Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear. AIM: To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events. METHODS: From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events). RESULTS: The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE. CONCLUSION: Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

Initial clinical experience with the novel POLARx FIT cryoballoon system for pulmonary vein isolation in patients with atrial fibrillation.

Background: The POLARx FIT system (Boston Scientific, MA, USA) is a novel cryoballoon (CB) ablation technology in which the balloon diameter can be expanded from 28 to 31 mm. The aim of this study was to compare the benefits and safety of the new POLARx FIT system to those of the existing POLARx system currently in use for pulmonary vein (PV) isolation (PVI) in patients with atrial fibrillation. Methods: The first 70 consecutive patients who underwent CB-based PVI with the POLARx FIT system were retrospectively compared with 200 consecutive patients treated with the POLARx system at Sakakibara Heart Institute from October 2021 to May 2023. Results: The POLARx FIT system yielded a higher mean ± standard deviation nadir temperature in the right inferior PV (-59.2 ± 5.29 °C vs. - 62.0 ± 5.08 °C, p = 0.006), but this required a balloon size reduction to 28 mm in 30 % of cases. No significant differences were detected in the time to isolation and thaw time of any PV between the two groups. After the CB-based PVI procedure, no residual PV carina potentials were observed with the POLARx FIT system, whereas 4/20 were with the POLARx system (p = 0.04). Conclusions: The POLARx FIT system had comparable effectiveness and safety to the basic POLARx system. This technology may improve the ablation area, including the PV carina. However, the 31-mm balloon alone was not sufficient to isolate certain PVs.

The circulating furin-cleaved/mature PCSK9 ratio has a potential prognostic significance in statin-naïve patients with acute ST elevation myocardial infarction.

Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates as mature and furin-cleaved forms, but their biological functions are uncertain. We investigated whether their levels associate with prognosis in patients with acute ST elevation myocardial infarction (STEMI). Methods: We enrolled 160 statin-naïve patients with acute STEMI and followed for 3 years. PCSK9 subtype levels were determined by an enzyme-linked immunosorbent assay before and at five timepoints up to 48 h after emergent coronary intervention. The occurrence of coronary and cardiac events was compared between subjects stratified by the PCSK9 level. Results: One hundred and twenty-six patients completed 3 years of follow-up. In the acute phase, both PCSK9 subtype levels decreased, and thereafter increased from 6 to 48 h (mature: from 198 ± 67 to 334 ± 116 ng/mL, furin-cleaved: from 20 ± 7 to 39 ± 16 ng/mL, both p < 0.01). Major cardiac events occurred in 46 patients. The furin-cleaved/mature PCSK9 ratio at 48 h after coronary intervention predicted the likelihood of experiencing of events; patients in the third tertile had lower event-free survival than those in the first and second tetiles in Kaplan-Meier analysis (p = 0.004). Multivariate Cox regression analysis revealed that this ratio had a greater impact (HR: 1.92; 95% CI: 1.06-3.45, p = 0.03) on events than other known atherosclerosis risk factors. Conclusions: The furin-cleaved/mature PCSK9 ratio was associated with 3-year cardiovascular events in statin-naïve patients with acute STEMI, suggesting a potential link between furin cleavage process of PCSK9 and its effect on prognosis. (249 words).

Monitoring the roles of prothrombin activation fragment 1 and 2 (F1 + 2) in patients with atrial fibrillation receiving rivaroxaban and apixaban.

Factor Xa (FXa) inhibitors are recommended for use in fixed doses without laboratory monitoring. However, prior studies reported the importance of establishing biomarkers representing anticoagulation intensity related to bleeding or thrombotic events. To test the hypothesis that prothrombin activation fragment 1 and 2 (F1 + 2), a non-specific marker of thrombin generation, could be altered during FXa inhibitor treatment in patients with atrial fibrillation. We conducted the study in two different clinical settings. First, the interrelations among biomarkers representing coagulation/fibrinolysis were investigated in 80 patients in an outpatient clinic. Second, these biomarkers were evaluated in 75 patients who underwent radiofrequency catheter ablation. Plasma concentration of FXa inhibitors was evaluated using an anti-FXa chromogenic assay (C-Xa). In the outpatient study, only F1 + 2 exhibited a significant and negative association with C-Xa (rS = - 0.315, p = 0.026), and 37% of the variance could be explained by C-Xa levels. F1 + 2 levels above the reference range (> 229 pmol/L) could be considered as a cut-off to identify poor patient compliance or under-dosing. In the peri-ablation study, increased F1 + 2 levels were associated with decline of C-Xa levels after periprocedural discontinuation of FXa inhibitors, which was greater in the rivaroxaban group than in the apixaban group. F1 + 2 showed modest and inverse association with plasma concentration of rivaroxaban and apixaban in patients with atrial fibrillation. Larger study to test the hypothesis that continued thrombin generation despite anticoagulation is associated with a heightened risk of clinical events is required.

A case of cardiac resynchronization therapy in a patient with coronary sinus ostial atresia and persistent left superior vena cava.

Coronary sinus ostial atresia is rare and usually not clinically relevant, but it should be noted in cases of cardiac resynchronization therapy. A rare case of successful left ventricular lead implantation for cardiac resynchronization therapy via the left superior vena cava in a patient with coronary sinus ostial atresia is reported. The persistent left superior vena cava associated with these cases tends to be smaller than usual in its diameter and difficult to identify, since the direction of venous drainage is reversed. Therefore, in the present case, it was useful to use a small-diameter, soft inner catheter as a guiding catheter to perform selective imaging and avoid vascular injury. In addition, it appeared to be important to plan the surgical strategy using prior imaging information, since it would be difficult to obtain the backup needed for lead insertion. 〈: Learning objective: Cardiac resynchronization therapy via the left superior vena cava with coronary sinus ostial atresia is generally possible without problems if prior imaging information is available, such as three-dimensional computed tomography and the venous phase of coronary angiography. It is important to determine whether there is a persistent left superior vena cava before the procedure. Thromboprophylaxis remains controversial in this situation.〉.