Comparative Review of the State of the Art in Research on the Porcine Epidemic Diarrhea Virus and SARS-CoV-2, Scope of Knowledge between Coronaviruses.

This review presents comparative information corresponding to the progress in knowledge of some aspects of infection by the porcine epidemic diarrhea virus (PEDV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronaviruses. PEDV is an alphacoronavirus of great economic importance due to the million-dollar losses it generates in the pig industry. PEDV has many similarities to the SARS-CoV-2 betacoronavirus that causes COVID-19 disease. This review presents possible scenarios for SARS-CoV-2 based on the collected literature on PEDV and the tools or strategies currently developed for SARS-CoV-2 that would be useful in PEDV research. The speed of the study of SARS-CoV-2 and the generation of strategies to control the pandemic was possible due to the knowledge derived from infections caused by other human coronaviruses such as severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). Therefore, from the information obtained from several coronaviruses, the current and future behavior of SARS-CoV-2 could be inferred and, with the large amount of information on the virus that causes COVID-19, the study of PEDV could be improved and probably that of new emerging and re-emerging coronaviruses.

Insomnia and Early Incident Atrial Fibrillation: A 16-Year Cohort Study of Younger Men and Women Veterans.

Background There is growing consideration of sleep disturbances and disorders in early cardiovascular risk, including atrial fibrillation (AF). Obstructive sleep apnea confers risk for AF but is highly comorbid with insomnia, another common sleep disorder. We sought to first determine the association of insomnia and early incident AF risk, and second, to determine if AF onset is earlier among those with insomnia. Methods and Results This retrospective analysis used electronic health records from a cohort study of US veterans who were discharged from military service since October 1, 2001 (ie, post-9/11) and received Veterans Health Administration care, 2001 to 2017. Time-varying, multivariate Cox proportional hazard models were used to examine the independent contribution of insomnia diagnosis to AF incidence while serially adjusting for demographics, lifestyle factors, clinical comorbidities including obstructive sleep apnea and psychiatric disorders, and health care utilization. Overall, 1 063 723 post-9/11 veterans (Mean age=28.2 years, 14% women) were followed for 10 years on average. There were 4168 cases of AF (0.42/1000 person-years). Insomnia was associated with a 32% greater adjusted risk of AF (95% CI, 1.21-1.43), and veterans with insomnia showed AF onset up to 2 years earlier. Insomnia-AF associations were similar after accounting for health care utilization (adjusted hazard ratio [aHR], 1.27 [95% CI, 1.17-1.39]), excluding veterans with obstructive sleep apnea (aHR, 1.38 [95% CI, 1.24-1.53]), and among those with a sleep study (aHR, 1.26 [95% CI, 1.07-1.50]). Conclusions In younger adults, insomnia was independently associated with incident AF. Additional studies should determine if this association differs by sex and if behavioral or pharmacological treatment for insomnia attenuates AF risk.

Variation in hospital use of cardiac resynchronization therapy-defibrillator among eligible patients and association with clinical outcomes.

BACKGROUND: Despite strong guideline recommendations for cardiac resynchronization therapy-defibrillator (CRT-D) in select patients, this therapy is underutilized with substantial variation among hospitals, and the association of this variation with outcomes is unknown. OBJECTIVE: The purpose of this study was to assess whether facility variation in CRT-D utilization is associated with differences in hospital-level outcomes. METHODS: We linked Medicare claims data with the National Cardiovascular Data Registry's ICD Registry from 2010 to 2015. We calculated the intraclass correlation coefficient to quantify the degree of variation in patient-level CRT use that can be explained by interfacility variation on a hospital level. To quantify the degree of hospital variation in patient-level outcomes (all-cause mortality, readmissions, and cardiac readmissions) that can be attributed to variations in CRT-D use, we utilized multilevel modeling. RESULTS: The study included 30,134 patients across 1377 hospitals. The median rate of CRT-D implantation in those meeting guideline indications was 89%, but there was a wide variation across hospitals. After adjustment, most of the variation (74%) in hospital rates of CRT-D utilization was attributable to the hospital in which the patient was treated. Differences in hospital CRT-D utilization was associated with 8.76%, 5.26%, and 4.71% of differences in hospital mortality, readmissions, and cardiac readmission rates, respectively (P < .001 for all outcomes). CONCLUSION: There is a wide variation in the use of CRT-D across hospitals that was not explained by case mix. Hospital-level variation in CRT-D utilization was associated with clinically significant differences in outcomes. A measure of CRT-D utilization in eligible patients may serve as a useful metric for quality improvement efforts.

Contemporary approach to catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy.

Nonischemic cardiomyopathy (NICM) comprises a heterogenous group of disorders with myocardial dysfunction unrelated to significant coronary disease. As the use of implantable defibrillators has increased in this patient population, catheter ablation is being utilized more frequently to treat NICM patients with ventricular tachycardia (VT). Progress has been made in identifying multiple subtypes of NICM with variable scar patterns. The distribution of scar is often mid-myocardial and subepicardial, and identifying and ablating this substrate can be challenging. Here, we will review the current understanding of NICM subtypes and the outcomes of VT ablation in this population. We will discuss the use of cardiac imaging, electrocardiography, and electroanatomic mapping to define the VT substrate and the ablation techniques required to successfully prevent VT recurrence.

Predicted 3D model of the M protein of Porcine Epidemic Diarrhea Virus and analysis of its immunogenic potential.

The membrane protein M of the Porcine Epidemic Diarrhea Virus (PEDV) is the most abundant component of the viral envelope. The M protein plays a central role in the morphogenesis and assembly of the virus through protein interactions of the M-M, M-Spike (S) and M-nucleocapsid (N) type. The M protein is known to induce protective antibodies in pigs and to participate in the antagonistic response of the cellular antiviral system coordinated by the type I and type III interferon pathways. The 3D structure of the PEDV M protein is still unknown. The present work exposes a predicted 3D model of the M protein generated using the Robetta protocol. The M protein model is organized into a transmembrane and a globular region. The obtained 3D model of the PEDV M protein was compared with 3D models of the SARS-CoV-2 M protein created using neural networks and with initial machine learning-based models created using trRosetta. The 3D model of the present study predicted four linear B-cell epitopes (RSVNASSGTG and KHGDYSAVSNPSALT peptides are noteworthy), six discontinuous B-cell epitopes, forty weak binding and fourteen strong binding T-cell epitopes in the CV777 M protein. A high degree of conservation of the epitopes predicted in the PEDV M protein was observed among different PEDV strains isolated in different countries. The data suggest that the M protein could be a potential candidate for the development of new treatments or strategies that activate protective cellular mechanisms against viral diseases.

The Impact of the COVID-19 Pandemic on Cardiac Electrophysiology Training: A Survey Study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant decrease in volume of electrophysiology (EP) procedures. There has been concern that trainees may not achieve the procedural numbers required to graduate as independent electrophysiologists within the usual timeline. We sought to determine the impact of the COVID-19 pandemic on the percentage of clinical cardiac EP (CCEP) fellows in jeopardy of not meeting procedural volume requirements and overall sentiments regarding preparedness of fellows for independent practice. METHODS: We surveyed CCEP fellows and program directors about baseline procedural volumes, curriculum changes due to the pandemic, and attitudes about preparedness for board examinations and independent practice. RESULTS: Ninety-nine fellows and 27 program directors responded to the survey. Ninety-eight percent of responding fellows reported a decrease in procedural volume as a result of the pandemic. Program directors reported an overall decrease in annual number of ablations and device procedures performed by each fellow during the 2019-2020 academic year compared to the preceding year. Despite this, a minority of fellows and program directors reported concerns about meeting Accreditation Council for Graduate Medical Education procedural requirements for devices (9% and 4%, respectively) and ablation (19% and 9%) or preparedness for independent practice after a 2-year fellowship. CONCLUSIONS: The COVID-19 pandemic has resulted in a decrease in procedural volume for CCEP trainees, but the majority of fellows and program directors do not anticipate major barriers to timely graduation. This may change with COVID-19 resurgence and further interruptions in training.

Comparison of Mortality and Readmission in Non-Ischemic Versus Ischemic Cardiomyopathy After Implantable Cardioverter-Defibrillator Implantation.

Data is lacking on the contemporary risk of death and readmission following implantable cardioverter-defibrillator (ICD) implantation in patients with non-ischemic cardiomyopathies (NICM) compared with ischemic cardiomyopathies (ICM) in a large nationally representative cohort. We performed a retrospective cohort study using the National Cardiovascular Data Registry ICD Registry linked with Medicare claims from April 1, 2010 to December 31, 2013. We established a cohort of NICM and ICM patients with a left ventricular ejection fraction ≤35% who received a de novo, primary prevention ICD. We compared mortality and readmission using Kaplan-Meier curves and Cox proportional hazard regressions models. We also evaluated temporal trends in mortality. In 31,044 NICM and 68,458 ICM patients with a median follow up of 2.4 years, 1-year mortality was significantly higher in ICM patients (12.3%) compared with NICM (7.9%, p < 0.001). The higher mortality in ICM patients remained significant after adjustment for covariates (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.36 to 1.45), and was consistent in subgroup analyses. These findings were consistent across the duration of the study. ICM patients were also significantly more likely to be readmitted for all causes (adjusted HR 1.15, CI 1.12 to 1.18) and for heart failure (adjusted HR 1.25, CI 1.21 to 1.31). In conclusion, the risks of mortality and hospital readmission after primary prevention ICD implantation were significantly higher in patients with ICM compared with NICM which was consistent across all patient subgroups tested and over the duration of the study.

Association of Physician Specialty With Long-Term Implantable Cardioverter-Defibrillator Complication and Reoperations Rates.

Background Patients undergoing implantable cardioverter-defibrillator (ICD) implantations have high rates of long-term device-related complications and reoperations. Whether physician specialty training is associated with differences in long-term outcomes following ICD implantation is unclear. Methods and Results We linked data from the National Cardiovascular Data Registry ICD Registry with Medicare fee-for-service claims to identify physicians who performed ≥10 index ICDs from 2006 to 2009. We used data from the American Board of Medical Specialties to group the specialty of the implanting physician into mutually exclusive categories: electrophysiologists, interventional cardiologists, general cardiologists, thoracic surgeons, and other specialties. Primary outcomes were long-term device-related complications requiring reoperations or hospitalizations and reoperations for reasons other than complications. We compared the cumulative incidence rates and case-mix adjusted rates of long-term outcomes of index ICD implantations across physician specialties. Our analysis had a median follow-up of 47 months and included 107 966 index ICD implantations. Electrophysiologists had the lowest rates of incident long-term device-related complications (14.1%; interventional cardiologists, 15.3%; general cardiologists, 15.4%; thoracic surgeons, 16.4%; other specialists, 15.2%; P<0.001) and reoperations for reasons other than complications (electrophysiologists, 16.7%; interventional cardiologists, 17.0%; general cardiologists, 18.0%; thoracic surgeons, 18.4%; other specialists, 18.0%; P<0.001). Compared with patients whose ICDs were implanted by electrophysiologists, patients with implantations performed by nonelectrophysiologists were at higher risk of having long-term device-related complications (relative risk for interventional cardiologists: 1.16 [95% CI, 1.08-1.25]; general cardiologists: 1.13 [1.08-1.18]; thoracic surgeons: 1.20 [1.06-1.37]; all P<0.001, but not other specialists: 1.08 [0.99-1.17]; P=0.07). Compared to patients with implantations performed by electrophysiologists, patients with implantations performed by general cardiologists and thoracic surgeons were at higher risk of reoperation for noncomplication causes (relative risk for general cardiologists: 1.10 [1.05-1.15]; thoracic surgeons: 1.16 [1.00-1.33]; both P<0.05). Conclusions Patients with ICD implantations performed by electrophysiologists had the lowest risks of having long-term device-related complications and reoperations for noncomplication causes. Consideration of physician specialty before ICD implantation may represent an opportunity to minimize long-term adverse outcomes.

Downstream overdrive pacing and intracardiac concealed fusion to guide rapid identification of atrial tachycardia after atrial fibrillation ablation.

Aims: Atrial tachycardia (AT) related to atrial fibrillation (AF) ablation frequently poses a diagnostic challenge. Downstream overdrive pacing (DOP) can be used to rapidly detect reentry and assess proximity of a pacing site to an AT circuit or focus. We hypothesized that systematic DOP using multielectrode catheters would facilitate AT mapping. Methods and results: DOP identified constant fusion when the post-pacing interval (PPI)-tachycardia cycle length (TCL) <40 ms and stimulus to adjacent upstream atrial electrogram interval >75% of TCL. Mapping was performed as follows: (i) CS DOP, (ii) DOP at left atrial (LA) roof, (iii) DOP at selected LA sites based on prior DOP attempts, and (iv) mapping and ablation at regions of fractionated electrograms in region of AT. Activation mapping was performed at operator discretion. AT diagnosis was confirmed by successful ablation or additional mapping when ablation was unsuccessful. Fifty consecutive patients with sustained AT underwent mapping of 68 ATs, of whom 42 (62%) were macroreentrant, 19 were locally reentrant (28%), and 7 (10%) were focal. AT was correctly identified with a median of three DOP attempts. All macroreentrant ATs were identified with ≤6 DOP attempts. One AT (1.6%) was terminated by DOP, and three ATs (4.8%) required activation mapping. Intracardiac concealed fusion was seen in 26 ATs (38%), each of which was successfully ablated. Conclusion: Reentry could be demonstrated in a substantial majority of AF ablation-related AT. A stepwise diagnostic approach using DOP and recognition of intracardiac concealed fusion can be used to rapidly identify and ablate reentrant AT.

Remote monitoring of implantable cardiac devices: current state and future directions.

PURPOSE OF REVIEW: Recent evidence has demonstrated substantial benefits associated with remote monitoring of cardiac implantable electronic devices (CIEDs), and treatment guidelines have endorsed the use of remote monitoring. Familiarity with the features of remote monitoring systems and the data supporting its use are vital for physicians' care for patients with CEIDs. RECENT FINDINGS: Remote monitoring remains underutilized, but its use is expanding including in new practice settings including emergency departments. Patient experience and outcomes are positive, with earlier detection of clinical events such as atrial fibrillation, reductions in inappropriate implantable cardioverter-defibrillator (ICD) shocks and potentially a decrease in mortality with frequent remote monitoring utilizaiton. Rates of hospitalization are reduced among remote monitoring users, and the replacement of outpatient follow-up visits with remote monitoring transmissions has been shown to be well tolerated. In addition, health resource utilization is lower and remote monitoring has been associated with considerable cost savings. A dose relationship exists between use of remote monitoring and patient outcomes, and those with early and high transmission rates have superior outcomes. SUMMARY: Remote monitoring provides clinicians with the ability to provide comprehensive follow-up care for patients with CIEDs. Patient outcomes are improved, and resource utilization is decreased with appropriate use of remote monitoring. Future efforts must focus on improving the utilization and efficiency of remote monitoring.

Determinants of Heparin Dosing and Complications in Patients Undergoing Left Atrial Ablation on Uninterrupted Rivaroxaban.

BACKGROUND: Patients on rivaroxaban have variable international normalized ratios (INRs) but it is uncertain if INR impacts procedural heparin requirement during left atrial ablation. We sought to examine the determinants of heparin dosing in this patient population. METHODS: We reviewed consecutive patients who received rivaroxaban within 24 hours of left atrial ablation and compared them to patients on uninterrupted warfarin. The determinants of heparin requirement were evaluated using regression analysis. We then tested a weight-based heparin dose prospectively in rivaroxaban patients. RESULTS: There were 258 patients on rivaroxaban and 213 on warfarin. The mean INR was 1.4 in the rivaroxaban group and 2.3 in the warfarin group (P < 0.01). To achieve an activated clotting time (ACT) >350 seconds, rivaroxaban patients required significantly more heparin (166.9 vs. 78.3 units/kg, P < 0.001). In the rivaroxaban group, body weight was the strongest predictor of heparin dose (r = 0.52), while INR was weakly correlated (r = -0.21). In the prospective group, 25 patients were given an initial heparin dose of 120 units/kg with 22/25 (88%) achieving an ACT > 300 seconds. There were seven and three cases of pericardial effusion in rivaroxaban and warfarin patients, respectively (P = 0.41). The average volume drained in the rivaroxaban group was elevated (988.6 vs. 275.0 mL, P = 0.21). CONCLUSIONS: Body weight is the strongest predictor of procedural heparin requirement during left atrial ablation in patients on uninterrupted rivaroxaban, even in those with an elevated INR. A heparin dose of 120 units/kg achieves an ACT > 300 seconds in the majority of patients. In cases of pericardial effusion, bleeding may be prolonged.

Impact of general anesthesia on initiation and stability of VT during catheter ablation.

BACKGROUND: Radiofrequency ablation of ventricular tachycardia (VT) may be performed with general anesthesia (GA) or conscious sedation; however, comparative data are limited. OBJECTIVE: The purpose of the study was to assess the effects of GA on VT inducibility and stability. METHODS: A retrospective comparison of 226 patients undergoing radiofrequency ablation for scar-related VT under GA or intravenous conscious sedation was performed. Data were then prospectively collected in 73 patients undergoing noninvasive programmed stimulation (NIPS) while awake, followed by GA and invasive programmed stimulation for VT induction. RESULTS: In the retrospective study, groups did not differ in VT inducibility, complications, or abolition of clinical VT. Intravenous hemodynamic support was used more often in the GA group. In the prospective group, 12 patients (16%) were noninducible with NIPS. Of the 61 patients with inducible VT with NIPS, 5 (8%) were noninducible with GA, 25 (41%) were inducible with more aggressive simulation, and 31 (51%) were inducible with the same or less aggressive stimulation. Of the 56 patients who were inducible with NIPS and under GA, 28 (50%) had the same induced VTs and 28 (50%) had different induced VTs. In 23 of 56 patients, the clinical VT morphology was known. The clinical VT was reproduced with NIPS in 17 of 23 patients (74%) and under GA in 13 of 23 patients (59%). Under GA, nonclinical VTs were more often induced in patients with a lower ejection fraction and nonischemic cardiomyopathy. CONCLUSION: GA does not prevent inducible VT in the majority of patients. GA is associated with an increased use of hemodynamic support, but this did not adversely affect VT stability or procedure outcomes.

Better outcome of ablation for sustained outflow-tract ventricular tachycardia when tachycardia is inducible.

AIMS: In patients presenting with spontaneous sustained ventricular tachycardia (VT) from the outflow-tract region without overt structural heart disease ablation may target premature ventricular contractions (PVCs) when VT is not inducible. We aimed to determine whether inducibility of VT affects ablation outcome. METHODS AND RESULTS: Data from 54 patients (31 men; age, 52 ± 13 years) without overt structural heart disease who underwent catheter ablation for symptomatic sustained VT originating from the right- or left-ventricular outflow region, including the great vessels. A single morphology of sustained VT was inducible in 18 (33%, SM group) patients, and 11 (20%) had multiple VT morphologies (MM group). VT was not inducible in 25 (46%) patients (VTni group). After ablation, VT was inducible in none of the SM group and in two (17%) patients in the MM group. In the VTni group, ablation targeted PVCs and 12 (48%) patients had some remaining PVCs after ablation. During follow-up (21 ± 19 months), VT recurred in 46% of VTni group, 40% of MM inducible group, and 6% of the SM inducible group (P = 0.004). Analysis of PVC morphology in the VTi group further supported the limitations of targeting PVCs in this population. CONCLUSION: Absence of inducible VT and multiple VT morphologies are not uncommon in patients with documented sustained outflow-tract VT without overt structural heart disease. Inducible VT is associated with better outcomes, suggesting that attempts to induce VT to guide ablation are important in this population.