Intravascular ultrasound-guided vs angiography-guided drug-eluting stent implantation in complex coronary lesions: Meta-analysis of randomized trials.

The relative outcomes of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI with drug-eluting stent (DES) in complex lesions have not been established. We sought to compare the efficacy and safety of IVUS-guided PCI with angiography-guided PCI in patients with complex coronary lesions treated with DES. METHODS: Electronic databases were searched to identify all randomized trials comparing IVUS-guided vs angiography-guided DES implantation. We evaluated major adverse cardiac events (MACE), all-cause and cardiovascular death, myocardial infarction, target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis outcomes at the longest reported follow-up. Random-effects modeling was used to calculate pooled relative risk (RR) and 95% CIs. RESULTS: Eight trials comprising 3,276 patients (1,635 IVUS-guided and 1,641 angiography-guided) enrolling only patients with complex lesions were included. Mean follow-up was 1.4±0.5years. Compared with angiography-guided PCI, patients undergoing IVUS-guided PCI had significantly lower MACE (RR 0.64, 95% CI 0.51-0.80, P=.0001), TLR (RR 0.62, 95% CI 0.45-0.86, P=.004), and TVR (RR 0.60, 95% CI 0.42-0.87, P=.007). There were no significant differences for stent thrombosis, cardiovascular death, or all-cause death. In meta-regression analysis, IVUS-guided PCI was of greatest benefit in reducing MACE in patients with acute coronary syndromes, diabetes, and long lesions. CONCLUSIONS: The present meta-analysis demonstrates a significant reduction in MACE, TVR, and TLR with IVUS-guided DES implantation in complex coronary lesions.

Sources of variability in the measurement of perfusion defect size using commercially available software programs: Are there gender differences?

We recently showed that Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox (ECTb) and 4-Dimension-Myocardial SPECT (4DM) yielded discordant results in the assessment of perfusion defect size (PDS) in patients with known or suspected coronary artery disease. In this report, we examined the sources of variability in the measurement of PDS using ECTb (VarECTb), 4DM (Var4DM) and QPS (VarQPS) and found that gender is a source of variability in the assessment of PDS. In 120 patients, VarECTb was lower in men, compared with women, whereas Var4DM and VarQPS were similar between both genders. Among men, VarECTb was lowest, compared with VarQPS and Var4DM, whereas, VarECTb, VarQPS, and Var4DM were not different among women. Future studies should account for gender differences when comparing the 3 software programs.

Comparison of failure rates of crossing side branch with pressure vs. coronary guidewire: a meta-analysis.

OBJECTIVES: The aim of this study was to compare the failure rates of crossing side branch (SB) with pressure guidewire vs. coronary guidewire after main vessel (MV) stenting in coronary bifurcation lesions (CBL). BACKGROUND: Percutaneous coronary intervention of CBL is technically difficult. The European Bifurcation Club recommends performing either fractional flow reserve (FFR) estimation of the SB or final kissing balloon inflation (FKBI) after the MV stenting when a significant SB ostial stenosis is present. Even though FFR is recommended in CBL, there is concern about SB crossing with pressure guidewire among interventionists. MATERIALS AND METHODS: We undertook a comprehensive literature search to identify all relevant studies reporting the failure rates of SB crossing after MV stenting with either pressure or coronary guidewire. A random effects model was used to compare the failure rates between the two approaches. RESULTS: Our search identified six studies that reported failure rates of SB crossing with a pressure guidewire (n = 648) and 11 studies that reported failure rates of SB crossing with a coronary guide-wire (n = 2601). Estimated pooled failure rate was 3·9% (95% CI: 1·5% to 9·6%) for inability to cross SB with pressure guidewire. Estimated pooled failure rate of SB crossing with coronary guidewire was 3·1% (95% CI: 1·5% to 6·2%). There was no significant difference between the failure rates in the two groups (P = 0·70). CONCLUSION: The failure rates of SB crossing after MV stenting are low with both pressure and coronary guidewire procedures, with no significant difference between the two approaches.

Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies.

OBJECTIVE: To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. BACKGROUND: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. METHODS: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. RESULTS: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. CONCLUSIONS: All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.

Ryanodine receptor-mediated calcium leak drives progressive development of an atrial fibrillation substrate in a transgenic mouse model.

BACKGROUND: The progression of atrial fibrillation (AF) from paroxysmal to persistent forms remains a major clinical challenge. Abnormal sarcoplasmic reticulum (SR) Ca(2+) leak via the ryanodine receptor type 2 (RyR2) has been observed as a source of ectopic activity in various AF models. However, its potential role in progression to long-lasting spontaneous AF (sAF) has never been tested. This study was designed to test the hypothesis that enhanced RyR2-mediated Ca(2+) release underlies the development of a substrate for sAF and to elucidate the underlying mechanisms. METHODS AND RESULTS: CREM-IbΔC-X transgenic (CREM) mice developed age-dependent progression from spontaneous atrial ectopy to paroxysmal and eventually long-lasting AF. The development of sAF in CREM mice was preceded by enhanced diastolic Ca(2+) release, atrial enlargement, and marked conduction abnormalities. Genetic inhibition of Ca(2+)/calmodulin-dependent protein kinase II-mediated RyR2-S2814 phosphorylation in CREM mice normalized open probability of RyR2 channels and SR Ca(2+) release, delayed the development of spontaneous atrial ectopy, fully prevented sAF, suppressed atrial dilation, and forestalled atrial conduction abnormalities. Hyperactive RyR2 channels directly stimulated the Ca(2+)-dependent hypertrophic pathway nuclear factor of activated T cell/Rcan1-4, suggesting a role for the nuclear factor of activated T cell/Rcan1-4 system in the development of a substrate for long-lasting AF in CREM mice. CONCLUSIONS: RyR2-mediated SR Ca(2+) leak directly underlies the development of a substrate for sAF in CREM mice, the first demonstration of a molecular mechanism underlying AF progression and sAF substrate development in an experimental model. Our work demonstrates that the role of abnormal diastolic Ca(2+) release in AF may not be restricted to the generation of atrial ectopy but extends to the development of atrial remodeling underlying the AF substrate.

Beta-blockers in heart failure with preserved ejection fraction: a meta-analysis.

Beta-blockers are established drugs in heart failure with reduced ejection fraction, but their role in heart failure with preserved ejection fraction (HFpEF) is not established. Hence, we undertook a meta-analysis to evaluate the efficacy of beta-blockers on mortality and morbidity in HFpEF patients. A systematic search using PubMed, Embase, Scopus and Cochrane databases was performed to identify all relevant studies on beta-blockers and HFpEF. A random-effects model was performed to assess the role of beta-blockers on all-cause mortality and HF hospitalization. Overall 15 observational studies and two randomized control trial involving a total of 27,099 patients were included in the analysis. In the observational studies, beta-blocker therapy was associated with lower all-cause mortality [RR 0.81 (0.72-0.90), p < 0.001], but not HF hospitalization [RR 0.79 (0.57-1.10), p < 0.001]. However, in the two RCTs, the use of beta-blocker was not associated with all-cause mortality [RR 0.94 (0.67-1.32), p = 0.72] or HF hospitalization [0.90 (0.54-1.49), p = 0.68]. The results were consistent by geographic region (USA vs. rest of world) and ejection fraction subgroups. Subgroup analysis revealed that the beneficial survival effect of beta-blocker was limited to studies with mean age <75 years. Observational studies showed a significant benefit from the use of beta-blockers for all-cause mortality, but not for HF hospitalization. Beta-blockers in the two RCTs were not associated with significant reduction in all-cause mortality or HF hospitalization; however, both the trials were not adequately powered and had high loss to follow-up rates. Further large sampled well-conducted randomized trials are warranted to confirm the effects of beta-blockers on mortality and hospitalization.

Alterations in ryanodine receptors and related proteins in heart failure.

Sarcoplasmic reticulum (SR) Ca(2+) release plays an essential role in mediating cardiac myocyte contraction. Depolarization of the plasma membrane results in influx of Ca(2+) through l-type Ca(2+) channels (LTCCs) that in turn triggers efflux of Ca(2+) from the SR through ryanodine receptor type-2 channels (RyR2). This process known as Ca(2+)-induced Ca(2+)release (CICR) occurs within the dyadic region, where the adjacent transverse (T)-tubules and SR membranes allow RyR2 clusters to release SR Ca(2+) following Ca(2+) influx through adjacent LTCCs. SR Ca(2+) released during systole binds to troponin-C and initiates actin-myosin cross-bridging, leading to muscle contraction. During diastole, the cytosolic Ca(2+) concentration is restored by the resequestration of Ca(2+) into the SR by SR/ER Ca(2+)-ATPase (SERCA2a) and by the extrusion of Ca(2+) via the Na(+)/Ca(2+)-exchanger (NCX1). This whole process, entitled excitation-contraction (EC) coupling, is highly coordinated and determines the force of contraction, providing a link between the electrical and mechanical activities of cardiac muscle. In response to heart failure (HF), the heart undergoes maladaptive changes that result in depressed intracellular Ca(2+) cycling and decreased SR Ca(2+) concentrations. As a result, the amplitude of CICR is reduced resulting in less force production during EC coupling. In this review, we discuss the specific proteins that alter the regulation of Ca(2+) during HF. In particular, we will focus on defects in RyR2-mediated SR Ca(2+) release. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

The effect of bone marrow mononuclear stem cell therapy on left ventricular function and myocardial perfusion.

BACKGROUND: Bone marrow stem cell (BMC) transfer is an emerging therapy with potential to salvage cardiomyocytes during acute myocardial infarction and promote regeneration and endogenous repair of damaged myocardium in patients with left ventricular (LV) dysfunction. We performed a meta-analysis to examine the association between administration of BMC and LV functional recovery as assessed by imaging. METHODS AND RESULTS: Our meta-analysis included data from 32 trials comprising information on 1,300 patients in the treatment arm and 1,006 patients in the control arm. Overall, BMC therapy was associated with a significant increase in LV ejection fraction by 4.6% ± 0.7% (P < .001) (control-adjusted increase of 2.8% ± 0.9%, P = .001), and a significant decrease in perfusion defect size by 9.5% ± 1.4% (P < .001) (control-adjusted decrease of 3.8% ± 1.2%, P = .002). The effect of BMC therapy was similar whether the cells were administered via intra-coronary or intra-myocardial routes and was not influenced by baseline ejection fraction or perfusion defect size. CONCLUSIONS: BMC transfer appears to have a positive impact on LV recovery in patients with acute coronary syndrome and those with stable coronary disease with or without heart failure. Most studies were small and a minority used a core laboratory for image analysis.

Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging.

BACKGROUND: The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. METHODS AND RESULTS: In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score ≥4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's ρ = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (ρ = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. CONCLUSION: There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging.

New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility.

BACKGROUND: It is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α(1),ß(1),ß(2)-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions. METHODS AND RESULTS: In 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II-IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF(c)). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF(c)-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF(c) relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months. CONCLUSIONS: Despite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.

Association of systolic blood pressure with mortality in patients with heart failure with reduced ejection fraction: a complex relationship.

BACKGROUND: In ambulatory patients with heart failure with reduced ejection fraction (HFrEF), high systolic blood pressure (SBP) is associated with better outcomes. However, it is not known whether there is a ceiling beyond which high SBP has a detrimental effect. Thus, our aim was to assess the linearity of association between SBP and mortality. METHODS: We used the External Peer Review Program (EPRP) and Digitalis Investigation Group (DIG) trial databases of HFrEF patients. Linearity of association of SBP with mortality was assessed by plotting Martingale residuals against SBP. To assess the patterns of relationship of SBP with mortality, we used restricted cubic spline analysis with Cox proportional hazards model. RESULTS: In patients with mild-to-moderate left ventricular systolic dysfunction (LVSD) (30% ≤ LVEF < 50%), SBP had a nonlinear association with mortality in both EPRP (n = 3,693) and DIG (n = 3,263) databases. In these patients, SBP had a significant U-shaped association with mortality in EPRP and a trend toward U-shaped relationship in DIG database. In patients with severe LVSD (LVEF <30%), SBP had a linear association with mortality in both EPRP (n = 2,906) and DIG (n = 3,537) databases, with lower SBP being associated with increased mortality. CONCLUSIONS: Systolic blood pressure has a complex nonlinear association with mortality in patients with heart failure. Whereas it has a U-shaped association in patients with mild-to-moderate LVSD, it has a linear association with mortality in patients with severe LVSD. Recognition of this pattern of association of blood pressure profile may help clinicians in providing better care for their patients and help improve existing prediction models.

Turning a New Chapter in Neurosurgery Outpatient Services: Telemedicine A "Savior" in this Pandemic.

BACKGROUND: Teleconsultation services in India, especially in neurosurgery, are relatively new. Despite its large-scale adoption during the COVID-19 pandemic, comprehensive analyses of patients' perspectives and hurdles are lacking. MATERIALS AND METHODS: We conducted an anonymized telephonic survey of consecutive neurosurgical patients who availed telemedicine services at our institute, using a validated, structured questionnaire. To prevent bias, interviewers were not involved in the study design/analyses. Patients' perception of usefulness and performance of teleconsultation was graded on a 5-point Likert scale. RESULTS: Of the 330 patients who availed teleconsultation services, 231 (70%) completed the survey. Even though 91% of the respondents had access to a smartphone, only 10% received a video-based teleconsult. As per respondents, the challenges included poor network (7%), suboptimal communication/discussion (5.6%), lack of physical examination (6%), and misinterpretation of prescription by pharmacists/patients (6%). The majority of the respondents (58%) either agreed/strongly agreed that teleconsultation helped them tide over the medical exigency during the lockdown; however, the clinical diagnosis did not influence this response (P = 0.21). The vast majority of the respondents felt that teleconsultation is beneficial (97%), as it minimizes their exposure to COVID-19. One-third of the patients preferred this service over physical visits and 60% agreed to its continuation till resumption of routine care. Access to video-teleconsultation was the chief suggestion in 39 of 74 suggestions received. CONCLUSIONS: Telemedicine in neurosurgery offers favorable patient satisfaction during this pandemic and may be a satisfactory alternative to physical outpatient services in the future. Video-based teleconsults should be the preferred modality of communication for neurosurgery patients.

Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification.

OBJECTIVE: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. METHODS: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/µL [to convert to cells ×109/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality. RESULTS: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score. CONCLUSION: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.

Anemia, Mortality, and Hospitalizations in Heart Failure With a Preserved Ejection Fraction (from the TOPCAT Trial).

In this post-hoc analysis of the TOPCAT trial, we evaluated the prognostic role of anemia in adverse cardiovascular (CV) outcomes in heart failure with a preserved ejection fraction (HFpEF). Anemia was defined as hemoglobin of <12 g/dl in females and <13 g/dl in males. The primary outcome was a composite of CV mortality, aborted cardiac arrest (ACA), and heart failure (HF) hospitalization. Secondary outcomes were components of the primary outcome, all-cause, CV and non-CV mortality, cause-specific CV and non-CV mortality, all-cause and HF hospitalization, myocardial infarction, and stroke. Among 1,748 patients from TOPCAT-Americas, patients with anemia had a 52% higher risk of the primary outcome (hazard ratio [HR] 1.52, 95% confidence interval 1.27, 1.83, p<0.05) during a median follow up of 2.4 years. These patients were also at higher risk of all-cause and CV mortality with no difference in non-CV mortality. Among CV causes, patients with anemia had higher risk of sudden cardiac death (SCD)/ACA and presumed CV death with no difference in death due to pump failure. Among non-CV causes, patients with anemia had higher risk of death due to malignancy (HR 2.61, p<0.05). Patients with anemia had higher risk of all-cause and HF hospitalizations (HR 1.26 and 1.56, respectively, p<0.05 for both). There was no difference in the risk of myocardial infarction or stroke. In conclusion, patients with HFpEF and anemia are at higher risk of mortality and hospitalization. Anemia is a significant risk factor for SCD/ACA, death due to presumed CV causes and malignancy in HFpEF.

Effect of Left Ventricular Systolic Dysfunction on Response to Warfarin.

Candidates for chronic warfarin therapy often have co-morbid conditions, such as heart failure, with reduced left ventricular ejection fraction. Previous reports have demonstrated an increased risk of over-anticoagulation due to reduced warfarin dose requirement in patients with decompensated heart failure. However, the influence of left ventricular systolic dysfunction (LVSD), defined as left ventricular ejection fraction <40%, on warfarin response has not been evaluated. Here, we assess the influence of LVSD on warfarin dose, anticoagulation control (percent time in target range), and risk of over-anticoagulation (international normalized ratio >4) and major hemorrhage. Of the 1,354 patients included in this prospective cohort study, 214 patients (16%) had LVSD. Patients with LVSD required 11% lower warfarin dose compared with those without LVSD (p <0.001) using multivariate linear regression analyses. Using multivariate Cox proportional hazards model, patients with LVSD experienced similar levels of anticoagulation control (percent time in target range: 51% vs 53% p = 0.15), risk of over-anticoagulation (international normalized ratio >4; hazard ratio 1.01, 95% confidence interval 0.82 to 1.25; p = 0.91), and risk of major hemorrhage (hazard ratio 1.11; 95% confidence interval 0.70 to 1.74; p = 0.66). Addition of LVSD variable in the model increased the variability explained from 35% to 36% for warfarin dose prediction. In conclusion, our results demonstrate that patients with LVSD require lower doses of warfarin. Whether warfarin dosing algorithms incorporating LVSD in determining initial doses improves outcomes needs to be evaluated.

Safety of hydrophilic guidewires used for side-branch protection during stenting and proximal optimization technique in coronary bifurcation lesions.

BACKGROUND AND PROPOSE: In coronary bifurcation lesions (CBL), hydrophilic guidewires used for side-branch (SB) protection can be withdrawn from underneath the stent easier than other wires. However, the safety of which has not been investigated. METHODS/MATERIALS: We performed scanning electron microscopic (SEM) examination of hydrophilic wires - the Whisper and Runthrough wires - used for SB protection during stenting and proximal optimization technique (POT) in 30 patients with CBL. The distal 15cm of the wire was examined every 1mm by SEM and 4500 segments were analyzed to investigate for wire fracture, polymer shearing (PS), and its correlations with post-stenting creatine kinase (CK)-MB release. RESULTS: SEM examination showed no evidence for wire fracture. The total area of PS and the largest defect on the wire were significantly larger with the Whisper wire versus the Runthrough wire (0.15±0.04mm2 vs. 0.026±0.01mm2 and 0.04±0.05mm2 vs. 0.01±0.01mm2; P<0.05, respectively). The total length of PS and the longest defect on the wire were significantly longer with the Whisper wire vs. the Runthrough wire (12.1±14.5mm vs. 2.7±3.0mm and 2.9±4.2mm vs. 1.0±1.2mm; P<0.05, respectively), but there were weak correlations between the extents of PS with CK-MB release. CONCLUSIONS: Hydrophilic guidewires may be safely used for SB protection during stenting and POT in CBLs. The extent of PS was significantly greater with the Whisper wire than with the Runthrough wire, but its correlation with post-stenting CK-MB release was weak.

Comparison of Approaches for Stroke Prophylaxis in Patients with Non-Valvular Atrial Fibrillation: Network Meta-Analyses of Randomized Controlled Trials.

BACKGROUND: Multiple novel oral anticoagulants and left atrial appendage closure devices (WATCHMAN) have been tested against dose-adjusted vitamin K antagonists in randomized controlled trials for stroke prophylaxis in non-valvular atrial fibrillation. No direct comparisons of these strategies are available from randomized controlled trials. We conducted the current analyses by combining efficacy and safety characteristics of all FDA approved stroke prophylaxis treatment strategies for patients with non-valvular atrial fibrillation. MATERIALS AND METHODS: We searched SCOPUS from 1945 till October 2015 for randomized controlled trials comparing these strategies and reporting efficacy and safety outcomes. Six randomized controlled trials were identified and included in the final analyses and review. We followed PRISMA guidelines for network meta-analyses while reporting the current analyses. We collected data on ischemic stroke, major bleeding, and the composite primary safety endpoint as defined by various randomized controlled trials. Network meta-analyses were conducted using consistency and inconsistency models for efficacy and safety outcomes. Surface under the cumulative ranking curve were then utilized to cluster rank these treatments for safety and efficacy. RESULTS: Six randomized controlled trials with 59,627 patients comparing six treatment strategies were eligible for the analyses. All prophylaxis strategies had comparable rates of ischemic stroke. Apixaban was associated with the least number of primary safety endpoint events as compared with all other treatments. In the cluster analyses assessing safety and efficacy, apixaban, edoxaban and dabigatran ranked best followed by vitamin K antagonists and rivaroxaban, whereas the WATCHMAN left atrial appendage closure device ranked last. CONCLUSIONS: Dose-adjusted vitamin K antagonists, novel oral anticoagulants, and the WATCHMAN left atrial appendage closure devices are equally efficacious for ischemic stroke prevention but these treatments have different safety profiles. More randomized controlled trials are needed to directly compare these strategies.

Catheter-directed treatment for acute pulmonary embolism: Systematic review and single-arm meta-analyses.

BACKGROUND: We sought to estimate the efficacy and safety outcomes of catheter-directed treatment (CDT) for patients with acute pulmonary embolism (PE). METHODS: We searched SCOPUS for studies reporting outcomes after CDT for acute PE. Studies were categorized in three groups for analyses due to heterogeneity in the classification of acute PE: 1) patients with PE causing right ventricular dysfunction and haemodynamic instability: unstable haemodynamic status, 2) patients with PE causing right ventricular dysfunction where study outcomes were not stratified by haemodynamic status: stable and unstable haemodynamic status, and 3) patients with PE causing right ventricular dysfunction who remained haemodynamically stable: stable haemodynamic status. Efficacy and safety outcomes were estimated and presented as point estimates with 95% confidence intervals. RESULTS: In 35 studies with 1253 patients, 1277 CDTs were performed. The in-hospital mortality rates for the unstable haemodynamic status, stable and unstable haemodynamic status, and stable haemodynamic status groups were 18.1% (7.3-38.2%), 7.1% (5.0-10.1%), and 2.6% (0.8-7.3%), respectively. The major bleeding rates across the groups were estimated to be 4.5, 8.5 and 3.9 per 100 CDTs, respectively. Minor bleeding occurred in 6.2, 11.9 and 9.1 per 100 CDTs, respectively. After CDT, all groups had improvements in mean pulmonary artery pressure and right ventricular function. CONCLUSIONS: We provide descriptive measures of efficacy and safety for patients who underwent CDT for acute PE.

Comparison of Approaches to Revascularization in Patients With Multivessel Coronary Artery Disease Presenting With ST-Segment Elevation Myocardial Infarction: Meta-analyses of Randomized Control Trials.

BACKGROUND: Significant controversy exists regarding the best approach for nonculprit vessel revascularization in patients with multivessel coronary artery disease presenting with ST-segment elevation myocardial infarction. We conducted a systematic investigation to pool data from current randomized controlled trials (RCTs) to assess optimal treatment strategies in this patient population. METHODS AND RESULTS: A comprehensive search of SCOPUS from inception through May 2015 was performed using predefined criteria. We compared efficacy and safety outcomes of different approaches by categorizing the studies into 3 groups: (1) complete revascularization (CR) versus culprit lesion revascularization (CL) at index hospitalization, (2) CR at index hospitalization versus staged revascularization (SR) of nonculprit vessels at a separate hospitalization, and (3) comparison of SR versus CL. Eight eligible RCTs met the inclusion criteria: (1) CR versus CL (6 RCTs, n=1727) (2) CR versus SR (3 RCTs, n=311), and (3) SR versus CL (1 RCT, n=149). We observed significantly lower rates of major adverse cardiovascular events, revascularization, and repeat percutaneous coronary interventions among patients treated with CR and SR compared with a CL approach (P<0.05). The rates of all-cause mortality, cause-specific mortality, major bleeding, reinfarction, stroke, and contrast-induced nephropathy did not differ in the CR arm compared with the CL arm. The rates of these outcomes were similar in the CR and SR arms. CONCLUSION: Results suggest that CR and SR compared with CL reduce major adverse cardiovascular event and revascularization rates primarily by lowering repeated percutaneous coronary intervention rates. We did not observe any increase in the rate of adverse events while using a CR or SR strategy compared with a CL approach. Current guidelines discouraging CR need to be reevaluated, and clinical judgment should prevail in treating multivessel coronary artery disease patients with ST-segment elevation myocardial infarction as data from larger RCTs accumulate.

Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions.

Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF.