MARCH5 restores endothelial cell function against ischaemic/hypoxia injury via Akt/eNOS pathway.

MARCH5 is a critical regulator of mitochondrial dynamics, apoptosis and mitophagy. However, its role in cardiovascular system remains poorly understood. This study aimed to investigate the role of MARCH5 in endothelial cell (ECs) injury and the involvement of the Akt/eNOS signalling pathway in this process. Rat models of myocardial infarction (MI) and human cardiac microvascular endothelial cells (HCMECs) exposed to hypoxia (1% O2 ) were used in this study. MARCH5 expression was significantly reduced in ECs of MI hearts and ECs exposed to hypoxia. Hypoxia inhibited the proliferation, migration and tube formation of ECs, and these effects were aggravated by knockdown of MARCH5 but antagonized by overexpressed MARCH5. Overexpression of MARCH5 increased nitric oxide (NO) content, p-eNOS and p-Akt, while MARCH5 knockdown exerted the opposite effects. The protective effects mediated by MARCH5 overexpression on ECs could be inhibited by eNOS inhibitor L-NAME and Akt inhibitor LY294002. In conclusion, these results indicated that MARCH5 acts as a protective factor in ischaemia/hypoxia-induced ECs injury partially through Akt/eNOS pathway.

Efficacy and Safety of Emergent Transcatheter Aortic Valve Implantation in Patients with Acute Decompensated Aortic Stenosis: Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of emergent transcatheter aortic valve implantation (TAVI) in patients with decompensated aortic stenosis (AS) by comparing the clinical outcomes with the patients who had received the elective TAVI. METHODS: By searching PubMed, EMBASE, and Cochrane databases, we obtained the studies comparing the clinical outcomes of emergent TAVI and elective TAVI. Finally, 14 studies were included. RESULTS: A total of 14 eligible articles with 73,484 patients were included in this meta-analysis. Emergent TAVI was associated with a higher mortality during hospitalization (HR 2.09, 95% CI [1.39 to 3.14]), 30 days (HR 2.29, 95% CI [1.69 to 3.10]), and 1 year (HR 1.96, 95% CI [1.55 to 2.49]). Consistently, the incidence of acute kidney injury (AKI) (RR 2.48, 95% CI [1.85 to 3.32]), dialysis (RR 2.37, 95% CI [1.95 to 2.88]), bleeding (RR 1.62, 95% CI [1.27 to 2.08]), major bleeding (RR 1.05, 95% CI [1.00 to 1.10]), and 30-day rehospitalization (RR 1.30, 95% CI [1.07, 1.58]) were more common in patients receiving emergent TAVI. No statistical differences were found in the occurrence rate of vascular complications (RR 1.11, 95% CI [0.90, 1.36]), major vascular complications (RR 1.14, 95% CI [0.52, 2.52]), permanent pacemaker (PPM) placement (RR 1.05, 95% CI [0.99, 1.11]), cerebrovascular events (RR 1.11, 95% CI [0.98, 1.25]), moderate to severe paravalvular leakage (PVL) (RR 1.23, 95% [CI 0.94 to 1.61]), and device success (RR 0.99, 95% CI [0.97, 1.01]). CONCLUSION: Emergent TAVI is associated with some postoperative complications and increased mortality compared with elective TAVI. Emergent TAVI should be implemented cautiously and individually.

Treating patients with excessively large annuli with self-expanding transcatheter aortic valves: insights into supra-annular structures that anchor the prosthesis.

BACKGROUND: Some patients referred for transcatheter aortic valve replacement (TAVR) have excessively large annuli (ELA) without device options according to current sizing charts. This retrospective study aims to summarize the presentation and outcomes of ELA patients receiving first-generation self-expanding valves. METHODS: The TAVR database was reviewed in search for cases of self-expanding valves. Patients who had annuli exceeding the perimeter limit on the device sizing chart were referred to as the ELA group. Patients who had annuli within the range covered by the two largest sizes and received the corresponding valve size served as the control group (CG). Baseline, procedures, outcomes, and imaging characteristics on multislice computed tomography (MSCT), such as native anatomy and postimplant stent geometry, were compared. RESULTS: A total of 28 patients were included in the ELA group and 82 in the CG. The patients in the ELA group were younger than those in the CG (72.5 ± 6.2 vs. 75.4 ± 5.8 years, P = 0.03). The median intended perimeter oversizing in relation to the annulus in the ELA group was much smaller than in the CG (-0.4 [-4.6, 4.1] % vs. 16.1 [11.7, 20.8] %, P < 0.01). The calcium burden in the aortic root was around 1.3-fold greater in the ELA group than the CG (756.0 [534.5, 1670.9] vs. 582.1 [310.3, 870.9] mm3, P = 0.01). The need for second valve implantation was higher in ELA (21.4% vs. 12.2%, P = 0.23) but no valve embolization was encountered. The 1­year follow-up was comparable, including >mild paravalvular leak. CONCLUSION: Under cautious patient selection using MSCT, TAVR with self-expanding valves in patients with ELA appears feasible. Supra-annular structures likely provide the extra anchoring.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

OBJECTIVES: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. METHODS: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. RESULTS: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. CONCLUSIONS: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Effect of concomitant aortic regurgitation on early hypo-attenuated leaflet thickening after transcatheter aortic valve replacement in patients with symptomatic severe aortic stenosis.

OBJECTIVE: We hypothesize that different degree of pre-existing aortic regurgitation (AR) may affect the presence of hypo-attenuated leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR). BACKGROUND: The mechanism of the presence of HALT post-TAVR is not fully understood. METHODS: We retrospectively evaluated the post-procedural multi-slice computed tomography (MSCT) before discharge for evidence of HALT. Patients were grouped according to the degree of pre-existing AR. Baseline, native anatomy and procedure details were compared, then multivariate regression was performed. RESULTS: MSCT analyzed was performed at a median of 6 days post-TAVR in 179 patients. HALT was detected in 10.6% of patients. After adjusting for variables that were significantly different between groups, pre-existing ≥ moderate AR was protective to the risk of HALT (OR 0.15, 95% CI 0.03-0.84, p = .03). Stratifying for factors that might explain the impact of pre-existing AR on HALT, patients with a small Sinus of Valsalva, non-eccentric remodeling and receiving a large bioprosthesis experienced a sevenfold higher risk for HALT (OR 7.16, 95% CI 2.05-25.08, p = .002). CONCLUSIONS: Patients underwent TAVR with pre-existing ≥ moderate AR appeared to experience a lower incidence of early HALT compared to those patients with less than moderate AR, which may be explained by a larger Sinus of Valsalva and a higher proportion of LV eccentric remodeling.

Differences in metabolic profiles between bicuspid and tricuspid aortic stenosis in the setting of transcatheter aortic valve replacement.

BACKGROUND: To explore why bicuspid aortic stenosis has certain clinical differences from the tricuspid morphology, we evaluated the metabolomics profile involved in bicuspid aortic valve (BAV) aortic stenosis prior to and after transcatheter aortic valve replacement (TAVR) in comparison with tricuspid aortic valve (TAV). METHODS: In this TAVR cohort with prospectively collected data, blood samples were obtained before TAVR valve deployment and at the 7th day after TAVR, which were then sent for liquid and gas chromatography-mass spectrometry detection. Besides comparisons between BAV and TAV, BAV patients were also divided in subgroups according to baseline hemodynamics (i.e. maximal transaortic velocity, Vmax) and post-procedural reverse left ventricular (LV) remodeling (i.e. the change in LV mass index from baseline, ∆LVMI) for further analysis. Metabolic differences between groups were identified by integrating univariate test, multivariate analysis and weighted correlation network analysis algorithm. RESULTS: A total of 57 patients were enrolled including 33 BAV patients. The BAV group showed lower arginine and proline metabolism both before and post TAVR than TAV represented by decreased expression of L-Glutamine. In BAV subgroup analysis, patients with baseline Vmax > 5 m/s (n = 11) or the 4th quartile of change in ∆LVMI at one-year follow-up (i.e. poorly-recovered LV, n = 8) showed elevated arachidonic acid metabolism compared with Vmax < 4.5 m/s (n = 12) or the 1st quartile of ∆LVMI (i.e. well-recovered LV, n = 8) respectively. CONCLUSIONS: Difference in arginine and proline metabolism was identified between BAV and TAV in TAVR recipients. Elevated arachidonic acid metabolism may reflect more severe baseline hemodynamics and worse LV reserve remodeling after TAVR in BAV.

The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction.

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis Having Coronary Cusp Fusion versus Mixed Cusp Fusion Nonraphe Bicuspid Aortic Valve.

OBJECTIVES: We aimed to assess the procedural and clinical results of transcatheter aortic valve replacement (TAVR) for nonraphe bicuspid aortic stenosis (AS) with coronary vs mixed cusp fusion. BACKGROUND: It remains unclear whether cusp fusion morphology affects TAVR outcomes in patients with nonraphe bicuspid AS. METHODS: This retrospective study enrolled consecutive patients with severe symptomatic AS and type-0 bicuspid aortic valve, who underwent TAVR at our institution between 2012 and 2017. TAVR outcomes were defined based on the Valve Academic Research Consortium-2 recommendations. RESULTS: Compared to patients with mixed cusp fusion (44/71), those with coronary cusp fusion (27/71) had a larger ellipticity index for the aortic annulus (21.9% ± 9.0% vs 15.6% ± 9.3%, p=0.007) and increased left ventricular outflow tract obstruction (31.1% ± 9.4% vs 26.9% ± 7.5%, p=0.04) but comparable rates of second valve implantation (15.9% vs 14.8%), mild paravalvular leakage (PVL, 38.5% vs 30.2%), permanent pacemaker implantation (PPM, 25.9% vs 15.9%), and 30-day mortality (7.4% vs 6.8%). Use of a first-generation transcatheter heart valve was associated with higher risk for mild PVL (odds ratio (OR) = 4.37; 95% confidence interval (95% CI) = 1.14-16.75; p=0.03) but not PPM (OR = 0.77; 95% CI = 0.22-2.62; p=0.67), whereas a larger oversizing ratio tended to be associated with a higher PPM rate (OR = 1.49; 95% CI = 0.46-4.86; p=0.51) but lower incidence of mild PVL (OR = 0.51; 95% CI = 0.19-1.35; p=0.17). CONCLUSIONS: In AS patients with type-0 bicuspid valves, cusp fusion morphology does not affect the procedural or clinical results of TAVR. Use of second-generation transcatheter heart valves may provide more favorable results in such patients. This trial is registered with NCT01683474.

The triglyceride paradox in the mortality of coronary artery disease.

BACKGROUND: The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients. METHODS: A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality. RESULTS: The mean follow-up time was 26.9 ± 13.6 months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3 = 10.3% vs. 8.6% vs. 6.3%, log rank test for overall p = 0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction. CONCLUSIONS: This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients. TRIAL REGISTRATION: ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.

Permanent pacemaker implantation after transcatheter aortic valve replacement in bicuspid aortic valve patients.

BACKGROUND: Studies of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) specifically for bicuspid aortic valve (BAV) patients are lacking. We aim to delineate possible aspects that might affect the incidence of PPI in a retrospective cohort of BAV patients treated with early-generation self-expanding devices. METHODS: A total of 80 patients with bicuspid morphology who successfully underwent TAVR by self-expanding devices without prior PPI were included. Baseline clinical, echocardiographic, and angiographic characteristics, procedural and post-procedural details were collected. RESULTS: The incidence of PPI after early-generation self-expanding valves in this BAV cohort was 26.3%. Baseline characteristics were comparable between patients requiring PPI post-TAVR or not. Perimeter oversizing greater than 20% significantly increased the risk of PPI compared with an oversizing of 10-20% (OR 5.08 [1.22, 21.07], P = 0.03). The proportion of patients with a depth of implantation greater than 6 mm was significantly higher in those who required PPI (82.4% vs 54.3%, P = 0.04). When testing the impact of depth of implantation >6 mm and oversizing in different morphologies, only in type 1 bicuspid patients and by oversizing>20% increased the risk of PPI (OR 12.00 [1.25, 115.36], P = 0.03) compared with an oversizing of 10-20%. CONCLUSIONS: Excessive perimeter oversizing in relation to aortic annulus and depth of implantation greater than 6 mm should be avoided to improve PPI post-TAVR for BAV patients receiving self-expanding devices, especially for type 1 BAV.

Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement.

The imaging finding of hypo-attenuated leaflet thickening (HALT) on bioprosthesis after transcatheter aortic valve replacement (TAVR) has been reported. The underlying mechanism is not clear, but leaflet thrombosis is speculated to be the cause. Heterogeneous antiplatelet responses may play a role in the process. This is a prospective, single-center pilot study in patients who received successful TAVR from June 2012 to November 2016. HALT on post-procedural multi-detector computed tomography. We thoroughly genotyped 34 SNPs and 8 SNPs that have been reported for clopidogrel and aspirin resistance. A total of 148 patients were enrolled. There were 15 patients demonstrating signs of HALT. Patients with HALT had a higher rate of atrial fibrillation (AF) pre-TAVR (33.3 vs. 7.5%, P = 0.01). We found that rs4244285 G>A polymorphism of the CYP2C19 gene was associated with the risk of HALT in the overdominant model (OR 4.00 [1.15-13.97], P = 0.02 for GA vs. GG+AA) adjusted by sex and the presence of pre-TAVR AF. Antiplatelet drug resistance is a reasonable possibility involved in HALT. Potential directions were suggested in polymorphisms of the CYP2C19 gene.

No modifying effect of nutritional status on statins therapy in relation to all-cause death in older patients with coronary artery disease.

BACKGROUND: Statins therapy in the secondary prevention of coronary artery disease (CAD) is associated with a lower risk of adverse cardiovascular events. However, little is known regarding the association of elderly patients with nutritional risk on statin therapy. AIMS: To investigate whether older patients with CAD who were at nutritional risk gain similar survival benefit from statins therapy as their counterparts without nutritional risk. METHODS: We conducted a retrospective hospital-based cohort study among 1705 patients with CAD who were older than 65 years of age, using coronary heart disease database from 2008 to 2012. Nutritional status of included patients was gauged using the geriatric nutritional risk index. After stratification by nutritional status, the hazard of all-cause death was compared between those with or without statins therapy. RESULTS: Of the 1705 patients included in the study (mean age 72 years; 73% male), all-cause death occurred in 146 (9.2%) patients with statins use and in 33 (26.2%) patients without statins use. The rate of all-cause death was higher in patients not receiving statins irrespective of nutritional status. After adjustments for potential confounders, the HR with statins use was 0.33 (95% CI 0.20-0.55) in patients without nutritional risk and 0.47 (95% CI 0.22-1.00) in patients with nutritional risk. No interaction effect was detected between nutritional status and statins use in relation to all-cause death (P value for interaction effect 0.516). CONCLUSION: Despite of the patient's nutritional status, statins therapy as a secondary prevention in elderly CAD patients was associated with decreased risk of all-cause death.

Acute Myocardial Infarction as the Initial Manifestation of Delayed Bioprosthesis Thrombosis After Transcatheter Aortic Valve Replacement.

Bioprosthesis thrombosis after transcatheter aortic valve replacement (TAVR) raised concerns about further clinical events. We report the case of a patient who suffered acute myocardial infarction (AMI) after TAVR for 3 years. Thrombosis was confirmed in the right coronary sinus of Valsalva by transthoracic echocardiography. Coronary angiography demonstrated the ostium of the right coronary artery was occluded. As an attempt to perform percutaneous coronary intervention (PCI) was unsuccessful, long-term therapeutic anticoagulation with warfarin was undertaken. Within 2 weeks, symptoms were relieved, and the right coronary ostium thrombus disappeared on computed tomography (CT) angiography. This case highlights the AMI as initial manifestation of delayed bioprosthesis thrombosis and the importance of anticoagulation against the bioprosthesis thrombosis. Meanwhile, the difficulty of PCI after TAVR is not only the stent frame of bioprosthesis, but also the location of the thrombosis.

Transcatheter aortic valve implantation with the self-expandable venus A-Valve and CoreValve devices: Preliminary Experiences in China.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been demonstrated to be an effective alternative to surgical aortic valve replacement (SAVR) in patients with aortic stenosis who are deemed high risk or inoperable. Currently, TAVI procedures in China mostly make use of the domestic Venus A-Valve and the CoreValve; however, there is no data on their comparative performance. METHODS: Consecutive patients undergoing TAVI with the aforementioned devices were included. The outcomes were reported according to the Valve Academic Research Consortium-2 (VARC) definitions. RESULTS: A total of 54 TAVI procedures were performed, 27 with the CoreValve and the other 27 with the Venus A-Valve. An additional valve was required in 4 (14.8%) and 3 (11.1%) patients, and the VARC-2 device success rates were 81.5 and 85.2%, respectively. The incidences of common complications were similar, except for the significantly less frequent pacemaker insertion in the Venus A-Valve group (7.4 vs. 37.0%, P = 0.03). Within 30 days, 2 (3.7%) patients died, 1 in each group, and both had a bicuspid aortic valve (BAV). No other serious complications, such as annular rupture, coronary obstruction and aortic dissection, occurred in the 32 BAV patients treated with the Venus A-Valve (14) or the CoreValve (18). After 2-years of follow-up, there was no significant difference between CoreValve group and Venus-A group (11.1 vs. 7.4%, P = 0.64). CONCLUSION: TAVI with the domestic Venus A-Valve is feasible, safe, and can produce favorable short-term outcomes comparable to those with the CoreValve in inoperable or high-risk patients with tricuspid and bicuspid aortic valve stenosis. © 2017 Wiley Periodicals, Inc.

The influence of body composition on renal function in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

OBJECTIVE: We try to analyse the effect of renal functions on death in CAD patients with different body compositions. METHODS: A retrospective analysis was conducted in 2989 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into two categories: basically preserved renal function (PRF) (eGFR ≥60 ml/min) and obviously reduced renal function (RRF) (eGFR <60 ml/min). The influence of renal insufficiency on mortality of CAD was detected in every tertile of body composition, including body mass index (BMI), body fat (BF) and lean mass index (LMI). The end points were all-cause mortality. RESULTS: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 271 cases. The percentage of patients with RRF was positively correlated with BF and inversely correlated with the LMI, but no relationship to BMI. The survival curves showed that the risk of death was significantly higher in the RRF patients in all subgroups stratified using BMI, BF, or LMI (log rank test, all p < 0.001). The COX multivariate regression analysis showed that the risk of death was significantly higher in the RRF patients with high BF (HR 1.95, CI 1.25-3.05) and low LMI (HR 1.82, CI 1.19-2.79). Meanwhile, risk of death was significantly higher in RRF patients with a high BMI (HR 2.08, CI 1.22-3.55) or low BMI (HR 1.98, CI 1.28-3.08) but this risk was not significant in patients with a medium BMI (HR 1.12, 0.65-1.94). The subgroup analysis of patients with acute coronary syndrome (ACS) showed similar results. CONCLUSIONS: For patients with CAD, renal insufficiency was positively correlated with BF, inversely correlated with LMI, and unrelated to BMI. The effect of renal insufficiency on the risk of death of CAD was related to body composition.

The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation--A systematic review and meta-analysis.

OBJECTIVE: The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI). BACKGROUND: Controversies regarding the relationship between COPD and TAVI have intensified. METHODS: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random-effect and fixed-effect models were used, depending on the between-study heterogeneity. RESULTS: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short-term and long-term all-cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14-1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12-1.61). COPD was also associated with increased short-term and mid-term cardiac-cause mortality (30 days: OR, 1.29, 95% CI, 1.02-1.64; 1 year: HR: 1.09, 1.02-1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29-3.0) predicted post-TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1-1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06-1.27) predicted TAVI futility in patients with COPD. CONCLUSION: COPD is common among patients undergoing TAVI, and COPD impacts both short- and long-term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility.

Association Between Bisphosphonates Therapy and Incident Myocardial Infarction: Meta-analysis and Trial Sequential Analysis.

BACKGROUND: Bisphosphonates have shown potential to inhibit atherosclerosis in animal experiments; however, whether bisphosphonates therapy lowers the risk of incidence of myocardial infarction (MI) is debated. We performed the meta-analysis and trial sequential analysis (TSA) to investigate the relation between bisphosphonates therapy and incident MI. METHODS: Pubmed and Embase databases were systematically searched in April 2015 to identify studies, which compared the incidence of MI in subjects receiving bisphosphonates with that in subjects not receiving the agents. Meta-analysis was conducted using random effects model in consideration of statistical heterogeneity between studies. Reliability of the results from meta-analysis was examined using TSA. RESULTS: Six observational studies (n = 440261) and 3 randomized control trials (RCTs, n = 11,024) met the eligible criteria. In the pooled analysis of observational studies, bisphosphonates therapy was not associated with reduced risk of MI either using unadjusted estimates (relative risk 0.93, 95% confidence interval (CI), 0.75-1.15) or estimates adjusted for confounding factors (hazard ratio 1.01, 95% CI, 0.84-1.21). Furthermore, hazard of incident MI did not differ between alendronate users and nonusers. TSA showed that evidence from observational studies firmly precluded the association between bisphosphonates and incident MI. Pooled analysis of RCTs also suggested no benefits of decrease in incident MI associated with bisphosphonates therapy (relative risk 1.05, 95% CI, 0.53-2.09). However, TSA demonstrated that evidence from RCTs was insufficient to draw a conclusion. CONCLUSIONS: Despite the encouraging findings from animal studies, bisphosphonates therapy is not associated with reduced risk of MI.

Target lesion calcification and risk of adverse outcomes in patients with drug-eluting stents. A meta-analysis.

BACKGROUND: Studies focusing on the relationship between calcified lesions and adverse outcomes in the drug-eluting stent (DES) era have presented inconsistent conclusions. The aim of this study was to assess the association between target lesion calcification and adverse outcomes in patients undergoing DES implantation. METHODS: A systematic search was conducted on Medline (Ovid SP, 1946 to 28 February 2014), Embase (Ovid SP, 1974 to 28 February 2014), and the Chinese Biomedical Literature Database (CBM, 1978 to 28 February 2014). Abstracts from the 2012 and 2013 scientific meetings of the American College of Cardiology and American Heart Association were manually searched. Hazard ratios (HRs) were pooled using a fixed or random effects model in the context of heterogeneity. RESULTS: A total of 13 studies comprising 66,361 patients were included. Target lesion calcification was associated with an increased risk of all-cause mortality (HR = 1.41; 95 % CI = 1.27-1.56), cardiac death (HR = 1.97; 95 % CI = 1.68-2.31), myocardial infarction (HR = 1.33; 95 % CI = 1.13-1.57), target lesion revascularization (TLR; HR 1.47, 95 % CI 1.18-1.83), stent thrombosis (HR 1.63, 95 % CI 1.36-1.96), and major cardiovascular events (HR 1.37, 95 % CI 1.19-1.58). The results proved robust in subgroup analyses for TLR and stent thrombosis. CONCLUSION: Calcified target lesions are risk factors for adverse outcomes in the DES era. Further studies focusing on comprehensive therapy in patients with coronary calcification are urgently needed.

Subclassification of left ventricular hypertrophy based on dilation stratifies coronary artery disease patients with distinct risk.

BACKGROUND: A new 4-tired classification of left ventricular hypertrophy (LVH) based on LV concentricity and dilation has been proposed; however, the association between the new categorization of LV geometry and outcomes in patients with coronary artery disease (CAD) is still unknown. METHODS: All the 2297 patients with CAD included underwent echocardiographic examination prior to discharge. Left ventricular mass (LVM) was calculated, and left ventricular end-diastolic volume (EDV) was indexed by body surface area (BSA). Study cohort was divided into five groups according to LV geometry: (i) eccentric nondilated LVH (normal LVM/EDV((2/3)) and EDV/BSA) (n = 129); (ii) eccentric dilated LVH (normal LVM/EDV((2/3)) with increased EDV/BSA) (n = 222); (iii) concentric nondilated LVH (increased LVM/EDV((2/3)) with normal EDV/BSA) (n = 441); (iv) concentric dilated LVH (increased LVM/EDV((2/3)) and EDV/BSA) (n = 118); and (v) normal LV mass (n = 1387). RESULTS: Dilated LVH was associated with a higher event rates of all-cause death (eccentric 13·1% vs. 3·1%; concentric 13·6% vs. 8·4%) and composite events (eccentric: 17·6% vs. 5·4%; concentric: 18·6% vs. 12·7%) compared with nondilated LVH. While eccentric nondilated LVH had comparable risk for adverse outcomes compared with normal LV mass (all-cause death: relative risk (RR) 0·68, 95% confidential interval (CI) 0·25-1·85; composite events: RR 0·75, 95% CI 0·36-1·58). Cox regression analyses showed that eccentric dilated LVH had the highest propensity to all-cause death (adjusted hazard ratio [aHR] 2·752 [95% CI 1·749-4·328], P < 0·001) and composite events (aHR 2·462 [95% CI 1·688-3·592], P < 0·001). CONCLUSION: In patients with CAD, dilated LVH and nondilated LVH provide distinct prognostic information. Eccentric nondilated LVH does not predict adverse outcomes.

Platelet-activating factor acetylhydrolase and premature ovarian failure.

Premature ovarian failure (POF) appears to be a complex disease entity with several underlying etiopathogenic contributions including the possibility of multiple distinctly different autoimmune mechanisms, in which inflammatory autoimmunity targeted to ovarian-specific germline antigens (e.g., zona pellucida proteins or Mater) or differentiation/regulatory factors (e.g. inhibin-alpha) were regarded as one of the most crucial factors. Platelet-activating factor (PAF) and PAF class oxidized phospholipids stimulate the occurrence and development of inflammation and atherosclerosis. PAF acetylhydrolase (PAF-AH) can hydrolyze PAF and PAF class oxidized phospholipids and eventually prevent the body from the damage of these inflammatory mediators. These findings indicate a potential relationship between PAF-AH and POF thus have major implications for the future health of women who suffer with premature ovarian failure.