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The article discusses the 40th anniversary of the TIMI Study Group, which began in 1955 with a focus on identifying determinants of myocardial oxygen supply and demand. Over the years, the TIMI trials have made significant contributions to cardiovascular care, including advancements in antithrombotic therapy, lipid-lowering therapy, and antiplatelet therapy. The TIMI trials have enrolled over 400,000 patients and have been instrumental in developing evidence-based medicine practices in cardiovascular care. [Extracted from the article]

In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease, most but not all randomized trials have reported that complete revascularization (CR) offers advantages over culprit vessel-only revascularization. In addition, the optimal timing and assessment methods for CR remain undetermined. The purpose of this study was to identify the optimal revascularization strategy in patients with STEMI and multivessel disease, using a network meta-analysis of randomized controlled trials. We searched PUBMED and EMBASE for randomized trials evaluating revascularization strategies in patients with STEMI and multivessel disease through July 2024. A network meta-analysis was performed analyzing CR vs culprit vessel-only revascularization as well as the timing of CR (immediate CR vs staged CR). Outcomes were also assessed with 4 CR strategies based on whether revascularization was immediate or staged and whether it was angiographically guided or functionally guided. The primary outcome was major adverse cardiovascular events (MACE). A total of 26 randomized trials that enrolled 15,902 patients were included. The mean weighted duration of follow-up was 25.2 ± 15.7 months. MACE was reduced with both immediate CR and staged CR compared with culprit-vessel-only treatment (RR: 0.48; 95% CI: 0.36-0.64 and RR: 0.65; 95% CI: 0.52-0.82, respectively), whether with angiographic or functional guidance. Immediate CR was associated with reduced MACE compared with staged CR (RR: 0.74; 95% CI: 0.56-0.97), whether CR was guided angiographically or functionally (RR: 0.77; 95% CI: 0.61-0.99 and RR: 0.49; 95% CI: 0.27-0.89, respectively) caused by reductions in MI. However, when the analysis was restricted to studies that reported both all MI and nonprocedural MI, the benefit of immediate CR in reducing MI compared with staged CR was diminished after excluding procedural MI (RR: 0.44; 95% CI: 0.27-0.71 with procedural MI vs RR: 0.65; 95% CI: 0.36-1.16 without procedural MI). Among patients with STEMI and multivessel disease, outcomes were better with immediate or staged CR compared with culprit vessel-only treatment, whether with angiographic or functional guidance. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between rural and urban hospitals are limited. Methods: We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. Results: We enrolled 1,583,271 patients with acute ischemic stroke from 1930 hospitals, comprising 1086 (56.3%) rural sites with 735,452 patients and 844 (43.7%) urban sites with 847,891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs 28.3%; difference: –2.3% (–2.5% to −2.0%)), endovascular treatment (0.6% vs 1.9%; difference: –1.3% (–1.3% to −1.2%)), vessel assessment (88.5% vs 92.0%; difference: –3.5% (95% confidence interval (CI): –3.6% to −3.4%)), and anticoagulants for atrial fibrillation at discharge (42.9% vs 47.7%; difference: –4.8% (95% CI: –5.4% to −4.2%)). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs 8.0%; adjusted odds ratio (OR): 1.22 (95% CI: 1.20–1.23); adjusted risk difference (aRD): 1.3% (95% CI: 1.2%–1.4%)) and a slightly lower rate of complications (10.9% vs 13.0%; aOR: 0.83 (95% CI: 0.82–0.84); aRD: –1.3% (95% CI: –1.3% to –1.3%)). No notable rural-urban differences were observed in MACE and disability at discharge. Conclusion: Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. Data access statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request. [ABSTRACT FROM AUTHOR]

Background: This meta‐analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs). Methods: We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non‐ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random‐ or fixed‐effects models. Results: Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow‐up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non‐ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all‐grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non‐ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs. Conclusion: The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy. [ABSTRACT FROM AUTHOR]

Aim: To explore the association between the non‐high‐density lipoprotein cholesterol (HDL‐C)/HDL‐C ratio (NHHR) and the risk of major adverse cardiovascular events (MACEs) and overall mortality in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: NHHR, calculated as (total cholesterol – HDL‐C)/HDL‐C, was evaluated in 10,188 participants. Cox proportional hazard regression models were employed to assess the association of NHHR with future risk of MACEs and overall mortality. Restricted cubic spline analysis, smooth curve fitting and piecewise regression models were utilized to explore the non‐linear correlation and establish the threshold. Subgroup and interaction analyses verified the robustness of the findings. The area under the receiver operating characteristic area under the curve assessed the additional predictive value of NHHR beyond conventional risk factors. Results: After adjusting for confounding factors, each 1‐unit increase in NHHR was associated with a 12% increased risk of MACEs (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.07–1.16; p < 0.0001), a 5% increase in overall mortality (HR: 1.05, 95% CI: 1.01–1.10; p = 0.0256), a 10% increase in cardiovascular disease mortality (HR 1.10, 95% CI: 1.03–1.18; p = 0.0074), an 12% increase in non‐fatal myocardial infarction (HR: 1.12, 95% CI: 1.05–1.18; p = 0.0002), and an 11% increase in non‐fatal stroke (HR: 1.11, 95% CI: 1.02–1.20; p = 0.0123). Analyses showed a non‐linear relationship between NHHR and MACEs in patients with T2DM (non‐linearity p < 0.001). A two‐stage linear regression model identified a threshold for MACEs at 6.28. Integration NHHR into the conventional model significantly enhanced predictive accuracy for MACEs. Conclusions: NHHR is a predictor of the risk of developing MACEs and overall mortality in patients with T2DM, with higher NHHR values independently associated with increased future MACE risks after full adjustment for confounders. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to assess the impact of varying degrees of initial serum sodium change among patients with type 2 diabetes (T2D) starting sodium–glucose cotransporter‐2 inhibitor (SGLT2i) therapy and their subsequent clinical outcome. Methods: We used medical data from a multicentre health care provider in Taiwan and recruited 4400 patients with T2D with baseline normal serum sodium (135–145 mmol/L) and follow‐up serum sodium measures available after 3 months of SGLT2i treatment from 1 June 2016 to 31 December 2021. Results: After a median of 2.9 (2.4, 3.4) months of SGLT2i treatment, overall, there was a minimal change in serum sodium levels (from 139.6 ± 2.4 to 139.5 ± 3.7 mmol/L). Most patients (87.8%) maintained normal sodium levels, while 8.6% (n = 378) experienced hyponatraemia (<135 mmol/L) and 3.6% (n = 158) hypernatraemia (>145 mmol/L). Factors independently associated with hyponatraemia included cancer history, chronic lung disease, insulin use, higher glycated haemoglobin, impaired liver function, lower baseline sodium and greater initial decline in kidney function. Conversely, factors linked to hypernatraemia included older age, absence of cancer history, loop diuretic and non‐steroidal anti‐inflammatory drug use, higher baseline sodium and a lesser initial decline in kidney function. Over a median of 26.0 months of follow‐up, hyponatraemia shortly after starting SGLT2i therapy was associated with significantly increased risks of major adverse cardiovascular events [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.83–3.48], heart failure for hospitalization (HR: 1.66; 95% CI: 1.16–2.37), major adverse renal events (HR: 2.27; 95% CI: 1.73–2.96) and all‐cause death (HR: 2.98; 95% CI: 2.17–4.11) after adjusting for clinically relevant factors. Non‐linear analysis indicated that a more pronounced initial decline in serum sodium levels correlated steeply with higher risks of these adverse events. Conclusion: While most patients with T2D maintain stable serum sodium homeostasis on SGLT2i therapy, a subset may experience dysnatraemic events with potential worse clinical consequences. Physicians should be vigilant about monitoring sodium levels and considering the associated risks when initiating SGLT2i therapy in patients with risk. [ABSTRACT FROM AUTHOR]

Rationale: Inhaled corticosteroids (ICSs) are the cornerstone of asthma treatment and significantly improve morbidity and mortality. Adverse effects of oral corticosteroids are well documented, but less is known about ICS. Objectives: The aim of this study was to determine the risk of adverse effects from short-term ICS use in people with asthma. Methods: We conducted observational studies in adults with asthma using two different United Kingdom nationwide datasets: Clinical Practice Research Datalink Aurum and Clinical Practice Research Datalink GOLD. The exposure was incident ICS; the outcomes were a major adverse cardiac event (MACE), arrhythmia, pulmonary embolism (PE), and pneumonia over 12 months. Our main analyses used a cohort method with stabilized inverse probability treatment weighting to balance confounding between exposed and unexposed patients. Secondary analyses included nested case–control studies and self-controlled case series. ICS use was treated as both a categorical and a continuous variable. Absolute risk was estimated using weighted flexible parametric models. Measurements and Main Results: Among 162,202 patients in our main cohort, there was an association with all outcomes at the medium daily ICS dose or higher (hazard ratios [HRs] at 201–599 μg: MACE, 2.63 [95% confidence interval (CI), 1.66–4.15]; arrhythmia, 2.21 [95% CI, 1.60–3.04]; PE, 2.10 [95% CI, 1.37–3.22]; and pneumonia, 2.25 [95% CI, 1.77–2.85]; HRs at ≥600 μg: MACE, 4.63 [95% CI, 2.62–8.17]; arrhythmia, 2.91 [95% CI, 1.72–4.91]; PE, 3.32 [95% CI, 1.69–6.50]; and pneumonia, 4.09 [95% CI, 2.98–5.60]). There were no associations with lower doses of ICSs. Secondary analyses produced similar results. The number needed to harm using 12 months of ICS at 201 to 599 μg was as follows: MACE, 473 (95% CI, 344–754); arrhythmia, 567 (95% CI, 395–1,006); PE, 1,221 (95% CI, 744–3,388); and pneumonia, 230 (95% CI, 177–327). The number needed to harm using ICS at ≥600 μg was as follows: MACE, 224 (95% CI, 148–461); arrhythmia, 396 (95% CI, 228–1,523); PE, 577 (95% CI, 309–4,311); and pneumonia, 93 (95% CI, 69–141). Conclusions: Short-term use of low-dose ICS was not associated with adverse effects. Moderate to high daily ICS doses were associated with an increased risk, but low frequencies, of cardiovascular events, PE, and pneumonia. It is important for clinicians to adhere to guideline recommendations to use the lowest effective ICS dose. [ABSTRACT FROM AUTHOR]

Objective: The objective was to review the safety and efficacy of daprodustat, a hypoxia-inducible factor–prolyl hydroxylase inhibitor (HIF-PHI) in the treatment of anemia of chronic kidney disease (CKD). Data Sources: A literature search was conducted in MEDLINE, EMBASE, and ClinicalTrials.gov using the keywords "daprodustat," "GSK1278863," and "hypoxia-inducible factor-prolyl hydroxylase inhibitors" from January 2010 through November 2023. Study Selection and Data Extraction: Literature was included if it evaluated pharmacology, pharmacokinetics, efficacy, and/or safety of daprodustat in human subjects and was reported in English. The manufacturer's product monograph was also utilized. Data Synthesis: Daprodustat significantly increased hemoglobin levels in CKD patients on dialysis (difference 0.18 g/dL) and not on dialysis (difference 0.08 g/dL) over 52-week treatment periods compared with erythropoiesis stimulating agents (ESA) in Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat (ASCEND)-D and ASCEND-ND, respectively. First occurrence of major adverse cardiovascular events (MACEs) was similar between daprodustat and ESAs in both trials. Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Daprodustat can be used in patients with CKD on dialysis and already receiving an ESA for at least 6 weeks to further increase serum hemoglobin levels without increasing the risk of MACE. Adverse effects of daprodustat that may occur more than ESAs include headache, emesis, and thrombosis. Conclusions: Daprodustat is a novel oral, non-iron therapy for treatment of anemia of CKD. It was Food and Drug Administration approved in 2023 in patients already receiving dialysis for at least 4 months but not in non-dialysis patients. Long-term data for safety and additional benefits are pending. [ABSTRACT FROM AUTHOR]

Background Remnant cholesterol (RC) is considered a significant risk factor for atherosclerotic cardiovascular diseases, and the progression of non-culprit coronary lesions (NCCLs) is also a prominent issue affecting the prognosis of patients with coronary artery disease. However, the relationship between residual cholesterol and vulnerable plaques in NCCLs that progress to major adverse cardiovascular events (MACE) is not well understood. Objective To explore the predictive value of RC for vulnerable plaques in NCCLs that develop MACE and its correlation with long-term prognosis. Methods A total of 488 patients with coronary artery disease admitted to the Cardiac Center of the First Affiliated Hospital of Xinjiang Medical University from February 2015 to February 2022 were selected as the study subjects. Baseline data of the patients were collected through the electronic medical record system, and coronary angiography and optical coherence tomography (OCT) were performed. Enrolled patients received scheduled follow-up at 1, 3, 6, and 12 months after discharge. Spearman's rank correlation test was used to explore the correlation between RC and the characteristics of thin-cap fibroatheroma (TCFA) plaques in NCCLs. Multiple Logistic regression analysis was used to explore the influencing factors of MACE in TCFA of NCCLs. The receiver operating characteristic curve (ROC curve) was plotted, and the area under the ROC curve (AUC) was calculated to explore the predictive value of RC for MACE in TCFA of NCCLs. Results A total of 488 coronary artery disease patients were included, and patients were divided into MACE group (n=38) and non-MACE group (n=450) based on whether NCCLs developed MACE. Plaque characteristics of NCCLs were identified by OCT, and a total of 749 NCCL plaques were analyzed, with 304 NCCL plaques having a minimum lumen area (MLA)

The editorial discusses the potential harm caused to asthma patients by using high-dose inhaled corticosteroids (ICSs). While ICSs are effective in controlling asthma symptoms, they can lead to serious adverse effects, especially at higher doses. A study by Bloom and colleagues found that medium to high doses of ICSs significantly increased the risk of cardiovascular events, pulmonary embolism, and pneumonia, with the highest risk associated with high-dose ICSs. The study suggests that high-dose ICSs, especially over the long term, should be avoided, and emphasizes the importance of step-back or step-down strategies in asthma management. [Extracted from the article]

Intravascular ultrasound (IVUS) guides deferral decision-making regarding the left main coronary artery (LMCA) and improves outcomes. Further studies regarding coronary physiology to guide revascularization in the LMCA are needed. Our aim was to evaluate the outcome of LMCA deferral using IVUS or coronary physiology via instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR). Between January 2014 and February 2022, patients undergoing evaluation with either IVUS or coronary physiology in the LMCA were included from the SWEDEHEART registry. Exclusion criteria were a minimum luminal area < 6 mm2, iFR ≤ 0.89, FFR ≤ 0.80, ad hoc percutaneous coronary intervention of lesions in the LMCA, proximal left anterior descending artery, and proximal circumflex artery, planned elective revascularization, and planned valvular surgery. The primary outcome was major adverse cardiac events (MACE), defined as a composite of all-cause death, myocardial infarction, and unplanned revascularization. Kaplan−Meier event rates and multivariable Poisson regression were used for the statistical analyses. Deferral of revascularization in the LMCA was performed in 1552 patients, 33.6 % with IVUS and 66.4 % with coronary physiology (iFR 11.3 % vs. FFR 55.0 %). The median follow-up time was 2.7 years. No significant difference was seen in MACE (IVUS 40.2 % vs. coronary physiology 35.5 %; adjusted RR: 1.18; 95 %CI: 0.97–1.44; p = 0.09). The results were consistent across all investigated subgroups. The rate of all-cause death was higher in the IVUS group (adjusted RR: 1.38; 95 %CI: 1.03–1.83; p = 0.03). Deferral of coronary revascularization in LMCA lesions using IVUS or coronary physiology did not differ in our combined endpoint. We observed a higher risk of all-cause death using IVUS. • Five years of follow-up in a real-world population with IVUS or coronary physiology. • No difference in MACE, comparing IVUS to coronary physiology of iFR or FFR. • An increase in all-cause and cardiovascular deaths in the IVUS group. [ABSTRACT FROM AUTHOR]

Epicardial Adipose Tissue (EAT) volume is associated with the risk of cardiovascular events, which can be assessed by cardiac computed tomography. However, he optimal method and their prognostic utility in patients following transcatheter aortic valve replacement (TAVR) is unknown. We evaluated 258 participants, focusing on changes in EAT volume using cardiac CT enhancement. EAT volume was automatically computed as three-dimensional voxels between −190 to −30 HU on contrast-enhanced slices. Univariate and multivariable Cox regression analyses were conducted to assess the association of various clinical parameters and EAT volume indices with major adverse cardiovascular events (MACE). During a median follow-up of 2.0 years [IQR, 1.8–2.3 years], 34 participants (median age 73 [IQR: −13.1 to −8.3) years, 55.4 % male) experiencing MACE. The optimal cutoff values for EAT volume change fraction (EATVCF) was 15.2 %, determined by the Youden-index. Kaplan-Meier curve analysis revealed that patients with high EATVCF were at higher risk (p <.01). In Cox regression, EATVCF (hazard ratio [HR]: 0.92, 95 % CI: 0.87 to 0.97, p =.001) remained significantly associated with MACE after adjusting for clinical factors. The addition of EATVCF to the clinical model increased the net Reclassification Improvement (NRI) by 30.1 % (95 % CI: 0.07–1.16). EAT volume change fraction emerged as a significant predictor of MACE post-TAVR, highlighting the clinical value of EAT volume assessment in cardiovascular risk stratification. • EAT volume change fraction is a significant predictor of cardiac risks post-TAVR. • EAT volume change fraction serves as a crucial indicator of patient outcomes. • Integrating EAT volume change with clinical factors enhances predictive capability. • Monitoring EAT volume changes improves patient care post-TAVR. [ABSTRACT FROM AUTHOR]

The no-reflow phenomenon is a significant complication during excimer laser coronary angioplasty (ELCA) procedures, which can lead to adverse outcomes. This study explores the efficacy of intracoronary administration of a cocktail solution comprising nitroglycerin, heparin, and verapamil on preventing no-reflow during ELCA in patients with in-stent restenosis (ISR). This study included patients undergoing ELCA with contrast infusion for ISR. Based on whether receiving the intracoronary cocktail solution during ELCA, participants were divided into two groups: the cocktail (+) group and the cocktail (−) group. The primary endpoint was the incidence of no-reflow, which was defined as the cessation of blood flow into the distal coronary artery in the absence of a clear angiographic explanation for impairment of flow. A total of 54 lesions in 51 patients were included. The mean age of the study population was 61.8 ± 9.7 years, with 84.3 % male. Baseline clinical characteristics were well-balanced. The incidence of no-reflow was significantly lower in the cocktail (+) group compared to the cocktail (−) group (0 % vs. 17.9 %, P = 0.024). No cases of hypotension, major bleeding or coronary perforation in either group. Major adverse cardiac events (MACE) within 6-month were no significant difference between the groups (4.0 % vs. 3.8 %, P = 0.977). The pilot study suggests that intracoronary administration of a cocktail comprising heparin, nitroglycerin, and verapamil may reduce the incidence of no-reflow during ELCA in patients with ISR. However, given the limited sample size and the non-randomized design, these findings should be considered hypothesis-generating. Future validation needs to be confirmed through multicenter studies with larger sample sizes. • ELCA combined with contrast infusion shows efficacy in the treatment of in-stent restenosis. • The incidence of no-reflow reached 17.9 % during the treatment of in-stent restenosis with ELCA combined with contrast infusion technique. • Intracoronary administration of a cocktail comprising heparin, nitroglycerin, and verapamil may reduce the incidence of no-reflow during ELCA in patients with ISR. [ABSTRACT FROM AUTHOR]

The fibrinogen-to-albumin ratio (FAR) has been identified as a new inflammatory marker for predicting the risk of cardiovascular diseases. Nevertheless, its prognostic relevance in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) remains uncertain. This study included a total of 1031 hospitalized patients diagnosed with MINOCA, enrolled consecutively. The primary outcome was the occurrence of major adverse cardiovascular events (MACE). Based on the median FAR value, patients were divided into high FAR (FAR H) and low FAR (FAR-L) groups. Baseline clinical characteristics and the incidence of adverse events during the follow-up period were compared between the two groups. Various statistical methods were applied, including restricted cubic spline modeling, Kaplan-Meier survival analysis, and Cox proportional hazards modeling. The median follow-up duration was 42.3 months, during which 157 patients (15.2 %) experienced MACE. The FAR-H group had a significantly higher incidence of MACE compared to the FAR-L group (21.2 % vs. 9.3 %, p < 0.001). Multivariate Cox regression analysis revealed that a higher FAR was an independent predictor of long-term MACE in MINOCA patients (hazard ratio = 2.76, 95 % confidence interval: 1.95–3.89, p < 0.001), after adjusting for relevant clinical variables. An elevated FAR is linked to a poor long-term prognosis in patients with MINOCA. [ABSTRACT FROM AUTHOR]

Pretreatment with a P2Y 12 inhibitor may be considered in patients with ST-segment elevation myocardial infarction (STEMI) referred to percutaneous coronary intervention (PCI). Intravenous cangrelor is an alternative in this setting, where oral absorption can be hindered. The aim of this study was to compare cangrelor administered after coronary angiography (i.e., "downstream") and ticagrelor pretreatment (i.e., "upstream"). STEMI patients undergoing PCI from October 2019 to June 2023 were included. The primary outcome was the composite of in-hospital major adverse cardiovascular events (MACE). Secondary outcomes included individual components of the primary outcome and in-hospital major bleeding. Univariable and multivariable regression analyses were performed in unmatched and propensity-matched cohorts. Of 6086 patients enrolled in the prospective CAST registry, 761 were included: 383 (50.3 %) received downstream cangrelor and 378 (49.7 %) upstream ticagrelor. In the matched population, no between-group differences were observed in MACE (odds ratio [OR] 1.30; 95 % confidence interval [CI] 0.79–2.17; P 0.308), all-cause death (OR 1.91; 95 % CI 0.87–4.54; P 0.124), myocardial infarction (OR 2.64; 95 % CI 0.76–12.14; P 0.154), stent thrombosis (OR 0.38; 95 % CI 0.06–1.80; P 0.255), unplanned repeat revascularization (OR 1.22; 95 % CI 0.32–4.98; P 0.766) and major bleeding (OR 0.98; 95 % CI 0.50–1.93; P 0.955). Cardiogenic shock and bailout administration of glycoprotein IIb/IIIa inhibitors were independent predictors of MACE, while radial access showed an inverse association with the primary outc. In P2Y 12 -naïve STEMI patients undergoing primary PCI, no significant differences were noted in the risk of in-hospital ischemic and bleeding events between downstream cangrelor and upstream ticagrelor. Abbreviations: adjOR, adjusted odds ratio; CI, confidence interval; GPI, glycoprotein IIb/IIIa inhibitors; MACE, major adverse cardiovascular events; OR, odds ratio; PCI, percutaneous coronary interventions; STEMI, ST-segment elevation myocardial infarction [Display omitted] • Oral pretreatment can be hindered in patients with ST-segment elevation myocardial infarction. • Previous did not specifically enroll STEMI patients, used mixed controls or did not define a specific administration timing for the oral drug. • In this propensity score-matched study, downstream cangrelor and upstream ticagrelor were associated with comparable in-hospital outcomes. • Downstream cangrelor represents a viable alternative when the oral administration route is not desirable or feasible. [ABSTRACT FROM AUTHOR]

Plaques associated with abnormally low physiological flow reserve indices are appropriate for percutaneous coronary intervention (PCI). However, recent trials demonstrate that PCI of ischemia-producing lesions does not reduce major adverse cardiac events (MACE). Low endothelial shear stress (ESS) or high ESS gradient (ESSG) are associated with MACE wherever they occur along the plaque. This study aims to determine the presence of high-risk ESS metrics in obstructive coronary plaques with high-risk (<0.80) vs. borderline-risk (0.80–0.89) vs. normal Instantaneous Wave-free Ratio (iFR) (>0.89). We included 50 coronary arteries (50 patients) with variable iFR values who underwent coronary angiography and optical coherence tomography (OCT), followed by 3D reconstruction and computational fluid dynamics calculations of ESS/ESSG. The cohort was divided into 3 groups: iFR < 0.80, iFR 0.80–0.89, and iFR > 0.89. Spatial distribution of ESS metrics was reported along the course of each plaque, and high-risk ESS metrics and their location were compared among the 3 iFR subgroups. High-risk ESS features (Minimal ESS, Maximum ESSG) were similarly distributed along the course of the atherosclerotic plaque in the three iFR subgroups, both in absolute value and in location: Min ESS: 0.5 ± 0.3 vs. 0.4 ± 0.2 vs. 0.4 ± 0.2 Pa respectively (p = 0.60); Max ESSG any direction: 13.7 ± 9.4 vs. 10.4 ± 10.6 vs. 10.0 ± 7.8 Pa/mm respectively (p = 0.30). ESS metrics were spatially located up to ≥18 mm from the plaque minimal luminal area (MLA) in both directions. High-risk ESS metrics are similarly observed in plaques with normal or abnormal iFR, both in absolute value and spatial location in reference to the MLA. Utilizing iFR to identify plaques likely to cause MACE would miss the majority of plaques mechanistically at high-risk to destabilize and cause future adverse cardiac events. [Display omitted] • The high-risk ESS metrics are equally distributed along the course of the coronary atherosclerotic plaques. • The distribution of the ESS metrics is not related to the degree of anatomical or physiological indices of ischemia. • A revascularization decision based on iFR value only can miss a high-risk plaque located at a distance from the MLA site. [ABSTRACT FROM AUTHOR]

Transcatheter Aortic Valve Implantation (TAVI) has revolutionized the management of severe aortic stenosis (AS), but the impact of sex on TAVI outcomes remains unclear. In this study, we examined differences between men and women in the post-procedural outcomes of TAVI, including healthcare burden and readmission rates. The Nationwide Readmissions Database (2016–2020) was utilized to identify hospitalizations for TAVI. A propensity score matching (PSM) model was used to match males and females. Outcomes were examined using Pearson's chi-squared test. Among 320,324 hospitalizations for TAVI, 142,054 (44.3 %) procedures were performed in women. After propensity matching (N = 165,894 with 82,947 hospitalizations in each group), women had higher in-hospital mortality (2.48 % vs 2.11 %, p: 0.001), stroke (2.14 % vs 1.49 %, p < 0.001), post-procedural bleeding (2.34 % vs 1.72 %, p < 0.001), vascular complications (1.2 % vs 0.7 %, p < 0.001), pericardial complications (1.13 % vs 0.60 %, p < 0.001), acute respiratory failure (ARF) (5.10 % vs 4.63 %, p < 0.001), need for transfusion (7 % vs 5.56 %, p < 0.001), need for vasopressors (2.48 % vs 2.11 %, p < 0.001) and major adverse cardiac and cerebrovascular events (MACCE) (7.53 % vs 6.85 %, p < 0.001). Meanwhile, women had modestly lower incidence of acute kidney injury (AKI) (10.17 % vs 11.88 %, p < 0.001), sudden cardiac arrest (SCA) (0.96 % vs 1.06 %, p: 0.042), cardiogenic shock (1.69 % vs 2.05 %, p < 0.001) and mechanical circulatory support (MCS) requirement (0.69 % vs 0.84 %, p < 0.001). With regard to readmissions, men had higher readmission rates at 30 days (16.07 % vs 14.75 %, p < 0.001) and 90 days (23.8 % vs 21.9 %, p < 0.001). No significant difference was observed in 180-day readmission rates between men and women after TAVI. Notably, procedure-related mortality decreased for both sexes from 2016 to 2020, accompanied by faster recovery times and reduced hospitalization costs (p-trend <0.001). In conclusion, women had higher mortality and post-procedural complication rates, while men had higher readmission rates, cardiogenic shock, AKI and need for mechanical circulatory support. While procedure-related mortality and resource utilization for TAVI have improved over time from 2016 to 2020, irrespective of sex, our findings highlight that significant disparities exist in TAVI outcomes. • Women undergoing TAVI had higher sin-hospital mortality, procedural complications, and MACE compared men. • Men had higher short-term (30- and 90-day) readmission rates, cardiogenic shock and need for mechanical circulatory support. • Diabetes, CKD, pulmonary disease, anemia, and heart failure were found to be significant predictors of readmission. • Between 2016 and 2020, there was a notable decline in procedure-related mortality and LOS in men and women undergoing TAVI. [ABSTRACT FROM AUTHOR]

Cholesterol crystals (CCs) are recognized as a risk factor for vulnerable atherosclerotic plaque rupture (PR) and major adverse cardiovascular events. However, their predictive factors and association with plaque vulnerability in patients with acute myocardial infarction (AMI) remain insufficiently explored. Therefore, This study aims to investigate the association between CCs and plaque vulnerability in culprit lesions of AMI patients, identify the factors influencing CCs formation, and develop a predictive model for CCs. A total of 431 culprit lesions from AMI patients who underwent pre-intervention optical coherence tomography (OCT) imaging were analyzed. Patients were divided into groups based on the presence or absence of CCs and PR. The relationship between CCs and plaque vulnerability was evaluated. A risk nomogram for predicting CCs was developed using the least absolute shrinkage and selection operator and logistic regression analysis. CCs were identified in 64.5 % of patients with AMI. The presence of CCs was associated with a higher prevalence of vulnerable plaque features, such as thin-cap fibroatheroma (TCFA), PR, macrophage infiltration, neovascularization, calcification, and thrombus, compared to patients without CCs. The CCs model demonstrated an area under the curve (AUC) of 0.676 for predicting PR. Incorporating CCs into the TCFA model (AUC = 0.656) significantly enhanced predictive accuracy, with a net reclassification improvement index of 0.462 (95 % confidence interval [CI]: 0.263–0.661, p < 0.001) and an integrated discrimination improvement index of 0.031 (95 % CI: 0.013–0.048, p = 0.001). Multivariate regression analysis identified the atherogenic index of plasma (odds ratio [OR] = 2.417), TCFA (OR = 1.759), macrophage infiltration (OR = 3.863), neovascularization (OR = 2.697), calcification (OR = 1.860), and thrombus (OR = 2.430) as independent risk factors for CCs formation. The comprehensive model incorporating these factors exhibited reasonable discriminatory ability, with an AUC of 0.766 (95 % CI: 0.717–0.815) in the training set and 0.753 (95 % CI: 0.704–0.802) in the internal validation set, reflecting good calibration. Decision curve analysis suggested that the model has potential clinical utility within a threshold probability range of approximately 18 % to 85 %. CCs were associated with plaque vulnerability in the culprit lesions of AMI patients. Additionally, this study identified key factors influencing CCs formation and developed a predictive model with potential clinical applicability. • CCs were associated with plaque vulnerability in culprit lesions of AMI. • Elevated AIP levels significantly correlate with the formation of CCs. • A nomogram for predicting CCs formation has been developed, demonstrating promising potential for clinical application. [ABSTRACT FROM AUTHOR]

Signs and symptoms of myocarditis may vary among men and women. This study aimed to analyze sex-specific differences in the presentation and outcomes of patients with suspected myocarditis. Patients meeting clinical ESC criteria for suspected myocarditis were included from two tertiary centers between 2002 and 2021. Baseline characteristics, cardiac magnetic resonance (CMR), and outcomes (i.e. major adverse cardiovascular events (MACE), including all-cause death, ventricular tachycardia, hospitalization for heart failure, and recurrent myocarditis) in women and men were compared. 776 consecutive patients (mean age 48 ± 16 years, 286 [36.9 %] women) were followed for a median of 3.7 years. Compared to men, women presented more often with severe dyspnea (NYHA III-IV: 25.9 % versus 19.2 % of men; p = 0.029), while chest pain was more frequent in men (39.8 % versus 32.2 % in women; p = 0.037). There was no difference in left ventricular ejection fraction at the time of presentation (women: 48.5 ± 15.4 % versus men: 48.6 ± 15.1 %; p = 0.954). Further, no sex-specific difference in the occurrence of MACE was noted; however, women were more often hospitalized for heart failure than men (women: 9.8 % versus men: 5.3 %, p = 0.018). Accordingly, female sex was independently associated with heart failure hospitalization in an adjusted model (HR: 2.31, 95 % CI:1.25–4.26; p = 0.007). The prognostic value of CMR markers was similar in both sex. Significant sex-specific differences in presentations and imaging findings are found in patients with suspected myocarditis. Female sex is associated with a twofold increase in the risk of heart failure hospitalization, which should be considered in risk stratification. Central Illustration: Sex-differences in presentation and outcome in patients with myocarditis. Abbreviations:BMI: body mass index, CI: confidence intervals, HR: hazard ratio, LGE: late gadolinium enhancement, LVEF: left ventricular ejection fraction. [Display omitted] • Female sex independently predicts heart failure hospitalizations but not MACE, needing sex-specific care approaches. • Women often present with dyspnea and show higher ECV but less LGE on CMR compared to men, without LVEF differences. • More research is needed to address sex differences in myocarditis to improve personalized risk stratification and outcomes. [ABSTRACT FROM AUTHOR]

Chronic Total Occlusion (CTO) involves severe coronary artery blockage that impairs blood flow and affects 15–20 % of patients undergoing coronary angiography and over 40 % with diabetes or heart failure. Percutaneous Coronary Intervention (PCI) is used to restore blood flow in such cases. The retrograde approach, developed due to lower success with the antegrade method in complex cases, improves outcomes but increases complications. This meta-analysis compares the efficacy and safety of both approaches to guide clinical practice. A comprehensive literature search was conducted on PubMed, Embase, Google Scholar, and Scopus until June 5, 2024, to find studies comparing antegrade and retrograde approaches in CTO-PCI patients. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using R software (version 4.4.1), with significance set at p < 0.05. Random-effects models were used for all analyses. Our analysis included 22 observational studies with 49,152 CTO-PCI patients: 35,844 in the antegrade arm and 13,308 in the retrograde arm. The antegrade approach showed significantly lower risks of in-hospital outcomes, including mortality [RR: 0.45; p < 0.001], myocardial infarction [RR: 0.37; p < 0.001], major adverse cardiovascular events [RR: 0.34; p < 0.001], and cerebrovascular events [RR: 0.50; p = 0.011]. Long-term outcomes, such as all-cause mortality [RR: 0.71; p = 0.157] and myocardial infarction [RR: 0.76; p = 0.438], were comparable between both approaches. The antegrade technique shows better outcomes and procedural advantages over retrograde revascularization, though long-term outcomes are similar. Further studies, especially randomized controlled trials are needed to confirm these findings. • Meta-analysis comparing antegrade vs. retrograde approaches in patients undergoing PCI for CTO. • Antegrade approach for CTO-PCI had significantly lower risks of short-term outcomes. • Both approaches showed similar risks for long-term outcomes, including mortality and myocardial infarction. • Though the antegrade approach may offer safer short-term outcomes, more research is needed on long-term benefits. [ABSTRACT FROM AUTHOR]

• Elevated copeptin predicts major adverse cardiovascular events in maintenance hemodialysis patients. • Combining copeptin with NT-proBNP or hs-cTnT enhances cardiovascular risk stratification. • Copeptin serves as a valuable addition to traditional cardiac biomarkers for prognosis, as multi-biomarker approach improves prediction of adverse outcomes in hemodialysis. End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population. [ABSTRACT FROM AUTHOR]

The triglyceride-glucose (TyG) index has been proposed as an independent predictor of coronary artery disease (CAD). In this retrospective study, we further examine this association and its utility as a predictor for major adverse cardiovascular events (MACE). A total of 870 patients who underwent coronary angiography between May 2008 and June 2009 were included in this retrospective study. The TyG index was calculated using the formula Ln [fasting TG (mg/dL) × FBG (mg/dL)/2]. The association of the TyG index with the presence and severity of CAD, cardiovascular risk factors, and inflammatory markers was evaluated at baseline. In the longitudinal study, the multivariate-adjusted Cox hazard model was used to investigate the associations of the TyG index with the occurrence of MACE during a 5-yr follow-up, which was defined as the endpoint. The TyG index was significantly associated with the presence and severity of CAD. Multiple linear regression analysis showed that a high TyG index, together with inflammatory markers and dyslipidemia, was independently associated with greater stenotic occlusion of coronary arteries (adjusted R 2 = 0.031, P < 0.001). Kaplan-Meier survival curve (free of MACE) by tertiles of the TyG index showed a higher incidence of MACE in the upper tertile (log-rank test, P = 0.02). Multivariate Cox analysis demonstrated that the risk of incident MACE during the follow-up was associated with higher levels of the TyG index, even after adjusting for inflammatory parameters and cardiovascular risk factors: hazard ratio = 1.54 (95% confidence interval: 1.18-2.13; P < 0.01). We conclude that an elevated TyG index is independently associated with a higher risk of CAD and a poor prognosis for MACE. NEW & NOTEWORTHY This retrospective study demonstrates significant associations between the TyG index and the occurrence and severity of CAD, as well as indicates the clinical value of the TyG index as a potential predictor for MACE.