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Abstract: Background: The ability to better predict outcome with exercise testing in patients with heart failure (HF) and left ventricular systolic dysfunction (LVSD) may prove extremely valuable in determining which patients are at increased risk. This study evaluated the ability of heart rate recovery (HRR) to predict outcome in patients with HF and validate previous findings in LVSD. Methods and Results: HRR was measured at 1-, 2-, 3-, and 5-minute time points after treadmill testing in 2,193 males being evaluated for chest pain at the Palo Alto and Long Beach VA Hospitals. Left ventricular ejection fraction (LVEF) was calculated using biplane ventriculography and patients were considered to have LVSD if they had an LVEF <50%. Angiographic and clinical data was available for all patients. Of the 2,193 patients, 314 patients had LVSD and 109 had a history of HF. Both HF patients and patients with LVSD with a normal HRR at 2 minutes had improved survival compared with patients that had an abnormal HRR at 2 minutes when adjusted for age and β-blocker use (HF adjusted odds ratio 0.25, 95% CI 0.10–0.66, P < .006; LVSD alone adjusted odds ratio 0.25, 95% CI 0.13–0.47, P < .0001). Stepwise proportional hazard regression analysis revealed that only 2-minute HRR, age, LVEF, and chronic obstructive pulmonary disorder were significant predictors of mortality in patients with LVSD and only HRR at 2 minutes and LV hypertrophy were significant predictors of mortality in patients with HF. Conclusion: HRR is a significant predictor of mortality in patients with HF and patients with LVSD and may be useful in better determining prognosis. [Copyright &y& Elsevier]

An abstract of the article "Stress cardiac MRI provides excellent prognostic risk stratification in coronary artery disease: a systematic review of the literature," by Michael J. Lipinski, Courtney M. McVey, Jeffrey S. Berger, Christopher M. Kramer, and Michael Salerno is presented.

The article presents a letter to the editor discussing the article "The genetics revolution and primary care pediatrics," by TL Cheng, RD Cohn, and GJ Dover, published in a previous issue.

Background Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. Methods MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. Results From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up ( P < .001) compared with both negative. Conclusion High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up. [ABSTRACT FROM AUTHOR]

Although metallic coronary stents significantly reduce angina pectoris compared with optimal medical therapy, angina after percutaneous coronary intervention (PCI) remains frequent. We, therefore, sought to compare the incidence of any angina during the 1 year after PCI among the spectrum of commercially available metallic stents. Metallic stent type was classified as bare metal stent, Cypher, Taxus Express, Xience V, Promus Element, and Resolute. The primary end point was patient-reported angina within 1 year of PCI. Multivariable logistic regression was performed to assess the independent association of stent type with any angina at 1 year. Overall, 8,804 patients were queried in regard to angina symptoms; 32.3% experienced angina at some point in the first year after PCI. Major adverse cardiovascular events, a composite of all-cause mortality, target vessel revascularization, and Q-wave myocardial infarction, increased with angina severity: 6.8% for patients without angina, 10.0% for patients with class 1 or 2 angina, and 19.7% for patients with class 3 or 4 angina (p <0.001 for trend). After multivariable adjustment, there was no significant association between stent type and angina at 1 year after PCI. Baseline Canadian Cardiovascular Society class 3 or 4 angina, history of coronary artery bypass grafting, and history of PCI were associated with a higher likelihood of angina at 1 year; increasing age, male gender, presentation with acute coronary syndrome, and higher stented length were associated with less angina. In conclusion, metallic stent type is not associated with the occurrence of angina at up to 1 year after PCI. [ABSTRACT FROM AUTHOR]

Objective: We evaluate the prevalence of complications and failure rates between the most commonly used "active" anchoring vascular closure device (VCD), AngioSeal™ and the "passive" anchoring VCD, Mynx™, in all-comers undergoing percutaneous coronary intervention (PCI).Methods: A total of 4,074 patients between 2008 and 2014, representing an era when both devices were available, were included. Thirty-two percent were acute coronary syndromes (37% STEMI). VCD choice was at the operator's discretion and included AngioSeal (n = 2,910) or Mynx (1,164). Cardiogenic shock or patients receiving intra-aortic balloon pumps were excluded. Safety was assessed by vascular complications defined as either vascular injury (perforation, dissection, acute limb ischemia, arteriovenous fistula, pseudoaneurysm with thrombin injection, or surgical repair) or access-site bleed (hemoglobin droP >3 g/dL requiring transfusion, retroperitoneal bleed, or hematoma >5 cm, or the composite of both. Efficacy was evaluated by device failure and defined as inability to achieve immediate hemostasis or use of additional hemostatic mechanisms. Outcomes at 30-days were evaluated.Results: Groups (AngioSeal vs Mynx) were fairly balanced with regards to bleeding risk factors of gender (male, 65% vs 66%), body mass index (30 ± 6 vs 30 ± 7), heart failure class III/IV (5% vs 6%), chronic kidney disease (15% vs 17%), use of glycoprotein IIb/IIIa inhibitor (5% vs 4%), or bivalirudin (86% vs 88%), all P >0.5. The AngioSeal group was slightly younger (64 ± 12 vs 65 ± 12, P < 0.001) with less peripheral arterial disease (11.3% vs 13.9%, P = 0.03), and increased 7F sheath use compared with Mynx (59% vs 22%, P < 0.001). Safety and efficacy outcomes were similar between groups.Conclusions: AngioSeal and Mynx appear to be equally safe and efficacious VCDs following PCI. The passive anchoring system may prove desirable as no intra-arterial anchor remains upon device removal. [ABSTRACT FROM AUTHOR]

Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway. [ABSTRACT FROM AUTHOR]

Background: Clinical trial data show overall favorable outcomes of paclitaxel-eluting stents for treatment of femoro-popliteal (FP) occlusive disease. However, external validity of trial results may be restricted to less complex FP lesions, and limited data on outcomes of paclitaxel-eluting stents in real world practice have been published.Methods: This is a retrospective analysis of data of all patients who received Zilver® PTX® for FP lesion from February 2013 to October 2014 at our center. The primary endpoint was primary patency, defined as peak systolic velocity ratio <2.0 by Doppler ultrasound, or angiographic diameter stenosis <50%, or freedom from clinically driven target lesion revascularization.Results: Seventy-eight patients received Zilver® PTX® for FP lesions in the pre-specified time period. Of them, 63 had follow-up data and were included in this study. Mean patient age was 66.3±9.4years, and 57.1% of the patients were men. Participants had a high prevalence of diabetes (49.2%), hypertension (93.7%), hyperlipidemia (93.7%), previous coronary revascularization (52.4%), or previous peripheral arterial disease (77.8%). Critical limb ischemia was present in 25.4% of the patients, Trans-Atlantic Inter-Society Consensus (TASC) class C or D in 76.2%, in-stent restenosis (ISR) in 36.5%, and total occlusion in 69.8%. Mean lesion length was 218.9±128.3mm, mean number of stents was 2.02±1.0, and total stent length was 189.0±128.5mm. Mean follow-up was 270.4±190.3days. Primary patency rate at 1year was 66.7% by Kaplan-Meier survival curve. When compared with patients with primary patency at follow up, those with an adverse outcome had higher prevalence of TASC II class C or D lesions (100% vs. 68.8%, p=0.013), and were more likely to have ISR (66.7% vs. 27.1%, p=0.012), longer lesion (291.3±138.7 vs. 195.7±117.1, p=0.011), and incomplete coverage of the lesion (full coverage of lesions: 40% vs. 77.1%, p=0.011).Conclusion: Post marketing use of Zilver® PTX® for the treatment of FP lesions is associated with lower patency rates compared with clinical trial data. This may be related to the high prevalence of TASC II class C or D lesions and ISR in real world practice. Future studies should be more representative of contemporary clinical practice. [ABSTRACT FROM AUTHOR]

Currently, percutaneous endovascular intervention is considered a first line of therapy for treating patients with critical limb ischemia. As the result of remarkable development of techniques and technologies, percutaneous endovascular intervention has led to rates of limb salvage comparable to those achieved with bypass surgery, with fewer complications, even in the presence of lower rates of long-term patency. Currently, interventionalists have a multiplicity of access routes including smaller arteries, with both antegrade and retrograde approaches. Therefore, the choice of the optimal access site has become an integral part of the success of the percutaneous intervention. By understanding the technical aspects, as well as the advantages and limitations of each approach, the interventionalists can improve clinical outcomes in patients with severe peripheral arterial disease. This article reviews the access routes in critical limb ischemia, their advantages and disadvantages, and the clinical outcomes of each. [ABSTRACT FROM AUTHOR]

Objective To assess the safety and efficacy everolimus-eluting stents (EES) compared with first-generation drug-eluting stents (DES) in patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). Background EES have been associated with improved clinical outcomes compared to paclitaxel-eluting stents (PES) and with similar outcomes compared to sirolimus-eluting stents (SES). Methods A total of 520 patients who presented with ST-elevation myocardial infarction (STEMI) from 2003 to 2013, who underwent primary PCI with DES, were retrospectively analyzed. Of these, 247 received SES, 136 PES, and 137 EES. Patients were followed up to 2 years for major adverse cardiac events (MACE). Univariate and multivariate models detected correlates to outcome. Results EES implantation, compared with PES and SES, resulted in comparable rates of MACE (8.8% vs. 16.2%, p = 0.06 and 8.8% vs. 12.6%, respectively, p = 0.26), stent thrombosis, MI, and target lesion revascularization. Patients who received EES had lower rates of all-cause mortality (3.7% vs. 12.6% vs. 9.4%, p = 0.03) at 1-year follow up. However, in the univariate and multivariate analyses, stent type was not independently associated with the primary outcome or with all-cause mortality. Diabetes mellitus and number of stents implanted were independently associated with the primary outcome. Conclusion While EES seem to be associated with better outcome when compared to PES, the main correlates of STEMI patients are the presence of diabetes and number of stents implanted, and not the type of stent used for intervention. [ABSTRACT FROM AUTHOR]

Background Patients presenting with ST-segment elevation myocardial infarction (STEMI) represent a high-risk group for in-hospital adverse events and bleeding. The safety and outcomes of eptifibatide in addition to bivalirudin in this population have not been determined. Methods Over an 11-year period, we identified 1849 STEMI patients undergoing primary percutaneous coronary intervention (PCI), of which 1639 received bivalirudin monotherapy compared with 210 patients who received both bivalirudin and provisional eptifibatide. Safety of combination therapy was assessed by the occurrence of thrombolysis in myocardial infarction (TIMI) major bleeding. In-hospital event rates of death, Q-wave myocardial infarction (MI), and acute stent thrombosis were evaluated for efficacy. Multivariate analysis was used to adjust for significant differences between groups. Results Patients treated with bivalirudin plus eptifibatide, when compared with patients with bivalirudin monotherapy, had increased rates of cardiogenic shock (15.7% vs. 9.4%), aspiration thrombectomy (48.5% vs. 23.7%), pre-TIMI flow ≤ 1 (63.5% vs. 40%), and higher peak troponin I (93.65 ± 92.7 vs. 49.16 ± 81.59; all p < 0.01). These, however, were not associated with differences in the primary end point after adjusting for significant baseline and procedural characteristics (OR: 1.63; 95% CI, 0.90–2.96, p = 0.12). Importantly, TIMI major bleeding was not significantly different between groups (OR 1.78; 95% CI, 0.79–2.95, p = 0.20). Conclusion The addition of eptifibatide to bivalirudin during primary PCI reflects a high-risk STEMI population. This therapy results in similar in-hospital outcomes without an increase in major bleeding. Therefore, when required, combination therapy may be considered in this population. [ABSTRACT FROM AUTHOR]

The effect of left atrial (LA) structural remodeling and dilatation on the outcome of ablation of atrial fibrillation (AF) remains unknown. We correlated potential prognostic markers of AF ablation, including LA volume from computed tomography, with AF recurrence after ablation. We studied 73 consecutive patients (52 with paroxysmal AF, 21 with persistent AF) undergoing AF ablation. LA volume was calculated by axial slice summation from 3-dimensional computed tomography. Follow-up was through 12 months, with success of ablation determined by electrocardiography and lack of symptoms (unless symptoms proved not AF by Holter monitor). Overall procedure success was 66% (including 15% repeat ablations, 12% on antiarrhythmics). Pulmonary vein isolation was performed, with additional linear ablation in 44 (60%). Mean LA volume (95% confidence interval) for those with recurrent AF was 119 ml (104 to 135) versus 98 ml (90 to 106) for no recurrence (p = 0.01, rank-sum test). Wide variation in LA volume occurred in the 2 groups, but, of the 15% of patients with very large LA volumes (>135 ml), 82% had recurrent AF. A cutpoint of 135 ml yields 36% sensitivity and 96% specificity for recurrence. In multivariable regression analysis, only LA volume and number of cardiovascular co-morbidities were associated with more recurrence (p = 0.02 and p = 0.03, respectively). In conclusion, LA volume varies greatly in those with and without successful AF ablations, mean LA volume is significantly larger in those with recurrence, and patients with LA volumes >135 ml are very likely to develop recurrent AF. [Copyright &y& Elsevier]

Objectives: Our purpose was to perform a systematic review and meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) of the infarct-related artery (IRA) with medical therapy in patients randomized >12 h after acute myocardial infarction (AMI). Background: There is ongoing uncertainty about the risk–benefit ratio of late PCI in stable patients with AMI. Methods: PubMed, CENTRAL, and other databases were searched (July 2007). Studies were included if they compared PCI with medical management and randomized patients >12 h and up to 60 days after AMI, and were excluded if patients were hemodynamically unstable. Odds ratios (ORs) were pooled for dichotomous outcomes, with all-cause mortality as the primary end point. Left cardiac remodeling parameters were also pooled with generic inverse-variance weighting. Results: We retrieved 10 studies that enrolled 3,560 patients, with median time from AMI to randomization of 12 days (range 1 to 26 days), and follow-up of 2.8 years (42 days to 10 years). Randomization allocated 1,779 subjects to PCI and 1,781 to medical treatment. There were 112 (6.3%) and 149 (8.4%) deaths in the 2 groups, respectively, yielding significantly improved survival in the PCI group (OR 0.49 [95% confidence interval (CI) 0.26 to 0.94], p = 0.030). These benefits were associated with similarly favorable effects on cardiac remodeling, such as improved left ventricular ejection fraction in the PCI group (+4.4% change [95% CI 1.1 to 7.6], p = 0.009). Conclusions: Percutaneous coronary intervention of the IRA performed late (12 h to 60 days) after AMI is associated with significant improvements in cardiac function and survival. [Copyright &y& Elsevier]

Aims: ST-segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). In this study, we sought to evaluate the effect of anakinra, a recombinant interleukin-1 receptor antagonist, on the incidence of HF., Methods and Results: We performed a pooled analysis of three early phase randomized clinical trials. The endpoints included the composite of all-cause death and new-onset HF, and the composite of all-cause death and hospitalization for HF at 1-year follow-up. Safety events, including injection site reaction and serious infections, were also recorded. We analysed 139 patients with STEMI from three separate trials: VCUART (N = 10), VCUART2 (N = 30), and VCUART3 (N = 99). Of these, 84 (60%) patients were randomized to anakinra and 55 (40%) to placebo. Treatment with anakinra significantly reduced the incidence of all-cause death or new-onset HF (7 [8.2%] vs. 16 [29.1%], log-rank P = 0.002) and of all-cause death or HF hospitalization (0 [0] vs. 5 [9.1%], log-rank P = 0.007). Patients treated with anakinra had significantly higher injection site reactions (19 [22.6%] vs. 3 [5.5%], P = 0.016) without a significant difference in the incidence of serious infections (11 [13.1%] vs. 7 [12.7%], P = 0.435). Treatment with anakinra significantly reduced the area under the curve for high-sensitivity C-reactive protein between baseline and 14 days (75.48 [41.7-147.47] vs. 222.82 [117.22-399.28] mg day/L, P < 0.001)., Conclusion: IL-1 blockade with anakinra for 14 days in patients with STEMI reduces the incidence of new-onset HF or hospitalization for HF at 1 year following STEMI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background ST-segment-elevation myocardial infarction is associated with an intense acute inflammatory response and risk of heart failure. We tested whether interleukin-1 blockade with anakinra significantly reduced the area under the curve for hsCRP (high sensitivity C-reactive protein) levels during the first 14 days in patients with ST-segment-elevation myocardial infarction (VCUART3 [Virginia Commonwealth University Anakinra Remodeling Trial 3]). Methods and Results We conducted a randomized, placebo-controlled, double-blind, clinical trial in 99 patients with ST-segment-elevation myocardial infarction in which patients were assigned to 2 weeks treatment with anakinra once daily (N=33), anakinra twice daily (N=31), or placebo (N=35). hsCRP area under the curve was significantly lower in patients receiving anakinra versus placebo (median, 67 [interquartile range, 39-120] versus 214 [interquartile range, 131-394] mg·day/L; P <0.001), without significant differences between the anakinra arms. No significant differences were found between anakinra and placebo groups in the interval changes in left ventricular end-systolic volume (median, 1.4 [interquartile range, -9.8 to 9.8] versus -3.9 [interquartile range, -15.4 to 1.4] mL; P =0.21) or left ventricular ejection fraction (median, 3.9% [interquartile range, -1.6% to 10.2%] versus 2.7% [interquartile range, -1.8% to 9.3%]; P =0.61) at 12 months. The incidence of death or new-onset heart failure or of death and hospitalization for heart failure was significantly lower with anakinra versus placebo (9.4% versus 25.7% [ P =0.046] and 0% versus 11.4% [ P =0.011], respectively), without difference between the anakinra arms. The incidence of serious infection was not different between anakinra and placebo groups (14% versus 14%; P =0.98). Injection site reactions occurred more frequently in patients receiving anakinra (22%) versus placebo (3%; P =0.016). Conclusions In patients presenting with ST-segment-elevation myocardial infarction, interleukin-1 blockade with anakinra significantly reduces the systemic inflammatory response compared with placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01950299.

Patients with diabetes mellitus are prone to increased adverse outcomes after percutaneous coronary intervention, even with contemporary drug-eluting stents. Randomized controlled trials have demonstrated comparable clinical outcomes between an ultrathin bioresorbable-polymer sirolimus-eluting stent (BP-SES) and a thin-strut durable-polymer everolimus-eluting stent (DP-EES) that has specific labeling for patients with diabetes. We aimed to evaluate the safety and efficacy of the BP-SES in patients with diabetes mellitus. To determine the performance of the BP-SES in diabetic patients, patient-level data from the BIOFLOW II, IV, and V randomized controlled trials were pooled. The primary end point was target lesion failure (TLF), defined as the composite of cardiovascular death, target-vessel myocardial infarction, ischemia-driven target lesion revascularization, and definite or probable stent thrombosis, at 1 year. Among 1,553 BP-SES and 791 DP-EES patients, 757 diabetic patients were identified. Of the diabetic patients included in this analysis (494 BP-SES vs 263 DP-EES), the proportion of insulin- and noninsulin-treated patients was similar between groups. The 1-year TLF rate in the diabetic population was 6.3% in the BP-SES group and 8.7% in the DP-EES group (hazard ratio 0.82, 95% confidence interval 0.047 to 1.43, p = 0.493). There were no significant differences, based on stent type or diabetes treatment regimen, in TLF hazards. In a patient-level pooled analysis of the diabetic population from randomized trials, 1-year clinical safety and efficacy outcomes were similar in patients treated with ultrathin BP-SES and thin-strut DP-EES., (Copyright © 2019. Published by Elsevier Inc.)

The aim of this network meta-analysis is to assess the impact of strut thickness on clinical outcomes in patients who underwent percutaneous coronary intervention. We searched Medline/PubMed and performed a Bayesian network meta-analysis to compare outcomes of patients who underwent percutaneous coronary intervention with drug-eluting stents (DES) of different strut thicknesses (ultrathin 60 to 80 μm; thin 81 to 100 μm; intermediate 101 to 120 μm; thick ≥120 μm). Studies comparing DES with similar strut thickness, bare metal stents, and fully bioresorbable scaffolds were excluded. Odds ratios with credible intervals (OR [CrIs]) were generated with random-effects models to compare outcomes. Our primary end point was stent thrombosis (ST). We identified 69 RCTs including 80,885 patients (ultrathin group = 10,219; thin group = 36,575; intermediate group = 11,399; thick group = 22,692). Mean age was 64 ± 11 years and 75% were male gender. When compared with thick-strut DES, ultrathin struts had significant less ST and myocardial infarction (OR 0.43 [CrI 0.27 to 0.68]; and OR 0.73 [CrI 0.62 to 0.92], respectively). Sensitivity analysis including only studies with permanent polymer DES gave similar results. Improvement in DES technology with thinner struts is associated with significant reduction in ST and myocardial infarction compared with thicker struts., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The advent of biologic therapy has enhanced our ability to augment disease in an increasingly targeted manner. The use of biologics in cardiovascular disease (CVD) has steadily increased over the past several decades. Much of the early data on biologics and CVD were derived from their use in rheumatologic populations. Atherosclerosis, myocardial infarction, and heart failure have been closely linked to the inflammatory response. Accordingly, cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 have been targeted. Noninflammatory mediators, such as proprotein convertase subtilisin kexin type 9 (PCSK9), have been selected for therapeutic intervention as well. Furthermore, RNA interference (RNAi) therapy has emerged and may serve as another targeted therapeutic mechanism. Herein, we will review the history, obstacles, and advances in using biologic therapy for CVD.

Permanent pacemaker (PPM) implantation remains common after transcatheter aortic valve implantation (TAVI). Invasive electrophysiology studies (EPSs) may reduce PPM implantation rates by identifying patients who do not require long-term pacing. At our institution, a new strategy in which patients with equivocal indications for pacing underwent EPSs to determine the need for PPM implantation was adopted. We compared baseline demographics, TAVI procedural details, and outcomes in patients without any conduction disturbance after TAVI, patients with new PPM implantation, and patients with EPS ± new PPM implantation. After exclusion for preexisting PPMs, of a total of 614 consecutive TAVI patients, 117 (19.1%) required new PPM implantation for unequivocal pacing indications, and 95 (15.5%) underwent EPSs. Of those patients who underwent EPSs, 28 (29.5%) required PPM implantation and 67 (70.5%) did not. The overall rate of new PPM implantation was higher for self-expanding versus balloon-expandable valves (34.0% vs 19.9%, p = 0.0011). PPM implantation increased intensive care and hospital length of stay compared with patients without any conduction disturbance (10.7 ± 8.3 vs 8.5 ± 6.4 days, p = 0.003). A negative EPS did not prolong length of stay. There were no significant differences in 30-day and 1-year mortality between groups. In conclusion, among TAVI patients with new-onset conduction disturbance, EPS is a safe strategy to identify those who require PPM implantation and those in whom PPMs can be avoided., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The use of optical coherence tomography (OCT) in PCI guidance is limited perhaps by the lack of adequately powered studies which compare its efficacy and outcomes to the other more popular imaging modalities. We therefore performed a meta-analysis to compare clinical outcomes following OCT-guided PCI with the other imaging modalities in two separate comparisons. We abstracted data from randomized control trials and observational comparative studies focusing on OCT versus either angiography- or IVUS-guided PCI outcomes identified following a systematic search (April 2006 and May 2017). This meta-analysis included a total of 2781 patients; OCT-guidance versus Angiography guidance (n = 1753) and OCT-guidance versus IVUS-guidance (n = 1028). Pooled estimates of outcomes, presented as odds ratios (OR) [95% confidence intervals], were generated with random-effect models. OCT guidance showed lower rates of MACE (OR 0.70 [0.49, 1.00] p = 0.05) and cardiac deaths (OR 0.40 [0.18, 0.90] p = 0.03) compared to Angiography-guidance alone but no statistical significant results for myocardial infarction (OR 0.70 [0.42, 1.16] p = 0.17), stent thrombosis (OR 1.17 [0.40, 3.43] p = 0.77) and target lesion revascularizations (OR 1.07 [0.48, 2.38] p = 0.86).No statistical significance was observed in the OCT versus IVUS comparison; MACE (OR 0.89 [0.46, 1.73] p = 0.73), cardiac deaths (OR 0.56 [0.12, 2.70] p = 0.47), MI (OR 0.56 [0.12, 2.70] p = 0.47), ST (OR 0.43 [0.06, 2.95] p = 0.39), and TLR(OR 0.99 [0.45, 2.18] p = 0.99). OCT-guided PCI in comparison with angiography-guided was associated with reduction in adverse events for the composite of cardiac deaths, myocardial infarction and repeat revascularizations. There was no statistically significant difference in clinical outcomes observed in the comparison between OCT- and IVUS-guidance.

Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway.

Chest pain or other symptoms concerning for acute coronary syndrome continues to remain a major reason for presentation to the emergency department. However, there is significant heterogeneity in the spectrum of risk severity of these patients. The electrocardiogram (ECG) remains a critically valuable tool in the physician's arsenal to diagnose patients and help with risk stratification. There are multiple high-risk ECG findings that are suggestive of adverse outcome and may benefit from rapid transfer for coronary angiography. This article reviews specific high-risk ECG patterns that may represent acute myocardial infarction or identify impending acute myocardial infarction that benefit from early diagnostic coronary angiography., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Recent studies suggest the Orsiro sirolimus-eluting stent (O-SES), which has ultrathin struts with a biodegradable sirolimus-eluting polymer coating, performed better than contemporary drug-eluting stents (DES). We performed a meta-analysis to compare clinical outcomes for all randomized controlled trials (RCTs) of O-SES vs contemporary DES., Methods/materials: PubMed, Cochrane CENTRAL, and meeting abstracts were searched for all RCTs comparing O-SES with contemporary DES. Pooled estimates of longest available clinical outcomes at a minimum of one-year follow-up, presented as odds ratios (OR) [95% confidence intervals], were generated with random-effect models., Results: We included 8 RCTs with a total of 11,176 patients (5444 O-SES and 5732 contemporary DES [3537 EES, 1295 ZES, and 1264 BP-BES) with a mean age of 65±11, 74% were male, 40% underwent PCI for stable angina, and 56% for ACS. We assessed outcomes comparing O-SES vs. everolimus-eluting stents, vs. permanent-polymer DES, and vs. all DES including biodegradable-polymer DES. Orsiro performed comparably in all categories with a trend toward a reduction in myocardial infarction (0.83 [0.68, 1.02], p=0.07) and stent thrombosis (0.75 [0.54, 1.04], p=0.08)., Conclusion: Overall, the Orsiro SES had similar clinical outcomes to contemporary DES with a trend toward reduction in myocardial infarction and stent thrombosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Patients at high bleeding risk (HBR) are at increased risk of bleeding following percutaneous coronary intervention (PCI) with drug-eluting stents (DES) due to the need for longer dual antiplatelet duration. We sought to evaluate the likelihood of receiving DES during PCI in HBR populations and to characterize DES utilization trends over time. Consecutive patients who underwent PCI from April 2003 to September 2015 were identified. HBR is defined as patients fulfilling 1 or more of the HBR criteria: age ≥75 years, anticoagulation use at discharge, history of stroke, cancer in previous 3 years, glucocorticoid use, hemoglobin (Hgb) <11 g/dl, platelet count <100,000/mm 3 , or creatinine clearance (CCr) <40 ml/min. Multivariate analysis was performed to identify which variables predicted DES selection. There were 10,594 patients (41.6%) who the met HBR definition. When adjusting for known risk factors, HBR patients were less likely to receive a DES compared with non-HBR patients (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.54 to 0.62, p <0.001). A preprocedural Hgb <11 g/dl had the greatest association with choosing DES during PCI (OR 0.51, 95% CI 0.45 to 0.57, p <0.001). Within the HBR patients, having 3 or more HBR criteria versus <3 HBR criteria had lower likelihood of receiving a DES (OR 0.50, 95% CI 0.44 to 0.57, p <0.001). In conclusion, presence of HBR has a significant impact upon the decision to use DES., (Copyright © 2017 Elsevier Inc. All rights reserved.)

With steady growth in the use of drug-eluting stents (DES), the indications for bare metal stents (BMS) have significantly changed over the last decade. This study aims to describe trends in the use of BMS and the evolution of the population receiving them over the past 10 years and determine patient characteristics associated with using BMS. Consecutive patients who underwent percutaneous coronary intervention (PCI) at the Washington Hospital Center from January 2005 through March 2015 were included. Baseline characteristics and inhospital outcomes of patients who underwent PCI with BMS versus DES were compared during 2 different time periods: from 2005 to 2010 and from 2011 to 2015. Multivariable analyses were performed for each period of time to determine independent variables associated with the choice of BMS rather than DES; 20,321 patients who underwent PCI were included in the present study. The mean age was 65.0 ± 12.5 years, 65.2% were men, and 30.4% were black. BMS use peaked in 2007 (47%) but has fallen steadily since; BMS accounted for only 10% of stents used in 2015. Presentation with acute coronary syndrome or cardiogenic shock was more common in patients receiving a BMS; this was reflected in higher rates of inhospital mortality and major bleeding among patients receiving BMS versus DES. Covariables independently associated with receiving a BMS common to both time periods included black race, Hispanic ethnicity, cardiogenic shock or acute coronary syndrome, oral anticoagulation, current smoking, increasing age, lower hematocrit, and history of chronic renal insufficiency. In conclusion, there has been a precipitous decline in the use of BMS over the last decade. Newer stent technology that promises shorter duration of dual antiplatelet therapy is likely to lead to the extinction of BMS over the next decade., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ticagrelor, a potent platelet inhibitor, has primarily been studied in white patients. Platelet reactivity among black patients with acute coronary syndrome (ACS) on ticagrelor, however, is unknown. Our objective was to compare platelet reactivity in black versus white patients with ACS treated with ticagrelor. We conducted a prospective, pharmacodynamic study of 29 black patients with ACS treated with ticagrelor. Platelet reactivity was assessed at 1, 4, and 8 hours after a loading dose of ticagrelor 180 mg and at 30 days on a maintenance dose of ticagrelor 90 mg twice daily. Assays included light transmission aggregometry, VerifyNow P2Y12, and vasodilator-stimulated phosphoprotein. We provided comparison with a historical white cohort. Platelet reactivity among blacks with ACS on ticagrelor was similar to that in whites, except that blacks had lower values at 4 hours, 8 hours, and on maintenance therapy for light transmission aggregometry with 20 μmol/L adenosine diphosphate. Among blacks, high-on-treatment platelet reactivity for all 3 assays was uncommon at 1 hour and nonexistent at 4 hours, 8 hours, and while on maintenance therapy. Blacks preloaded with clopidogrel (n = 17) had significantly lower results of VerifyNow (64 ± 65 vs 198 ± 86, p <0.001) and vasodilator-stimulated phosphoprotein (12.8 ± 21.6 vs 58.9 ± 19.9, p <0.001) at 1 hour compared with those with no clopidogrel preload. In conclusion, among patients with ACS receiving ticagrelor, levels of platelet reactivity in blacks are similar to that in whites. This suggests that the cardiovascular benefits of ticagrelor observed in the platelet inhibition and patient outcomes (PLATO) trial are likely to be observed in blacks and whites., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: In the drug-eluting stent (DES) era, patients with acute coronary syndrome (ACS) had a higher risk of early stent thrombosis compared with stable patients. The present study aimed to evaluate whether the same is true for the bioresorbable vascular scaffold (BVS) (Abbott Vascular, Santa Clara, CA, USA)., Methods and Results: We assessed the relationship between the incidence of definite/probable scaffold thrombosis (ScT) (overall ScT and early ScT) and ACS percentage with the latest publications, including the most recent large randomised controlled trials. Out of a total study population of 13,708 devices in 45 trials, overall ScT was observed in 185 devices (1.35%) at a weighted mean follow-up period of 9.4 months, while early ScT was reported in 125 devices (0.97%) out of 12,896 devices in 44 trials. Meta-regression analysis demonstrated no significant correlation between overall/early ScT and the percentage of patients with ACS (overall ScT: R2=0.030, p=0.255; early ScT: R2=0.067, p=0.090)., Conclusions: ACS appeared to have little impact on the incidence of ScT after the implantation of BVS. Further clinical study is warranted to investigate the predictors of ScT using multivariate analysis with sufficient statistical power.

Objective: Comparison of transradial versus transfemoral access for complex percutaneous coronary intervention (PCI) with regard to both complications and long-term outcomes., Background: Radial access has been shown to confer superior results in patients undergoing PCI, especially in patients with acute coronary syndromes. However, radial access has limitations of sheath and device size, which may increase procedure time and result in inferior outcomes., Methods: Patients undergoing PCI for complex lesions, defined as type C according the ACC/AHA classification system, were included in this study. Propensity matching was performed to adjust for differences in baseline characteristics. Transradial patients were then compared to transfemoral patients in regard to procedural, in-hospital, and 6-month outcomes., Results: Among 2142 patients with 2591 lesions treated, 1876 had femoral access and 267 had radial access. Radial access patients were more likely to be male (75% vs. 66%, P = 0.003) and less likely to present with acute myocardial infarction (27% vs. 42%, P < 0.001). Procedural characteristics demonstrated lower use of heparin in the femoral group (17% vs. 73%, P < 0.001) with similarly low use of glycoprotein inhibitors (5.6% vs. 3.4%, P = 0.14). Patients in the femoral group had higher rates of transfusions (3.7% vs. 0%, P = 0.004) and vascular complications (1.7% vs. 0%, P = 0.03). Following propensity matching, there was no difference in mid-term outcomes between radial and femoral groups., Conclusions: In patients with complex coronary lesions undergoing PCI, the radial approach demonstrates similar mid-term outcomes as the femoral approach with a potentially lower rate of complications. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Newer P2Y12 inhibitors have more rapid onset of platelet inhibition compared with clopidogrel, especially the intravenous P2Y12 inhibitor cangrelor. Direct comparisons between cangrelor and oral P2Y12 inhibitors ticagrelor and prasugrel do not exist. Thus, we performed a network meta-analysis to directly and indirectly compare different P2Y12 inhibitors in patients undergoing percutaneous coronary intervention (PCI)., Methods: MEDLINE/PubMed and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared at least two P2Y12 inhibitors including cangrelor, clopidogrel, prasugrel, and ticagrelor. Network meta-analysis with a Bayesian approach was performed to directly and indirectly compare the effects of the aforementioned P2Y12 inhibitors on clinical outcomes. Odds ratios with credible intervals (OR [CrIs]) were generated with random-effects models to compare outcomes., Results: This analysis included 15 RCTs with 54,025 patients randomized to cangrelor (n=12,475), clopidogrel (n=26,903), prasugrel (n=7455), or ticagrelor (n=7192) at time of PCI. Patients had a mean age of 63±10, 74% were male, and 82% underwent PCI for acute coronary syndrome. No significant differences between cangrelor and clopidogrel were found with respect to cardiovascular death (OR 1.01 [CrI 0.23-4.39]), myocardial infarction (OR 0.94 [CrI 0.69-1.25]), major adverse cardiac events (OR 0.91 [CrI 0.69-1.18]), stent thrombosis (OR 0.66 [CrI 0.37-1.19]), or major bleeding (OR 1.52 [CrI 0.79-2.98]). Rank probability data suggested that ticagrelor and prasugrel were better than cangrelor for reducing ischemic events, though these differences were not significant., Conclusion: Despite rapid platelet inhibition provided by cangrelor, newer oral P2Y12 inhibitors such as ticagrelor and prasugrel have comparable clinical outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Right ventricular (RV) dysfunction was shown to be associated with adverse outcomes in a variety of cardiac patients and is considered a risk factor for adverse outcome according to the updated Valve Academic Research Consortium criteria., Objective: Our goal was to assess the impact of RV function at baseline on 1-year mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR)., Methods: All patients with severe AS treated with TAVR from May 2007 to March 2015 at our center were included in the present study, and baseline and procedural characteristics were recorded for each patient. The patients were categorized according to RV function at baseline as assessed by current guidelines, and a comparison of mortality rates up to 1 year was performed., Results: Among 650 patients, 606 had adequate echocardiogram quality and 146 (24%) had RV dysfunction. There were significant differences between the 2 groups, as patients with RV dysfunction were younger (81±9 vs 84±7 years, P=.01) and were more likely to be male (65% vs 42%, P<.001). In addition, patients with RV dysfunction had higher rates of prior myocardial infarction (26% vs 16%, P=.02) and atrial fibrillation (51% vs 39%, P=.02). Echocardiographic parameters demonstrated higher rates of left ventricular ejection fraction <40% (40% vs 18%, P<.001), tricuspid regurgitation above moderate (16% vs 9%, P=.04), and higher pulmonary artery systolic pressure (50±17 vs 44±16 mm Hg, P<.001) among patients with severe AS and RV dysfunction compared with patients with normal RV function. Despite the unfavorable cardiac function, patients with severe AS undergoing TAVR have similar functional class (P=.22) and mortality rates at 1year (27% vs 23%, log-rank P=.45)., Conclusions: Patients with severe AS and RV dysfunction have similar 1-year mortality and functional class after TAVR to patients with normal RV function. The presence of RV dysfunction does not correlate with outcome in patients with severe AS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rationale: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in heart failure, an entity in which excessive chronic inflammation may play a pivotal role., Objective: To assess the safety and preliminary efficacy of intravenously administered ischemia-tolerant MSCs (itMSCs) in patients with nonischemic cardiomyopathy., Methods and Results: This was a single-blind, placebo-controlled, crossover, randomized phase II-a trial of nonischemic cardiomyopathy patients with left ventricular ejection fraction ≤40% and absent hyperenhancement on cardiac magnetic resonance imaging. Patients were randomized to intravenously administered itMSCs (1.5×10 6 cells/kg) or placebo; at 90 days, each group received the alternative treatment. Overall, 22 patients were randomized to itMSC (n=10) and placebo (n=12) at baseline. After crossover, data were available for 22 itMSC patients. No major differences in death, hospitalization, or serious adverse events were noted between the 2 treatments. Change from baseline in left ventricular ejection fraction and ventricular volumes was not significantly different between therapies. Compared with placebo, itMSC therapy increased 6-minute walk distance (+36.47 m, 95% confidence interval 5.98-66.97; P=0.02) and improved Kansas City Cardiomyopathy clinical summary (+5.22, 95% confidence interval 0.70-9.74; P=0.02) and functional status scores (+5.65, 95% confidence interval -0.11 to 11.41; P=0.06). The data demonstrated MSC-induced immunomodulatory effects, the magnitude of which correlated with improvement in left ventricular ejection fraction., Conclusions: In this pilot study of patients with nonischemic cardiomyopathy, itMSC therapy was safe, caused immunomodulatory effects, and was associated with improvements in health status and functional capacity., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02467387., (© 2016 American Heart Association, Inc.)

HF patients with signs and symptoms of worsening heart failure (HF), despite optimal medical therapy, have a poor prognosis. The pathways contributing to HF are multiple, probably accounting, in part, for current treatment approaches not being more effective. Stem cells, particularly mesenchymal stem cells (MSCs), have a broad range of activities, making them particularly interesting candidates for a new HF therapeutic. This review presents an overview of the studies examining the efficacy of stem cell studies administered to HF patients, focusing mainly on MSCs. It examines the issues surrounding autologous vs. allogenic stem cells, the results of different routes of administration, and implications deriving from the belief that for stem cells to be effective, they must engraft in the myocardium and exert local effects. Since intravenous administration of stem cells leads to sparse cardiac engraftment, stem cell delivery strategies have uniformly involved catheter-based delivery systems. This becomes problematic in a disease that will almost certainly require delivery of the therapeutic throughout the course of the disease. Importantly, it appears that a critical contributing cause of the progressive cardiac dysfunction experienced by HF patients is the existence of a persistent inflammatory response. Since MSCs exert potent anti-inflammatory effects through paracrine mechanisms, it is possible that intravenous delivery of MSCs may be therapeutically effective. If this concept is valid, it could lead to a transformational change in stem cell delivery strategies.

Background/purpose: Numerous GPIs are available for PCI. Although they were tested in randomized controlled trials, a comparison between the different GPI strategies is lacking. Thus, we performed a Bayesian network meta-analysis to compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin and bivalirudin for percutaneous coronary intervention (PCI)., Methods: MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two independent reviewers for randomized controlled trials comparing high-dose bolus tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare between different anticoagulation strategies for all-cause mortality, myocardial infarction, major adverse cardiovascular events, major bleeding, minor bleeding, need for transfusion, and thrombocytopenia., Results: A total of 41 randomized controlled trials with 38,645 patients were included in the analysis, among which 2654 were randomized to high-dose bolus tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070 to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose bolus tirofiban was associated with a significant reduction in all-cause mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less myocardial infarction and major adverse cardiovascular events but greater bleeding compared with heparin and bivalirudin. There was no difference among the GPI therapies for other outcomes, including myocardial infarction, major adverse cardiovascular events, and major bleeding., Conclusions: Our network meta-analysis of 38,645 patients demonstrated that GPI regimens were associated with a reduction in recurrent myocardial infarction or major adverse cardiovascular events for PCI, while bivalirudin was associated with the lowest risk of bleeding., (Copyright © 2016. Published by Elsevier Inc.)

Transcatheter aortic valve implantation (TAVI) decreases mortality in high-risk patients with severe aortic stenosis, but it remains unclear if female gender is associated with more favorable outcomes after TAVI. All patients who underwent TAVI at a single institution were retrospectively analyzed and stratified by gender. Procedural, in-hospital, 30-day, and 1-year outcomes were defined according to the second Valve Academic Research Consortium. The primary end point was all-cause mortality at 1 year. Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were conducted. Overall, 755 patients underwent TAVI and were included in the study; 50.7% were women. Average age was 83.0 ± 7.7 years, with a mean Society of Thoracic Surgeons score of 8.9 ± 4.6. Women were older than men and more likely to be black. Most co-morbidities were less common among women, and they were more likely than men to suffer both in-hospital (8.4% vs 4.3%, p = 0.021) and 30-day (9.4% vs 5.4%, p = 0.035) all-cause mortality. Life-threatening bleeding, transfusion, and iliofemoral dissection or perforation were more common among women. There was no difference in mortality between women and men at 1 year (20.6% vs 21.5%, log-rank p = 0.87). After multivariable adjustment, however, female gender was independently associated with lower mortality at 1 year after TAVI. In conclusion, despite higher rates of major bleeding, vascular complications, and 30-day mortality, female gender was independently associated with improved survival at 1 year after TAVI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model., Methods: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging., Results: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium., Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported., Methods: A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed., Results: Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups., Conclusion: Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: New oral anticoagulants (NOAC) and the Watchman device represent an alternative to warfarin for stroke prophylaxis in atrial fibrillation (AF) patients. However, no studies compare these new treatments. We performed a network meta-analysis to indirectly compare Watchman and NOACs among AF patients., Methods: We performed a MEDLINE search for studies comparing warfarin with NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) or Watchman in AF patients with reported clinical outcomes. Mixed treatment comparison model generation was performed to directly and indirectly compare NOACs, warfarin and Watchman., Results: 14 studies with 246,005 patients were included in the analysis, among which 124,823 were treated with warfarin, 120,450 were treated with NOACs and 732 had Watchman implanted. Mean age was 72 ± 9 years, 53% were male, and mean CHADS2 score was 2.1 ± 1.6. Both NOACs and Watchman were superior to warfarin in hemorrhagic stroke prevention (OR = 0.46 [0.30-0.82] and OR = 0.21 [0.05-0.99], respectively). NOACs significantly reduced total stroke (OR = 0.78 [0.58-0.96]) and major bleeding (OR = 0.78 [0.65-0.91]) compared with warfarin. Indirect comparison between NOAC and Watchman revealed no significant differences in outcomes, though there was a trend toward higher rates of ischemic stroke with Watchman compared with NOAC (OR 2.60 [0.60-13.96]) with the opposite findings with hemorrhagic stroke (OR = 0.44 [0.09-2.14])., Conclusions: NOAC therapy was superior to warfarin for multiple outcomes while Watchman reduced hemorrhagic stroke. Further studies are needed to assess Watchman versus NOAC to optimize therapy for stroke prevention in AF patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)