HR, 2.76; 95% CI, 1.20-6.35) were linked to MALE alone. ConclusionsFactors related to MALE differed from those related to minor revascularization. Lesion length and smoking were linked to minor revascularization, whereas CLTI, Black race/ethnicity, and elevated low-density lipoprotein were linked to MALE.

Prognostic Value of PRECİSE DAPT Score on Short- and Long-Term Outcomes in MINOCA Patients with Acute Coronary Syndrome.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) constitutes a significant subset of acute myocardial infarctions (AMI) with uncertain prognostic markers. Early risk assessment is crucial to identify MINOCA patients at risk of adverse outcomes. This study aimed to evaluate the predictive capacity of the PRECISE-DAPT score in assessing short- and long-term prognoses in MINOCA patients presenting with ST-segment elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). Among 741 MINOCA patients, the PRECISE-DAPT score was computed to analyze its association with in-hospital and follow-up major adverse cardiovascular events (MACE). Parameters showing significance in MACE (+) groups underwent statistical analysis: univariate logistic regression for in-hospital events and univariate Cox regression for follow-up events. For statistical significance, a predefined level of α = 0.05 was adopted. Parameters demonstrating significance proceeded to multiple logistic regression for in-hospital events and multivariate Cox regression for follow-up events. In-hospital MACE occurred in 4.1% of patients, while 58% experienced follow-up MACE. Hemoglobin levels and the PRECISE-DAPT Score were identified as independent parameters for in-hospital MACE. Furthermore, ejection fraction (EF%) and the PRECISE-DAPT Score emerged as independent predictors of follow-up MACE. The study revealed that a higher PRECISE-DAPT score was significantly associated with increased risks of both in-hospital and long-term major adverse cardiovascular events in MINOCA patients presenting with acute coronary syndrome (ACS), underscoring the score's potential in risk stratification for this patient cohort. _ PRECISE-DAPT score predicts MACE risk in MINOCA patients. _ Hemoglobin level and PRECISE-DAPT score predict in-hospital MACE. _ Ejection fraction and PRECISE-DAPT score predict long-term MACE.

CLINICAL AND ANGIOGRAPHIC OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION IN CHRONIC TOTAL OCCLUSION PATIENTS: A RETROSPECTIVE STUDY AT A TERTIARY CARE HOSPITAL

Chronic total occlusion (CTO) presents a unique challenge in percutaneous coronary intervention (PCI), requiring specialised techniques to achieve successful revascularisation. Despite the complexity, PCI in CTO cases has evolved significantly, showing promising outcomes. Objectives: To assess percutaneous coronary intervention's clinical and angiographic outcomes in chronic total occlusion patients. Methods: This retrospective observational study was conducted at NICVD Karachi, Pakistan, following approval from the hospital's ethical committee. It reviewed the medical records of 150 patients who underwent percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) from January 2024 to July 2024. Data was collected retrospectively from electronic medical records, including demographic details (age, gender, cardiovascular risk factors, and comorbidities), baseline clinical characteristics (presentation, symptoms, angina status, and prior cardiac history), and angiographic data (pre- and post-procedural findings, including the Thrombolysis in Myocardial Infarction (TIMI) flow grade). Clinical outcomes were assessed for both short-term and long-term results, including major adverse cardiac events (MACE) such as myocardial infarction, repeat revascularisation, target lesion revascularisation, and all-cause mortality. Statistical analysis was performed using SPSS Version 25. Results: 150 patients were enrolled, with a mean age of 54.81±8.97 years. The cohort included 54.7% males (82 patients) and 45.3% females (68 patients). Before PCI, 87.3% of patients (131) had no blood flow in the occluded artery, while 12.7% (19) had minimal flow. Post-PCI, 91.3% (137 patients) achieved full blood flow (TIMI Flow Grade 3), and 8.7% (13 patients) had partial flow. The procedural success rate was 91.3%. In terms of short-term major adverse cardiac events (MACE), 116(77.3%) patients had no events, while 22.7% (34 patients) experienced a myocardial infarction (MI). For long-term MACE, 84.0% (126 patients) had no adverse events, 10.0% (15 patients) required target lesion revascularisation, 4.7% (7 patients) underwent repeat revascularisation, and 1.3% (2 patients) experienced mortality. Conclusion: This study confirms the efficacy and safety of PCI for CTO patients, demonstrating high procedural success rates, significant clinical improvements, and relatively low long-term adverse events. However, advancing procedural techniques and fostering specialised training are essential to enhance patient outcomes due to the risks and complexities involved. Further research, including large-scale randomised controlled trials, is needed to validate these results and refine patient selection and management strategies for CTO PCI.

Five-Year Prostate-Specific Membrane Antigen Positron Emission Tomography-Based Outcomes of Spot-Scanning Proton Radiation Therapy for Localized Prostate Cancer: A Single Institution Experience

PURPOSE: We report 5-year oncologic outcomes of a prospective series of patients with prostate cancer treated with spot-scanning proton therapy (SSPT).METHODS AND MATERIALS: A prospective registry identified patients with prostate cancer treated with SSPT between January 2016 and December 2018. Five-year overall survival (OS), local control (LC), biochemical failure (BF), regional and distant failures, and adverse events (AEs) were assessed. Biochemical failure was defined as rise in PSA ≥ 2.0 ng/mL above nadir PSA. Baseline-adjusted toxicities were assigned using CTCAE v5.0.RESULTS: With a median follow up of 4.4 years, 284 prostate cancer patients were treated with SSPT. Median total radiation dose was 79.2 Gy over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for conventional fractionation (CF), hypofractionation (HF), and stereotactic body radiation therapy (SBRT), respectively. Biochemical failure rate for all patients was 6.7%. Five-year LC rates for CF, HF, and SBRT were 100%, 100%, and 97.3%, respectively (p = 0.07). Regional recurrences occurred in 12 (4.2%) patients: 8 treated with CF, 2 with HF, and 2 with SBRT (p = 0.62). Distant failures occurred in 12 patients (4.2%): 5 treated with CF, 7 with HF, and none with SBRT (p = 0.05). Five-year OS for patients treated with CF, HF, and SBRT SSPT were 88.1%, 86.1%, and 97.2%, respectively (p = 0.1). Acute and chronic grade 2+ GI AEs occurred in 8 (2.8%) and 51 (18.0%) patients, respectively. Acute and chronic grade 3+ GI AEs occurred in 3 (1.1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ GU-related AEs were observed in 71 (25%) and 63 (22.2%) patients, respectively. Acute and chronic grade 3+ GU toxicity were observed in 3 (1.1%) and 6 (2.1%) patients, respectively.CONCLUSIONS: SSPT provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates.

624. LONG-TERM OUTCOME OF NEOADJUVANT CHEMOTHERAPY FOLLOWED BY ESOPHAGECTOMY VERSUS DEFINITIVE PROTON BEAM THERAPY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Proton beam therapy (PBT) for esophageal squamous cell carcinoma (ESCC) is a promising curable treatment to avoid surgery, however the long-term outcomes have not enough been reported. Herein, we compared the survival outcomes of PBT with those of esophagectomy after neoadjuvant chemotherapy, which is the standard of care in Japan. Methods Patients with thoracic ESCC, clinical stage II or III, who underwent neoadjuvant chemotherapy plus radical resection and proton beam therapy between 2011 and 2020 were identified from database of our institute. The chemotherapy regimen was 5FU, CDDP (CF) with/without docetaxel. PBT was defined as irradiation of 50 GyE or more to the primary tumor, prophylactic irradiation, and concurrent chemotherapy (CF). Patients with other severe diseases and patients who could not be followed up were excluded. To adjust confounding factors, propensity score matching was performed; covariates included T and N-factor, age, gender, time of treatment and site of tumor. We retrospectively evaluated overall survival time of the surgery and PBT groups as primary outcome in this study. Results 244 patients were selected from the database. Median age was 71 years, 209 were male, 102 had esophagectomy after chemotherapy, and 142 had PBT. After propensity score matching, 46 patients in each group were selected by propensity score matching. Median survival was 42.8:44.6 months in the surgery and PBT groups, respectively (p=0.784). There were no treatment-related deaths, and Grade 3 or higher adverse events occurred in 8 and 8 patients (p=1.00), respectively. Conclusion PBT for stages II and III ESCC was comparable to neoadjuvant chemotherapy followed by surgery in long-term outcomes and adverse events.