Risk stratification and prognosis prediction using cardiac biomarkers in COVID-19: a single-centre retrospective cohort study.

OBJECTIVE: There is a need for a robust tool to stratify the patient's risk with COVID-19. We assessed the prognostic values of cardiac biomarkers for COVID-19 patients. METHODS: This is a single-centre retrospective cohort study. Consecutive laboratory-confirmed COVID-19 patients admitted to the Kobe City Medical Center General Hospital from July 2020 to September 2021 were included. We obtained cardiac biomarker values from electronic health records and institutional blood banks. We stratified patients with cardiac biomarkers as high-sensitive troponin I (hsTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase (CK) and CK myocardial band (CK-MB), using the clinically relevant thresholds. Prespecified primary outcome measure was all-cause death. RESULTS: A total of 917 patients were included. hsTnI, NT-proBNP, CK and CK-MB were associated with the significantly higher cumulative 30-day incidence of all-cause death (hsTnI: <5.0 ng/L group; 4.3%, 5.0 ng/L-99%ile upper reference limit (URL) group; 8.8% and ≥99% ile URL group; 25.2%, p<0.001. NT-proBNP: <125 pg/mL group; 5.3%, 125-900 pg/mL group; 10.5% and ≥900 pg/mL group; 31.9%, p<0.001. CK:

Improved seizure liability detection by combining rat hippocampal brain slice electrophysiology with in vivo behavior observation following intracerebroventricular drug administration.

An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good candidates. Firstly, in vitro electrophysiological measurement by a multielectrode array system in rat hippocampal brain slices was employed to confirm an increase in electrically evoked population spike (PS) area, the occurrence of multiple population spikes (MPSs), and thereby the seizure liability of five positive control chemicals: picrotoxin, 4-aminopyridine, pentylenetetrazole, penicillin G, and chlorpromazine. Aspirin, a negative control, did not affect PS area or generate MPSs. Furthermore, baclofen, an anticonvulsant drug, decreased PS area and inhibited the increase in PS area or occurrence of MPSs induced by picrotoxin. A comparative study of seizure liability among carbapenem antibiotics revealed that tienam > carbenin > omegacin and finibax. Despite leading to a strong decrease in PS area, physostigmine, cisplatin, and paroxetine still produced MPSs. Therefore, the increase in PS area or the occurrence of the MPS are considered significant evaluation parameters for seizure liability. In contrast, the in vitro electrophysiological measurement could not detect the seizure liability of diphenhydramine or fluvoxamine. A follow-up study of in vivo mouse behavioral change induced by intracerebroventricular administration of these drugs clearly detected convulsions. The in vitro electrophysiological study using hippocampal brain slices combined with in vivo behavior observation study of drug candidates administered by intracerebroventricular injection can implement to assess the seizure liability of even small amounts, especially in the early stages of drug development.

Evaluation after implementation of chemical bowel preparation for surgical site infections in elective colorectal cancer surgery and role of antimicrobial stewardship pharmacist: Retrospective cohort study.

BACKGROUND: We evaluated the predictive factors for surgical site infections (SSIs) in elective colorectal cancer surgery and the role of antimicrobial stewardship (AS) pharmacists in modifying the clinical pathway. MAIN BODY: Between February 2017 and January 2022, 414 elective colorectal cancer surgeries were performed. The results of multivariate analysis by SSI incidence were adjusted odds ratio (aOR): 0.45; 95% confidence interval (CI): 0.22-0.96 (P = 0.039) for sex (female), aOR: 0.27; 95% CI: 0.13-0.58 (P < 0.001) for laparoscopy, aOR: 0.42; 95% CI: 0.19-0.91 (P = 0.029) for chemical bowel preparation. The median (interquartile range) postoperative length of stay was 12 (10.0-18.5) vs. 10 (9.0-13.0) days before and after the clinical pathway was modified (P < 0.001). CONCLUSION: The role of AS pharmacists was primarily to conduct a literature search to explore whether SSIs could be ameliorated by pharmacotherapy, coordinate the addition of chemical bowel preparation, and epidemiologically confirm their effectiveness.

Association of HFA-PEFF score with clinical outcomes after catheter ablation for atrial fibrillation.

BACKGROUND: The Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing and final aetiology (HFA-PEFF) score has been developed for diagnosing heart failure with preserved ejection fraction (HFpEF), which is frequently associated with atrial fibrillation (AF). We aimed to investigate whether preprocedural HFA-PEFF score could be used to predict clinical outcomes in patients with AF who underwent catheter ablation (CA). METHODS: Overall, 1679 patients with AF who underwent primary CA (71±10 years, 1218 males (72.5%), median follow-up duration 3.3 years) from July 2011 to December 2019 were included in this retrospective study. HFpEF was defined as an HFA-PEFF score ≥5. The primary study outcome was 5-year major adverse cardiovascular and cerebrovascular events (MACCE), which is a composite of all-cause death, hospitalisation for heart failure (HF) and hospitalisation for stroke. RESULTS: The prevalence of HFpEF was 32.3%, but only 7.7% were diagnosed with HF at the time of CHADS2 scoring. Five-year MACCE occurred in 77 patients (4.6%). The cumulative 5-year incidence of MACCE was significantly higher in the HFpEF group than in the non-HFpEF group (11.2% vs 4.8% at 5 years, p<0.001). In the multivariable analysis, HFpEF by the HFA-PEFF score was associated with MACCE (adjusted HR 1.65, 95% CI 1.02 to 2.65, p=0.041). CONCLUSIONS: Early detection of HFpEF using the HFA-PEFF score may have clinical applications in guiding therapeutic decision-making and improving prognosis by preventing HF and stroke in patients with AF undergoing CA.

Characteristics of two different cryoballoon systems for treatment of paroxysmal atrial fibrillation: study protocol for a multicenter randomized controlled trial (CONTRAST-CRYO Trial).

BACKGROUND: Single-shot pulmonary vein isolation (PVI) utilizing cryothermal energy is an effective and safe treatment for atrial fibrillation (AF) patients. A novel cryoballoon system, POLARx™, has been recently introduced. The aim of this study was to compare the efficacy, safety, and biophysical parameters of PVI between the novel cryoballoon system, POLARx™, and the standard cryoballoon system, Arctic Front Advance Pro™ (AFA-Pro), in patients with paroxysmal AF. METHODS: The CONTRAST-CRYO trial is a prospective, multicenter, open-label, randomized controlled study performed at seven large cardiac centers. This study was approved by the central ethics committee or the local ethics committee of each participating hospital and has been registered at UMIN Clinical Trials Registry (UMIN000049948). The trial will assign 200 patients with paroxysmal AF undergoing PVI to POLARx™ and AFA-Pro in a 1:1 randomization. The primary endpoint is the one-shot acute success rate of the right inferior pulmonary vein. Second endpoints include freedom from documented atrial fibrillation, atrial flutter, or atrial tachycardia without antiarrhythmic drugs at 12 months after the procedure, freedom from re-do procedures, the incidence of procedure-related adverse events, freezing duration, and the biophysical parameters during applications for each PV, total procedure and fluoroscopy time, and PVI durability during re-do procedures. CONCLUSION: The CONTRAST-CRYO trial is a prospective, multicenter, randomized study designed to elucidate the difference in the efficacy, safety, and biophysical parameters between POLARx™ and AFA-Pro in paroxysmal AF patients undergoing PVI. The findings from this trial may provide a valuable indication for selecting the optimal cryoballoon system. CLINICAL TRIAL REGISTRATION:  UMIN000049948.

Importance of the relative epicardial connection locations and right-sided pulmonary vein isolation line for successful pulmonary vein isolation.

INTRODUCTION: The presence of an epicardial connection (EC) decreases the success rate of pulmonary vein isolation (PVI); however, the effect of designing isolation lines has not been evaluated. We sought to clarify the effects of designing an anterior line for right-sided PVI considering the presence and location of the EC. METHODS: Seventy-four consecutive patients who underwent initial catheter ablation for atrial fibrillation were retrospectively included in this study. The presence of the EC was determined by the left atrial (LA) activation map during right atrial pacing, and patients were divided into EC-positive (n = 23, 31%) and EC-negative (n = 51, 69%) groups. EC-positive patients were further subdivided based on the EC location: on-the-line group, (EC on the PVI line, n = 11); inside-line group (EC on the pulmonary vein [PV] side, n = 10); and outside-line group (EC on the LA side, n = 2). The PVI parameters were compared among the three groups. RESULTS: The success rates of the first-pass isolation were comparable between the EC-negative and EC-positive groups (70.6% vs. 60.9%, ns), but the success rate was significantly higher in the on-the-line group than in the inside-line group (91% vs. 20%, p = 0.002). First-pass isolation was successful in both patients in the outside-line group. Additional carina ablation was required only in the inside-line group. CONCLUSIONS: The association between the EC site and the right-sided PV anterior isolation line affected the success rate of first-pass isolation. For successful right-sided PVI, it is important to consider the EC site when designing the PVI line.

Long-Term Clinical Outcomes in Patients With Severe Tricuspid Regurgitation.

Background The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR. Methods and Results Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left-sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all-cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow-up period of 26.5 (interquartile range, 6.0-57.9) months. The 5-year event-free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01-1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01-1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002-1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36-0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m2) revealed a graded increase in the risk of adverse events (P<0.001). Conclusions The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.

Impact of coronavirus disease 2019 (COVID-19) pandemic on antimicrobial consumption and antimicrobial resistance at a small, local hospital in Japan.

The coronavirus disease 2019 (COVID-19) pandemic negatively affected antimicrobial stewardship programs at hospitals throughout Japan by diverting resources toward managing the pandemic. However, antimicrobial stewardship needs to continue regardless of hospital size or supervening crises. Herein, we discuss the impact of COVID-19 on antimicrobial stewardship at a small, local hospital in Japan.

Diagnostic Accuracy of the 2016 Guideline-Based Echocardiographic Algorithm to Estimate Invasively-Measured Left Atrial Pressure by Direct Atrial Cannulation.

BACKGROUND: Although estimation of left ventricular filling pressure (LVFP) using an integrated echocardiographic algorithm is recommended, the usefulness of this algorithm has not been fully validated. OBJECTIVES: The purpose of this study was to investigate the reliability of an algorithmic classification system using invasively measured left atrial pressure (LAP) in a large-scale cohort. METHODS: The authors enrolled 1,967 patients (age 68 ± 10 years) whose LAP was directly measured within the left atrium during catheter ablation for atrial fibrillation. Patients were classified into 3 groups based on the echocardiographic algorithm: normal (group N, n = 1,282), undetermined (group U, n = 160), and elevated (group E, n = 346) LAP groups. Invasively measured LAP and echocardiographic parameters estimating LVFP were compared among the groups. RESULTS: The median LAP was 12.6 ± 5.7 mm Hg in the entire cohort. LAP was significantly higher in group E than that in the other groups (groups E vs U vs N, 14.2 ± 6.3 mm Hg vs 13.5 ± 5.9 mm Hg vs 12.0 ± 5.5 mm Hg; P < 0.001). Among group E patients, 43.1% had elevated LAP (≥15 mm Hg), whereas 56.9% had normal LAP (<15 mm Hg). Of the patients in group N, 69.0% had normal LAP, whereas 31% had elevated LAP. Although the correlation between invasively measured LAP and E/e', peak tricuspid regurgitant velocity, and left atrial volume index was modest, the number of abnormal values correlated significantly with elevated LAP (P < 0.001). CONCLUSIONS: The classification using combined echocardiographic parameters in the recommendations may be useful for detecting patients with normal LVFP but may be limited for detecting elevated LVFP.

Effectiveness of a manual dragging laser irradiation technique using the first-generation endoscopic laser balloon ablation system for pulmonary vein isolation.

Background: Although high efficacy of laser balloon (LB) ablation for atrial fibrillation (AF) has been shown, the conventional point-by-point technique requires a long procedure time. We investigated the clinical effectiveness of the manual dragging laser technique. Methods: We enrolled 51 consecutive patients with paroxysmal AF who underwent pulmonary vein isolation (PVI) using first-generation LB (LB1) at our institution. The first 25 patients underwent PVI using a point-by-point laser irradiation maneuver (point-by-point group). The latter 26 patients underwent PVI using a manually dragging laser irradiation maneuver (dragging group). The power and delivery time for the laser energy were selected from a preset protocol with 5.5-12 W and 20-30 s for each application. The dragging irradiation method was performed by manually rotating approximately 1.5°/s during one irradiation application. Results: PVI was successful in all cases. The duration of PVI was shorter (66 ± 20 vs. 116 ± 39 min, p < 0.0001), and the number of laser irradiations for the 4PVs were significantly less in the dragging group. There were four recurrent cases (16%) in the point-by-point group and 1 (4%) in the dragging group. There was no significant difference in the survival rate free from recurrence after the blanking period between the two groups (log-rank p = 0.1570). The complications were similar between the groups (4% vs. 4%, ns). Conclusions: The manual dragging laser irradiation technique using LB1 could shorten the PVI procedure time while preserving clinical effectiveness.

Effects of microsampling on toxicity assessment of hematotoxic compounds in a general toxicity study in rats.

Microsampling (MS) has been increasingly used in toxicity studies reducing animal use for toxicokinetic analysis. However, especially for drugs with hematotoxic properties, the potential effects of MS on hematological parameters and subsequent toxicity assessment should be considered, while such properties are frequently unknown at the discovery stage. Here, we conducted a rat 2-week study of hematotoxic compounds and evaluated the effects of MS on toxicity assessment. Six-week-old female SD rats were orally dosed with vehicle, methylene blue trihydrate (MB: 300 mg/kg/day), or azathioprine (AZP: 12 and 24 mg/kg/day) for 2 weeks. Each treatment group was divided into non-MS and MS subgroups, and in the MS subgroups, 50 µL/time point of blood was collected from the jugular vein at 7 time points each on Days 1 and 13 of dosing. The test items included clinical signs, body weight, urinalysis, hematology, blood chemistry, necropsy, organ weight, and histopathology. In the MB non-MS subgroup, there were low values in red blood cell parameters, high values in reticulocytes and bilirubin, and increased extramedullary hematopoiesis, reflecting hemolytic anemia. In the AZP non-MS subgroup, there were low values of red and white blood cell parameters and decreased cellularity in the bone marrow, reflecting myelosuppression. The effects of MB and AZP were similarly observed in the MS subgroups, and the effects of MS on the toxicological endpoints were generally small. Based on these results, the effects of MS on toxicity assessment were considered to be small in rat toxicity studies even for hematotoxic compounds.

Transvenous pacing approach for atrioventricular block in fontan - Possibility of transvenous approach by electrophysiological assessment.

In extracardiac Fontan, an epicardial pacemaker implantation has many limitations, especially given that it is highly invasive and a high-risk procedure due to repeat thoracotomy. Herein we illustrate a case with the possibility of transvenous pacing in extracardiac Fontan being less invasive and lower risk transvenous dual-chamber pacemaker implantation by electrophysiological assessment. .

Mechanism of improvement in atrial functional mitral regurgitation after catheter ablation for atrial fibrillation: Three-dimensional analysis using multislice computed tomography.

BACKGROUND: Several factors associated with atrial functional mitral regurgitation development have been reported; however, geometric changes in the mitral apparatus after catheter ablation for atrial fibrillation have not been sufficiently investigated. This study aimed to clarify what determines improvements in atrial functional mitral regurgitation after sinus rhythm restoration in patients who underwent catheter ablation for atrial fibrillation by using multislice computed tomography. METHODS: We analysed volumetric multislice computed tomography images of 44 atrial fibrillation patients with significant atrial functional mitral regurgitation (moderate or worse) before and after catheter ablation. We measured the three-dimensional geometry of the mitral apparatus including the mitral annular area and interpapillary muscle distance. We calculated the differences before and after catheter ablation (Δmitral annular area, Δinterpapillary muscle distance) and assessed mitral regurgitation severity based on the mitral regurgitant jet area and its changes before and after catheter ablation (Δjet area) using transthoracic echocardiography. RESULTS: After catheter ablation, the jet area was significantly decreased. The left ventricular ejection fraction was significantly increased and the left ventricular volume had a decreasing trend. The Δjet area was significantly correlated with the Δinterpapillary muscle distance (r = .43; p = .004). The Δinterpapillary muscle distance was the strongest determinant of improvements in atrial functional mitral regurgitation severity (p = .026). CONCLUSIONS: Decreased interpapillary muscle distance was strongly associated with improvements in atrial functional mitral regurgitation. Amelioration of left ventricular dysfunction by sinus rhythm restoration might be related to improvements in atrial functional mitral regurgitation after catheter ablation.

Comparison of Cryoballoon and Contact Force-Sensing Radiofrequency Ablation for Persistent Atrial Fibrillation in Clinical Practice.

BACKGROUND: Outcomes of cryoballoon ablation for persistent atrial fibrillation (AF) are unclear, especially in Japanese patients, so the effectiveness and safety of cryoballoon ablation in clinical practice were retrospectively compared with those of contact force-sensing radiofrequency (CFRF) ablation including the high-power protocol.Methods and Results:Consecutive patients with persistent AF were reviewed, and 253 and 265 patients who underwent cryoballoon and CFRF ablation, respectively, were enrolled. The primary endpoint was atrial arrhythmia recurrence. The secondary endpoints were periprocedural complications and repeat ablation. The rate of additional left atrial (LA) ablation after pulmonary vein isolation (PVI) was similar between groups (68.8% cryoballoon vs. 74.0% CFRF, P=0.19). Freedom from atrial arrhythmia recurrence was comparable between groups over a follow-up of 25.5±12.5 months (72.3% cryoballoon vs. 69.8% CFRF; adjusted hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.59-1.21, P=0.36). Outcomes were similar in the subgroups of PVI alone and PVI plus additional LA ablation. LA posterior wall isolation, absence of defragmentation, and low creatine clearance, but not catheter selection, were associated with the primary endpoint. Periprocedural complications (adjusted HR 0.73, 95% CI 0.34-1.54, P=0.41) and repeat ablation (adjusted HR 1.11, 95% CI 0.71-1.74, P=0.64) were similar for both procedures. CONCLUSIONS: Cryoballoon ablation for persistent AF in Japanese clinical practice had acceptable outcomes comparable to those of advanced CFRF ablation.

Persistence of left atrial abnormalities despite left atrial volume normalization after successful ablation of atrial fibrillation.

BACKGROUND: Left atrial volume index (LAVI) of >34 mL/m2 is the cutoff value for identifying an enlarged left atrium. The definition of left atrial (LA) reverse remodeling after atrial fibrillation (AF) ablation is undetermined. We hypothesized that patients with LA dilatation who achieve normal LA volume (LAVI<34 mL/m2) after AF ablation have better long-term outcomes than those who do not. Furthermore, we investigated whether patients with a normal LA volume can also achieve normal LA function with AF ablation. METHODS: We enrolled 140 AF patients with baseline LAVI of ≥34 mL/m2, without AF recurrence for 1 year after the initial AF ablation. We acquired conventional and speckle-tracking echocardiographic parameters within 24 hour and at 1 year after the procedure. To define the normal range of LA function, age- and sex-matched controls without a history of AF were also enrolled. RESULTS: After restoration of sinus rhythm, LA structural and functional parameters significantly improved, and 75 patients (54%) had normal LA volume. During a median follow-up of 44 (31-61) months, 32 patients (23%) experienced a late recurrence of AF (AF recurrence >1 year). Patients who achieved normal LA volume after AF ablation had fewer late recurrences than those who did not (P < .01). However, LA abnormalities, especially LA dysfunction, persisted in AF patients even when the LA volume was normalized compared with controls. CONCLUSION: Patients who achieved normal LA volume had better long-term outcomes of AF ablation than those who did not; however, LA abnormalities persisted even after successful ablation of AF.

[A Case of Malignant Lymphoma of the Ileum and Uterine Cervix with Perforating Peritonitis of Ileum Tumor Detected during Chemotherapy].

A 77-year-old woman was admitted to our hospital because of right lower abdominal pain. CT revealed tumors in the ileum and uterine cervix. After a gynecological biopsy of the uterine tumor, we diagnosed Stage Ⅳ diffuse large B-cell lymphoma. We treated her with R-THPCOP chemotherapy. On day 8 after the first chemotherapy, she developed perforated peritonitis, and an emergency partial ileum resection was performed. Histopathologically, viable cells were not found in the resected intestine. Chemotherapy was resumed on postoperative day 21, and she achieved a complete response 8 months after the surgery. Gastrointestinal malignant lymphoma is sometimes reported in cases requiring emergency surgery. Therefore, information sharing between hematologist and surgeon is recommended.

Early experiences with three types of balloon-based ablation catheters in patients with paroxysmal atrial fibrillation.

BACKGROUND: Although balloon-based ablation catheters are expected to improve the feasibility and quality of pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), they must be introduced to physicians in the proper setting to ensure their correct usage. OBJECTIVE: To identify the optimal clinical settings for learning the techniques for 3 balloon-based ablation catheters (Cryoballoon, Hotballoon, and Laserballoon). METHODS: We introduced 3 balloon catheters in 50 consecutive patients with paroxysmal AF each during the introduction periods. Clinical parameters were compared among the groups and between these groups and their steady-state controls. RESULTS: The completion rate of PVI by sole balloon procedures was 56% with the Hotballoon catheter, which was lower than those of the Cryoballoon and Laserballoon catheters (each 88%). Radiofrequency touch-up was most frequently required at the bottom aspect of the inferior pulmonary veins (PVs) in the Cryoballoon group and at the anterior aspect of the superior PVs in the Hotballoon and Laserballoon groups. The Laserballoon catheter had the longest average PVI procedural time (89.2 ± 40 vs 58.4 ± 22 minutes for Hotballoon, 65.1 ± 25 minutes for Cryoballoon, P < .001), but the difference was ultimately removed by the learning curve. There was no significant difference in the major complication or recurrence-free survival rates among the catheter types. CONCLUSIONS: All 3 balloon-based catheter types allowed feasibility and quality for PVI, even during the learning period. To introduce these new catheters without complications, an experiences of 20 cases with specific clinical settings should be met for each catheter type.

Alcohol Consumption Reduction and Clinical Outcomes of Catheter Ablation for Atrial Fibrillation.

[Figure: see text].