Prolonged dual antiplatelet therapy for Chinese ACS patients undergoing emergency PCI with drug-eluting stents: Benefits and risks.

Background: In patients with acute coronary syndrome (ACS), prolonged dual antiplatelet therapy (DAPT) may reduce ischemic events and increase the risks of bleeding events differently in different ethnic groups. However, whether prolonged DAPT in Chinese patients with ACS following emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DES) will be beneficial or dangerous remains unclear. This study aimed to examine the potential benefits and risks of prolonged DAPT in Chinese patients with ACS who have undergone emergency PCI with DES. Methods: This study included 2,249 patients with ACS who underwent emergency PCI. If DAPT was continued for 12 or 12-24 months, it was classified as the standard (n = 1,011) or prolonged (n = 1,238) DAPT group, respectively. The incidence of the following endpoint events was determined and compared between the two groups: composite bleeding event (BARC 1 or 2 types of bleeding and BARC 3 or 5 types of bleeding) and major adverse cardiovascular and cerebrovascular events (MACCEs) [ischemia-driven revascularization, non-fatal ischemia stroke, non-fatal myocardial infarction (MI), cardiac death, and all-cause death]. Results: After a median period of 47 months of follow-up [47 (40, 54)], the rate of composite bleeding events was 13.2% (n = 163) in the prolonged DAPT group and 7.9% (n = 80) in the standard DAPT group [odds ratio (OR) 1.765, 95% confidence interval (CI) 1.332-2.338, p < 0.001]. The rate of MACCEs was 11.1% (n = 138) in the prolonged DAPT group and 13.2% (n = 133) in the standard DAPT group (OR 0.828, 95% CI 0.642-1.068, p = 0.146). The DAPT duration was further shown to be insignificantly correlated with MACCEs as per the multivariable Cox regression model (HR, 0.813; 95% CI, 0.638-1.036; p = 0.094). No statistically significant difference was observed between the two groups. However, the DAPT duration was a separate predictor of composite bleeding events according to the multivariable Cox regression model (HR 1.704, 95% CI 1.302-2.232, p < 0.001). Compared with the standard DAPT group, the prolonged DAPT group had substantially more BARC 3 or 5 types of bleeding events (3.0 vs. 0.9% in those with standard DAPT, OR 3.430, 95% CI 1.648-7.141, p < 0.001) and BARC 1 or 2 types of bleeding events (10.2 vs. 7.0% in those with standard DAPT, OR 1.500, 95% CI 1.107-2.032, p = 0.008). Conclusion: The prolonged DAPT group had a considerably greater incidence of composite bleeding events than the standard DAPT group. No statistically significant difference was observed in the incidence of MACCEs between the two groups.

High triglyceride-glucose index is associated with poor cardiovascular outcomes in Chinese acute coronary syndrome patients without diabetes mellitus who underwent emergency percutaneous coronary intervention with drug-eluting stents.

Background: Previous research has supported the association between the triglyceride-glucose index (TyG index) and the incidence and prognosis of cardiovascular disease. However, the association between the TyG index and the prognosis of patients with acute coronary syndrome (ACS) without diabetes mellitus (DM) who underwent emergency percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) has not been thoroughly investigated, and these patients may easily be neglected. Therefore, this study aimed to investigate the association between the TyG index and major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese ACS patients without DM who underwent emergency PCI with DES. Methods: The total number of ACS patients without DM who underwent emergency PCI with DES for this study was 1650. Ln [fasting triglycerides (mg/dL) ×fasting plasma glucose (mg/dL)/2] is the formula used to calculate the TyG index. According to the TyG index, we classified the patients into two groups. The frequency of the following endpoint events was calculated and compared between the two groups: all-cause death, non-fatal myocardial infarction (MI), non-fatal ischemia stroke, ischemia-driven revascularization and cardiac rehospitalization. Results: After a median of 47 months of follow-up [47 (40, 54)], 437 (26.5%) endpoint events were recorded in total. The TyG index was further demonstrated to be independent of MACCE by multivariable Cox regression analysis (hazard ratio [HR], 1.493; 95% confidence interval [CI], 1.230-1.812; p<0.001). The TyG index≥7.08 group had a considerably greater incidence of MACCE (30.3% vs. 22.7% in the TyG index<7.08 group, p<0.001), cardiac death (4.0% vs. 2.3% in the TyG index<7.08 group, p=0.047), and ischemia-driven revascularization (5.7% vs. 3.6% in the TyG index<7.08 group, p=0.046) than the TyG index<7.08 group. Between the two groups, there was no discernible difference in all-cause death (5.6% vs. 3.8% in the TyG index<7.08 group, p=0.080), non-fatal MI (1.0% vs. 0.2% in the TyG index<7.08 group, p=0.057), non-fatal ischemic stroke (1.6% vs. 1.0% in the TyG index<7.08 group, p=0.272), and cardiac rehospitalization (16.5% vs. 14.1% in the TyG index<7.08 group, p=0.171). Conclusion: For ACS patients without DM who received emergency PCI with DES, the TyG index might be an independent predictor of MACCE.

Clinical characteristics, prognostic factors, and outcomes of ventricular septal rupture in patients with acute myocardial infarction.

Ventricular septal rupture (VSR) is a rare but devastating complication in patients with acute myocardial infarction (AMI). This was a retrospective single-center observational study which aimed to assess the characteristics and outcomes of VSR patients and identify risk factors for in-hospital mortality of VSR patients in the era of percutaneous intervention. Patients with VSR after AMI at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to December 2020 were enrolled. Among 5395 consecutive patients with AMI, 42 patients (0.78%) were diagnosed with VSR. Left anterior descending coronary artery was the culprit vessel in most cases (84.4%, 27/32). In the multivariate analysis, female sex (odds ratio (OR): 14.043, 95% confidence interval (CI): 1.396-141.283, p = 0.025) and lower platelet count on admission (OR: 0.979; 95% CI: 0.963-0.995; p = 0.009) were significant risk factors of in-hospital death in VSR patients. In all, 11 patients (26.2%) underwent surgical repair, and the rest were treated medically. The 1-year mortality was lower in the surgical group (36.4%, 4/11) than that in the conservative group (74.2%, 23/31) (p = 0.034). During the follow-up, VSR patients treated surgically tended to have a higher long-term survival rate than those treated medically (log rank χ2 = 5.005, p = 0.025). The prognosis of patients with VSR remained poor in this study. Female sex and lower platelet count were independent risk factors of in-hospital death in VSR patients. The long-term survival rate of patients treated with surgical repair was significantly better than that of patients treated conservatively.

Case Report: Extrinsic Compression of the Left Main Coronary Artery by a Giant Sinus of Valsalva Aneurysm.

Sinus of Valsalva aneurysm (SoVA) is an uncommon clinical entity, which is present in roughly 0. 09% of the general population. The cause can either be acquired or congenital. Clinically the SoVA of unruptured status are rarely captured or even diagnosed due to atypical clinical presentations. Here, we present a rare case of exertional angina pectoris and recurrent syncope due to an extrinsically compressed left coronary artery by a giant SoVA in a 50-year-old female patient. This SoVA was successfully repaired by the surgical exclusion and the patient was still doing well after 2 years of follow-up.

Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats.

In this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100 nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5 nm Au-NPs had some cardiac protective effect  but little accumulation in heart, probably due to smaller size Au-NPs can adapt to whole body easily in vivo. Histological analysis and TUNEL staining showed that Au-NPs can induce pathological alterations including cardiac fibrosis, apoptosis in control groups, however they can protect HHD groups from these harmful effects. Furthermore, transmission electron microscopy and western blotting employed on H9C2 cells showed that autophagy presented in Au-NPs treated cells and that Au-NPs can decrease LC3 II turning to LC3 I and decrease APG7 and caspase 12 in the process in HHD groups, while opposite effects on control groups were presented, which could be an adaptive inflammation reacts. As there are few animal studies about using nanoparticles in the treatment of heart disease, our in vivo and in vitro studies would provide valuable information before they can be considered for clinical use in general.

The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca(2+) homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2 (S/S)) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2 (S/S) hearts to connexin-43 (Cx43) and Nav1.5 expression and Na(+) current (I Na). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2 (S/S) hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2 (S/S) than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2 (S/S) compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced I Na in RyR2 (S/S) ventricles. We thus attribute arrhythmogenesis in RyR2 (S/S) ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing I Na, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak I Na of the AP but nonlinear relationships between peak I Na and maximum Na(+) permeability.

Apamin-Sensitive K+ Current Upregulation in Volume-Overload Heart Failure is Associated with the Decreased Interaction of CK2 with SK2.

Recent studies have shown that the sensitivity of apamin-sensitive K(+) current (I KAS, mediated by apamin-sensitive small conductance calcium-activated potassium channels subunits) to intracellular Ca(2+) is increased in heart failure (HF), leading to I KAS upregulation, action potential duration shortening, early after depolarization, and recurrent spontaneous ventricular fibrillation. We hypothesized that casein kinase 2 (CK2) interacted with small conductance calcium-activated potassium channels (SK) is decreased in HF, and protein phosphatase 2A (PP2A) is increased on the opposite, upregulating the sensitivity of I KAS to intracellular Ca(2+) in HF. Rat model of volume-overload HF was established by an abdominal arteriovenous fistula procedure. The expression of SK channels, PP2A and CK2 was detected by Western blot analysis. Interaction and colocalization of CK2 with SK channel were detected by co-immunoprecipitation analysis and double immunofluorescence staining. In HF rat left ventricle, SK3 was increased by 100 % (P < 0.05), and SK2 was not significantly changed. PP2A protein was increased by 94.7 % in HF rats (P < 0.05), whereas the level of CK2 was almost unchanged. We found that CK2 colocalized with SK2 and SK3 in rat left ventricle. With anti-CK2α antibody, SK2 and SK3 were immunoprecipitated, the level of precipitated SK2 decreased by half, whereas precipitated SK3 was almost unchanged. In conclusion, the increased expression of total PP2A and decreased interaction of CK2 with SK2 may underlie enhanced sensitivity of I KAS to intracellular Ca(2+) in volume-overload HF rat.