Protease-Activated Receptor Antagonist for Reducing Cardiovascular Events - A Review on Vorapaxar.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Growing role of SGLT2i in heart failure: evidence from clinical trials.

INTRODUCTION: : There is an unmet need for therapies that improve overall mortality and morbidity for patients with preserved ejection fraction, who comprise roughly half of all heart failure (HF) cases. The growing role of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcomes provides a paradigm shift in the treatment of HF. AREAS COVERED: : This review article provides a general overview of the growing role of SGLT2is and summarizes the mechanism of action, side effects, and contraindications for the treatment of HF. We also discuss recent clinical trials measuring the effects of different SGLT2is as possible treatment options for HF with reduced ejection fraction and HF with mid-range and preserved EF. We conducted a review of all the randomized, controlled studies with SGLT2is in patients with known heart failure with and without type-2 diabetes (T2DM). We performed a literature search in PubMed, Google Scholar, the Web of Science, and the Cochrane Library while screening results by the use of titles and abstracts. EXPERT OPINION: : The promising pathophysiological profile of SGLT2i and their role in cardioprotective effects demonstrate an invaluable discovery in the management of patients with HF irrespective of their diabetes status.

Dual Versus Triple Therapy in Patients with Acute Coronary Syndrome and an Anticoagulation Indication: A Systematic Review with Meta-Analysis and Trial-Sequential Analysis.

Choosing an antithrombotic regime in patients with acute coronary syndrome (ACS) and a concomitant indication for anticoagulation is a challenge commonly encountered by clinicians. Our aim in this article is to evaluate the safety and efficacy of triple antithrombotic therapy (TT, anticoagulant plus dual antiplatelet) versus dual antithrombotic therapy [dual therapy (DT), anticoagulant plus single antiplatelet] in patients with ACS. We included all randomized trials comparing the outcomes of single versus dual antiplatelet therapy in patients with ACS on anticoagulants. The primary outcome was major adverse cardiac events (MACE). Other outcomes studied were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stroke, stent thrombosis (ST), and major bleeding. The Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data. Six studies, with a total of 11,437 patients, met our selection criteria. With a follow-up duration of 9-14 months, there was no significant difference between DT and TT in terms of MACE [RR 0.96; 95% confidence interval (CI), 0.79-1.17], all-cause mortality (RR 1.00; 95% CI, 0.77-1.29), cardiovascular mortality (RR 1.03; 95% CI, 0.79-1.34), MI (RR 1.14; 95% CI, 0.90-1.45), stroke (RR 0.83; 95% CI, 0.56-1.23), and ST (RR 1.32; 95% CI, 0.87-2.01). Compared with TT, DT was associated with significant reductions in major bleeding 4.1% versus 6.5% (RR 0.61; 95% CI, 0.45-0.81; number needed to treat = 42), clinically significant bleeding 10.5% versus 16.4% (RR 0.62; 95% CI, 0.48-0.80) and intracranial hemorrhage 0.4% versus 0.8% (RR 0.43; 95% CI, 0.24-0.77). In patients on anticoagulant therapy, the strategy of single antiplatelet therapy (DT) confers a benefit of less major bleeding with no difference in MACE, all-cause mortality, cardiovascular mortality, MI, stroke, and ST.

Valvular Heart Disease in Pregnancy: Anticoagulation and the Role of Percutaneous Treatment.

Valvular heart disease is present in about 1% of pregnancies, and it poses a management challenge as both fetal and maternal lives are at risk of complications. Pregnancy is associated with significant hemodynamic changes, which can compromise the cardiac status in women with underlying valvular disorders. Management of valvular heart diseases has undergone considerable innovation and advancement with newer techniques, approaches and devices being employed. The decision regarding the management of anticoagulation, especially in patients with prosthetic valves, raises distinct questions and challenges. In this review, we describe the management of common valvular heart diseases encountered during pregnancy, role of percutaneous catheter based therapeutic interventions, the importance of a team-based approach, and the challenges given existing gaps in the literature.

Lipid inclusions in cardiac myocytes - a rare case of cardiolipotoxicity.

The heart oxidizes fatty acids for its energy production. The physiological balance between fatty acid uptake and its oxidation prevents lipid accumulation in cardiac myocytes. However, accumulation of lipids due to various processes such as obesity, diabetes, heart failure, myocardial ischemia or infarction can result in damage to the heart tissue, also known as cardiolipotoxicity. We present a unique case of a 69-year-old gentleman with a history of heart failure and ventricular tachycardia. Endomyocardial biopsy to assess for restrictive cardiomyopathy/amyloid showed no evidence of amyloid, significant inflammation or fibrosis, but did show intracellular accumulation of significant amorphous material in most cardiac myocytes. We review the literature regarding the pathogenesis of cardiolipotoxicity, which has no definite cause or treatment yet identified.

Corynebacterium Jeikeium Endocarditis: A Review of the Literature.

Corynebacterium jeikeium is a gram-positive, aerobic, pleomorphic, nonspore forming bacillus, commonly present on the skin surface. Infective endocarditis secondary to C. jeikeium most commonly affects left-sided heart valves and has a higher likelihood to require valve replacement compared to other Corynebacterium endocarditis. C. jeikeium endocarditis is extremely difficult to treat as it is characteristically resistant to penicillin, cephalosporins and aminoglycosides, and sensitivity to quinolones, macrolides, tetracyclines and rifampin is variable. Despite treatment, mortality rates as high as 33% have been reported. We hereby review the literature regarding the epidemiology, diagnosis and treatment of this deadly microorganism.

Clostridium septicum aortitis: A kiss of the devil.

BACKGROUND: Clostridium septicum aortitis is a lethal infection. C. septicum has a strong association with an underlying malignancy, most commonly in the colon. AIM: Early identification methods and management strategies of C. Septicum infection. MATERIALS AND METHODS: We present a 64-year-old man with aortic aneurysm and C. septicum bacteremia with unknown malignancy who passed away on the fourth day of hospitalization despite emergent endovascular intervention. Computed tomography showed periaortic gas which is the hallmark of infection. DISCUSSION: This case report highlights the need of prompt surgical treatment and its different modalities along with the early use of appropriate antibiotics due to the rapid spread of infection associated with high fatality. The authors also discuss the association of C. septicum aortitis with underlying occult malignancies. CONCLUSION: Delay in identification and treatment of C. Septicum is associated with very high mortality rates.

Mechanical Valve Thrombosis in a Pregnant Patient: A Case of Therapeutic Failure.

Mechanical valve thrombosis is life-threatening complication especially in pregnant patients. The optimal anticoagulation regimen is still not certain as there are different fetal and maternal risks associated with anticoagulation. A 37-year-old woman with a history of rheumatic heart disease with a mechanical mitral valve replacement 13 years prior presented to the hospital with dyspnea on mild exertion associated with orthopnea for three days. She was nine weeks pregnant, she had been on warfarin prior to pregnancy, and was switched to low molecular weight heparin (LMWH) in her 6th week of pregnancy. Fluoroscopy showed that one leaflet of the mitral valve was nearly fixed, while the other leaflet had restricted motion at maximal opening. Transesophageal echocardiogram (TEE) showed a very large thrombus approximately 3-4 cm2 encompassing the entire mechanical valve with one immobile leaflet and limited mobility in other leaflet. In view of her clinical status (dyspnea with NYHA Class IV symptoms), the patient underwent uncomplicated bioprosthetic mitral valve replacement. However, the fetus did not survive. Mechanical heart valve (MHV) thrombosis is life-threatening complication in pregnancy. The optimal anticoagulation therapy in pregnancy is unclear. This case report brings into light that in spite of adequate anticoagulation, pregnant patients with mechanical heart valves are still at a high risk of developing valve thrombosis. It highlights the use of transthoracic and transesophageal echocardiogram along with fluoroscopy in diagnosing this and discusses the therapeutic options for this unique condition.