Anti-inflammatory effects of proprotein convertase subtilisin/kexin 9 inhibitor therapy in the early phase of acute myocardial infarction.

This study examined the anti-inflammatory and endothelial function-enhancing effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor therapy in the early phase after acute myocardial infarction (AMI) by assessing changes in tumor necrosis factor-α (TNF-α) levels and the L-arginine/asymmetric-dimethylarginine (ADMA) ratio. This retrospective, single-center cohort study included patients who underwent successful timely primary percutaneous coronary intervention (PCI) for first-onset AMI between September 2017 and March 2018. The PCSK9 inhibitor group comprised patients who received 75 mg alirocumab up to 7 days after AMI, while the standard therapy group comprised patients who did not. We evaluated the change in TNF-α levels and the L-arginine/ADMA ratio at the time of hospital admission and prior to discharge. PCSK9 inhibitor therapy in the early phase after AMI suppressed TNF-α levels (standard therapy group, 1.64 ± 2.14 pg/mL vs. PCSK9 inhibitor group, 0.26 ± 0.33 pg/mL; p = 0.033) and increased the L-arginine/ADMA ratio (standard therapy group, - 13.0 ± 39.7 vs. PCSK9 inhibitor group, 23.2 ± 39.7; p = 0.042). Upon multiple regression analysis adjusted for sex, age, and peak creatine kinase levels, PCSK9 inhibitor therapy was associated with TNF-α suppression (p = 0.025; ß = - 0.235, 95% confidence interval [CI], - 0.436 to - 0.033). The L-arginine/ADMA ratio was also analyzed using multiple regression, adjusted for sex, age, peak creatine kinase levels, and smoking, showing a significant improvement in the ratio (p = 0.018; ß = 41.913, 95% CI, 10.337-73.491). Moreover, a weak negative correlation was suggested between the change in TNF-α levels and the change in L-arginine/ADMA ratio (r = - 0.393, p = 0.058). PCSK9 inhibitor therapy in the early phase after AMI suppresses TNF-α levels and improves the L-arginine/ADMA ratio, potentially indicating anti-inflammatory and endothelial function-enhancing effects.

Very short-term effects of a single dose of a proprotein convertase subtilisin/kexin 9 inhibitor before percutaneous coronary intervention: A single-arm study.

BACKGROUND AND AIMS: The short-term (within 6 weeks) effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on lipid plaques have not been adequately evaluated. We aimed to investigate whether a single dose of a PCSK9 inhibitor before percutaneous coronary intervention (PCI) could reduce the abundance of lipid-core plaques identified via near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) at target lesions within a very short period. METHODS: This prospective, single-arm, single-center interventional study enrolled 27 consecutive patients with coronary artery disease. These patients underwent NIRS-IVUS during coronary angiography and repeat NIRS-IVUS during PCI performed between 2 and 6 weeks after the single-dose administration of 420 mg evolocumab. Changes in lesion lipid-core burden index (LCBI) and maximal LCBI over any 4-mm segment (max-LCBI4mm) were assessed using NIRS at the target lesions, along with lipid profile. RESULTS: The max-LCBI4mm significantly decreased from 387 before PCSK9 inhibitor administration to 315 after its administration (interquartile range [IQR]: 268-572 and 221-488, respectively; p = 0.02) within a very short period. The lesion LCBI also decreased from 161 to 117 (IQR: 105-263 and 65-226, respectively; p = 0.02). No significant changes were observed in the minimum lumen area and diameter. After PCSK9 inhibitor administration, low-density lipoprotein (LDL) cholesterol (p < 0.001), lipoprotein(a) (p = 0.001), and malondialdehyde-modified LDL (p < 0.001) levels decreased compared with those before its administration. CONCLUSIONS: A single dose of the PCSK9 inhibitor administered before PCI reduced the abundance of lipid-core plaques identified via NIRS-IVUS at target lesions within a very short period of 2-6 weeks.

Evaluation of nontarget lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging.

BACKGROUND: In coronary artery disease (CAD), lipid-core-containing plaque (LCP) in nontarget lesions detected using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) was related to increased major adverse cardiovascular events in patients with CAD. In the endovascular therapy field, few previous studies using NIRS-IVUS revealed the presence of LCPs in severe stenotic lesions of femoropopliteal disease. AIM: This study aimed to assess the plaque morphology of nontarget lesions, especially LCPs, and compare it with that of target lesions using NIRS-IVUS in patients with femoropopliteal disease. METHODS: This single-center prospective observational study included 14 patients who underwent endovascular therapy for FP disease. NIRS-IVUS assessment was performed on the entire FP arterial segment. Forty-one LCP lesions with a maximum lipid-core burden index in any 4-mm region (max LCBI4mm) > 100 were detected using NIRS-IVUS. We evaluated the patient and lesion characteristics. LCP lesions were divided into the target (n = 18) and nontarget (n = 23) lesion groups for comparison. RESULTS: Patient characteristics were notable for advanced age (76.8 ± 6.6 years); high proportion of males (78.7%); and high incidence of hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%). Regarding NIRS findings, the target lesion group exhibited a significantly smaller proportion of LCPs concerning the lesion length (25.9 ± 15.7% vs. 50.6 ± 29.2%, p = 0.002) than the nontarget lesion group. Conversely, there were no significant differences in the value of max LCBI4mm (284.4 ± 153.4 vs. 289.5 ± 113.1, p = 0.90), length of LCP lesion (9.8 ± 9.7 mm vs. 10.7 ± 6.9 mm, p = 0.74), and distribution of LCPs (p = 0.08) between the groups. In addition, the number of LCPs in the target FP artery positively correlated with max LCBI4mm in the target FP artery (r = 0.671, p = 0.008). CONCLUSIONS: NIRS-IVUS findings demonstrated the presence of LCPs in nontarget lesions in patients with FP disease. Moreover, the abundance of LCPs in nontarget lesions was similar to that in target lesions in FP disease.

Declines in serum uric acid level after catheter ablation of atrial fibrillation.

BACKGROUND: Few studies have examined whether catheter ablation for AF patients improves biomarkers other than serum levels of brain natriuretic peptide (BNP) and renal function. This study was to explore whether catheter ablation for atrial fibrillation (AF) patients affects uric acid (UA), glucose and lipid metabolism. METHODS AND RESULTS: A total of 206 patients (66.6 ± 10.4 years; 132 men) who underwent initial AF ablation without changes to oral medications were included. Baseline BNP and UA levels significantly decreased at 1 year after ablation (p < 0.05 each). Changes in UA level correlated significantly with pre-procedural UA level (r = 0.57). In multivariable logistic regression modeling, pre-procedural UA level, persistent AF, and hemoglobin A1c (p < 0.05 each) were independent predictors of post-procedural UA level decline. Significant improvements in both persistent and paroxysmal AF patients were identified, and the magnitude of post-procedural serum UA level decline after ablation (ΔUA) was significantly greater in patients with persistent AF (0.8 ± 1.0 mg/dl) than in those with paroxysmal AF (0.2 ± 0.8 mg/dl, p < 0.001). Of the 48 patients with high UA level before procedure, 28 patients showed improvement in UA level to normal range. CONCLUSIONS: Catheter ablation for AF patients significantly improved serum UA levels without obvious influences of heart failure, renal function, or inflammation, suggesting that AF ablation may be effective for AF patients with hyperuricemia. Trial registration The study was approved by the Research Ethics Committee of University of Fukui (no. 20210132) and clinical trial registration (UMIN000044669).

Initial practice of left atrial appendage closure device in Japan; single-center experience.

BACKGROUND: The left atrial appendage closure (LAAC) device for patients with nonvalvular atrial fibrillation (NVAF) has recently been introduced in Japan. However, clinical data of Japanese patients are insufficient. METHODS: In this single-center study, 55 consecutive patients (mean age, 74 years) who received LAAC therapy from September 2019 to December 2020 were analyzed. The WATCHMAN implant procedure (Boston Scientific, St. Paul, MN, USA) was performed under transesophageal echocardiography and general anesthesia for all cases. RESULTS: The baseline CHA2DS2-VASc score was 4.6 ± 1.4, and the baseline HAS-BLED score was 3.8 ± 0.9. All procedures (98.2%) were successful, except for one, and no procedure-related complications were observed. After the procedures, various antithrombotic regimens were employed according to the bleeding risk of each patient; warfarin was used in 27 patients (49%), direct oral anticoagulants (DOACs) were used in 22 patients (40%), and dual antiplatelet therapy (DAPT) was employed in 6 patients. During a mean follow-up of 360 days, three cases of device-related thrombus (DRT) were detected. One DRT case was related to ischemic stroke. Nine patients had major bleeding during follow-up: two patients received DOACs, six patients received DAPT, and one patient received aspirin. CONCLUSIONS: In this initial Japanese experience, LAAC therapy for high bleeding risk patients with NVAF seems feasible. Optimal antithrombotic regimens are warranted for better clinical outcomes.