PSPC1 Binds to HCV IRES and Prevents Ribosomal Protein S5 Binding, Inhibiting Viral RNA Translation.

Hepatitis C virus (HCV) infects the human liver, and its chronic infection is one of the major causes of Hepatocellular carcinoma. Translation of HCV RNA is mediated by an Internal Ribosome Entry Site (IRES) element located in the 5'UTR of viral RNA. Several RNA Binding proteins of the host interact with the HCV IRES and modulate its function. Here, we demonstrate that PSPC1 (Paraspeckle Component 1), an essential paraspeckle component, upon HCV infection is relocalized and interacts with HCV IRES to prevent viral RNA translation. Competition UV-crosslinking experiments showed that PSPC1 interacts explicitly with the SLIV region of the HCV IRES, which is known to play a vital role in ribosomal loading to the HCV IRES via interaction with Ribosomal protein S5 (RPS5). Partial silencing of PSPC1 increased viral RNA translation and, consequently, HCV replication, suggesting a negative regulation by PSPC1. Interestingly, the silencing of PSPC1 protein leads to an increased interaction of RPS5 at the SLIV region, leading to an overall increase in the viral RNA in polysomes. Overall, our results showed how the host counters viral infection by relocalizing nuclear protein to the cytoplasm as a survival strategy.

Society for Cardiovascular Magnetic Resonance 2022 Cases of SCMR case series.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2022 digital collection of cases are presented in this manuscript.

Imaging of Cardiac Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Myocardial fibrosis (MF) is defined as excessive production and deposition of extracellular matrix (ECM) proteins, resulting in pathologic myocardial remodeling. Three types of MF have been identified: replacement fibrosis from tissue necrosis, reactive fibrosis from myocardial stress, and infiltrative interstitial fibrosis from progressive deposition of non-degradable material such as amyloid. While echocardiography, nuclear medicine, and CT play important roles in the assessment of MF, MRI is pivotal in the evaluation of MF, using the late gadolinium enhancement (LGE) technique as a primary endpoint. The LGE technique focuses on the pattern and distribution of gadolinium accumulation in the myocardium and assists the diagnosis and establishment of the etiology of both ischemic and non-ischemic cardiomyopathy. LGE MRI aids prognostication and risk stratification. In addition, LGE MRI is used to guide management of patients being considered for ablation for arrhythmias. Parametric mapping techniques, including T1 mapping and extracellular volume measurement, allow detection and quantification of diffuse fibrosis, which may not be detected by LGE MRI. These techniques also allow monitoring of disease progression and therapy response. This review provides an update on imaging of MF, including prognostication and risk stratification tools, electrophysiologic considerations, and disease monitoring.

A Comprehensive Guide to Sodium Glucose Cotransport Inhibitors.

Sodium-glucose cotransport 2 inhibitors (SGLT2i) are a class of drugs initially approved by the Food and Drug Association (FDA) as antihyperglycemic agents for patients with type 2 diabetes mellitus (DM). However, lately, these agents (Canagliflozin, Empagliflozin, Ertugliflozin, Sotagliflozin, and Dapagliflozin) have become better known for their cardiovascular (CV) and reno-protective effects. In this comprehensive review and analysis, we display the advancement of Sodium Glucose Cotransport Inhibitors have shown in cardiology, specifically heart failure in a concise, yet thorough manner.

Echocardiographic Evaluation of Pulmonary Embolism: A Review.

Pulmonary embolism (PE) is the third most common cause of cardiovascular death in the United States. Appropriate risk stratification is an important component of the initial evaluation for acute management of these patients. Echocardiography plays a crucial role in the risk stratification of patients with PE. In this literature review, we describe the current strategies in risk stratification of patients with PE using echocardiography and the role of echocardiography in the diagnosis of PE.

Association of exosomal miR-96-5p and miR-146a-5p with the disease severity in dengue virus infection.

Exosomes are small extracellular vesicles secreted by cells and have a major role in cell-to-cell signaling. As dengue infection progresses from a mild to a severe form of infection, the exosome's microRNA (miRNA) composition might change, which may contribute to pathogenesis. In this study, a comprehensive analysis of serum exosomal miRNAs was performed and their involvement in dengue virus-induced disease progression in an Indian cohort was assessed. Small RNA-seq showed 50 differentially expressed exosomal miRNAs that were significantly dysregulated during dengue infection. After extensive validation, miR-96-5p was found to be significantly upregulated, whereas miR-146a-5p was significantly downregulated with the progression of disease to severe form. Interestingly, a strong positive correlation was found between the expression levels of miR-96-5p and miR-146a-5p and the platelet levels of the patients. Further, study of miR-146a-5p showed that it regulates the expression of the proteins which are involved in the immune responses. These results suggest that miR-96-5p and miR-146a-5p could be used as diagnostic and prognostic markers for dengue disease progression, in addition to the already available biochemical and pathological parameters.

Usefulness of non-gated chest computed tomography scans in the diagnosis of acute myocardial infarction.

Contrast-enhanced computed tomography (CT) is frequently utilized to evaluate patients who present to the emergency department with chest pain for a pulmonary or aortic disease but is not routinely used to evaluate for acute myocardial infarction (AMI). Decreased myocardial enhancement in non-electrocardiogram-gated contrast-enhanced CT has been proposed to indicate AMI. These two cases highlight the importance of carefully evaluating the myocardium for perfusion defects on non-gated chest CT scans in patients suspected of having AMI.

Utilization of Non-Gated Chest Computed Tomography Scans in Predicting Acute Coronary Occlusion in Out-of-Hospital Cardiac Arrest.

Coronary artery disease is thought to be responsible for up to 60%-80% of out-of-hospital cardiac arrests. The utility of Computed Tomography (CT) chest when it comes to identifying acute coronary occlusion in patients following an arrest has not been studied. We evaluated whether myocardial perfusion on a contrast-enhanced chest CT performed for a non-cardiac cause can predict culprit coronary occlusion as the cause of cardiac arrest and if the absence of a perfusion defect can exclude an ischemic etiology. A retrospective cohort of 53 consecutive patients presenting with VT or VF arrest and successful resuscitation who had contrast chest CT before angiography were identified. CT scans were reviewed for myocardial perfusion defects by a cardiologist and radiologist blinded to angiogram findings. CT results were then compared with angiograms. On coronary angiography, 22 (42%) of the patients presenting with out-of-hospital arrest had critical stenosis. Sensitivity and specificity of perfusion defect on CT in identifying critical stenosis on catheterization was 0.45, 95% CI [0.24, 0.68] and 0.77, 95% CI [59%, 90%], respectively. The positive likelihood ratio was 2.01 (0.91, 4.46) and the negative likelihood ratio was 0.70 (0.46, 1.08). The diagnostic accuracy was 64.2%. Our study did not show much utility for the use of myocardial perfusion defect on an incidental pre-angiography contrast chest CT to predict acute thrombotic occlusion in out-of-hospital cardiac arrest patients. However, this shouldn't discourage further studies evaluating the utility of contrast-enhanced CT images in predicting acute coronary occlusion.

Transfemoral aortic valve replacement in a nonagenarian with aortic stenosis and cardiac amyloidosis: case report.

BACKGROUND: Cardiac amyloidosis (CA) is diagnosed with increasing frequency in the elderly population with severe aortic stenosis (AS), especially with the low-flow, low- gradient phenotype. Prognosis is poor with no treatment. CASE PRESENTATION: The patient is a 94-year-old active male who presented with a stroke that fully resolved. He was found to have low-flow, low-gradient severe AS, along with concomitant CA. Gradients across the aortic valve worsened with the dobutamine challenge test. He underwent successful transfemoral aortic valve replacement (TAVR) and did well postoperatively, where he remained in the hospital for only one day. Treatment of his CA with Tafamidis was recommended; however, the patient declined due to its cost and personal preference. CONCLUSION: To our knowledge, we report on one of the oldest patients to undergo TAVR for low-flow, low-gradient AS with concurrent CA (AS-CA). It might be prudent to screen elderly patients with AS for CA, as prognosis is worse with medical management alone. TAVR has overall improved survival in patients with AS-CA and is considered the procedure of choice, as these patients are typically older and at higher risk for surgical intervention.

Determination of sources of error and improvement in accuracy of left ventricular mass measurement by echocardiography.

Abnormal Left ventricular mass (LVM) prognosticates adverse cardiovascular events. Conventionally, LVM measured by echo assumes a prolate ellipsoid (PE) shape; however, it poorly correlates with reference standard of cardiac magnetic resonance imaging (CMR) derived LVM. PE model assumes LVL = 2 × LVID. We developed a new echo LVM formula based on LV length and tested for accuracy against CMR. A retrospective study of consecutive patients with an echocardiogram and CMR within 3 months. Derivation (n = 170) and validation cohorts (n = 54) were used to test the new formula. Following analysis of correlation of interventricular septum (IVS), LV internal dimension (LVID), posterior wall (PW) and LVL between echo and CMR, a novel paraboloid-shape linear regression (PLR) model was derived. LVM by both models were compared to CMR. Poor correlation observed between actual and assumed LVL (0.52 with CMR; 0.44 with echo). Strong correlation was noted between echo and CMR measured LVL, LVID, IVS (r > 0.80) and a moderate correlation with PW (r = 0.62). Strong correlation of LVL was harnessed to develop PLR model, which significantly decreased paired error in derivation cohort (from 64 ± 42 to 22 ± 21 gm) and validation cohort (from 63 ± 46 to 25 ± 18 gm). Furthermore, it demonstrates significant reduction in absolute, relative errors and variability along with superior correlation in both cohorts. Between echo and CMR, LVL demonstrates one of the best correlation among LV dimensions. The assumption, LVL = 2 × LVID appears inaccurate. PLR model incorporates LVL and significantly improves accuracy, reduces variability of LVM.

Society for Cardiovascular Magnetic Resonance 2019 Case of the Week series.

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

A systematic review of pharmacologic therapies for the cardiomyopathy of Duchenne muscular dystrophy.

OBJECTIVE: To perform a systematic review of studies evaluating pharmacologic therapies for the cardiomyopathy of Duchenne muscular dystrophy (DMD). METHODS: PubMed, Google Scholar, and Embase were searched through October 8, 2020. Articles were selected using pre-determined criteria; 26 underwent detailed review by two co-authors. Study quality was assessed with the Newcastle-Ottawa scoring system (NOS); GRADE assessment evaluated their overall clinical importance. RESULTS: There were few randomized controlled trials. Two of four trials of angiotensin converting enzyme inhibitors (ACEI) or ACEI plus beta-blockers (BB) found improved LV function. Two of two randomized trials of aldosterone antagonists (AA), when added to ACEI and BB therapy, demonstrated less decline of LV circumferential strain over 1 year of treatment. Observational studies of ACEI and BB had differing patient ages, symptomatology, cohort size, study duration and baseline heart function. LV function, assessed via unblinded imaging, was the most frequent outcome measure. LV dysfunction improved in some trials but was unconfirmed in others. Class IV heart failure patients had transient improvement of symptoms and LVEF. Most NOS scores reflected a low level of study quality. The Grade certainty rating, used for the summation of studies, was between "low" and "moderate." CONCLUSION: Randomized trial evidence was inconsistent that either ACEI or BB or their combination improve LV function and/or alter progressive LV dysfunction. When ACEI and BB therapy are initiated for symptomatic Class IV heart failure, symptoms and LVEF improve transiently. AAs retard the rate of decline of LV function when initiated in younger DMD patients.

Trends, management and outcomes of acute myocardial infarction in chronic liver disease.

AIMS: There are limited data on the management and outcomes of chronic liver disease (CLD) patients presenting with acute myocardial infarction (AMI), particularly according to the subtype of CLD. METHODS: Using the Nationwide Inpatient Sample (2004-2015), we examined outcomes of AMI patients stratified by severity and sub-types of CLD. Multivariable logistic regression was performed to assess the adjusted odds ratios (aOR) of receipt of invasive management and adverse outcomes in CLD groups compared with no-CLD. RESULTS: Of 7 024 723 AMI admissions, 54 283 (0.8%) had a CLD diagnosis. CLD patients were less likely to undergo coronary angiography (CA) and percutaneous coronary intervention (PCI) (aOR 0.62, 95%CI 0.60-0.63 and 0.59, 95%CI 0.58-0.60, respectively), and had increased odds of adverse outcomes including major adverse cardiovascular and cerebrovascular events (1.19, 95%CI 1.15-1.23), mortality (1.30, 95%CI 1.25-1.34) and major bleeding (1.74, 95%CI 1.67-1.81). In comparison to the non-severe CLD sub-groups, patients with all forms of severe CLD had the lower utilization of CA and PCI (P < .05). Among severe CLD patients, those with alcohol-related liver disease (ALD) had the lowest utilization of CA and PCI; patients with ALD and other CLD (OCLD) had more adverse outcomes than the viral hepatitis sub-group (P < .05). CONCLUSIONS: CLD patients presenting with AMI are less likely to receive invasive management and are associated with worse clinical outcomes. Further differences are observed depending on the type as well as severity of CLD, with the worst management and clinical outcomes observed in those with severe ALD and OCLD.

Role of Cardiovascular Magnetic Resonance in Ischemic Cardiomyopathy.

Ischemic heart disease is the most common cause of cardiovascular morbidity and mortality. Cardiac magnetic resonance (CMR) improves on other noninvasive modalities in detection, assessment, and prognostication of ischemic heart disease. The incorporation of CMR in clinical trials allows for smaller patient samples without the sacrifice of power needed to demonstrate clinical efficacy. CMR can accurately quantify infarct acuity, size, and complications; guide therapy; and prognosticate recovery. Timing of revascularization remains the holy grail of ischemic heart disease, and viability assessment using CMR may be the missing link needed to help reduce morbidity and mortality associated with the disease.

Procedures and devices to treat resistant hypertension in chronic kidney disease.

Treatment of resistant hypertension is a challenge, especially in patients who have chronic kidney disease. The choice of medications may be limited in this group, making the possibility of device-based therapies attractive. We explore 4 devices and procedures available to treat this vexing issue.

Sodium Glucose Co-transporter 2 Inhibitors and Heart Failure.

Sodium-glucose co-transporter 2 (SGLT2) receptors are primarily located in the proximal convoluted tubule of the nephron. These receptors are responsible for almost 90% to 95% of tubular reabsorption of the glucose in the nephron. In patients with diabetes mellitus, due to upregulation of SGLT2 receptors, glucose reabsorption is further increased. The Food and Drug Administration approved SGLT2 inhibitors, such as canagliflozin, empagliflozin, dapagliflozin, and ertugliflozin, for the treatment of type 2 diabetes. In addition to their positive effect on blood glucose, additional cardioprotective and renoprotective functions have been demonstrated in major trials such as EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI-58, and CREDENCE. Unlike other antihyperglycemic drugs, reduction in hospitalization for heart failure (HF) was also seen as a class effect with this group, mechanisms of which are probably multifactorial. Subgroup analysis from these major trials indicated a reduction in progression of nephropathy and HF readmission with SGLT2 inhibitors. Although this unique property of canagliflozin was further analyzed in the CREDENCE trial, similar trials for empagliflozin (EMPERIAL-Reduced and EMPERIAL-Preserved) and dapagliflozin (DAPA-HF) are currently underway. Recently released phase III results from DAPA-HF trial indicate that dapagliflozin shows significant reduction in death due to cardiovascular causes and hospitalization in HF compared with the placebo, in both diabetics and nondiabetics. In this review article, the authors attempt to explore the possible underlying molecular mechanisms and data from existing trials pertaining to the HF related outcomes associated with SGLT2 inhibitors.

SGLT-2 Inhibitors and Peripheral Artery Disease: A Statistical Hoax or Reality?

Inhibitors of sodium-glucose cotransporters type-2 are the most recent addition to the armamentarium of oral antidiabetic agents. This class of drugs has shown promising results in glycemic control and most importantly to reduce cardiovascular disease (CVD) mortality risk. Despite the encouraging data, there is concern regarding their potential for causing or worsening peripheral artery disease (PAD), which may increase the risk of lower extremity amputations. Following the publication of results of CANVAS and CANVAS-R trials, which revealed that leg and mid-foot amputations occurred about twice as often in patients treated with canagliflozin compared to placebo, the Food and Drug Administration (FDA) in the United States issued a black box warning of leg and foot amputations associated with canagliflozin use. In this article, our main aim is to review the available evidence in preclinical and clinical studies regarding SGLT-2 inhibitors and PAD events, the possible mechanisms related to increased risk of amputation, to evaluate whether it is a class effect or individual drug effect, and most importantly, implications for their continued use as antidiabetic agents. It also raises the issue of including PAD events among the end-points when assessing future antihyperglycemic agents. Thus, we also tried to analyze whether outcomes of SGLT2 inhibitors trials mostly focused on stroke, myocardial infarction, heart failure, and peripheral vascular disease-related outcomes remained underrated.

Ranolazine: Multifaceted Role beyond Coronary Artery Disease, a Recent Perspective.

Ranolazine is a piperazine derivative approved as an antianginal. Primarily used as a second-line antianginal in stable coronary artery disease. Ranolazine blocks the late Na + current and prevents the rise of cytosolic calcium. It decreases myocardial wall tension and improves coronary blood flow. Ranolazine is effective in atrial fibrillation (AF) as an adjunct to electrical or pharmacological cardioversion. It can be used in combination with amiodarone or dronedarone. It has also been used in AF arising after coronary artery bypass grafting surgery. Role of ranolazine is also being evaluated in pulmonary arterial hypertension, diastolic dysfunction, and chemotherapy-induced cardiotoxicity. Ranolazine has some anti-glycemic effect and has shown a reduction of hemoglobin A1c in multiple trials. The antianginal effect of ranolazine has also been seen to be more in patients with diabetes compared to those without diabetes. Ranolazine is being evaluated in patients with the peripheral arterial disease with intermittent claudication and hypertrophic cardiomyopathy. Pilot studies have shown that ranolazine may be beneficial in neurological conditions with myotonia. The evidence-base on the use of ranolazine in various conditions is rapidly increasing with results of further trials eagerly awaited. Accumulating evidence may see ranolazine in routine clinical use for many conditions beyond its traditional role as an antianginal.