Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction.

Sepsis-induced myocardial dysfunction (SIMD) is associated with poor prognosis and increased mortality in patients with sepsis. Cytokines are important regulators of both the initiation and progression of sepsis. Interleukin-15 (IL-15), a pro-inflammatory cytokine, has been linked to protective effects against myocardial infarction and myocarditis. However, the role of IL-15 in SIMD remains unclear. We established a mouse model of SIMD via cecal ligation puncture (CLP) surgery and a cell model of myocardial injury via lipopolysaccharide (LPS) stimulation. IL-15 expression was prominently upregulated in septic hearts as well as cardiomyocytes challenged with LPS. IL-15 pretreatment attenuated cardiac inflammation and cell apoptosis and improved cardiac function in the CLP model. Similar cardioprotective effects of IL-15 pretreatment were observed in vitro. As expected, IL-15 knockdown had the opposite effect on LPS-stimulated cardiomyocytes. Mechanistically, we found that IL-15 pretreatment reduced the expression of the pro-apoptotic proteins cleaved caspase-3 and Bax and upregulated the anti-apoptotic protein Bcl-2. RNA sequencing and Western blotting further confirmed that IL-15 pretreatment suppressed the activation of nuclear factor kappa B (NF-κB) signaling in mice with sepsis. Besides, the addition of NF-κB inhibitor can significantly attenuate cardiomyocyte apoptosis compared to the control findings. Our results suggest that IL-15 pretreatment attenuated the cardiac inflammatory responses and reduced cardiomyocyte apoptosis by partially inhibiting NF-κB signaling in vivo and in vitro, thereby improving cardiac function in mice with sepsis. These findings highlight a promising therapeutic strategy for SIMD.

Causal Relationship Between Gut Microbiota and Aneurysm: A Mendelian Randomization Study.

Observational studies have suggested a possible relationship between gut microbiota (GM) and aneurysm development. However, the nature of this association remains unclear due to the inherent limitations of observational research, such as reverse causation and confounding factors. To address this knowledge deficit, this study aimed to investigate and establish a causal link between GM and aneurysm development.

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. METHODS: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. RESULTS: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). CONCLUSIONS: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

Time-restricted eating with calorie restriction on weight loss and cardiometabolic risk: a systematic review and meta-analysis.

The effect of time-restricted eating (TRE) has been summarized in previous studies, but its benefits in combination with calorie restriction (CR) still need to be determined. The present meta-analysis aimed to evaluate the efficacy of TRE with CR on weight loss and cardiometabolic risk. PubMed, Embase, Cochrane Library, and gray literature databases were searched from inception to October 18, 2022, for potential randomized controlled trial (RCT) studies based on predefined inclusion and exclusion criteria. Body weight and other cardiometabolic risk factors were described as weighted mean difference (WMD) with a 95% confidence interval (CI). Eight RCTs involving 579 participants were enrolled in the present analysis. The pooled results showed that TRE with CR reduced the body weight, fat mass, and waist circumference significantly (WMD: -1.40, 95% CI: -1.81 to -1.00, and I2: 0%; WMD: -0.73, 95% CI: -1.39 to -0.07, and I2: 0%; WMD: -1.87, 95% CI: -3.47 to -0.26, and I2: 67.25%, respectively). However, compared with CR alone, TRE plus CR exhibited no significant benefit on the blood pressure, glucose profile, and lipid profile. Subgroup analysis suggested that early TRE is more effective in weight loss (WMD: -1.42, 95% CI: -1.84 to -1.01, and I2: 0%) and improving fat mass (WMD: -1.06, 95% CI: -1.91 to -0.22, and I2: 0%) than delayed or broader TRE when combined with CR. Although the combination of TRE and CR can effectively decrease body weight, fat mass, and waist circumference, the long-term effects, particularly those on cardiometabolic risk in participants with chronic cardiovascular disease and diabetes, remain to be explored.

The Efficacy and Safety of Cryoballoon Versus Radiofrequency Ablation for the Treatment of Atrial Fibrillation: A Meta-Analysis of 15 International Randomized Trials.

The purpose of this study was to evaluate the efficacy and safety of cryoballoon versus radiofrequency ablation for the treatment of atrial fibrillation (AF) by systematically reviewing randomized controlled trials (RCTs). Databases of Pubmed, Web of science, Embase, and Cochrane Library were searched for published studies up to June 31, 2022. Only RCTs comparing the efficacy and safety of cryoballoon vs radiofrequency ablation for the treatment of AF were enrolled in meta-analysis. Fifteen RCTs characterizing 2709 patients were finally included. Meta-analysis found that cryoballoon ablation was associated with a similar proportion of patients free from AF [risk ratio (RR): 1.02; 95% confidence interval (CI): 0.93 to 1.12, P = 0.65]. Acute pulmonary vein isolation rate [RR: 1.0; 95% CI: 0.98 to 1.01, P = 0.64] and fluoroscopy time (weighted mean difference: -0.03; 95% CI: -4.35 to 4.28; P = 0.99) were not statistically significant difference. The procedure time was shorter in the cryoballoon ablation (CBA) group (weighted mean difference : -18.76; 95% CI: -27.27 to -10.25; P < 0.0001). Transient phrenic nerve palsy was uniquely observed in the CBA group (RR = 6.66; 95% CI: 2.82 to 15.7, P < 0.0001) and resolved in all during the follow-up period, total complication was similar in both groups (RR = 1.24; 95% CI: 0.86 to 1.79, P = 0.24). Although the procedure time was shorter in CBA group, the efficacy and safety were similar in each group. Compared with radiofrequency ablation for the treatment of AF, patients receiving cryoballoon ablation have similar outcomes. CBA is associated with a shorter duration of procedure.

Association Between Aromatase Inhibitors and Myocardial Infarction Morbidity in Women With Breast Cancer: A Meta-Analysis of Observational Studies.

BACKGROUND: The cardiovascular toxicity of aromatase inhibitors (AIs) for women with estrogen receptor-positive breast cancer is controversial. We aimed to evaluate the association between AIs and the risk of myocardial infarction (MI) in women with estrogen receptor-positive breast cancer based on real-world studies. METHOD: PubMed, Embase, and Cochrane Library were searched to identify studies that estimated the association between MI risk and AIs. A random-effects model was used to evaluate the hazard ratio (HR) and 95% confidence intervals (CIs) of the predefined outcomes. RESULTS: A total of 134 476 patients from eight cohort studies were enrolled in our analysis. For MI incidence, no significant difference was found between the users of AIs and non-users (HR: .98, 95% CI: .83-1.17). The subgroup analysis of patients without a history of cardiovascular disease (CVD) suggested a reduced risk of MI (HR: .86, 95% CI: .77-.96). No significant difference was found for ischemic stroke (HR: .93, 95% CI: .82-1.07) and heart failure (HR: 1.24, 95% CI: .92-1.66) between the two groups. CONCLUSION: Based on real-world data, AIs may be a safe treatment route for patients with estrogen receptor-positive breast cancer and those with a history of CVD. AIs caused a major decrease in MI in patients without CVD history. However, more in-depth investigations are needed to explore the association between AI use and the incidence of MI in the treatment of estrogen receptor-positive breast cancer.

Electric field applications enhance the electron transfer capacity of dissolved organic matter in sludge compost.

Dissolved organic matter (DOM) plays an important role in heavy metal passivation and organic pollutant degradation owing to its redox ability. The structure and composition of DOM are determinants of redox ability changes during composting. Electric field-assisted aerobic composting (EAAC) has been shown to promote the degradation and humification of organic matter in compost. However, how EAAC affects the redox ability of DOM remains unclear. Hence, electron transfer capacity (ETC) of DOM extracted from EAAC was studied using the electrochemical method. Various spectral methods, such as excitation-emission matrix and ultraviolet and visible spectrophotometry were used to study the relationship of ETC with the compositional and structural changes of DOM. Results indicated that EAAC enhanced ETC of DOM at the later stage of composting, and ETC of DOM extracted from the final EAAC product was 10.4% higher than that of the control group. Spectral and correlation analyses showed that EAAC resulted in structural and compositional changes of DOM, and humification degree, aromatic compounds, molecular weight, and fulvic- and humic-like substance contents were improved in EAAC. This conversion increased ETC of DOM. Results of this study will contribute to the understanding of the redox of DOM and in expanding the application of EAAC products.

Anxiety Predicts Poor Prognosis in Patients With Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the prevalent inherited cardiomyopathy and a major contributor to sudden death and heart failure in young adults. Although depression has been associated with poor prognosis in patients with cardiovascular disease, the relationship between anxiety and HCM clinical outcomes has not been addressed. We aimed to determine the prevalence of anxiety symptoms in patients with HCM and the association between anxiety and adverse prognosis in this population. Methods: A total of 793 patients with HCM were prospectively enrolled and followed up for a mean of 4.1 years from March 2014 to January 2018. The primary endpoint was sudden cardiac death (SCD) events, and the secondary endpoint was HCM-related heart failure events. Anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) during outpatient visits or hospital stays. Results: Elevated scores on the HADS anxiety subscale (HADS-A ≥ 8) were defined as clinically significant anxiety. SCD and HCM-related heart failure events occurred in 76 and 149 patients, respectively, during the follow-up period. Kaplan-Meier survival curves demonstrated the significant association of anxiety with SCD events (log-rank P = 0.012) and HCM-related heart failure events (log-rank P = 0.001). Multivariable Cox regression analysis showed anxiety as a predictor of SCD events and HCM-related heart failure events (adjusted hazard ratio [HR] = 1.42, 95% confidence interval [CI] = 1.12-2.04, P = 0.03; adjusted HR = 2.9,2 95% CI = 1.73-4.03, P < 0.001), independent of conventional risk factors and depression. Besides, patients with comorbid anxiety and depression showed a fourfold higher risk of heart failure events and 3.5-fold higher risk of SCD versus those with neither (adjusted HR = 4.08, 95% CI = 2.76-5.91, P < 0.001; adjusted HR = 3.52, 95% CI = 2.24-4.67, P < 0.001, respectively). Conclusions: Anxiety was prevalent among Chinese patients with HCM, and it was independently associated with a higher risk of SCD and HCM-related heart failure events, particularly when comorbid with depression. Psychological assessment and intervention should be considered to alleviate anxiety symptoms in this population. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2000040759.

Effect of a Novel Pocket Compression Device on Hematomas Following Cardiac Electronic Device Implantation in Patients Receiving Direct Oral Anticoagulants.

Background: A pocket hematoma is a well-recognized complication that occurs after pacemaker or defibrillator implantation. It is associated with increased pocket infection and hospital stay. Patients suffering from atrial fibrillation and undergoing cardiovascular electronic implantable device (CIED) surgery are widely prescribed and treated with direct oral anticoagulants (DOACs). In this study, the use of a novel compression device was evaluated to examine its ability to decrease the incidence of pocket hematomas following device implantation with uninterrupted DOACs. Methods: A total of 204 participants who received DOACs and underwent CIED implantation were randomized into an experimental group (novel compression device) and a control group (elastic adhesive tape with a sandbag). The primary outcome was pocket hematoma, and the secondary outcomes were skin erosions and patient comfort score. Grade 3 hematoma was defined as a hematoma that required anticoagulation therapy interruption, re-operation, or prolonged hospital stay. Results: The baseline characteristics of both groups had no significant differences. The incidence of grades 1 and 2 hematomas was significantly lower in the compression device group than in the conventional pressure dressing group (7.8 vs. 23.5 and 2.0 vs. 5.9%, respectively; P < 0.01). Grade 3 hematoma occurred in 2 of 102 patients in the experimental group and 7 of 102 patients in the control group (2.0 vs. 6.9%; P = 0.03). The incidence rates of skin erosion were significantly lower, and the patient comfort score was much higher in the compression device group than in the control group (P < 0.01). Multivariable logistic regression analysis showed that the use of novel compression device was a significant protective factor for pocket hematoma (OR = 0.42; 95% CI, 0.29-0.69, P = 0.01). Conclusions: The incidence of pocket hematomas and skin erosions significantly decreases when the proposed compression device is used for patients undergoing device implantation with uninterrupted DOACs. Thus, the length of hospital stay and re-operation rate can be reduced, and patient comfort can be improved. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2100049430.

Sleep Quality, Sleep Duration, and the Risk of Adverse Clinical Outcomes in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with varying underlying etiologies and occurs in ~5-10% of patients with acute myocardial infarction. Sleep disorders and short sleep duration are common phenomena experienced by patients with coronary heart disease and are associated with poor clinical outcomes. However, the association between sleep quality, sleep duration, and the MINOCA prognosis is less clear. Methods: We performed a prospective observational study of 607 patients with MINOCA between February 2016 and June 2018. The mean follow-up period was 3.9 years. Sleep quality and sleep duration were measured by the Chinese version of the Pittsburgh Sleep Quality Index. The primary endpoint was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, stroke and heart failure hospitalization. Results: During the follow-up period, all-cause death occurred in 69 participants and 105 participants developed MACE. The Kaplan-Meier survival analysis demonstrated a significant association between poor sleep quality and all-cause mortality (log-rank P = 0.005) and MACE (log-rank P = 0.004). Multivariable Cox regression model indicated that poor sleep quality was an independent predictor of all-cause mortality as well as MACE [adjusted hazard ratio (HR) = 1.649; 95% confidence interval (CI), 1.124-2.790; P < 0.001; and adjusted HR = 1.432; 95% CI, 1.043-2.004; P = 0.003, respectively]. For sleep duration, short sleep duration (<6 h/d) was significantly associated with an increased risk of all-cause mortality and MACE (adjusted HR = 1.326; 95% CI, 1.103-1.812; P = 0.004; and adjusted HR = 1.443; 95% CI, 1.145-1.877; P < 0.001, respectively), whereas long sleep duration was not (>8 h/d). A poorer sleep profile (including poor sleep quality and short sleep duration) was associated with a 149.4% increased risk of death (HR = 2.494; 95% CI, 1.754-4.562; P < 0.001) and a 96.7% increased risk of MACE (HR = 1.967; 95% CI, 1.442-3.639; P < 0.001) than those with neither. Conclusion: Sleep disorders were common among Chinese patients with MINOCA. Poor sleep quality and short sleep duration were independently associated with an increased risk of all-cause mortality and MACE in the MINOCA population. Meanwhile, a poor sleep profile has an additive effect with regard to cardiovascular risks; in these populations, efforts should be made to improve both sleep quality and sleep duration for secondary cardiovascular prevention. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2000040701.

Effects of Intermittent Compared With Continuous Energy Restriction on Blood Pressure Control in Overweight and Obese Patients With Hypertension.

Background and Aims: Weight-loss diets reduce body weight and improve blood pressure control in hypertensive patients. Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight reduction. We aimed to compare the effects of IER with those of CER on blood pressure control and weight loss in overweight and obese patients with hypertension during a 6-month period. Methods: Two hundred and five overweight or obese participants (BMI 28.7 kg/m2) with hypertension were randomized to IER (5:2 diet, a very-low-calorie diet for 2 days per week, 500 kcal/day for women and 600 kcal/day for men, along with 5 days of a habitual diet) compared to a moderate CER diet (1,000 kcal/day for women and 1,200 kcal/day for men) for 6 months. The primary outcomes of this study were changes in blood pressure and weight, and the secondary outcomes were changes in body composition, glycosylated hemoglobin A1c (HbA1c), and blood lipids. Results: Of the 205 randomized participants (118 women and 87 men; mean [SD] age, 50.2 [8.9] years; mean [SD] body mass index, 28.7 [2.6]; mean [SD] systolic blood pressure, 143 [10] mmHg; and mean [SD] diastolic blood pressure, 91 [9] mmHg), 173 completed the study. The intention-to-treat analysis demonstrated that IER and CER are equally effective for weight loss and blood pressure control: the mean (SEM) weight change with IER was -7.0 [0.6] kg vs. -6.8 [0.6] kg with CER, the mean (SEM) systolic blood pressure with IER was -7 [0.7] mmHg vs. -7 [0.6] mmHg with CER, and the mean (SEM) diastolic blood pressure with IER was -6 [0.5] mmHg vs. -5 [0.5] mmHg with CER, (diet by time P = 0.62, 0.39, and 0.41, respectively). There were favorable improvements in body composition, HbA1c, and blood lipid levels, with no differences between groups. Effects did not differ according to completer analysis. No severe hypoglycemia occurred in either group during the trial. Conclusions: Intermittent energy restriction is an effective alternative diet strategy for weight loss and blood pressure control and is comparable to CER in overweight and obese patients with hypertension. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2000040468.

Association Between Depression and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.

Background Hypertrophic cardiomyopathy (HCM) is considered to be the most common cause of sudden death in young people and is associated with an elevated risk of mood disorders. Depression has emerged as a critical risk factor for development and progression of coronary artery disease; however, the association between depression and HCM outcomes is less clear. We sought to examine the impact of depression on clinical outcomes in patients with HCM. Methods and Results Between January 2014 and December 2017, 820 patients with HCM were recruited and followed for an average of 4.2 years. End points were defined as sudden cardiac death (SCD) events and HCM-related heart failure events. A Chinese version of the Structured Clinical Interview followed the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition and was used to diagnose depression. During the follow-up period, SCD events occurred in 75 individuals (21.8 per 1000 person-years), and HCM-related heart failure events developed in 149 individuals (43.3 per 1000 person-years). Kaplan-Meier cumulative incidence curves showed a significant association of depression disorders with SCD events (log-rank P=0.001) and HCM-related heart failure events (log-rank P=0.005). A multivariate Cox regression analysis indicated that depression was an independent predictor of SCD events and HCM-related heart failure events (41.9 versus 21.7 per 1000 person-years; adjusted hazard ratio [HR], 1.9; 95% CI, 1.6-2.3; P<0.001; and 69.9 versus 38.6 per 1000 person-years; HR, 1.8; 95% CI, 1.6-2.1; P<0.001, respectively). Conclusions Depression is common among patients with HCM. The diagnosis of depression is significantly and independently associated with an increased risk of SCD events and heart failure events in patients with HCM.

CXCL12 and CD3E as Indicators for Tumor Microenvironment Modulation in Bladder Cancer and Their Correlations With Immune Infiltration and Molecular Subtypes.

Bladder cancer (BLCA) represents the ninth most common malignant tumor in the world and is characterized by high recurrence risk. Tumor microenvironment (TME) plays an important role in regulating the progression of BLCA. Immunotherapy, including Bacillus Calmette-Guerin (BCG) and programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), is closely associated with TME and is widely used for treating BLCA. But parts of BLCA patients have no response to these treatment ways, thus a better understanding of the complex TME of BLCA is still needed. We downloaded the gene expression profile and corresponding clinical information of 414 BLCA patients from the TCGA database. Via the ESTIMATE and CIBERSORT algorithm, we identified the two hub genes (CXCL12 and CD3E) and explored their correlations with immune infiltration. We found that BLCA patients with higher expression of CXCL12 and lower expression of CD3E had prolonged survival. Gene set enrichment analysis (GSEA) revealed that both CXCL12 and CD3E were enriched in immune-related pathways. We also discovered that stromal score and the level of CXCL12 were higher in luminal subtype, and immune score and the level of CD3E were higher in the basal subtype. Furtherly, we found that CXCL12 was associated with naive B cells, resting mast cell, M2 macrophages, follicular helper T cells, and dendritic cells. CD8+ T cells, CD4+ T cells, regulatory T cells (Tregs), and macrophages were correlated with CD3E. In conclusions, we found that CXCL12 and CD3E might serve as indicators of TME modulation in BLCA. Therapy targeting CXCL12 and CD3E had the potential as novel therapeutic strategy.

Association Between Obstructive Sleep Apnea-Hypopnea Syndrome and Outcomes in Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease.

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5-10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA. Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke. Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan-Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286-2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201-2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications. Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

Association between anxiety and clinical outcomes in Chinese patients with myocardial infarction in the absence of obstructive coronary artery disease.

BACKGROUND: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) accounts for approximately 5% - 6% of acute myocardial infarction (AMI) patients. Anxiety symptoms are common in patients with coronary artery disease (CAD), and are associated with a poor prognosis. However, the association between anxiety and MINOCA outcomes is less clear. HYPOTHESIS: Anxiety will be associated with clinical outcomes in patients with MINOCA. METHODS AND RESULTS: Between November 2014 and December 2016, 620 hospitalized patients with MINOCA were recruited from a single center. Within 7 days of coronary angiography, anxiety was assessed using the Zung Self-Rating Anxiety Scale. The primary endpoint was all-cause mortality; secondary endpoint was any major adverse cardiovascular event (MACE). After 3 years, 87 deaths and 151 MACE had occurred. Kaplan-Meier curves indicated the unadjusted rates of all-cause mortality (log-rank P = .045) and MACE (log-rank P = .023) were significantly higher in the anxiety group compared with the control group of patients without anxiety. Multivariate Cox regression analysis showed that clinically significant anxiety was an independent prognostic factor for all-cause mortality as well as MACE (hazard ratio [HR] = 1.547; 95% confidence interval [CI], 1.006-2.380; P = .047; HR = 1.460; 95% CI, 1.049-2.031; P = .025; respectively). CONCLUSIONS: Anxiety is significantly and independently associated with an increased risk of all-cause mortality and MACE in patients with MINOCA.

Effect of exercise-based cardiac rehabilitation on clinical outcomes in patients with myocardial infarction in the absence of obstructive coronary artery disease (MINOCA).

BACKGROUND: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is characterized by clinical evidence of myocardial infarction with nonobstructive coronary stenosis on angiography (stenosis < 50%). Studies on the effect that exercise-based cardiac rehabilitation (CR) has on outcomes in MINOCA patients are lacking. Therefore, the purpose of this study was to determine the effect of exercise-based CR on clinical outcomes in patients with MINOCA. METHODS: A total of 524 participants with MINOCA were recruited in this prospective cohort study from August 2014 to October 2016 and followed for three years. We randomly divided 524 patients into an exercise-based cardiac rehabilitation group (CR+) and a control group (CR-). The CR+ group followed a home-based exercise-training program three times a week during the three years of moderate continuous training (MCT; 65%-75% of peak heart rate) on a bicycle or treadmill. RESULTS: After one year of follow-up, the Short Form 36 (SF-36) survey showed apparent improvement in the mean physical health score in the CR+ group compared with the CR- group (P < 0.01). During the three-year follow-up, all-cause mortality occurred in 60 individuals, and major adverse cardiovascular events (MACE) happened in 136 individuals. Kaplan-Meier curves indicated a significant reduction in all-cause mortality (log-rank P < 0.05) and MACE (log-rank P < 0.01) in the CR+ group. A multivariate Cox regression analysis indicated that exercise-based CR was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.483; 95% confidence interval [CI], 0.279-0.818; P < 0.01) and MACE (HR = 0.574; 95% CI, 0.403-0.827; P < 0.001). CONCLUSIONS: A long-term exercise-based CR program was associated with superior physical health and a significant reduction in all-cause mortality and MACE in patients with MINOCA.

Association Between Depression and Outcomes in Chinese Patients With Myocardial Infarction and Nonobstructive Coronary Arteries.

Background Myocardial infarction with nonobstructive coronary arteries ( MINOCA ) occurs in ≈10% of all patients with myocardial infarction. Studies on effects of depression on MINOCA outcomes are lacking. Therefore, the aim of this study was to examine the association of depression with clinical outcomes in Chinese patients with MINOCA . Methods and Results We conducted a prospective cohort study of 633 participants with MINOCA and followed up for 3 years. End points were defined as all-cause mortality and cardiovascular events. Diagnosis of depression was ascertained using the psychiatric interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). During the follow-up period, all-cause death occurred in 93 individuals and cardiovascular events developed in 170 individuals. Kaplan-Meier curves showed a significant association of depression with all-cause mortality (log-rank P<0.001) and cardiovascular events (log-rank P<0.001). Multiple Cox regression identified the new diagnosis of depression as an independent prognostic factor for all-cause mortality as well as cardiovascular events (adjusted hazard ratio, 7.250; 95% CI, 4.735-11.100; P<0.001; and hazard ratio, 3.411; 95% CI , 2.490-4.674; P<0.001, respectively). Conclusions The new diagnosis of depression at the time of myocardial infarction is associated with increased risk of adverse clinical outcomes in patients with MINOCA.

Efficacy and safety of phosphodiesterase type-5 inhibitors for pulmonary arterial hypertension: A meta-analysis focusing on 6MWD.

BACKGROUND AND OBJECTIVE: Phosphodiesterase type-5 inhibitors (PDE-5 inhibitors) have been suggested as a first-line drug for treating pulmonary arterial hypertension (PAH). The aim of present meta-analysis was to fully evaluate the efficacy and safety of treating PAH with PDE-5 inhibitors, focusing on the improvement of 6-min walk distance (6MWD). METHODS: Studies were identified from The Cochrane Library, EMBASE, and PUBMED databases. We calculated odds ratios (OR) for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. RESULTS: Six studies with a total of 1056 patients (729 patients in PDE-5 inhibitors treatment group and 327 patients in placebo group) were included. All-cause mortality rate in the control group and PDE-5 inhibitors group was 2.6% and 0.7%, respectively. In an average of 12.3-week follow-up, PDE-5 inhibitors treatment was associated with a 71% reduction in mortality (OR 0.29; 95 %CI 0.07-1.15; P = 0.08), and increased 6MWD by 40.17 m, improved NYHA functional class and hemodynamic parameters. As for monotherapy and combination therapy patients, 6MWD has improved by 48.94 m and 21.75 m, respectively. CONCLUSIONS: The results of present meta-analysis suggest that treatment with PDE-5 inhibitors improves the 6MWD, clinical symptoms, hemodynamic parameters, and a tendency of survival benefits. In patients treated with PDE-5 inhibitor monotherapy, the 6MWD significantly increased when compared to combination therapies.