Virome Sequencing in Patients With Myocarditis.

BACKGROUND: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. METHODS: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). RESULTS: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. CONCLUSIONS: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.

Discovery of two highly divergent negative-sense RNA viruses associated with the parasitic nematode, Capillaria hepatica, in wild Mus musculus from New York City.

Recent advances in high-throughput sequencing technology have led to a rapid expansion in the number of viral sequences associated with samples from vertebrates, invertebrates and environmental samples. Accurate host identification can be difficult in assays of complex samples that contain more than one potential host. Using unbiased metagenomic sequencing, we investigated wild house mice (Mus musculus) and brown rats (Rattus norvegicus) from New York City to determine the aetiology of liver disease. Light microscopy was used to characterize liver disease, and fluorescent microscopy with in situ hybridization was employed to identify viral cell tropism. Sequences representing two novel negative-sense RNA viruses were identified in homogenates of wild house mouse liver tissue: Amsterdam virus and Fulton virus. In situ hybridization localized viral RNA to Capillaria hepatica, a parasitic nematode that had infected the mouse liver. RNA from either virus was found within nematode adults and unembryonated eggs. Expanded PCR screening identified brown rats as a second rodent host for C. hepatica as well as both nematode-associated viruses. Our findings indicate that the current diversity of nematode-associated viruses may be underappreciated and that anatomical imaging offers an alternative to computational host assignment approaches.

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.

A viral metagenomic survey identifies known and novel mammalian viruses in bats from Saudi Arabia.

Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae.

Viral Diversity of House Mice in New York City.

The microbiome of wild Mus musculus (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manhattan, Queens, Brooklyn, and the Bronx over a period of 1 year. Unbiased high-throughput sequencing of feces revealed 36 viruses from 18 families and 21 genera, including at least 6 novel viruses and 3 novel genera. A representative screen of 15 viruses by PCR confirmed the presence of 13 of these viruses in liver. We identified an uneven distribution of diversity, with several viruses being associated with specific locations. Higher mouse weight was associated with an increase in the number of viruses detected per mouse, after adjusting for site, sex, and length. We found neither genetic footprints to known human viral pathogens nor antibodies to lymphocytic choriomeningitis virus.IMPORTANCE Mice carry a wide range of infectious agents with zoonotic potential. Their proximity to humans in the built environment is therefore a concern for public health. Laboratory mice are also the most common experimental model for investigating the pathobiology of infectious diseases. In this survey of mice trapped in multiple locations within New York City over a period of 1 year, we found a diverse collection of viruses that includes some previously not associated with house mice and others that appear to be novel. Although we found no known human pathogens, our findings provide insights into viral ecology and may yield models that have utility for clinical microbiology.

A case of swallow syncope.

Swallow syncope, also called deglutition syncope, is a rare disorder triggered by oral intake. Patients often have underlying esophageal or structural heart disease. In some cases, the condition can be treated conservatively by eliminating predisposing factors. We describe the case of a 65-year-old woman without cardiovascular or esophageal disease who presented after a motor vehicle accident that was attributed to syncope while driving and eating. In the hospital, the patient suddenly lost consciousness while eating solid food; complete heart block without ventricular escape was documented on continuous electrocardiographic monitoring. A dual-chamber permanent pacemaker was placed and completely resolved the symptoms. This case illustrates a high-risk manifestation of swallow syncope: asystole resulting from an exaggerated vago-glossopharyngeal reflex.

Off-Pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the Veterans Affairs Randomized On/Off Bypass (ROOBY) trial.

BACKGROUND: The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. METHODS AND RESULTS: From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P≤0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). CONCLUSIONS: Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630.

Clinical outcomes with contemporary endovascular therapy of iliac artery occlusive disease.

OBJECTIVES: We sought to evaluate the clinical outcomes of a consecutive series of patients treated for iliac artery occlusive disease (IAOD) using contemporary endovascular technology and techniques. BACKGROUND: As an increasingly complex spectrum of IAOD is treated using endovascular revascularization, there is a need to examine the rates of acute procedural success, complications, and patency to validate the role of an endovascular-first approach to revascularization in contemporary practice. METHODS: All patients with IAOD who were treated using endovascular therapy between September 2005 and September 2010 were identified from a prospectively collected database. Baseline patient characteristics, anatomic details, procedural data, and clinical outcomes were assessed retrospectively. Patency and mortality rates were estimated with the Kaplan-Meier method. RESULTS: A total 59 patients underwent 62 procedures. Trans-Atlantic Inter-Society Consensus (TASC) II types B, C, and D disease accounted for 59%, 7%, and 37% of patients, respectively. The procedure was technically successful in 60 of 62 cases (97%) with no procedure-related mortality. Major complications occurred in five procedures (8%). The mean (±standard deviation) duration of follow-up was 2.3 ± 1.4 years. In patients with a successful revascularization, primary and secondary patency rates were 86% and 94% at 1 year, and 77% and 91% at 2 years, respectively. The TASC II classification of disease did not predict the rate of acute technical success or medium-term patency rates. CONCLUSIONS: The acute and medium-term clinical outcomes of this series of patients with anatomically complex IAOD support the current paradigm of an endovascular-first approach to revascularization.

Safety and efficacy of dual-axis rotational coronary angiography vs. standard coronary angiography.

OBJECTIVE: To determine the safety and efficacy of dual-axis rotational coronary angiography (DARCA) by directly comparing it to standard coronary angiography (SA). BACKGROUND: Standard coronary angiography (SA) requires numerous fixed static images of the coronary tree and has multiple well-documented limitations. Dual-axis rotational coronary angiography (DARCA) is a new rotational acquisition technique that entails simultaneous LAO/RAO and cranial/caudal gantry movement. This technological advancement obtains numerous unique images of the left or right coronary tree with a single coronary injection. We sought to assess the safety and efficacy of DARCA as well as determine DARCA's adequacy for CAD screening and assessment. METHODS: Thirty patients underwent SA following by DARCA. Contrast volume, radiation dose (DAP) and procedural time were recorded for each method to assess safety. For DARCA acquisitions, blood pressure (BP), heart rate (HR), symptoms and any arrhythmias were recorded. All angiograms were reviewed for CAD screening adequacy by two independent invasive cardiologists. RESULTS: Compared to SA, use of DARCA was associated with a 51% reduction in contrast, 35% less radiation exposure, and 18% shorter procedural time. Both independent reviewers noted DARCA to be at least equivalent to SA with respect to the ability to screen for CAD. CONCLUSION: DARCA represents a new angiographic technique which is equivalent in terms of image quality and is associated with less contrast use, radiation exposure, and procedural time than SA.

Retrograde approach to recanalization of complex tibial disease.

A significant proportion (~ 20%) of patients with complex tibial artery occlusions cannot be treated using a conventional antegrade approach. We report our experience using the retrograde approach for the treatment of complex tibial artery occlusive disease using retrograde pedal/tibial access in 13 limbs from 12 patients. Retrograde pedal/tibial access was achieved in all cases (facilitated by surgical cutdown in one case), and procedural success was achieved in 11 of 13 limbs (85%). Based on this experience, a discussion of clinical and technical aspects of the retrograde pedal/tibial approach is provided, and a new classification for tibial artery occlusive disease is proposed.

Clinical feasibility of a fully automated 3D reconstruction of rotational coronary X-ray angiograms.

BACKGROUND: Although fixed view x-ray angiography remains the primary technique for anatomic imaging of coronary artery disease, the known shortcomings of 2D projection imaging may limit accurate 3D vessel and lesion definition and characterization. A recently developed method to create 3D images of the coronary arteries uses x-ray projection images acquired during a 180 degrees C-arm rotation and continuous contrast injection followed by ECG-gated iterative reconstruction. This method shows promise for providing high-quality 3D reconstructions of the coronary arteries with no user interaction but requires clinical evaluation. METHODS AND RESULTS: The reconstruction strategy was evaluated by comparing the reconstructed 3D volumetric images with the 2D angiographic projection images from the same 23 patients to ascertain overall image quality, lesion visibility, and a comparison of 3D quantitative coronary analysis with 2D quantitative coronary analysis. The majority of the resulting 3D volume images were rated as having high image quality (66%) and provided the physician with additional clinical information such as complete visualization of bifurcations and unobtainable views of the coronary tree. True-positive lesion detection rates were high (90 to 100%), whereas false-positive detection rates were low (0 to 8.1%). Finally, 3D quantitative coronary analysis showed significant similarity with 2D quantitative coronary analysis in terms of lumen diameters and provided vessel segment length free from the errors of foreshortening. CONCLUSIONS: Fully automated reconstruction of rotational coronary x-ray angiograms is feasible, produces 3D volumetric images that overcome some of the limitations of standard 2D angiography, and is ready for further implementation and study in the clinical environment.

Enhanced stent visualization: a case series demonstrating practical applications during PCI.

BACKGROUND: Visualization of coronary stents is increasingly challenging due to the reduction in stent strut thickness to improve deliverability. On the other hand stent expansion and precise implantation in the target vessel are important in optimizing short and long-term outcomes of stent-based revascularization. Stentboost Subtract is a novel X-ray technique that improves visualization of deployed stents in the coronary arteries. Using motion compensation and integration of multiple non-contrast projection images from a fixed gantry position, this new technique depicts stent morphology allowing assessment of stent expansion and extent of overlap with adjacent stents. We present a case series in which enhanced stent visualization (ESV) facilitated interventions. METHODS: The clinical and angiographic characteristics of 6 cases utilizing ESV were reviewed. All ESV acquisitions in this case series utilized an 8 in. field of view (FOV), 3 ml/sec. for a total of 6 ml of contrast, and placement of balloon markers in the region of interest. RESULTS: The cases presented significantly facilitated the identification of bifurcation stenting techniques, precise stent positioning, stent underexpansion and assisted with defining stent-vessel wall relationship that was additive to intravascular ultrasound. CONCLUSIONS: ESV is a novel tool used in coronary interventions that facilitates non-invasive assessment of stent positioning, expansion and stent-vessel interactions. This inexpensive ESV technique is complimentary to IVUS and in some cases obviates its need.

Rotational coronary angiography.

The numerous well-documented limitations of standard fixed-acquisition coronary angiography led to the development of rotational angiography. This acquisition method uses automated gantry movements while numerous angiographic projections are obtained, and thus overcomes many of the limitations of standard angiography. This article highlights the techniques, advantages, and disadvantages of each type of rotational angiography currently commercially available. Also included is a discussion of the evolution of rotational angiography, from its initial conception and pilot studies to its latest step forward on the developmental road towards enhanced coronary imaging.

Computer assistance for solving imaging problems.

Medical imaging has moved into an era of digital files and processing of images to yield three-dimensional models and reconstructions. This development has opened up opportunities to apply computer techniques in traditional imaging tasks. Two of the most common imaging tasks are those to correct the two-dimensional projection problems of foreshortening of lesions and of vessel overlap. This article explores the use of computers to assist in these tasks, to create databases for guiding decision making, to provide graphics to assist the physician, and to simulate cardiovascular procedures.

Use of the Boomerang catalyst advantage closure device to facilitate complex multistaged percutaneous revascularization procedures for the treatment of critical limb ischemia.

An increasing spectrum of complex peripheral arterial disease may be successfully treated using percutaneous revascularization techniques. A pair of challenging peripheral revascularization procedures in patients with critical limb ischemia is presented, where an array of interventional tools and techniques were required, and the off-label use of the Boomerang catalyst system closure device was important in managing a variety of complex arterial access issues and ultimately allowing procedural success.