EhSir2c, a Sir2 homolog from the human pathogen Entamoeba histolytica interacts with a DNA repair protein, EhRAD23: Protein-protein interaction, docking and functional study.

Chromosome segregation is a crucial phenomenon in the cell cycle and defects in genome segregation result in an abnormality in various cellular events. Unlike higher eukaryotes, chromosome segregation and a number of cell cycle events are unusual in the protozoan parasite Entamoeba histolytica (E. histolytica). Characterization of Sir2 proteins from E. histolytica may reveal its unique cellular events as they play role in diverse cellular processes including chromosome segregation. E. histolytica has four homologs of Sir2 proteins. EhSir2a and EhSir2b show sequence similarity towards eukaryotic Sir2 homologs, whereas EhSir2c and EhSir2d are more like prokaryotic sirtuins. Using both computational and experimental methods, EhSir2c has been characterized in this study. The three-dimensional structure of EhSir2c is predicted by homology modelling. The protein interactors of EhSir2c have been identified by yeast-two-hybrid screening against the cDNA library of E. histolytica. We have identified a novel interactor, EhRAD23 which is a homolog of UV excision repair protein RAD23. The interaction of EhSir2c and EhRAD23 was validated by pull-down assay. UV-C irradiation up-regulates the relative expression of EhSir2c, suggesting the necessity of EhSir2c in UV-induced stress in this parasite.Communicated by Ramaswamy H. Sarma.

The Emerging Role of FDG PET/CT in Diagnosing Endocarditis and Cardiac Device Infection.

Infective endocarditis and cardiac implantable electronic device infection (CIEDI) have witnessed an increasing incidence in clinical practice and associated with increasing health care expenditure. Expanding indications of CIED in various cardiovascular conditions have also contributed to the surge of these infections. Early diagnosis of these infections is associated with a favorable prognosis. Given the lack of a single definitive diagnostic method and the limitations of echocardiography, which is considered a central diagnostic imaging modality, additional imaging modalities are required. Recent studies have highlighted the diagnostic utility of FDG PET and CT. In this review article, we discuss the existing limitations of echocardiography, acquisition protocols of PET/CT, and indications of these advanced imaging modalities in infective endocarditis and CIEDI diagnosis.

In silico analysis of a Skp1 protein homolog from the human pathogen E. histolytica.

SCF complex consisting of Skp1, Cullins, F-box proteins, is the largest family of E3 ubiquitin ligases that promotes ubiquitination of many substrate proteins and controls numerous cellular processes. Skp1 is an adapter protein that binds directly to the F-box proteins. In this study, we have presented the first comprehensive analysis of the presence of peptides or proteins in the human pathogen Entamoeba histolytica having homology to Skp1protein. The occurrence of other protein components of the SCF complex has been identified from protein-protein interaction network of EhSkp1A. Studying the role of Skp1protein in this pathogen would help to understand its unique chromosome segregation and cell division which are different from higher eukaryotes. Further, owing to the development of resistance over several drugs that are currently available, there is a growing need for a novel drug against E. histolytica. Proteins from ubiquitin-proteasome pathway have received attention as potential drug targets in other parasites. We have identified four homologs of Skp1 protein in E. histolytica strain HM-1: IMSS. Molecular docking study between EhSkp1A and an F-box/WD domain-containing protein (EhFBXW) shows that the F-box domain in the N-terminal region of EhFBXW interacts with EhSkp1A. Therefore, the results of the present study shall provide a stable foundation for further research on the cell cycle regulation of E. histolytica and this will help researchers to develop new drugs against this parasite. Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-022-01523-0.

Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis.

Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.

A Brief Overview of Recurrent Pericarditis Management and the Potential of Rilonacept as a New Therapeutic Option.

Recurrent pericarditis affects 15-30% of patients after acute pericarditis. A large number of the patients with recurrent pericarditis can become corticosteroid dependent, leading to disease chronicity and drug dependence, with additional morbidity from long-term steroid use. Recent randomized trials indicate the efficacy of the interleukin-1 inhibitors anakinra and rilonacept in recurrent pericarditis, including colchicine-resistant and corticosteroid-dependent cases. In particular, rilonacept was assessed in the RHAPSODY clinical trial and found to be a potential treatment option that would decrease recurrent episodes, enabling patients to be weaned off steroids. Additionally, new data indicate that rilonacept should be considered as an option for patients with recurrent pericarditis, as add-on therapy to colchicine and nonsteroidal anti-inflammatory drugs, in place of steroids. We review the current management options for recurrent pericarditis as well as rilonacept as a prospective new addition to our armamentarium.

Eosinophilic Myocarditis: When Allergies Attack the Heart!

Eosinophilic myocarditis is a clinical condition whereby myocardial injury is mediated by eosinophilic infiltration. A number of underlying causes, including reactive, clonal, or idiopathic hypereosinophilic syndrome, may trigger eosinophilia. Disease presentation may vary from mild subclinical variants to fulminant myocarditis with thromboembolic complications, and in some cases, endomyocardial and valvular fibrosis may be seen. A detailed examination coupled with the use of multimodality imaging, and endomyocardial biopsy may help establish diagnosis. Treatment is aimed at symptomatic management and treating the underlying cause of eosinophilia, such as withdrawal of implicated drugs, antihelminthic therapy for infection, immunosuppression for autoimmune conditions, and targeted therapy with tyrosine kinase inhibitors in cases with clonal myeloid disorders.

In silico analysis and molecular identification of an anaphase-promoting complex homologue from human pathogen Entamoeba histolytica.

BACKGROUND: Amoebiasis, being endemic worldwide, is the second leading cause of parasite-associated morbidity and mortality after malaria. The human parasite Entamoeba histolytica is responsible for the disease. Metronidazole is considered as the gold standard for the treatment of amoebiasis, but this antibiotic is carcinogenic and the development of antibiotic resistance against E. histolytica is a major health concern. Chromosome segregation is irregular in this parasite due to the absence of a few cell cycle checkpoint proteins. Anaphase-promoting complex (APC/C or cyclosome) is an E3 ubiquitin ligase that synchronizes chromosome segregation and anaphase progression via the ubiquitin-proteasome system. Proteasome is considered to be an attractive drug target for protozoan parasites. For the present study, EhApc11 from E. histolytica, a homologue of Apc11 in humans, is selected for elucidating its structural and functional aspects by detailed in silico analysis and molecular methods. Its physicochemical characteristics, identification of probable interactors, 3D model and quality analysis are done using standard bioinformatics tools. cDNA sequence of EhAPC11 has been further cloned for molecular characterization. RESULT: Conserved domain analysis revealed that EhApc11 belongs to the RING (really interesting new gene) superfamily and has ligand binding capacity. Expression study in Escherichia coli BL21 (DE3) revealed that the molecular weight of glutathione S-transferase (GST)-tagged protein is ~ 36 kDa. CONCLUSION: EhApc11 is a hydrophilic, thermostable, extracellular protein with potent antigenicity. The study will serve as a groundwork for future in-depth analysis regarding the validation of protein-protein interaction of EhApc11 with its substrates identified by STRING analysis and the potential of EhApc11 to serve as an anti-amoebic drug target.

Impact of Pulmonary Hypertension on In-Hospital Outcomes and 30-Day Readmissions Following Percutaneous Coronary Interventions.

OBJECTIVE: To evaluate the impact of pulmonary hypertension (PH) on percutaneous coronary intervention (PCI) outcomes and 30-day all-cause readmissions by analyzing a national database. METHODS: We queried the 2014 National Readmissions Database to identify patients undergoing PCI using International Classification of Diseases, Ninth Revision, Clinical Modification codes. These patients were then subcategorized based on the coded presence or absence of PH and further analyzed to determine the impact of PH on clinical outcomes, health care use, and 30-day readmissions. RESULTS: Among 599,490 patients hospitalized for a PCI in 2014, 19,348 (3.2%) had concomitant PH. At baseline, these patients were older with a higher burden of comorbidities. Patients with PH had longer initial hospitalizations and higher 30-day readmission rates and mortality than their non-PH counterparts. This was largely driven by cardiac causes, most commonly heart failure (20.3% vs 9.0%, P<.001) and non-ST-segment elevation myocardial infarction. Recurrent coronary events (17.5% vs 9.5%, P<.05) including ST-segment elevation myocardial infarction predominated in the non-PH group. CONCLUSION: Patients with PH undergoing PCI are a high-risk group in terms of mortality and 30-day readmission rates. Percutaneous coronary intervention in patients with PH is associated with higher rates of recurrent heart failure and non-ST-segment elevation myocardial infarction, rather than recurrent coronary events or ST-segment elevation myocardial infarction. This perhaps indicates a predominance of demand ischemia and heart failure syndromes rather than overt atherothrombosis in the etiology of chest pain in these patients.

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence.

The burden and cost of heart failure management, primarily in the form of hospitalization in the setting of decompensated heart failure, continue to be some of the biggest clinical challenges in cardiovascular medicine. In recently published randomized controlled trials, including DAPA-HF, sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was shown to reduce hospitalization from heart failure or mortality associated with cardiovascular causes, when added to existing guideline-directed medical therapy. The American College of Cardiology (ACC) released a Clinical Pathway guideline that recommends the use of dapagliflozin in clinical management of heart failure, with or without diabetes. Furthermore, the results of the DAPA-CKD trial broaden the utility of dapagliflozin as a therapeutic option in patients with advanced kidney disease. In this article, the authors explore the existing evidence on dapagliflozin in heart failure with reduced ejection fraction and highlight the need for further research on uses of dapagliflozin in the world of heart failure.

30-day readmission following urgent and elective transcatheter aortic valve replacement: A Nationwide Readmission Database analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly used for decompensated severe symptomatic aortic stenosis. Data on urgent and elective TAVR readmission is scarce in the literature. Here, we have performed a retrospective cohort study with the Nationwide Readmission Database of 2016 to identify the rate of 30-day all-cause readmission, common causes of readmission, and distribution of morbidity in index admission and readmission after urgent and elective TAVR. METHODS: We used International Classification of Diseases, Tenth Revision codes (02R.F38H, 02R.F38Z, 02R.F48Z) for identification of all TAVR procedures done in 2016 in patients >18 years old. We found 8379 patients who underwent urgent TAVR and 32,006 patients who underwent elective TAVR in 2016. RESULT: The mean age of patients undergoing urgent TAVR was 79 ± 9.97 years with 44.6% women. The mean age of patients undergoing elective TAVR was 80.7 ± 8.25 years with 46.2% women. We found the 30-day all-cause readmission rate of 15.5% and 9.5% in patients undergoing urgent and elective TAVR, respectively (p < 0.001). The cardiac cause was the predominant cause of readmission in both groups (43.77% vs. 42.11%, p = 0.57), followed by pulmonary cause, gastrointestinal (GI) cause, and renal cause. Among cardiac causes, congestive heart failure (CHF) was predominant cause of readmission and was similar in both groups (18.73 in urgent TAVR vs. 15.73 in elective TAVR, p = 0.12). CONCLUSION: We found that the all-cause 30-day readmission rate was higher in patients who had undergone urgent TAVR. Further studies are needed to better understand this difference.

Contemporary narrative review on left atrial strain mechanics in echocardiography: cardiomyopathy, valvular heart disease and beyond.

Left atrial (LA) strain mechanics refer to the measurement of LA myocardial deformation expressed as a percentage, and have been gathering interest over the last decade with expanding research supporting their utility in multiple cardiovascular disorders. Measured through advanced dynamic imaging techniques which include tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE), LA strain mechanics are affected by left ventricular diastolic dysfunction prior to the onset of functional and structural changes in the left ventricle (LV). There is a need for practising cardiologists to become more familiar with the clinical utility of LA strain mechanics. In this article, we begin by reviewing the physiologic function of the LA, using this as a basis for understanding LA strain mechanics. The focus of this review article is to provide a contemporary update on the utility of LA strain mechanics in a range of cardiovascular disorders, including atrial fibrillation (AF), hypertrophic cardiomyopathy (HCM), valvular pathologies, coronary artery disease (CAD) as well as systemic diseases, such as hypertension (HTN), obesity and diabetes mellitus (DM). This article also highlights the current limitations in more widespread clinical applications of LA strain mechanics, as well as outlining the future perspectives on the clinical applications of LA strain mechanics.

Transformation of CuS/ZnS nanomaterials to an efficient visible light photocatalyst by 'photosensitizer' graphene and the potential antimicrobial activities of the nanocomposites.

We report the growth of CuS/ZnS (CZS) nanoparticles (NPs) on the graphene sheet by a facile green synthesis process. The CuS/ZnS-graphene (CZSG) nanocomposites exhibit enhanced visible light photocatalytic activity towards organic dye (methylene blue) degradation than that of CZS nanoparticles. To find the reason for the enhanced photo-activity, we propose a new photocatalytic mechanism where graphene in the CZSG nanocomposites acts as a 'photosensitizer' for CZS nanoparticles. This distinctive photocatalytic mechanism is noticeably different from all other previous research works on semiconductor-graphene hybrid photocatalysts where graphene behaves as an electron reservoir to capture the electrons from photo-excited semiconductor. This novel idea of the photocatalytic mechanism in semiconductor-graphene photocatalysts could draw a new track in thinking for designing of graphene-based photocatalysts for solving environmental pollution problems and they also show remarkable antimicrobial activities.

Cost of inpatient heart failure care and 30-day readmissions in the United States.

BACKGROUND: Heart failure hospitalizations are a major financial cost to healthcare systems. This study aimed to evaluate the costs associated with inpatient hospitalization. METHODS: Patients with a primary diagnosis of heart failure during a hospital admission between 2010 and 2014 in the U.S. Nationwide Readmission Database were included. The primary outcome was total cost defined by direct cost of index admission and first readmission within 30-days. RESULTS: A total of 2,645,336 patients with primary heart failure were included in the analysis. The mean ± SD total cost overall was $13,807 ± 24,145; with mean total costs of $15,618 ± 25,264 for patients with 30-day readmission and $11,845 ± 22,710 for patients without a readmission. The comorbidities strongly associated with increased cost were pulmonary circulatory disorder (OR 26.24 95% CI 20.06-34.33), valvular heart disease (OR 25.42 95% CI 20.65-31.28) and bleeding (OR 5.96 95% CI 5.47-6.50). Among hospitalized patients, 12.6% underwent an invasive diagnostic procedure or treatment. The mean cost for patients without invasive care was $10,995. This increased by $129,547, $119,769, $251,110 and $293,575 for receipt of circulatory support, intra-aortic balloon pump, LV assist device and heart transplant. The greatest mean additional cost annually was associated with receipt of coronary angiogram ($26,282 per person for a total of ($728.5 million) and mechanical ventilation ($54,529 per person for a total of $501.7 million). CONCLUSION: In conclusion, the costs associated with inpatient heart failure care are significant, and the major contributors to inpatient costs are comorbidities, invasive procedures and readmissions.

Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes.

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

Acute myocardial infarction in the young with diabetes mellitus- national inpatient sample study with sex-based difference in outcomes.

BACKGROUND: Mortality after AMI is on the decreasing trend; however, this favorable trend is not observed in the young, especially women. Therefore, we conducted a retrospective analysis using the Nationwide Inpatient Sample (NIS) to identify sex-based outcomes following AMI in young with diabetes. METHODS: NIS 2010-2014 was used to identify all patients with AMI using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Men (N = 30,950) and women (N = 17,928) patients diagnosed with diabetes were identified and stratified as young if age >18 and <45 years. RESULTS: Young women with AMI and concomitant diabetes having a higher burden of overall traditional and non-traditional comorbidities. NSTEMI was the major presentation in women as compared to men. Young women with AMI and concomitant diabetes were less likely to receive revascularization with PCI [51.1% vs. 58.2%; OR 0.86, CI 0.78-0.94] or CABG [7.9% vs. 10.1%; OR 0.64, CI 0.54-0.75]. Adjusted all-cause in-hospital mortality did not differ significantly between the two groups [OR 1.06, CI 0.74-1.52]. Women had lower odds of developing cardiogenic shock, ventricular arrhythmias, and AKI, and were more likely to develop major bleeding requiring transfusion, and mitral regurgitation. CONCLUSION: There were significant differences between young men and women with diabetes in terms of baseline characteristics and clinical presentation, use of revascularization, and cardiac complications, yet overall, in-hospital mortality does not appear to differ. More studies are needed to identify the interaction of sex and diabetes in young AMI population, and areas for practice improvement.

Trends of Cardiac Complications in Patients With Rheumatoid Arthritis: Analysis of the United States National Inpatient Sample; 2005-2014.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition. Chronic inflammation is associated with atherosclerosis, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), chronic kidney disease. But sparse data are available regarding the trends of cardiovascular diseases and complications in RA. We conducted a National Inpatient Sample database analysis to demonstrate the trends of cardiac complications in patients with RA. METHODS: We used National Inpatient Sample data from 2005 to 2014 to identify admissions with the diagnosis of RA and identified who had associated cardiovascular complications also. The International Classification of Diseases-9th Revision-Clinical Modification codes were used for the diagnoses of RA; congestive heart failure (CHF), acute myocardial infarction (AMI), and atrial fibrillation (AF). RESULTS: A statistically significant increasing trend of AMI, CHF, and AF was found. Independent predictors of mortality in RA patients with AMI were age (OR 1.03, CI 1.02-1.04; P < 0.001), COPD (OR 1.67, CI 1.40-2.00; P < 0.001), cerebrovascular disease (OR 2.207, CI 1.71-2.86; P < 0.001), renal disease (OR 1.42, CI 1.16-1.75; P = 0.001), and alcohol abuse (OR 2.73, CI 1.73-4.32; P < 0.001). Independent predictors of mortality in RA patients with CHF were age (odds ratio [OR] 1.02, confidence interval [CI] 1.017-1.024; P < 0.001]), COPD (OR 1.09, CI 1.01-1.18; P = 0.023), cerebrovascular disease (OR 1.67, CI 1.44-1.95; P < 0.001), renal disease (OR 1.16, CI 1.07-1.27; P = 0.001). Independent predictors of mortality in RA patients with AF were age (OR 1.02, CI 1.02-1.03; P < 0.001), race (OR 1.16, CI 1.02-1.31; P = 0.022), COPD (OR 1.56, CI 1.42-1.71; P < 0.001), peripheral arterial disease (OR 1.34, CI 1.16-1.53; P < 0.001), cerebrovascular disease (OR 2.27, CI 1.0-2.58; P < 0.001), renal disease (OR 1.60, CI 1.44-1.80; P < 0.001). The mortality trend has increased significantly in the CHF (P = 0.025) and AF (P = 0.042) groups during this study period. CONCLUSIONS: We have found a significant increase in trend of cardiovascular complications in RA patients. The proportion of patients, with cardiovascular comorbidities, have also been increased significantly.

Does Insurance Effect the Outcome in Patients With Acute Coronary Syndrome?: An Insight from the Most Recent National Inpatient Sample.

Several studies have shown disparities in outcome in the patients with Acute coronary syndrome (ACS) based on several factors. Treatment might differ based on insurance type. Therefore, we retrospectively analyzed National Inpatient Sample (NIS 2016) data to identify the impact of different types of insurances on mortality outcome in patients admitted with ACS. ICD-CM-10 codes were used to identify hospital discharges with a principal diagnosis of ACS. Observations were stratified based on insurance (Medicare, Medicaid, Private, and No insurance). Primary and secondary outcomes were in-hospital mortality, length of stay and total cost. Any potential confounders were adjusted using multivariate logistic regression. STATA/IC 15.1 Stata Corp LLC was used for analysis. A total of 8,01,195 hospitalizations with the primary diagnosis of ACS were identified, of which 59.2% had Medicare, 9.72% had Medicaid, 26.8% had Private insurance, and 4.3% had no insurance. Higher odds of mortality were seen in the patients with Medicare, Medicaid, and Noninsured group. Adjusted Odds ratio for mortality in Medicare was 1.01 (confidence interval [CI]: 0.94-1.1; P = 0.65), in Medicaid was 1.16 (CI: 1.03-1.30; P = 0.01) and in uninsured group was 1.46 (CI: 1.26-1.69; P ≤ 0.01). However, the patients with private insurance adjusted odds ratio for mortality were 0.77 (CI: 0.70-0.84; P ≤ 0.01) compared to the patients with other insurance groups. Above results show that the disparity exists in the outcome of patients admitted with ACS based on their insurance types, particularly for Medicaid patients. We need further studies to understand the root cause of this disparity.

Serum Bilirubin and Coronary Artery Disease: Intricate Relationship, Pathophysiology, and Recent Evidence.

Coronary artery disease (CAD) is a major cause of morbidity, mortality, and healthcare expenditure. A number of environmental and genetic risk factors have been known to contribute to CAD. More recently, a number of studies have supported as well as opposed a possible protective benefit of bilirubin in CAD, since it has anti-inflammatory, antioxidant, and antiaggregatory properties that may reduce atherogenesis. It also shares associations with different forms of CAD, namely stable CAD, unstable angina pectoris, stable angina pectoris, and acute myocardial infarction. Lack of sufficient evidence, however, has failed to elucidate a causal relationship between serum bilirubin level and risk of CAD. Therefore, in this update, we attempted to simplify this intricate relationship between bilirubin and CAD, revisit the pathophysiology of disease, how bilirubin may be protective, and to summarize the findings of the current literature.

Aspirin for Primary Prevention of Coronary Artery Disease.

Primary prevention of coronary artery disease (CAD) is an important means to reduce the burden of the disease. Aspirin has been widely prescribed over the last several decades as part of primary CAD prevention strategy. However, 3 recent hallmark trials - ARRIVE, ASCEND and ASPREE have raised serious questions about this common practice. Although, aspirin reduced incidence of non-fatal MI and stroke in these recent studies, bleeding risk was higher. In the present era, where regular exercise, healthy diet, smoking cessation, and statins are used to manage the risk factors of CAD, additional prescription of aspirin seems more harmful than beneficial. The guidelines of major societies such as European Society of Cardiology (ESC), American College of Cardiology (ACC), and American Heart Association (AHA) also reflect this shift. In this article, the authors aim to highlight the current evidence on aspirin use for primary prevention of CAD, in the context of evolving contrasting clinical trial data from the last 2 decades. We also highlight the pertinent sections of the most recent clinical guidelines of European Society of Cardiology, American College of Cardiology, and American Heart Association in this article.

Anticoagulation in Pulmonary Arterial Hypertension: Do We Know the Answer?

The shear stress and hypoxia in the pulmonary artery in patients with pulmonary arterial hypertension(PAH) causes endothelial dysfunction, smooth muscle proliferation and activation of thrombotic pathways leading to in situ thrombosis. Targeting the thrombotic pathways is a proposed mechanism to slow disease progression and improve survival. Over the years, the survival in patients with PAH has improved due to multiple factors with the increased use of anticoagulation as one of them. Both European Respiratory Society/European Society of Cardiology and American College of Cardiology/American Heart Association guidelines make grade II recommendations for using anticoagulation in PAH. The guidelines are based on weak observational studies with high risk of bias which have only studied warfarin as the choice of anticoagulation. In this article, we review the pathophysiology, rationale and the current literature investigating the role of anticoagulation in PAH.