Chronic thromboembolic pulmonary hypertension and the post-pulmonary embolism (PE) syndrome.

Over a third of patients surviving acute pulmonary embolism (PE) will experience long-term cardiopulmonary limitations. Persistent thrombi, impaired gas exchange, and altered hemodynamics account for aspects of the postpulmonary embolism syndrome that spans mild functional limitations to debilitating chronic thromboembolic pulmonary hypertension (CTEPH), the most worrisome long-term consequence. Though pulmonary endarterectomy is potentially curative for the latter, less is understood surrounding chronic thromboembolic disease (CTED) and post-PE dyspnea.

Fetal Supraventricular Tachycardia: What the Adult Cardiologist Needs to Know.

Fetal supraventricular tachycardia management is challenging, with consequences for both the fetus and the mother. If left untreated, fetal hydrops may ensue, at which point delivery and treatment of the arrhythmia is preferred. However, if the fetus is not at term nor near-term, significant doses of antiarrhythmics may be needed to achieve adequate transplacental bioavailability.

Thromboembolic complications of COVID-19.

The symptomology of patients afflicted with novel 2019 coronavirus disease (SARS-CoV-2 or COVID-19) has varied greatly, ranging from the asymptomatic state to debilitating hypoxemic respiratory failure caused by severe atypical viral pneumonia. Patients may also develop a hyper-inflammatory state that can lead to multi-organ failure. It has become increasingly apparent that, as part of the hyper-inflammatory state, COVID-19 infection increases susceptibility to systemic thromboembolic complications that can contribute to rapid clinical deterioration or demise.

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute pulmonary embolism: A multicenter comparison of patient-centered outcomes.

Both catheter-directed thrombolysis (CDT) and ultrasound-assisted thrombolysis (USAT) are novel treatment modalities for patients presenting with acute pulmonary embolism (PE). The objective of this study was to compare clinical and quality-of-life (QOL) outcomes for patients undergoing either treatment modality. We retrospectively studied 70 consecutive patients treated with either CDT or USAT over 3 years at a multicenter health system.

Re-evaluating the Appropriateness of Non-invasive Arterial Vascular Imaging and Diagnostic Modalities.

Imaging modalities to detect and diagnose vascular disease have become increasingly popular in recent years, owing in large part to their availability and accessibility. The American College of Cardiology Foundation published a two-part Appropriate Use Criteria (AUC) guidance document for both peripheral vascular imaging and physiologic testing several years ago. In the years since their publication, a number of important studies have challenged previously held beliefs about appropriateness of vascular diagnostic testing.

Building a Successful Superficial Venous Program.

As the treatment of superficial venous insufficiency transitioned from the hospital to the office setting, a remarkable increase in provider interest developed. However, the novelty of the disease process and procedural opportunities are tempered by the challenges associated with knowledge acquisition, skill development, strategic planning, and program development. Only a unique recipe of clinical growth, technical acumen, management skill, operational efficiency, and financial sense lead to program success.

Building a Critical Limb Ischemia Program.

The need to develop highly qualified, multidisciplinary critical limb ischemia (CLI) programs has gained significant momentum. Due to the systemic nature of the disease, patients with CLI are inherently medically complex and often present with multiple comorbidities. Successful care for these patients depends on community screening, early referral, accurate diagnosis, risk stratification, risk factor modification, invasive and non-invasive treatment strategies, and appropriate surveillance.

The fluoro-less and contrast-less peripheral endovascular intervention: a concept for the future today.

Introduction: Percutaneous endovascular revascularization requires fluoroscopic guidance and radiopaque contrast use. This approach becomes problematic, especially in patients with advanced renal disease or allergies to iodinated contrast medium. The direct (exposure) and indirect (lead garment) burden of radiation affects patients and operators alike.

The S curve: a novel morphological finding in the internal carotid artery in patients with fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease commonly affecting the renal and internal carotid arteries (ICAs). A previously unrecognized finding is a redundancy of the mid-distal ICA in FMD patients causing an 'S'-shaped curve. Carotid artery duplex ultrasounds were reviewed in 116 FMD patients to determine S-curve prevalence.

Oral anticoagulants in the management of venous thromboembolism.

Despite advances in diagnosis, prevention, and management, venous thromboembolism (VTE) remains a common cause of morbidity and mortality. For decades, antithrombotic therapy for prevention and treatment of VTE was limited to parenteral agents related to heparin and oral vitamin K antagonists (VKAs). Both classes of anticoagulants are effective, but have limitations, including considerable variability in dose-response, narrow therapeutic margins between the risks of thrombosis and bleeding, and the need to monitor anticoagulation intensity.

Peripheral artery disease. Part 2: medical and endovascular treatment.

The treatment of peripheral artery disease (PAD) focuses on risk factor modification, cardiovascular event reduction, limb viability, and symptom improvement. Hypertension, hyperlipidemia, and diabetes mellitus should all be controlled to recommended target levels, and smoking cessation is vital. Antiplatelet therapies, such as aspirin or clopidogrel, should be administered in all patients unless contraindicated.

Peripheral artery disease. Part 1: clinical evaluation and noninvasive diagnosis.

Peripheral artery disease (PAD) is a marker of systemic atherosclerosis. Most patients with PAD also have concomitant coronary artery disease (CAD), and a large burden of morbidity and mortality in patients with PAD is related to myocardial infarction, ischemic stroke, and cardiovascular death. PAD patients without clinical evidence of CAD have the same relative risk of death from cardiac or cerebrovascular causes as those diagnosed with prior CAD, consistent with the systemic nature of the disease.

Evaluation of right ventricular function and post-operative findings using cardiac computed tomography in patients with left ventricular assist devices.

Background: Right ventricular (RV) failure is a major contributor to morbidity and mortality after left ventricular assist device (LVAD) implantation. Accurate evaluation of RV function in patients with LVAD remains challenging. We hypothesized that, after LVAD implantation, electrocardiographic-gated cardiac computed tomography (CCT) allows RV evaluation with higher feasibility and reproducibility compared with echocardiography.

Imaging approaches for the study of cell-based cardiac therapies.

Despite promising preclinical data, the treatment of cardiovascular diseases using embryonic, bone-marrow-derived, and skeletal myoblast stem cells has not yet come to fruition within mainstream clinical practice. Major obstacles in cardiac stem cell investigations include the ability to monitor cell engraftment and survival following implantation within the myocardium. Several cellular imaging modalities, including reporter gene and MRI-based tracking approaches, have emerged that provide the means to identify, localize, and monitor stem cells longitudinally in vivo following implantation.

Advanced lipoprotein testing: recommendations based on current evidence.

Low-density lipoprotein cholesterol (LDL-C) level currently is used as the major determinant of lipid- and lipoprotein-associated risk for ischemic cardiovascular disease, and varying levels have become the standard goals of lipid-altering treatment. The predictive value of the LDL-C cholesterol level, however, often is less than that provided by other variables such as non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and the number of LDL particles measured by nuclear magnetic resonance spectroscopy. This article reviews studies that compare these different lipoprotein variables, describes advanced methodologies of lipoprotein testing, and suggests goals of treatment and clinical situations in which these tests might be ordered.

A hybrid IRF9-STAT2 protein recapitulates interferon-stimulated gene expression and antiviral response.

Type I interferon (IFN) signaling induces the heterotrimeric transcription complex, IFN-stimulated gene factor (ISGF) 3, which contains STAT1, STAT2, and the DNA binding subunit, interferon regulatory factor (IRF) 9. Because IRF9 is targeted to the nucleus in the absence of IFN stimulation, the potential of IRF9 protein for gene regulation was examined using a GAL4 DNA binding domain fusion system. GAL4-IRF9 was transcriptionally active in reporter gene assays but not in the absence of cellular STAT1 and STAT2.

Role of metazoan mediator proteins in interferon-responsive transcription.

The interferon (IFN)-induced signal transduction and transcription activation complex, ISGF3, is assembled from three proteins, STAT1, STAT2, and IRF9. Of these components, STAT2 provides a fundamental and essential transcriptional activation function for ISGF3. In the present study, we show that ISGF3-mediated transcription is dependent on STAT2 interactions with DRIP150, a subunit of the multimeric Mediator coactivator complex.

STAT2 acts as a host range determinant for species-specific paramyxovirus interferon antagonism and simian virus 5 replication.

The antiviral state induced by alpha/beta interferon (IFN-alpha/beta) is a powerful selective pressure for virus evolution of evasive strategies. The paramyxoviruses simian virus 5 (SV5) and human parainfluenza virus 2 (HPIV2) overcome IFN-alpha/beta responses through the actions of their V proteins, which induce proteasomal degradation of cellular IFN-alpha/beta-activated signal transducers and activators of transcription STAT1 and STAT2. SV5 infection induces STAT1 degradation and IFN-alpha/beta inhibition efficiently in human cells but not in mouse cells, effectively restricting SV5 host range.

Mechanisms of Type I interferon cell signaling and STAT-mediated transcriptional responses.

The interferons are pleiotropic cytokines that are induced in response to virus infection and act in a paracrine fashion to elicit an antiviral state in nearby cells. Binding of interferons to their cell surface receptors induces a tyrosine kinase signaling cascade that leads to the activation of latent cytoplasmic signal transducer and activator of transcription (STAT) factors. Activated STATs then translocate into the nucleus and are targeted to conserved promoter-enhancer sites to induce the transcription of interferon-responsive genes that encode for proteins with potent antiviral, growth-inhibitory, antitumor, and immunomodulatory properties.

Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction.

The alpha/beta interferon (IFN-alpha/beta)-induced STAT signal transduction pathway leading to activation of the ISGF3 transcription complex and subsequent antiviral responses is the target of viral pathogenesis strategies. Members of the Rubulavirus genus of the Paramyxovirus family of RNA viruses have acquired the ability to specifically target either STAT1 or STAT2 for proteolytic degradation as a countermeasure for evading IFN responses. While type II human parainfluenza virus induces STAT2 degradation, simian virus 5 induces STAT1 degradation.