Direct Oral Anticoagulants and Coronary Artery Disease.

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Acute coronary syndrome as a first presentation is common and patients with established disease have a high rate of recurrent ischemic events, despite antiplatelet therapy. Over the past several years, direct oral anticoagulants have become available and have been studied in patients with coronary artery disease. These medications directly inhibit either thrombin or factor Xa which contribute to atherothrombosis. This review will summarize the clinical data regarding the use of direct oral anticoagulants in different patient populations with coronary disease and the balance between protection against ischemia and bleeding. Additionally, the review will summarize the available data on the use of direct oral anticoagulants periprocedurally in patients undergoing percutaneous coronary intervention. The future direction of coronary artery disease and the role of direct oral anticoagulants will rely on further studies determining the optimal combination of antiplatelet and oral anticoagulant regimens that derive ischemic benefit without increased rates of bleeding. Additional upstream blockade of the coagulation cascade with factor XIIa and factor XIa inhibitors may also improve treatment in the future.

Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.

The coexistence of cardiovascular disease and erectile dysfunction is widespread, possibly owing to underlying endothelial dysfunction in both diseases. Millions of patients with cardiovascular disease are prescribed phosphodiesterase-5 (PDE5) inhibitors for the management of erectile dysfunction. Although the role of PDE5 inhibitors in erectile dysfunction therapy is well established, their effects on the cardiovascular system are unclear. Preclinical studies investigating the effect of PDE5 inhibitors on ischemia-reperfusion injury, pressure overload-induced hypertrophy, and chemotoxicity suggested a possible clinical role for each of these medications; however, attempts to translate these findings to the bedside have resulted in mixed outcomes. In this review, we explore the biologic preclinical effects of PDE5 inhibitors in mediating cardioprotection. We then examine clinical trials investigating PDE5 inhibition in patients with heart failure, coronary artery disease, and ventricular arrhythmias and discuss why the studies likely have yet to show positive results and efficacy with PDE5 inhibition despite no safety concerns.

Iso-osmolar versus low-osmolar contrast media and outcomes after percutaneous coronary intervention: Insights from the VA CART Program.

OBJECTIVES: To assess whether contrast media type is associated with outcomes in veterans undergoing percutaneous coronary intervention (PCI). BACKGROUND: There is uncertainty about the impact of iso-osmolar contrast medium (IOCM) versus low-osmolar contrast medium (LOCM) on acute kidney injury (AKI) and other major adverse renal or cardiovascular events (MARCE) after PCI. We assessed the association between contrast media type and MARCE in patients who underwent PCI within the Veterans Administration Healthcare System. METHODS: We reviewed PCIs performed between 2009 and 2019 using data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. The primary endpoint was MARCE, a composite of myocardial infarction, stroke, all-cause death, AKI, and dialysis onset at 30 days. RESULTS: The analysis cohort consisted of 50,389 patients of whom 25,555 received LOCM and 24,834 received IOCM. There was significant variation in contrast type across sites. After adjustment for comorbidities, no significant association between contrast media type and MARCE was observed in both site-unadjusted (odds ratio [OR] for IOCM: 0.99; 95% confidence interval [CI]: 0.92-1.08; p = 0.97) and site-adjusted (OR: 1.06; 95% CI: 0.95-1.18; p = 0.30) analyses. Similar results were obtained when contrast volume was imputed or the data was subset to individuals with available contrast volume. CONCLUSION: In a large cohort of veterans undergoing PCI, we found considerable site variation in the type of contrast media used but no significant association between contrast media type and the incidence of MARCE, both before and after adjustment for the site.

Novel oral anticoagulants in the treatment of radial artery occlusion.

Transradial access of the vascular system for coronary angiography and percutaneous coronary intervention has become the primary approach in several cardiac catheterization laboratories across the world. The paradigm shift from transfemoral access has been driven by improved outcomes in patients undergoing these cardiac procedures by transradial access. Radial artery occlusion is the most common vascular complication of transradial coronary procedures. Only a few studies have reported on the optimal treatment of radial artery occlusion, with ulnar artery compression and anticoagulation, especially with low-molecular-weight heparin, having shown the best results. In this case series, four patients who were found to have evidence of post-cardiac catheterization radial artery occlusion on ultrasound imaging were treated with a 30-day course of apixaban. Three of the four patients showed complete resolution of radial artery occlusion with addition of apixaban to current standard therapeutic strategies. This case series shows that treatment with novel oral anticoagulants can be an alternative and more convenient option compared to subcutaneous injection of low-molecular heparin for anticoagulation in patients with post-coronary angiography radial artery occlusion.

Safety and efficacy of switching from unfractionated heparin to bivalirudin during primary percutaneous coronary intervention.

OBJECTIVES: To evaluate the safety and efficacy of switching to bivalirudin during primary percutaneous coronary intervention (PCI) for patients who received preprocedure unfractionated heparin (UFH). BACKGROUND: Current guidelines favor bivalirudin for primary PCI in patients at high risk of bleeding, particularly when femoral access is used. However, patients with ST-segment elevation myocardial infarction frequently receive UFH before arrival in the catheterization laboratory. METHODS: Scientific databases and websites were searched for randomized controlled trials. Patients were divided into those who received heparin with or without glycoprotein IIb/IIIa inhibitors (heparin group); those switched to bivalirudin during primary PCI from preprocedure UFH (switch group); and those who received bivalirudin without preprocedure UFH (Biv-alone group). Both traditional pairwise meta-analyses using moderator analyses and network meta-analyses using mixed-treatment comparison models were performed. RESULTS: Data from five trials including13,547 patients were analyzed. In mixed-comparison models, switching to bivalirudin during primary PCI was associated with lower rates for all-cause mortality and major adverse cardiovascular events (MACEs) compared to the other strategies. Rates for all-cause mortality, MACEs, and net adverse clinical events (NACEs) were similar for the heparin and Biv-alone groups. Switching strategies was also associated with lower major bleeding rates compared to heparin alone. Similarly, in a standard pairwise model, both the switch and Biv-alone groups were associated with decreased bleeding risk compared to the heparin group. However, only the switch strategy was associated with decreased all-cause mortality (RR, 0.47; 95% CI, 0.30-0.75; P = 0.001), MACE (RR, 0.67; 95% CI, 0.49-0.91; P = 0.012), and NACE (RR, 0.61; 95% CI, 0.41-0.92; P = 0.019) compared with heparin alone. CONCLUSIONS: During primary PCI, use of bivalirudin for those receiving preprocedure UFH was associated decreased rates for major bleeding, NACEs, MACEs, and all-cause mortality compared to heparin +/- GPI. This strategy was also associated with decreased rates for MACEs and all-cause mortality compared to bivalirudin alone without preprocedure UFH.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

Stent "Hygiene".

Studies demonstrate ideal Stent expansion with prolonged inflations. Longer inflations, a mediator of greater stent expansion, lower immediate, subacute, and late stent failure. Research should focus on components of stent deployment that optimize early and late stent outcomes.

A comprehensive meta-analysis of randomized controlled trials comparing drug-eluting stents with bare-metal stents in saphenous vein graft interventions.

BACKGROUND: Several large randomized controlled trials (RCTs) have proven the superiority of drug-eluting stents (DESs) over bare-metal stents (BMSs) for native coronary stenosis. However, RCTs comparing DESs with BMSs for SVG lesions have predominantly been small in size and have yielded conflicting results. Therefore, we conducted an updated comprehensive meta-analysis of RCTs comparing DESs versus BMSs for SVG interventions using the largest sample size to date. METHODS: Scientific databases and websites were searched to find RCTs. Data from six RCTs involving 1,582 patients were included. Pooled risk ratios (RRs) were calculated using random-effects models. The primary outcome of this meta-analysis was target vessel revascularization (TVR). The secondary outcomes were major adverse cardiac events (MACEs), myocardial infarction (MI), stent thrombosis, all-cause mortality, and cardiac mortality. RESULTS: Data from six RCTs involving 1,582 patients were included. Saphenous vein graft interventions with DESs reduced TVR (RR, 0.52; 95% CI, 0.30-0.88; P = 0.017) and MACE rate (RR, 0.60; 95% CI, 0.42-0.87; P = 0.007) compared to BMSs. No difference between the stents were found in rates of MI (RR, 0.69; 95% CI, 0.43-1.10; P = 0.123), stent thrombosis (RR, 0.61; 95% CI, 0.27-1.41; P = 0.255), all-cause mortality (RR, 1.13; 95% CI, 0.74-1.71; P = 0.554), or cardiac mortality. CONCLUSION: For SVG intervention, the MACE rate was lower for DESs compared to BMSs, driven primarily by decreased non-MI-related TVR. Rates of MI, all-cause mortality, cardiac mortality, and stent thrombosis were not different between the stents.

Perioperative Cardiovascular Evaluation for Orthotopic Liver Transplantation.

Patients with advanced liver disease have a high prevalence of cardiovascular risk factors, but many of them are asymptomatic. Cardiovascular risk stratification prior to liver transplant can be done by dobutamine stress echocardiography, stress myocardial perfusion imaging, cardiac computer tomography, and coronary angiography, but there are no clear recommendations regarding what method should be used and who should be screened. Because of this and because of inherent risk profile in this population, the variations in practice are significant. Careful screening and rigorous management of cardiovascular risk factors are important to ensure optimal cardiovascular outcomes in the immediate post-transplantation period and in the long term as well.

Adjunctive anticoagulation during peripheral vascular intervention.

Endovascular techniques for the treatment of peripheral arterial disease are becoming an increasingly common alternative to open surgery, yet the degree of anticoagulation and choice of anticoagulant to optimize outcomes in these procedures remain uncertain. To date, few randomized trials have directly compared different anticoagulants for use during peripheral vascular interventions. It is also unclear if the approach to anticoagulation should be individualized to each vascular bed or if common principles are shared among them. This has led practitioners across different specialties to use a variety of different methods for anticoagulation, with most extrapolated from techniques used in percutaneous coronary interventions. In this review, we analyze the current literature for anticoagulation used during peripheral vascular intervention of the lower extremity, renal, carotid, and aortic arteries, with special consideration to the choice of anticoagulant used to maximize safe and effective procedural outcomes.

Comparison of transradial coronary procedures via right radial versus left radial artery approach: A meta-analysis.

INTRODUCTION: Coronary angiography and angioplasty via transradial approach is shown to be associated with significant reduction in access site complications. Due to a lack of sufficient data, the use of the right or left radial approach is still operator-dependent. We performed a meta-analysis of prospective randomized studies to compare right versus left radial artery approach for coronary procedures. METHODS: We found 12 randomized studies meeting the predetermined inclusion criteria. A total of 6,450 patients were included in the meta-analysis of which 3,217 patients underwent coronary procedures via right radial approach and 3,233 patients via left radial approach. The primary endpoint was the comparison of fluoroscopy time, procedure time, contrast use and cross-over rates between two radial approaches. RESULTS: Pooled analysis of the included studies showed a similar rate of cross-over events (4.2% for right radial approach vs. 4.1% for left radial approach, odds ratio (OR)=1.08, P = 0.68), and similar total procedure times (18.8 ± 10.3 min vs. 18.1 ± 10.0 min, standard difference (SD) of the mean = 0.09, P = 0.162) between the two radial approaches. However, the right radial approach was found to be associated with minimally longer fluoroscopy times (5.8 ± 4.4 min vs. 5.3 ± 4.2 min, SD of the mean = 0.157, P < 0.001) and greater contrast use (84 ± 35 mL vs. 82 ± 34 mL, SD of the mean = 0.082, P = 0.003). Access site complications and the incidence of stroke were similar between two radial approaches. CONCLUSION: Our meta-analysis suggests a small but statistically significant difference in terms of contrast use and fluoroscopy time in favor of coronary procedures performed via left radial approach in comparison to right radial approach without any significant difference in access site or other procedural complications between the two radial approaches. © 2016 Wiley Periodicals, Inc.

The influence of clopidogrel on ischemia diagnosed by myocardial perfusion stress testing.

BACKGROUND: Clopidogrel is a platelet adenosine receptor antagonist which can influence coronary vascular tone and thus can potentially interfere with myocardial perfusion imaging. We investigated whether clopidogrel can hamper the diagnosis of ischemia in patients undergoing myocardial perfusion testing. METHODS: Data from a database of 6349 myocardial perfusion stress tests were analyzed. Using a propensity analysis, patients who were taking clopidogrel were compared with patients not taking clopidogrel for the presence of reversible perfusion defects on myocardial single-photon emission computed tomography scans. RESULTS: Of the 6349 tests, the stress technique was adenosine in 2713 patients and exercise in 3636. At the time of the stress test, 277 (4.3%) of the patients were taking clopidogrel. The odds ratio (OR) for patients taking clopidogrel to have a reversible perfusion defect was 2.75 (95% confidence interval [CI] 2.09-3.62; P < .01). After adjusting for the propensity to take clopidogrel, the OR was 1.06 (CI 0.76-1.49; P = .73) for patients undergoing adenosine stress tests and 1.60 (CI 0.85-3.00; P = .14) for patients undergoing exercise stress tests. CONCLUSIONS: We found no evidence that the use of clopidogrel decreases the likelihood of ischemia on adenosine or exercise stress myocardial perfusion scans.

Anticoagulation in transradial percutaneous coronary intervention.

Transradial percutaneous coronary intervention (PCI) is associated with significant reductions in access site complications and major bleeding as compared with the transfemoral approach. Bivalirudin is now the most commonly used anticoagulant for transradial PCI in the United States, while weight adjusted unfractionated heparin remains the most common choice outside the United States. A growing number of reports suggest that transradial intervention may offer improved outcomes across a variety of clinical situations, including those at the highest risk of bleeding complications, such as those with acute myocardial infarction. The following review provides an overview of the studies evaluating anticoagulation in transradial PCI and a rationale for the combination of the transradial approach to coronary interventions with an optimal anticoagulant strategy to reduce both access site and nonaccess site-related bleeding.

Acute Kidney Injury in Patients Undergoing Both Right and Left Heart Catheterization with Coronary Angiography Vs Right Heart Catheterization Only.

BACKGROUND: Recent studies have challenged the reported causal association between acute kidney injury and iodinated contrast administration, ascribing some cases to changes in renal function that are independent of contrast administration. METHODS: We studied 1779 consecutive patients undergoing right heart catheterization (RHC) at a Veterans Administration Medical Center. We compared the incidence of acute kidney injury and of nephropathy at 3 months in veterans undergoing right and left heart catheterization and coronary angiography (R&LHC) to the incidence of acute kidney injury and of nephropathy at 3 months in patients undergoing RHC only. RESULTS: The incidence of acute kidney injury at 3 days was 47 (9.7%) in the R&LHC group and 58 (9.6%) in the RHC group (P = .99). The incidence of nephropathy at 3 months was 115 (17%) in the L&RHC group and 141 (19.2%) in the RHC group (P = 0.31). In a propensity score-paired analysis of 782 patients and after adjustment for baseline characteristics, the odds ratio for acute kidney injury at 3 days among patients undergoing R&LHC was 1.25 (95% confidence interval, 0.65-2.42; P = .50), and the odds ratio for nephropathy at 3 months was 0.69 (95% confidence interval, 0.46-1.04; P = .08). CONCLUSION: The incidence of changes in creatinine consistent with acute kidney injury at 3 days and of nephropathy at 3 months was not significantly different in patients undergoing R&LHC compared with patients undergoing RHC only. This supports the thesis that not all changes in creatinine after procedures involving administration of contrast are caused by the contrast.

Coronary events in patients undergoing orthotopic liver transplantation: perioperative evaluation and management.

Patients with advanced liver disease have a high prevalence of cardiac risk factors. The stress of liver transplant surgery predisposes these patients to major cardiac events, such as myocardial infarction or ventricular arrhythmias in addition to heart failure exacerbation. Liver transplant patients who experience coronary events in the perioperative period have a decreased five-yr survival rate. Cardiovascular risk stratification prior to liver transplant can be accomplished by dobutamine stress echocardiography, stress myocardial perfusion imaging, cardiac computed tomography, and coronary angiography. Pre-liver transplant management of cardiovascular pathology includes cardiovascular intervention like percutaneous coronary intervention, coronary bypass graft surgery, or medical management. Thorough screening and optimal management of underlying cardiovascular pathology and cardiovascular risk factors should decrease the incidence of new cardiac events in liver transplant recipients.

The safety of preoperative vardenafil in patients undergoing coronary artery bypass graft surgery.

Phosphodiesterase 5 inhibitors are cardioprotective against myocardial reperfusion ischemic injury in animal models but are contraindicated in patients with coronary disease who take nitrates because of a risk for hypotension. We investigated the safety of vardenafil in patients undergoing coronary artery bypass grafting (CABG) surgery. A single dose of vardenafil was given to 10 patients before CABG surgery. The postoperative course of these 10 patients was compared with the postoperative course of 47 patients who did not receive vardenafil before CABG surgery. There were no perioperative deaths and no episodes of hypotension in the group receiving vardenafil. The clinical and operative characteristics of the 2 study groups were similar. There were no significant differences in postoperative serum troponin levels (9.1 ± 8.3 vs 12.5 ± 9.3 ng/mL; P = 0.29, respectively), duration of postoperative intubation (21.4 ± 10.1 vs 27.4 ± 15.2 hours; P = 0.14, respectively), or length of hospital stay (11.1 ± 13.2 vs 10.0 ± 4.7 days; P = 0.8, respectively) between the group receiving vardenafil and the control group. This pilot study of 10 patients suggests that vardenafil use is safe in patients before CABG surgery. A larger study is needed to explore the myocardial protective effect of the drug.

A designed zinc-finger transcriptional repressor of phospholamban improves function of the failing heart.

Selective inhibition of disease-related proteins underpins the majority of successful drug-target interactions. However, development of effective antagonists is often hampered by targets that are not druggable using conventional approaches. Here, we apply engineered zinc-finger protein transcription factors (ZFP TFs) to the endogenous phospholamban (PLN) gene, which encodes a well validated but recalcitrant drug target in heart failure. We show that potent repression of PLN expression can be achieved with specificity that approaches single-gene regulation. Moreover, ZFP-driven repression of PLN increases calcium reuptake kinetics and improves contractile function of cardiac muscle both in vitro and in an animal model of heart failure. These results support the development of the PLN repressor as therapy for heart failure, and provide evidence that delivery of engineered ZFP TFs to native organs can drive therapeutically relevant levels of gene repression in vivo. Given the adaptability of designed ZFPs for binding diverse DNA sequences and the ubiquity of potential targets (promoter proximal DNA), our findings suggest that engineered ZFP repressors represent a powerful tool for the therapeutic inhibition of disease-related genes, therefore, offering the potential for therapeutic intervention in heart failure and other poorly treated human diseases.

Beta-Blockers in the Prevention and Treatment of Ischemic Heart Disease: Evidence and Clinical Practice.

Coronary artery disease (CAD) is the most prevalent cardiovascular disease characterized by atherosclerotic plaque buildup that can lead to partial or full obstruction of blood flow in the coronary arteries. Treatment for CAD involves a combination of lifestyle changes, pharmacologic therapy, and modern revascularization procedures. Beta-adrenoceptor antagonists (or beta-blockers) have been widely used for decades as a key therapy for CAD. In this review, prior studies are examined to better understand beta-adrenoceptor antagonist use in patients with acute coronary syndrome, stable coronary heart disease, and in the perioperative setting. The evidence for the benefit of beta-blocker therapy is well established for patients with acute myocardial infarction, but it diminishes as the time from the index cardiac event elapses. The evidence for benefit in the perioperative setting is not strong.

Risk Factors and Cardiovascular Events in Orthotopic Liver Transplantation.

BACKGROUND AND AIMS: Patients undergoing liver transplantation often have significant cardiovascular risk factors and may experience cardiac-related morbidity and mortality. The aim of this study was to assess the frequency of cardiovascular risk factors and outcomes in this population, and to identify factors predictive of post-transplant cardiac morbidity and mortality. METHODS: We studied 261 patients who underwent liver transplantation at a single Veterans' Affairs Medical center between 1997 and 2015 to evaluate new cardiovascular events post-transplantation. RESULTS: The cohort consisted of 261 patients (253 men and 8 women) with a mean age of 58.3 (± 6.5 years), mean model for end-stage liver disease score of 18.0 (±7.2), and mean Framingham risk score of 8.1 (± 4.9). After a median follow-up of 82 months a total of 75 (28.7%) patients died, with 13 deaths (17.3%) attributed to a primary cardiovascular event and 9 (12%) deaths due to a coronary-specific event. Coronary events and/ or the need for revascularization post-transplant occurred in 24 (9.2%) patients. The strongest pre-transplant predictors of mortality were age (p=0.01), Framingham risk score (p=0.01), preexisting coronary artery disease (p=0.01), and preexisting dyslipidemia (p=0.01). The strongest post-transplant predictors of mortality were new-onset hypertension (p=0.01) and new-onset diabetes mellitus (p=0.03) post-transplant. CONCLUSIONS: In this cohort of veterans, coronary artery disease was significantly associated with mortality in the post liver transplantation population; however, the majority of deaths after transplant were attributable to other causes.

Cellularity and structure of fresh human coronary thrombectomy specimens; presence of cells with markers of progenitor cells.

Acute coronary syndromes and acute myocardial infarctions are often related to plaque rupture and the formation of thrombi at the site of the rupture. We examined fresh coronary thrombectomy specimens from patients with acute coronary syndromes and assessed their structure and cellularity. The thrombectomy specimens consisted of platelets, erythrocytes and inflammatory cells. Several specimens contained multiple cholesterol crystals. Culture of thrombectomy specimens yielded cells growing in various patterns depending on the culture medium used. Culture in serum-free stem cell enrichment medium yielded cells with features of endothelial progenitor cells which survived in culture for a year. Immunohistochemical analysis of the thrombi revealed cells positive for CD34, cells positive for CD15 and cells positive for desmin in situ, whereas cultured cell from thrombi was desmin positive but pancytokeratin negative. Cells cultured in endothelial cell medium were von Willebrand factor positive. The content of coronary thrombectomy specimens is heterogeneous and consists of blood cells but also possibly cells from the vascular wall and cholesterol crystals. The culture of cells contained in the specimens yielded multiplying cells, some of which demonstrated features of haematopoietic progenitor cells and which differentiated into various cell-types.