Antithrombotic Therapy in Patients With Atrial Fibrillation and Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

AIM: The objective of this article is to review the contemporary literature on the use of antithrombotic therapy in patients with atrial fibrillation (AF) and coronary artery disease after undergoing percutaneous coronary intervention (PCI). Special consideration was given to the type and duration of therapy, treatment strategies for the elderly (≥65 years of age), and strategies to reduce bleeding. METHODS: Relevant studies were searched through MEDLINE/PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov, and Google Scholar. Of the 236 publications retrieved, 76 were considered relevant including 35 randomized controlled trials, 17 meta-analyses, 16 observational studies, and 8 published major guidelines. RESULTS: Most trials, meta-analyses, and guidelines support 1 month of triple therapy (TT) with an oral anticoagulant (OAC), dual antiplatelet agents (DAPT) with aspirin (ASA)/clopidogrel, and, afterward, dual therapy (DT) with OAC and single antiplatelet agent for an additional 11 months, or alternatively DT alone for 12 months after PCI. Individual consideration is given to the risk and impact of stent thrombosis (ST), thromboembolism, and bleeding. Several trials and meta-analyses have also suggested that shorter DAPT duration (≤6 months) may be safer than longer therapy (≥6 months) when weighing the risk of bleeding with ischemic outcomes, especially with newer generation drug-eluting stents. The selective use of proton-pump inhibitors in patients prone to gastrointestinal bleeding who are subjected to prolonged exposure with TT or DT may be beneficial. In the elderly, the risk of bleeding from TT, compared with DT, outweighs the benefit of reducing ischemic events. CONCLUSIONS: In conclusion, tailoring therapy to the individual patient is recommended considering the ischemic and bleeding risk as well as the risk of thromboembolism. For most patients with AF, 1 month of TT and subsequently DT for additional 11 months are recommended.

New Oral Anticoagulants in Nonvalvular Atrial Fibrillation.

The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs. However, both dabigatran 150 twice daily and rivaroxaban have a slightly higher incidence of gastrointestinal bleeding when compared with VKAs. The article will delineate the current knowledge as well as scientific gaps related to the choice and dosage of anticoagulation regimens for various NVAF subsets and will address certain common clinical scenarios requiring special considerations. The article also addresses the shortcomings of NOACs: lack of therapeutic pharmacokinetic and pharmacodynamic targets, absence of tools to assess compliance and efficacy, rigid and limited dosage options, and absence of effective and inexpensive reversal agents.

Energy drinks and their adverse health effects: A systematic review of the current evidence.

PURPOSE: With the rising consumption of so-called energy drinks over the last few years, there has been a growing body of literature describing significant adverse health events after the ingestion of these beverages. To gain further insight about the clinical spectrum of these adverse events, we conducted a literature review. METHODS: Using PubMed and Google-Scholar, we searched the literature from January 1980 through May 2014 for articles on the adverse health effects of energy drinks. A total of 2097 publications were found. We then excluded molecular and industry-related studies, popular media reports, and case reports of isolated caffeine toxicity, yielding 43 reports. CONCLUSION: Energy drink consumption is a health issue primarily of the adolescent and young adult male population. It is linked to increased substance abuse and risk-taking behaviors. The most common adverse events affect the cardiovascular and neurological systems. The most common ingredient in energy drinks is caffeine, and it is believed that the adverse events are related to its effects, as well as potentiating effects of other stimulants in these drinks. Education, regulation, and further studies are required.

Use of antiplatelet agents in patients with atherosclerotic disease.

Platelets play a key role in the initiation of hemostatic mechanisms during vascular injury. When contemplating prescription of antiplatelet agents (APAs) for patients as primary prevention for cardiovascular events, the physician should carefully weigh the potential benefits of cardiovascular risk reduction with the likelihood of harm, related mostly to hemorrhagic complications. The role of APAs in secondary prevention of atherosclerosis and coronary artery disease is well established, however, optimal duration of therapy and intensity of patient treatment are not settled and probably need to be individualized per patient. We describe the data emerging from contemporary trials on the efficacy and safety of the use of oral APAs in various patient subpopulations. We also discuss the advantages and potential roles of new APAs during and following acute coronary syndromes, percutaneous coronary interventions, and symptomatic atherosclerosis. We propose certain strategies and directions for future research to enhance the safety and efficacy prevention by optimizing the beneficial effects of APAs along with other contemporary treatment modalities of primary and secondary prevention.

Renal artery stenosis - an update.

Renal artery stenosis (RAS) is a common form of peripheral arterial disease. The most common cause of RAS is atherosclerosis. It is predominantly unilateral. The pathophysiologic mechanism stems from renal underperfusion resulting in the activation of the renin- angiotensin-aldosterone pathway. Even though the majority of patients with RAS are asymptomatic, it can clinically present with hypertension, nephropathy and congestive heart failure. This progressive disease can lead to resistant hypertension and end stage kidney failure. Screening patients for RAS with either Doppler ultrasonography, computed tomographic angiography, or magnetic resonance angiography is preferred. Adequate blood pressure control, goal-directed lipid-lowering therapy, smoking cessation, and other preventive measures form the foundation of management of patients with RAS. Catheter-based percutaneous revascularization with angioplasty and stenting showed modest clinical benefit for patients in small retrospective studies, but data from randomized clinical trials failed to confirm these beneficial results. The current ongoing Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial may provide more concrete data regarding the role of stenting in RAS. Surgical revascularization is considered only if catheter-based revascularization is unsuitable or unsuccessful. The American College of Cardiology/American Heart Association guidelines on evaluation and management of patients with RAS provide the framework for determining individualized assessment and treatment plans for patients with RAS.

Developing a new hybrid revascularization program: a road map for hospital managers and physician leaders.

Hybrid coronary revascularization, which involves minimally invasive direct coronary artery bypass surgery using the left internal mammary artery to left anterior descending and percutaneous coronary intervention using drug-eluting stents for the remaining diseased coronary vessels, is an innovative approach to decrease the morbidity of conventional surgery. Little information is available to guide hospital managers and physician leaders in implementing a hybrid revascularization program. In this article, we describe the people-process-technology issues that managers and leaders are likely to encounter as they develop a hybrid revascularization program in their practice.

Acute ST-segment elevation myocardial infarction: a rare initial presentation of previously undiagnosed essential thrombocythemia.

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by hemorrhagic and thrombotic complications. We describe a rare case of ST-segment elevation myocardial infarction (STEMI) in a patient with previously undiagnosed ET, confirmed by gene mutation. A 68-year-old man presented with severe acute chest pain and was diagnosed with STEMI. Primary coronary angiography showed severe stenosis with thrombus in the proximal left anterior descending coronary artery. Percutaneous aspiration thrombectomy was performed with no residual stenosis. The patient was discharged on antiplatelet agents, aspirin, and clopidogrel. Further investigations for intracoronary thrombus with no underlying atherosclerotic disease revealed positive Janus kinase 2 (JAK2) V617F gene mutation, and this was consistent with a diagnosis of ET with elevated platelet count. This case describes a rare initial presentation of previously undiagnosed ET with acute STEMI and highlights the potential importance of secondary workup for non-atherosclerotic causes of STEMI with isolated intracoronary thrombus otherwise normal coronary vasculature with no focal atherosclerosis.

Metabolic syndrome: definition and therapeutic implications.

The collection of impaired glucose metabolism, central obesity, elevated blood pressure, and dyslipidemia is identified as metabolic syndrome (MetS). It is estimated that approximately 25% of the world's population has MetS. In the United States, MetS is more common in men and Hispanics, and its incidence increases with age. Metabolic syndrome increases the risk of developing cardiovascular disease and type 2 diabetes mellitus. The underlying risk factors include insulin resistance and abdominal obesity. Confusion about MetS exists in part due to the lack of a consensus definition and treatment protocol. Treatment of MetS begins with therapeutic lifestyle changes and then pharmacologic treatment of the syndrome's individual components. Effective interventions include diet modification, exercise, and use of pharmacologic agents to treat risk factors. Weight loss and increasing physical activity significantly improve all aspects of MetS. A diet that includes more fruits, vegetables, whole grains, monounsaturated fats, and low-fat dairy products will benefit most patients with MetS. Physicians can be most effective in advising patients by customizing specific lifestyle recommendations after assessing patients for the presence of risk factors.

Influence of predictive modeling in implementing optimal heart failure therapy.

INTRODUCTION: A gap remains between evidence-based guidelines in the treatment of heart failure (HF) and current pharmacologic and device therapy. The Seattle Heart Failure Model (SHFM) is an accurate predictive tool that allows the clinician to quantitatively assess the influence of pharmacologic and device therapy on HF. The authors hypothesized that graphically demonstrating the improvement in survival using such a tool may well modify physician practice behavior. METHODS: The authors examined 50 randomly selected patients from 10 primary care physicians having HF with a left ventricular ejection fraction <40%. Twenty-one data elements were entered into the SHFM to create a survival estimate before and after implementation of interventions known to be beneficial, both pharmacologic (addition of angiotensin-converting enzyme/angiotensin receptor blocker, statin, ß-blocker and aldosterone blocker) and device based (consideration for automatic implantable cardioverter-defibrillator, biventricular pacer and biventricular implantable cardioverter-defibrillator). The influence of therapeutic change was presented in a focused clinical session with the primary care physician. RESULTS: The mean age of the population examined was 73 ± 10 years with New York Heart Association class 2.2 ± 0.5 symptoms. In the 50 patients examined, the authors altered device or medical therapy in 82%. This included advancement of medical therapy in 50%, consideration for device referral in 10% or both (medical therapy and device referral) in 22%. This augmentation of therapy resulted in an increase in estimated mean life expectancy from 8.8 to 10.9 years (P < 0.001). CONCLUSION: Use of the SHFM significantly impacted intensification of HF therapy in this ambulatory HF population.

Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death.

BACKGROUND: L-type calcium channel (LTCC) mutations have been associated with Brugada syndrome (BrS), short QT (SQT) syndrome, and Timothy syndrome (LQT8). Little is known about the extent to which LTCC mutations contribute to the J-wave syndromes associated with sudden cardiac death. OBJECTIVE: The purpose of this study was to identify mutations in the α1, ß2, and α2δ subunits of LTCC (Ca(v)1.2) among 205 probands diagnosed with BrS, idiopathic ventricular fibrillation (IVF), and early repolarization syndrome (ERS). CACNA1C, CACNB2b, and CACNA2D1 genes of 162 probands with BrS and BrS+SQT, 19 with IVF, and 24 with ERS were screened by direct sequencing. METHODS/RESULTS: Overall, 23 distinct mutations were identified. A total of 12.3%, 5.2%, and 16% of BrS/BrS+SQT, IVF, and ERS probands displayed mutations in α1, ß2, and α2δ subunits of LTCC, respectively. When rare polymorphisms were included, the yield increased to 17.9%, 21%, and 29.1% for BrS/BrS+SQT, IVF, and ERS probands, respectively. Functional expression of two CACNA1C mutations associated with BrS and BrS+SQT led to loss of function in calcium channel current. BrS probands displaying a normal QTc had additional variations known to prolong the QT interval. CONCLUSION: The study results indicate that mutations in the LTCCs are detected in a high percentage of probands with J-wave syndromes associated with inherited cardiac arrhythmias, suggesting that genetic screening of Ca(v) genes may be a valuable diagnostic tool in identifying individuals at risk. These results are the first to identify CACNA2D1 as a novel BrS susceptibility gene and CACNA1C, CACNB2, and CACNA2D1 as possible novel ERS susceptibility genes.

Clinical outcomes following drug-eluting versus bare metal stent implantation for lesion subsets excluded from pivotal clinical trials: findings from the GHOST Study (Guthrie Health System Off-Label StenT Study).

OBJECTIVES: We assessed outcomes of patients undergoing drug-eluting stent (DES) vs. bare metal stent (BMS) implantation for complex lesions excluded from pivotal clinical trials of DES. BACKGROUND: Although DES improve target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) compared to BMS in randomized trials, data on safety and efficacy of DES in complex lesions are insufficient. METHODS: In a single-center registry of 1,354 patients who underwent stent implantation for complex lesions between July 2001 and December 2005, we compared the incidence of death, death or myocardial infarction (MI), stent thrombosis [definite or probable by the Academic Research Consortium (ARC) criteria], TVR, and MACE between patients who received DES (n = 483) versus those who received BMS (n = 871). Mean duration of follow-up was 494 versus 838 days in DES and BMS groups, respectively. RESULTS: Clinical outcomes in DES versus BMS groups were as follows: death 5.2% versus 11.5% (log-rank P = 0.042); death/MI 11.2% versus 16.7% (P = 0.47), stent thrombosis 2.9% versus 2.6% (P = 0.61), TVR 6.6 versus 18.5% (P < 0.0001), MACE 14.9% versus 29.7% (P = 0.0002), respectively. After adjustment for baseline differences, DES implantation was associated with lower TVR (adjusted hazards ratio HR = 0.38, 95% CI 0.26-0.56, P < 0.0001) and MACE (HR = 0.56, CI 0.42-0.74, P < 0.0001) without significant impact on other outcomes. In 933 patients who underwent DES (n = 483) or BMS (n = 450) implantation in the year 2003 or later, DES implantation similarly lowered TVR and MACE without affecting other outcomes. CONCLUSIONS: Our findings support the safety and efficacy of DES in patient subsets excluded from pivotal randomized clinical trials of DES.

A comparison of contemporary definitions of contrast nephropathy in patients undergoing percutaneous coronary intervention and a proposal for a novel nephropathy grading system.

Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) has multiple definitions. We attempted to identify the optimal definition of CIN. In 985 patients undergoing PCI (derivation group), we assessed the prognostic significance of 4 commonly used contemporary definitions of CIN (increases in serum creatinine after PCI [deltaCr] >1.0 mg/dl, >0.5 mg/dl, and >25% after PCI; and the American College of Cardiology National Cardiovascular Data Registry definition) with respect to 6-month major adverse cardiovascular events (MACEs) and all-cause mortality (at 863 +/- 324 days). Incidence of CIN ranged widely (2.0% to 15%) depending on the definition used. Only 2 definitions (deltaCr >0.5 mg/dl, >25%) consistently correlated with study outcomes. Using these 2 definitions, we devised a new grading system (grade 0 deltaCr 25% but 0.5 mg/dl). Nephropathy grades (0 vs 1 vs 2) showed significant correlation with 6-month MACEs (12.4 vs 19.4 vs 28.6%, p = 0.003) and all-cause mortality (10.2 vs 10.4 vs 40.9%, p <0.0001). In multivariate analyses, the grading system showed an independent association with MACEs and mortality. The prognostic value of nephropathy grades was prospectively confirmed in an independent validation group of 539 patients. In conclusion, of the 4 contemporary definitions of CIN, only deltaCr >25% and >0.5 mg/dl consistently predicted adverse events after PCI. By unifying these 2 definitions, we devised a novel nephropathy grading system that is predictive of 6-month MACEs and all-cause mortality after PCI.

Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study.

OBJECTIVES: The goal of this work was to determine whether rheolytic thrombectomy (RT) as an adjunct to primary percutaneous coronary intervention (PCI) reduces infarction size and improves myocardial perfusion during treatment of ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Primary PCI for STEMI achieves brisk epicardial flow in most patients, but myocardial perfusion often remains suboptimal. Distal embolization of thrombus during treatment may be a contributing factor. METHODS: This prospective, multicenter trial enrolled 480 patients presenting within 12 h of symptom onset and randomized to treatment with RT as an adjunct to PCI (n = 240) or to PCI alone (n = 240). Visible thrombus was not required. The primary end point was infarct size measured by sestamibi imaging at 14 to 28 days. Secondary end points included final Thrombolysis In Myocardial Infarction (TIMI) flow grade, tissue myocardial perfusion (TMP) blush, ST-segment resolution, and major adverse cardiac events (MACE), defined as the occurrence of death, new Q-wave myocardial infarction, emergent coronary artery bypass grafting, target lesion revascularization, stroke, or stent thrombosis at 30 days. RESULTS: Final infarct size was higher in the adjunct RT group compared with PCI alone (9.8 +/- 10.9% vs. 12.5 +/- 12.13%; p = 0.03). Final TIMI flow grade 3 was lower in the adjunct RT group (91.8% vs. 97.0% in the PCI alone group; p < 0.02), although fewer patients had baseline TIMI flow grade 3 in the adjunct RT group (44% vs. 63% in the PCI alone group; p < 0.05). There were no significant differences in TMP blush scores or ST-segment resolution. Thirty-day MACE was higher in the adjunct RT group (6.7% vs. 1.7% in the PCI alone group; p = 0.01), a difference primarily driven by very low mortality rate in patients treated with PCI alone (0.8% vs. 4.6% in patients treated with adjunct RT; p = 0.02). CONCLUSIONS: Despite effective thrombus removal, RT with primary PCI did not reduce infarct size or improve TIMI flow grade, TMP blush, ST-segment resolution, or 30-day MACE.