Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury.

INTRODUCTION: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). METHODS: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. RESULTS: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753-0.956), but not for the patients with AKI (HR 0.988, CI 0.808-1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584-0.989) but not for stage II and III AKI (HR 1.200, CI 0.899-1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. CONCLUSION: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.

The effect of fibrates on lowering low-density lipoprotein cholesterol and cardiovascular risk reduction: a systemic review and meta-analysis.

AIMS: The effect of fibrate treatment on cardiovascular risk is inconsistent. This meta-analysis aimed to assess the effect of fibrates on major adverse cardiovascular outcome (MACE) reduction. METHODS AND RESULTS: PubMed, Embase, and Cochrane library databases were searched up to February 2023 for randomized controlled trials comparing fibrate therapy against placebo and reporting cardiovascular outcomes and lipid profile changes. The primary outcome was the clinical outcomes of each trial that most closely corresponding to MACE, a composite of cardiovascular death, acute myocardial infarction, stroke, and coronary revascularization. A pre-specified meta-regression analysis to examine the relationship between the changes in lipid levels after fibrate treatment and the risk of MACE was also performed. Twelve trials were selected for final analysis, with 25 781 patients and 2741 MACEs in the fibrate group and 27 450 patients and 3754 MACEs in the control group. Overall, fibrate therapy was associated with decreased risk of MACE [RR 0.87, 95% confidence interval (CI) 0.81-0.94] with moderate heterogeneity (I2 = 47%). In meta-regression analysis, each 1 mmol/L reduction in low-density lipoprotein cholesterol (LDL-C) after fibrate treatment reduced MACE (RR 0.71, 95% CI 0.49-0.94, P = 0.01), while triglyceride level changes did not show a significant association (RR per 1mmol/L reduction 0.96, 95% CI 0.53-1.40, P = 0.86). A sensitivity analysis with the composite outcome of cardiovascular death or acute myocardial infarction produced similar results. CONCLUSION: Treatment with fibrates was associated with decreased risk of MACE. The reduction in MACE risk with fibrate therapy appears to be attributable to LDL-C reduction rather than a decrease in triglyceride levels.

A systematic review and meta-analysis including 12 trials and 53 231 patients were performed to investigate the effect of fibrates on lowering cardiovascular risk. Overall, fibrate therapy was associated with significantly decreased risk of cardiovascular events. In further analysis, the decrease in cardiovascular risk achieved with fibrate treatment was found to be largely attributable to low-density lipoprotein cholesterol reduction.

Facile and Efficient Production of Biomass-Derived Isosorbide Dioxides via Epoxidation Using In situ-generated DMDO under Ultrasonication.

Herein, we present a facile synthetic process for producing biomass-derived isosorbide (ISB) dioxides using dimethyl dioxirane (DMDO) as an efficient oxidizing agent, which was generated in situ from acetone and KHSO5 . To achieve high conversion and product yield, the KHSO5 concentration, KHSO5 flow rate, and reaction temperature were optimized. Under the optimal conditions, rapid and efficient epoxidation using the in situ-generated DMDO was observed under ultrasonication, yielding the desired product within 35 min at 0 °C. This study offers a convenient and efficient method for generating biomass-derived ISB building blocks, which have significant potential for the fabrication of bioplastics.

Predictors for early cardiac death after discharge from successfully treated acute myocardial infarction.

Background: The use of a cardioverter defibrillator for the primary prevention of sudden cardiac death is not recommended within 40 days after acute myocardial infarction (AMI). We investigated the predictors for early cardiac death among patients who were admitted for AMI and successfully discharged. Methods: Consecutive patients with AMI were enrolled in a multicenter prospective registry. Among 10,719 patients with AMI, 554 patients with in-hospital death and 62 patients with early non-cardiac death were excluded. Early cardiac death was defined as a cardiac death within 90 days after index AMI. Results: Early cardiac death after discharge occurred in 168/10,103 (1.7%) patients. A defibrillator was not implanted in all patients with early cardiac death. Killip class ≥3, chronic kidney disease stage ≥4, severe anemia, cardiopulmonary support usage, no dual antiplatelet therapy at discharge, and left ventricular ejection fraction (LVEF) ≤35% were independent predictors for early cardiac death. The incidence of early cardiac death according to the number of factors added to LVEF criteria in each patient was 3.03% for 0 factor, 8.11% for 1 factor, and 9.16% for ≥2 factors. Each model that sequentially added the factors in the presence of LVEF criteria showed a significant gradual increase in predictive accuracy and an improvement in reclassification capability. A model with all factors showed C-index 0.742 [95% CI 0.702-0.781], p < 0.001; IDI 0.024 [95% CI 0.015-0.033], p < 0.001; and NRI 0.644 [95% CI 0.492-0.795], p < 0.001. Conclusion: We identified six predictors for early cardiac death after discharge from AMI. These predictors would help to discriminate high-risk patients over current LVEF criteria and to provide an individualized therapeutic approach in the subacute stage of AMI.

Case report: Constrictive pericarditis after coronary artery perforation during percutaneous coronary intervention.

A 77-year-old man underwent percutaneous coronary intervention (PCI) at the right coronary artery, which was complicated by coronary artery perforation (CAP). After prolonged balloon tamponade proximal to the CAP there was no more contrast extravasation, and the CAP was thought to have resolved. Computed tomography (CT) and echocardiography the following day did not find evidence of continued bleeding, and the patient was discharged. Echocardiograms and chest CT scans obtained one week and two months after PCI detected no remarkable interval change. The patient complained of progressive dyspnea and abdominal distension seven months after PCI however, and echocardiography found an increased amount of pericardial effusion and constrictive physiology. The patient underwent pericardiectomy due to congestive hepatopathy, and progressive dyspnea. The pericardium was thickened and adhesive, and a dark bloody effusion was found. Pathology was unremarkable except for thick fibrosis. After the operation the patient made full recovery, and is stable three years after surgery.

New Therapeutic Approaches to the Treatment of Dyslipidemia 2: LDL-C and Lp(a).

Dyslipidemia is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). There are abundant and unequivocal data to indicate that low-density lipoproteins (LDL) are a cause of ASCVD. Reduction of plasma low-density lipoprotein cholesterol (LDL-C) by medical therapy such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have proven to significantly reduce the risk of cardiovascular events. However, for many reasons, many patients are not able to achieve LDL-C levels recommended by guidelines on currently available therapies. This has led to the development of new drugs lowering LDL-C, such as inclisiran, bempedoic acid, and evinacumab, in the hope of reducing cardiovascular (CV) risk. Drugs targeting lipoprotein (a) (Lp[a]) also have a role in the prevention of atherosclerosis, with genetic studies having established that 20%-30% of the human population inherits plasma Lp(a) levels in the atherogenic range. In this paper, we will review the recent progress made in the approaches to LDL-C and Lp(a) therapeutic modulation.

Clinical Outcomes of Biodegradable versus Durable Polymer Drug Eluting Stents in Rotational Atherectomy: Results from ROCK Registry.

BACKGROUND: The aim of this study was to compare the clinical outcomes of biodegradable polymer (BP) versus durable polymer (DP) drug eluting stents (DES) in patients with calcified coronary lesions who underwent rotational atherectomy (RA) and percutaneous coronary intervention (PCI). METHODS: This study was based on a multicenter registry which enrolled patients with calcified coronary artery disease who received PCI using RA during between January 2010 and October 2019 from 9 tertiary centers in Korea. The primary outcome was 3-year all-cause mortality, and the secondary outcomes were cardiovascular death and target-lesion failure. RESULTS: A total of 540 patients who underwent PCI using RA were enrolled with a follow-up period of median 16.1 months. From this registry, 272 patients with PCI using DP-DES and 238 patients with BP-SGDES were selected for analysis. PCI with BP-DES was associated with decreased all-cause mortality after propensity score matching (HR 0.414, CI 0.174-0.988) and multivariate Cox regression analysis (HR 0.458, HR 0.224-0.940). BP-DES was also associated with decreased cardiovascular mortality, but there was no difference in TLF between the two groups. CONCLUSIONS: BP-DES were associated with favorable outcomes compared to DP-DES in patients undergoing PCI using RA for calcified coronary lesions.

Characteristics and outcomes of heart transplant recipients with a pretransplant history of malignancy.

We aimed to investigate the characteristics and outcomes of HTx recipients with a history of pretransplant malignancy (PTM). Among 1062 HTx recipients between 1997 and 2013, 73 (7.1%) patients had PTMs (77 cancer cases). We analyzed post-HTx outcome, recurrence of PTM, and development of de novo malignancies. Post-HTx outcome included overall survival, 10-year survival, 10-year freedom from cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), any treated rejection (ATR), acute cellular rejection (ACR), and antibody-mediated rejection (AMR). Four most common PTMs were lymphoproliferative disorders (18.2%), prostate cancers (18.2%), non-melanoma skin cancers (18.2%), and breast cancers (13.0%). Median time from PTM and HTx was 9.0 years. During a median follow-up of 8.6 years after HTx, patients with PTM, compared to those without, showed significantly higher incidence of posttransplant malignancies (43.8% vs. 20.8%, p < .001) including 9.6% (n = 7) of PTM recurrences. However, patients with PTM, compared to those without, showed comparable overall survival, 10-year survival, 10-year freedom from CAV, NF-MACE, ATR, ACR, and AMR. Therefore, a history of PTM should not disqualify patients from HTx listing, while further research is necessary for early detection of posttransplant malignancies in these patients.

A dose-response relationship of renin-angiotensin system blockers and beta-blockers in patients with acute heart failure syndrome: a nationwide prospective cohort study.

AIMS: It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients. METHODS AND RESULTS: In total, 5331 patients in the Korean Acute Heart Failure registry were analysed based on the doses of RASBs and BBs at discharge. In AHFS patients, RASB use at discharge was associated with a significant reduction in all-cause mortality risk. This effect was dose-dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with reduced all-cause mortality in HFrEF patients but not in HFpEF patients. In an additional analysis of 4613 patients with dosage information at the first post-discharge follow-up visit, a significantly higher mortality risk was associated with the maintenance or withdrawal of RASBs compared with up-titrating the dose in HFrEF patients. CONCLUSION: Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASBs and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction.