SGLT2 inhibitors as a potential therapeutic option for pulmonary hypertension: mechanisms and clinical perspectives.

Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.

Impact of acute glycemic variability on short-term outcomes in patients with ST-segment elevation myocardial infarction: a multicenter population-based study.

BACKGROUND: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. RESULTS: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). CONCLUSION: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.

The efficacy and safety of direct oral anticoagulants compared with vitamin K antagonist in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: The benefit-risk profile of direct oral anticoagulants (DOAC) therapy in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) has not been well established yet. This study aimed to evaluate the efficacy and safety of DOAC compared with vitamin K antagonists (VKA) in patients with HCM and AF. METHODS: PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched to identify studies comparing DOAC with VKA in patients with HCM and AF. The primary endpoint was thromboembolic events. The relative risks and standard errors were pooled by random-effect models using the generic inverse variance method. RESULTS: Seven observational studies involving 9395 patients were included in this meta-analysis. Compared to the VKA group, the DOAC group displayed a similar risk of thromboembolic events [RR (95%CI): 0.93 (0.73-1.20), p = 0.59] and ischemic stroke [RR (95%CI): 0.65 (0.33-1.28), p = 0.22]. The incidence of major bleeding was comparable between the two groups [RR (95%CI): 0.75 (0.49-1.15), p = 0.19]. Meanwhile, DOAC therapy was superior to VKA therapy in reducing the incidences of all-cause death [RR (95%CI): 0.44 (0.35-0.55), p < 0.001], cardiovascular death [RR (95%CI): 0.41 (0.22-0.75), p = 0.004], and intracranial hemorrhage [RR (95%CI): 0.42 (0.24-0.74), p = 0.003]. CONCLUSION: In patients with HCM and AF, DOAC therapy was similar to VKA therapy in reducing the risk of thromboembolic events, without increasing bleeding risk. In addition, the DOAC group displayed significant advantages in reducing mortality and intracranial hemorrhage compared with the VKA group. Further randomized controlled trials are needed to provide more evidence for DOAC therapy in this population.

Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis.

BACKGROUND: Several studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial. OBJECTIVE: We sought to examine whether a dose-response association of DII and SARS-CoV-2 infection exists. DESIGN: A dose-response meta-analysis was performed to investigate the association of DII and SARS-CoV-2 infection. We conducted a systematic search of PubMed, Embase and Web of Science up to March 15th, 2023. The odds ratios (OR) of DII and COVID-19 risk and severity were computed. RESULTS: Totally, 5 studies were included (1 from UK and 4 from Iran), consisting of 197,929 participants with 12,081 COVID-19 cases. Although there was heterogeneity among studies, the results indicated that higher DII was independently related to higher SARS-CoV-2 infection incidence (OR = 1.57, 95% CI: 1.14, 2.17) and COVID-19 severity (OR = 1.11, 95% CI: 1.07, 1.15) but not COVID-19 mortality (risk ratio = 1.13, 95% CI: 1.00, 1.27). The incidence of SARS-CoV-2 infection increased by 31% for each 1-point increase in the E-DII (OR = 1.31, 95% CI: 1.20, 1.43). CONCLUSIONS: This meta-analysis suggests that an elevated DII score is associated with increased SARS-CoV-2 infectious risk and severity of COVID-19. There were not enough studies on COVID-19 mortality. Further large prospective studies in different countries are warranted to validate our results.

Causal impact of gut microbiota and associated metabolites on pulmonary arterial hypertension: a bidirectional Mendelian randomization study.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. METHODS: Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. RESULTS: Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100-4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019-2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358-0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245-0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367-0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231-0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. CONCLUSIONS: Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Mechanically induced photons from ultraviolet-C to near-infrared in Tm3+-doped MgF2.

Mechanoluminescence (ML) plays a vital role in various fields, and has gained increasing popularity over the past two decades. The widely studied materials that are capable of generating ML can be classified into two groups, self-powered and trap-controlled. Here, we demonstrate that both self-powered ML and trap-controlled ML can be achieved simultaneously in MgF2:Tm3+. Upon stimulation of external force, the 1I6→3H6 and 3H4→3H6 transitions of Tm3+ are observed, ranging from the ultraviolet-C to near-infrared. After exposure to X-rays, MgF2:Tm3+ presents a stronger ML than the uncharged sample. After cleaning up at high temperatures, the ML returns to the initial level, which is a typical characteristic of trap-controlled ML. In the end, we demonstrate the potential applications of MgF2:Tm3+ in dynamic anti-counterfeiting, and structure inspection.

Mechanical force induced luminescence ratiometric thermometry in CaZnOS:Dy3.

The 4I15/2-6H15/2 and 4F9/2-6H15/2 transitions of Dy3+ are usually used for luminescent ratiometric thermometry in the form of photoluminescence. However, here we demonstrate the possibility of using this pair of lines for luminescent ratiometric thermometry in the model of mechanoluminescence (ML) in CaZnOS:Dy3+. Upon stimulation of an external mechanical force rather than light, CaZnOS:Dy3+ emits bright yellow luminescence. The intensity ratio of 4I15/2-6H15/2 to 4F9/2-6H15/2 transitions of Dy3+ is found to increase gradually with the rise of temperature, which makes Dy3+ a qualified temperature indicator. Our work enriches the family of optical thermometry.

A prediction model for left ventricular thrombus persistence/recurrence: based on a prospective study and a retrospective study.

BACKGROUND: It remains unknown whether anticoagulation for persistent left ventricular (LV) thrombus should be continued indefinitely. Identifying patients with a high risk of thrombus unresolved may be helpful to determine the optimum anticoagulation duration. This study aimed to develop a prediction model to forecast thrombus persistence or recurrence in patients with LV thrombus. METHODS: We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at the National Center of Cardiovascular Diseases of China. The two cohorts were then combined to derive predictive models of thrombus persistence/recurrence. The primary study comprised patients who received systemic oral anticoagulants and had imaging records available at the end of a 3-month follow-up period. The Lasso regression algorithm and the logistic regression were performed to select independent predictors. The calibration curve was generated and a nomogram risk prediction model was applied as a risk stratification tool. RESULTS: A total of 172 (64 in the prospective cohort and 108 in the retrospective cohort) patients were included, with 124 patients in a training set and 48 patients in a validation set. Six predictors were incorporated into the multivariate logistic regression prediction model. The area under the receiving operating characteristic was 0.852 in the training set and 0.631 in the validation set. Patients with protuberant thrombus and higher baseline D-dimer levels had a reduced risk of persistence/recurrence (OR 0.17, 95% CI 0.03-0.69, P = 0.025; OR 0.67, 95% CI 0.43-0.91, P = 0.030, separately), whereas thicker thrombus was linked to an increased rate of persistent thrombus (OR 1.11, 95% CI 1.05-1.20, P = 0.002). Additionally, patients with diverse diagnoses or receiving different antiplatelet treatments had different rates of LV thrombus persistence/recurrence at 3 months. CONCLUSIONS: This prediction model provides tools to forecast the occurrence of persistent/recurrent thrombus and allows the identification of characteristics associated with unresolved thrombus. To validate the model and determine the duration of anticoagulation in patients with persistent thrombus, prospective randomized trials are necessary.

An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE).

Evidence on the treatment for left ventricular (LV) thrombus is limited and mainly derives from retrospective studies. The aim of R-DISSOLVE was to explore the effectiveness and safety of rivaroxaban in patients with LV thrombus. R-DISSOLVE was a prospective, interventional, single-arm study, conducted from Oct 2020 to June 2022 at Fuwai Hospital, China. Patients with a history of LV thrombus < 3 months and with systemic anticoagulation therapy < 1 month were included. The thrombus was quantitatively confirmed by contrast-enhanced echocardiography (CE) at baseline and follow-up visits. Eligible patients were assigned to rivaroxaban (20 mg once daily or 15 mg if creatinine clearance was between 30 and 49 mL/min) and its concentration was determined by detecting anti-Xa activity. The primary efficacy outcome was the rate of LV thrombus resolution at 12 weeks. The main safety outcome was the composite of ISTH major and clinically relevant non-major bleeding. A total of 64 patients with complete CE results were analyzed for efficacy outcomes. The mean LV ejection fraction was 25.4 ± 9.0%. The dose-response curve of rivaroxaban was satisfactory based on the peak and trough plasma levels and all concentrations were in the recommended treatment range according to NOAC guidelines. The incidence rate of thrombus resolution at 6 weeks was 66.1% (41/62, 95% CI 53.0-77.7%), and of thrombus resolution or reduction was 95.2% (59/62, 95% CI 86.5-99.0%). At 12 weeks, the thrombus resolution rate was 78.1% (50/64, 95% CI 66.0-87.5%) while the rate of thrombus resolution or reduction was 95.3% (61/64, 95% CI 86.9-99.0%). The main safety outcome occurred in 4 of 75 patients (5.3%) (2 ISTH major bleeding and 2 clinically relevant non-major bleeding). In patients with LV thrombus, we reported a high thrombus resolution rate with acceptable safety by rivaroxaban, which could be a potential option for further LV thrombus treatment.Trial registration This study was registered at ClinicalTrials.gov as NCT04970381.

Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

Persistent visible luminescence of SrF2:Pr3+ for ratiometric thermometry.

Luminescence-based thermometry, especially the ratiometric temperature sensing technology, has attracted considerable attention recently due to its characteristics such as non-contact operating mode and strong capacity of resisting disturbance. Differing from the conventional strategy that usually needs continuous excitation, here an optical thermometry, which we have named the persistent luminescence intensity ratio (PLIR) thermometry, is proposed. The PLIR thermometry relies on the optical material SrF2:Pr3+ that could emit luminescence for several hours and even longer after being charged by X-ray. It has been demonstrated that the PLIR is sensitive to the variation of temperature and complies with the Boltzmann distribution. More importantly, the reliability of the proposed PLIR thermometry is verified. Our work may inspire others to develop more persistent luminescence thermometry.

Predictive value of the stress hyperglycemia ratio in patients with acute ST-segment elevation myocardial infarction: insights from a multi-center observational study.

BACKGROUND: Stress hyperglycemia is a strong predictor of adverse outcomes in patients with acute myocardial infarction (AMI). Recently, the stress hyperglycemia ratio (SHR) has been designed as an index to identify acute hyperglycemia with true risk; however, data regarding the impact of SHR on the prognosis of ST-segment elevation myocardial infarction (STEMI) remains limited. This study aimed to evaluate the predictive value of the SHR in patients with acute STEMI and to assess whether it can improve the predictive efficiency of the Thrombolysis in Myocardial Infarction (TIMI) risk score. METHODS: This study included 7476 consecutive patients diagnosed with acute STEMI across 274 emergency centers. After excluding 2052 patients due to incomplete data, 5417 patients were included in the final analysis. Patients were divided into three groups according to SHR tertiles (SHR1, SHR2, and SHR3) and were further categorized based on diabetes status. All patients were followed up for major cardiovascular adverse events (MACEs) and all-cause mortality. RESULTS: After 30 days of follow-up, 1547 MACEs (28.6%) and 789 all-cause deaths (14.6%) occurred. The incidence of MACEs was highest among patients in the SHR3 group with diabetes mellitus (DM) (42.6%). Kaplan-Meier curves demonstrated that patients with SHR3 and DM also had the highest risk for MACEs when compared with other groups (p < 0.001). Moreover, C-statistics improved significantly when SHR3 was added into the original model: the ΔC-statistics (95% confidence interval) were 0.008 (0.000-0.013) in the total population, 0.010 (0.003-0.017) in the DM group, and 0.007 (0.002-0.013) in the non-DM group (all p < 0.05). In the receiver operating characteristic analysis, the area under the curve (AUC) for the original TIMI risk score for all-cause death was 0.760. When an SHR3 value of 1 point was used to replace the history of DM, hypertension, or angina in the original TIMI risk score, the Delong test revealed significant improvements in the AUC value (∆AUC of 0.009, p < 0.05), especially in the DM group (∆AUC of 0.010, p < 0.05). CONCLUSION: The current results suggest that SHR is independently related to the risks of MACEs and mortality in patients with STEMI. Furthermore, SHR may aid in improving the predictive efficiency of the TIMI risk score in patients with STEMI, especially those with DM.

Boltzmann-distribution-dominated persistent luminescence ratiometric thermometry in NaYF4:Pr3.

A novel, to the best of our knowledge, optical temperature measurement method is proposed, i.e., persistent luminescence intensity ratio (PLIR) thermometry. The PLIR thermometry relies on the micro-sized NaYF4:Pr3+ material that can emit persistent luminescence (PersL) uninterruptedly after being charged by x ray irradiation. The 3P1→3H5 and 3P0→3H5 PersL transitions, locating separately at ∼ 522 and 538 nm, have been confirmed to follow the Boltzmann distribution. The emitting intensity ratio of this pair of PersL lines is thus found to be a good indicator of the variation of temperature. Our work is expected to enrich the optical temperature sensing family.

Mechanoluminescence ratiometric thermometry via MgF2:Tb3.

Mechanoluminescent materials have attracted considerable attention over the past two decades, owing to the ability to convert external mechanical stimuli into useful photons. Here we present a new, to the best of our knowledge, type of mechanoluminescent material, i.e., MgF2:Tb3+. In addition to the demonstration of traditional applications, such as stress sensing, we show the possibility of ratiometric thermometry using this mechanoluminescent material. Under stimulation of an external force, rather than the conventional photoexcitation, the luminescence ratio of 5D3→7F6 to 5D4→7F5 emission lines of Tb3+ is confirmed to be a good indicator of temperature. Our work not only expands the family of mechanoluminescent materials, but also provides a new and energy-saving route for temperature sensing.

Visible-to-ultraviolet-C upconverted photon for multifunction via Ca2SiO4:Pr3.

The ultraviolet C (UVC) photon plays a key role in a broad spectrum of fields. With the implementation of the Minamata Convention, searching for a new way to achieve UVC light is highly desired. Here we develop a material of Ca2SiO4:Pr3+ that can emit UVC light upon excitation of a 450-nm laser or even a very cheap 450-nm LED, a fact confirmed by using a solar blind camera to capture UVC emission from Ca2SiO4:Pr3+. In addition, smart anti-counterfeiting and inactivation of Bacillus subtilis applications using Ca2SiO4:Pr3+ are also confirmed.

Ultraviolet C random lasing at 230-280†nm from Pr3+ doped bulk crystal resonators by two-photon absorption.

Ultraviolet solid-state light sources, especially in the short-wave ultraviolet band, are attracting great attention for potential applications in high-density optical data storage, biomedical research, and water and air purification and sterilization. As one of the means to generate solid-state short-wavelength lasers, upconversion technology, which can transform a low-energy photon to a high-energy photon, has a simple structure and does not require strict phase-matching conditions. However, because of the high non-radiative decay rate during multiphoton absorption process, the short-wave upconversion ultraviolet lasing is still difficult to achieve. Here, under 450 nm blue laser excitation, we have successfully obtained ultraviolet C random lasing from a Pr3+ doped YPO4 single crystal via two-photon absorption. Presently, ultraviolet C random lasing with the wavelength range of 230-280 nm is the shortest wavelength for upconversion lasing emission.

Utility of a pharmacogenetic-driven algorithm in guiding dual antiplatelet therapy for patients undergoing coronary drug-eluting stent implantation in China.

PURPOSES: The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation. METHODS: A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5). RESULTS: Among 1046 patients with PRiS < 2 and 711 patients with PRiS ≥ 2, 34.2% and 38.3% of them were treated with ticagrelor, respectively. The PRiS ≥ 2 was an independent predictor for the 1-year incidence of MACE (HR(95%CI): 2.09 (1.37-3.20), p = 0.001). Multivariable Cox regression indicated that in the PRiS ≥ 2 group, ticagrelor was superior to clopidogrel in reducing the risk of MACE (HR(95%CI): 0.53 (0.29-0.98), p = 0.042), without increasing the bleeding risk. On the other hand, in the PRiS < 2 group, clopidogrel treatment was related to a remarkably lower rate of BARC class ≥ 2 bleeding (HR(95%CI): 0.39 (0.20-0.72), p = 0.003), but comparable incidences of MACE and BARC class ≥ 3 bleeding during 1-year follow-up. Similar associations between P2Y12 receptor inhibitors and 1-year endpoints in the PRiS < 2 and PRiS ≥ 2 group could also be identified in propensity score-weighted analysis and propensity score-matched analysis. CONCLUSION: Tailored DAPT based on the PRiS could assist in improving the prognosis of patients undergoing DES implantation. Further randomized controlled trials are required to provide more evidence for PRiS-guided DAPT.

Impact of renin-angiotensin-aldosterone-system inhibitor drugs on mortality in patients with atrial fibrillation and hypertension.

BACKGROUND: Renin-angiotensin-aldosterone-system inhibitors markedly play an active role in the primary prevention of atrial fibrillation (AF), but the impact of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the mortality of patients with AF remains unclear. This study aimed to examine the relationship between treatment with ACEIs or ARBs and mortality in emergency department (ED) patients with AF and hypertension. METHODS: This multicenter study enrolled 2016 ED patients from September 2008 to April 2011; 1110 patients with AF and hypertension were analyzed. Patients were grouped according to whether they were treated with ACEI/ARB or not and completed a 1-year follow-up to evaluate outcomes including all-cause death, cardiovascular death, stroke, and major adverse events (MAEs). RESULTS: Among the 1110 patients with AF and hypertension, 574 (51.7%) received ACEI/ARB treatment. During the 1-year follow-up, 169 all-cause deaths (15.2%) and 100 cardiovascular deaths (9.0%) occurred, while 98 strokes (8.8%) and 255 MAEs (23.0%) occurred. According to the multivariate Cox regression analysis, ACEI/ARB therapy was significantly associated with a reduced risk of all-cause death (HR, 0.605; 95% CI 0.431-0.849; P = 0.004). Moreover, ACEI/ARB therapy was independently associated with a reduced risk of cardiovascular death (HR 0.585; 95% CI 0.372-0.921; P = 0.020) and MAEs (HR 0.651, 95% CI 0.496-0.855, P = 0.002) after adjusting for other risk factors. CONCLUSIONS: Our results revealed that ACEI/ARB therapy was independently associated with a reduced risk of all-cause death, cardiovascular death, and MAEs in ED patients with AF and hypertension. These results provide evidence for a tertiary preventive treatment for patients with AF and hypertension.

Clinical characteristics and thrombotic risk of atrial fibrillation with obstructive sleep apnea: results from a multi-center atrial fibrillation registry study.

BACKGROUND: Sleep apnea is a risk factor for atrial fibrillation (AF) but it is underdiagnosed. Whether obstructive sleep apnea (OSA) is correlated with thrombotic risk in AF remains unclear. The aim of the present study was to analyze the clinical characteristics and assess the thrombotic risk of AF with OSA. METHODS: In the present registry study,1990 consecutive patients with AF from 20 centers were enrolled. The patients were divided into 2 groups depending on whether they presented with both AF and OSA. All the patients were followed up for 1 year to evaluate the incidences of stroke and non-central nervous system (CNS) embolism. RESULTS: Of the 1990 AF patients, 70 (3.5%) and 1920 (96.5%) patients were in the OSA group and non-OSA group, respectively. The results of the multivariate logistic model analysis showed that male sex, body mass index (BMI), smoking, and major bleeding history were independent risk factors for patients with AF and OSA. The comparison of the Kaplan-Meier curves using the log-rank test revealed that AF with OSA was correlated with an increased risk of non-CNS embolism (p < 0.01). After multivariate adjustments were performed, OSA remained an independent risk factor for non-CNS embolism (HR 5.42, 95% CI 1.34-22.01, p = 0.02), but was not correlated with the risk of stroke in patients with AF. CONCLUSIONS: The present study revealed that male sex, high BMI values, smoking, and major bleeding history were independent risk factors for patients with AF and OSA. Moreover, OSA was an independent risk factor for non-CNS embolism in AF. Our results indicate that non-CNS embolism requires focus in patients with AF and OSA.

Predictive performance of different bleeding risk scores in patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention.

This study aims to evaluate the predictive values of the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) who received both anticoagulant and antiplatelet therapy. 930 patients were consecutively recruited and followed up for 1 year. The primary endpoints were BARC class ≥3 bleeding and BARC class ≥2 bleeding. BARC class ≥3 bleeding occurred in 36 patients(3.9%), while BARC class ≥2 bleeding was seen in 134 patients (14.4%). The predictive performance of the HAS-BLED score for BARC class ≥3 bleeding was unsatisfactory (c-statistic = 0.575). The discrimination of the ATRIA, ORBIT, PARIS, and PRECISE-DAPT scores was also low-to-moderate. The REACH score was useless in bleeding risk stratification for this population. Multivariable logistic regression indicated that previous bleeding events and hemoglobin were two independent predictors of BARC class ≥3 bleeding. Compared to the HAS-BLED score, the model constructed by previous bleeding events and hemoglobin displayed a significant improvement in bleeding risk prediction [c-statistics: 0.704 vs. 0.575 (p = .008), NRI = 0.662,IDI = 0.049]. In patients with AF and ACS or undergoing PCI who received anticoagulant+antiplatelet therapy, the HAS-BLED, ORBIT, ATRIA, REACH, PARIS, and PRECISE-DAPT scores displayed only low-to-moderate performance in predicting BARC class≥3 bleeding. Future studies are required to develop more reliable scoring systems for bleeding risk evaluation in this population.