Cyclophilin D induces necrotic core formation by mediating mitochondria-associated macrophage death in advanced atherosclerotic lesions.

BACKGROUND AND AIMS: In advanced atherosclerotic lesions, macrophage deaths result in necrotic core formation and plaque vulnerability. Cyclophilin D (CypD) is a mitochondria-specific cyclophilin involved in the process of cell death after organ ischemia-reperfusion. However, the role of CypD in atherosclerosis, especially in necrotic core formation, is unknown. Therefore, this experiment aims to clarify the role of CypD in necrotic core formation. METHODS: To clarify the specific role of CypD, encoded by Ppif in mice, apolipoprotein-E/CypD-double knockout (Apoe-/-Ppif-/-) mice were generated. These mice were fed a high-fat diet containing 0.15 % cholesterol for 24 weeks to accelerate atherosclerotic lesion development. RESULTS: Deletion of CypD decreased the necrotic core size, accompanied by a reduction of macrophage apoptosis compared to control Apoe-/- mice. In RAW264.7 cells, siRNA-mediated knockdown of CypD attenuated the release of cytochrome c from the mitochondria to the cytosol induced by endoplasmic reticulum stress inducer thapsigargin. In addition, necroptosis, induced by TNF-α and caspase inhibitor, was attenuated by knockdown of CypD. Ly-6Chigh inflammatory monocytes in peripheral blood leukocytes and mRNA expression of Il1b in the aorta were decreased by deletion of CypD. In contrast, siRNA-mediated knockdown of CypD did not significantly decrease Il1b nor Ccl2 mRNA expression in RAW264.7 cells treated with LPS and IFN-γ, suggesting that inhibition of inflammation in vivo is likely due to decreased cell death in the atherosclerotic lesions rather than a direct action of CypD deletion on the macrophage. CONCLUSIONS: These results indicate that CypD induces macrophage death and mediates necrotic core formation in advanced atherosclerotic lesions. CypD could be a novel therapeutic target for treating atherosclerotic vascular diseases.

Updated pathophysiological overview of functional MR (ventricular and atrial).

Basic mechanism of ventricular functional mitral regurgitation (FMR) is subvalvular tethering. Left ventricular (LV) dilatation, in association with mitral valve (MV) annular dilatation, causes outward displacement of papillary muscles (PMs), which abnormally pulls or tethers MV leaflets, resulting in MV tenting, reduction in leaflets coaptation and MR. Because surgical annuloplasty does shorten distance between anterior and posterior MV annuli to improve coaptation but does not address this subvalvular tethering, ventricular FMR frequently persists or recurs in the chronic stage after surgical annuloplasty. This high incidence of persistent/recurrent MR requires additional procedures to reduce subvalvular tethering. Although patients occasionally show marked improvements after annuloplasty with surgical tethering reduction procedures such as PM approximation, evidence to support benefits of such surgery is limited, requiring further trials. Recently, MV adaptation or MV leaflets tissue growth associated with LV dilatation attracts attention. Patients with larger MV leaflets with significant LV dilatation/dysfunction show less MV tethering and MR compared to those with smaller MV leaflets but with similar LV remodeling, suggesting the protective or beneficial role of MV leaflets tissue growth against LV remodeling. The MV leaflets tissue growth has the potential to lead to novel strategies of treatment for ventricular FMR. It is well known that atrial FMR is frequent in patients with left atrial dilatation, typically in those with isolated atrial fibrillation. The degree of atrial FMR is usually mild, even when it is present, and occasionally moderate, and severe atrial FMR is really rare. It is known that only severe regurgitation causes heart failure in primary MR, resulting in description on indications of surgery or intervention for only severe MR in current guidelines. Therefore, this atrial FMR up to moderate degree did not attract attention for a long time. However, recent studies have shown that patients with only moderate atrial FMR develop severe heart failure, suggesting more aggressive indication of MV surgery or intervention for "moderate" regurgitation in patients with atrial FMR. Therefore, atrial FMR is now recognized highly important. The unveiled malignant nature of atrial FMR arises many questions, including (1) why patients with only moderate atrial FMR develop heart failure? (2) do patients with mild atrial FMR develop heart failure or not?, and many others. Atrial FMR seems even more mysterious after the unveiling of its significance.

Potential Effects of Mild Atrial Secondary Mitral Regurgitation in Patients With Isolated Atrial Fibrillation.

BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.

Unusual atrial pacing induced by type II far-field p-wave sensing in a patient with complete atrioventricular block.

An 88-year-old Japanese woman underwent DDD pacemaker (MicroPort KORA 250 DR, V lead: VEGA R52) implantation for complete atrioventricular block. A 12-lead electrocardiogram for a routine examination showed atrial pacing within the intrinsic P wave, followed by inhibition of ventricular pacing. Pacemaker interrogation revealed no abnormalities in the basic parameters; however, ventricular pacing was inhibited by far-field sensing of intrinsic atrial waves before atrial events; type II far-field P-wave sensing. As a result, unusual atrial pacing occurred due to the pause suppression algorithm, which is the one of the functions that prevent atrial fibrillation development.

Trial sequential analysis of efficacy and safety of direct oral anticoagulants and vitamin K antagonists against left ventricular thrombus.

Meta-analysis may increase the risk of random errors. Trial sequential analysis (TSA) has been developed to adjust for these random errors. We conducted TSA on the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in left ventricular thrombus (LVT) patients in order to estimate how many additional patients should be required to draw definite conclusions. PubMed, Scopus, and Cochrane Library databases were searched for articles directly comparing DOACs and VKAs for LVT in LV thrombus resolution, stroke, any thromboembolism, major bleeding, any bleeding, and all-cause death. TSA was conducted with a cumulative Z-curve, monitoring boundaries, and required sample size. A simulated trial was run and TSA estimated the sample sizes of trials needed to draw definite conclusions. Of 4749 articles, 25 studies were used for the analysis. TSA revealed the current sample size already demonstrated superiority of DOACs in LV thrombus resolution and stroke, and futility in any thromboembolism and all-cause death. Two other outcomes did not achieve the required sample size. The sample size of new trials needed to demonstrate the superiority of DOACs over VKAs was estimated 400 for any bleeding. Corresponding trials needed to demonstrate no significant differences could be estimated for major bleeding and any bleeding (n = 200 and n = 2000, respectively). Current results show that the sample size required to draw definite conclusions was not reached for two outcomes, and there was a risk of random error. Further randomized controlled trials with sample sizes estimated by TSA will work effectively to obtain valid conclusions.

Workplace Measures Against COVID-19 and Mistreatment in the Workplace Among Japanese Employees: A 1-Year Prospective Cohort Study.

OBJECTIVE: The purpose of this study was to identify the COVID-19 infection prevention measures that are at risk of being perceived by employees as mistreatment in the workplace. METHODS: This study included full-time workers who enrolled as subjects in a nationwide prospective cohort study. Baseline surveys performed during the pandemic were used to identify the workplace measures against COVID-19. A tracing survey was conducted 1 year later to assess workplace mistreatment. RESULTS: Of the 18,170 participants, 276 judged that they had experienced mistreatment by the measures. "Enforcing daily temperature measurement" and "stopping business trips" were associated with mistreatment. Meanwhile, "requesting that employees refrain from going to work when ill" and "restricting work-related social gatherings and entertainment" had the potential to reduce workplace mistreatment. CONCLUSIONS: Certain measures against COVID-19 can reduce or increase the burden on employees.

Genetic Testing Enables the Diagnosis of Familial Hypercholesterolemia Underdiagnosed by Clinical Criteria: Analysis of Japanese Early-Onset Coronary Artery Disease Patients.

Definitive diagnosis of familial hypercholesterolemia (FH) is paramount for the risk management of patients and their relatives. The present study aimed to investigate the frequency of gene variants contributing to low-density lipoprotein cholesterol (LDL-C) metabolism and their clinical relevance in patients with early-onset coronary artery disease (EOCAD). Among 63 consecutive patients with EOCAD (men <55 years or women <65 years) who underwent percutaneous coronary intervention (PCI) from 2013 to 2019 at Keio University Hospital, 52 consented to participate in this retrospective study. Targeted sequencing of LDLR, PCSK9, APOB, and LDLRAP1 was performed. Of the 52 patients enrolled (42 men; mean age: 50 ± 6 years), one (LDLR, c.1221_1222delCGinsT) harbored a pathogenic mutation, and one (APOB, c.10591A>G) harbored variants of uncertain significance. Both the patients harboring the variants were male, showing no history of diabetes mellitus or chronic kidney disease, no family history of EOCAD, and no physical findings of FH (i.e., tendon xanthomas or Achilles tendon thickening). Patients harboring the LDLR variant had three-vessel disease, were on a statin prescription at baseline, and had stable LDL-C levels; however, the case showed a poor response to the intensification of medication after PCI. Approximately 3.8% of patients with EOCAD harbored variants of gene related to LDL-C metabolism; there were no notable indicators in the patients' background or clinical course to diagnose FH. Given the difficulty in diagnosing FH based on clinical manifestations and family history, genetic testing could enable the identification of hidden risk factors and provide early warnings to their relatives.

Effects of contrast medium viscosity into flushing port on artefacts during optical coherence tomography imaging.

BACKGROUND: Optical coherence tomography (OCT) is becoming the standard imaging modality for percutaneous coronary intervention (PCI) because of its high resolution. To perform appropriate OCT-guided PCI, it is necessary to avoid artefacts and obtain high-quality images. We investigated the relationship between artefacts and the viscosity of contrast media, which were used to remove air before OCT imaging catheter was inserted into guiding catheter. METHODS: We retrospectively analyzed every pullback of OCT examinations from January 2020 to September 2021. Cases were divided into two groups according to the type of contrast media used for catheter flushing: low-viscosity (Iopamidol-300, Bayer, Nordrhein-Westfalen, Germany) vs. high-viscosity (Iopamidol-370, Bayer). We evaluated the artefacts and quality of each OCT image and performed ex vivo experiments to compare differences in artefact frequencies using the two contrast media. RESULTS: A total of 140 pullbacks in the low-viscosity group and 73 pullbacks in the high-viscosity group were analyzed. The percentage of grade 2 and 3 images (with good quality) in the low-viscosity group was significantly lower (68.1 % vs. 94.5 %, p < 0.001). Rotational artefacts were significantly more common in the low-viscosity group (49.3 % vs. 8.2 %, p < 0.001). In multivariate analysis, using low-viscosity contrast media was a significant factor influencing the appearance of rotational artefacts and affecting image quality (odds ratio, 9.42; 95 % confidence interval, 3.58 to 24.8; p < 0.001). In ex vivo experiments, using low-viscosity contrast media was also a significant predictor of artefact occurrence during OCT (p < 0.01). CONCLUSIONS: The viscosity of the contrast agent used while flushing the OCT imaging catheter contributes to the appearance of OCT artefacts.

Belt-type electrocardiograph for diagnosing palpitation occurring only during high-intensity exercise in athletes.

Belt-type ambulatory electrocardiograph (EV-201) is an arrhythmia diagnostic device that can record an electrocardiogram (ECG) for a maximum of 2 weeks. Here, we report the novel utility of EV-201 in detecting arrhythmias in two professional athletes. Treadmill exercise test and Holter ECG failed to detect arrhythmia because of insufficient exercise, electrocardiogram noise. However, by wearing EV-201 only during a marathon run, supraventricular tachycardia onset and termination were successfully detected. Throughout, both athletes were diagnosed with fast-slow atrioventricular nodal re-entrant tachycardia. Therefore, EV-201 enables long-term belt-type recording, thereby being useful in detecting tachyarrhythmias that occur infrequently and during strenuous exercises. Learning objective: Diagnosis of arrhythmias during high-intensity exercise in athletes by conventional electrocardiography is sometimes difficult due to inducibility and frequency of arrythmias or motion artifacts. The primary finding of this report is that EV-201 is useful in diagnosing such arrhythmias. The secondary finding is that fast-slow atrioventricular nodal re-entrant tachycardia is a common occurrence in arrhythmias among athletes.

Endovascular Treatment of Subclavian Artery Occlusion by Surgical Exposure of the Proximal Brachial Artery at the Side of an Arteriovenous Fistula.

A 76-year-old man undergoing hemodialysis complained of pain and discoloration of his right finger. The hemodialysis arteriovenous fistula was in the right upper extremity. Ultrasonography showed right subclavian artery occlusion. The lesion could not be approached from the lower extremity and olecranon artery. Thus, we performed the procedure after exposing the proximal brachial artery. We were able to recanalize the subclavian artery and restore blood flow to the right upper extremity. When the lesion is on the side of the arteriovenous fistula and approaching from the lower extremity is difficult, exposure of the proximal brachial artery can be considered.

Malnutrition leads to the progression of coronary artery calcification in hemodialysis patients.

BACKGROUND: Malnutrition is considered a risk factor for cardiovascular disease in patients with chronic kidney disease. However, no in vivo studies have reported on using optical coherence tomography to evaluate the effect of nutritional status on coronary atherosclerosis in hemodialysis patients. We aimed to conduct a detailed analysis of the effect of nutritional status on the coronary arteries in hemodialysis patients. METHODS: Among 64 hemodialysis patients who underwent percutaneous coronary interventions, 41 that underwent optical coherence tomography imaging were included in this study. And, among them, 24 patients that could also be evaluated using OCT also at the 6-month follow-up were included in this study. The patients were divided into two groups based on nutritional evaluation using the geriatric nutritional risk index. Culprit and non-culprit lesions were evaluated at baseline and after 6 months. RESULTS: In the culprit lesions at baseline, the length of the lipid plaque was significantly smaller in the malnutrition group. In contrast, the thickness and length of the calcified plaque and the angle of the calcified nodule were significantly larger (each p < 0.01). In the non-culprit lesions, the 6-month change in the angle of the calcified plaque was significantly greater in the malnutrition group (p = 0.02). The significant factors that affected the change in the angle of calcification were "malnutrition at geriatric nutritional risk index" [odds ratio, 8.17; 95% confidence interval, 1.79 to 37.33; p < 0.01] and "serum phosphorus level" (odds ratio, 3.73; 95% confidence interval, 1.42 to 9.81; p < 0.01). CONCLUSIONS: Appropriate management of nutritional status is crucial for suppressing the progression of coronary artery disease in hemodialysis patients.

Estimating right atrial pressure using upright computed tomography in patients with heart failure.

OBJECTIVES: Upright computed tomography (CT) can detect slight changes particularly in the superior vena cava (SVC) volume in healthy volunteers under the influence of gravity. This study aimed to evaluate whether upright CT-based measurements of the SVC area are useful for assessing mean right atrial pressure (mRAP) in patients with heart failure. METHODS: We performed CT in both standing and supine positions to evaluate the SVC (directly below the junction of the bilateral brachiocephalic veins) and inferior vena cava (IVC; at the height of the diaphragm) areas and analyzed their relationship with mRAP, measured by right heart catheterization in 23 patients with heart failure. RESULTS: The median age of enrolled patients was 60 (51-72) years, and 69.6% were male. The median mRAP was 3 (1-7) mmHg. The correlations between the standing position SVC and IVC areas and mRAP were stronger than those in the supine position (SVC, ρ = 0.68, p < 0.001 and ρ = 0.43, p = 0.040; IVC, ρ = 0.57, p = 0.005 and ρ = 0.46, p = 0.026; respectively). Furthermore, the SVC area in the standing position was most accurate in identifying patients with higher mRAP (> 5 mmHg) (SVC standing, area under the receiver operating characteristic curve [AUC] = 0.91, 95% confidence interval [CI], 0.77-1.00; SVC supine, AUC = 0.78, 95% CI, 0.59-0.98; IVC standing, AUC = 0.77, 95% CI, 0.55-0.98; IVC supine, AUC = 0.72, 95% CI, 0.49-0.94). The inter- and intraobserver agreements (evaluated by intraclass correlation coefficients) for all CT measurements were 0.962-0.991. CONCLUSIONS: Upright CT-based measurement of the SVC area can be useful for non-invasive estimation of mRAP under the influence of gravity in patients with heart failure. KEY POINTS: • This study showed that the superior vena cava (SVC) area in the standing position was most accurate in identifying patients with heart failure with higher mean right atrial pressure. • Upright computed tomography-based measurements of the SVC area can be a promising non-invasive method for estimating mean right atrial pressure under the influence of gravity in patients with heart failure. • Clinical management of patients with heart failure based on this non-invasive modality may lead to early assessment of conditional changes and reduced hospitalization for exacerbation of heart failure.

Preoperative decline in skeletal muscle strength of patients with cardiovascular disease affects postoperative pulmonary complication occurrence: a single-center retrospective study.

BACKGROUND: Dynapenia, defined as age-related skeletal muscle strength decline, has been reported as a poor prognostic factor in patients with cardiovascular disease. Decline in skeletal muscle strength (DS), the main symptom of dynapenia, may be an important clinical indicator in patients undergoing cardiac surgery. However, the relationship between DS and postoperative pulmonary complication occurrence is unclear. Herein, we investigated the relationship between preoperative DS and postoperative pulmonary complication occurrence in patients undergoing cardiac surgery. METHODS: We enrolled 125 patients who underwent cardiac surgery. DS was determined by low grip strength and quadriceps isometric strength. The patients were divided into DS and non-DS groups. The relationship between the clinical characteristics and preoperative physical function was compared, and factors associated with postoperative pulmonary complication occurrence were investigated using multivariate logistic regression analysis. RESULTS: There were 42 (33.6%) patients in the DS group and 83 (66.4%) patients in the non-DS group. Compared with the non-DS group, the DS group was significantly older and had a higher body mass index and Japan SCORE (operative mortality rate and major complication rate). The DS group also had a lower estimated glomerular filtration rate and preoperative Barthel index than the non-DS group. Furthermore the DS group had a significantly higher incidence of postoperative pulmonary complications and length of intensive care unit stay, and their postoperative rehabilitation was prolonged compared to the non-DS group. Multivariate logistic regression analysis revealed that DS was a determinant of postoperative pulmonary complications (odds ratio 4.26, 95% confidence interval 1.63‒11.14). CONCLUSIONS: We showed that preoperative DS was an independent risk factor for postoperative pulmonary complications in patients undergoing cardiac surgery. Skeletal muscle strength before cardiac surgery may be an important clinical indicator for predicting the prognosis of patients from post-surgery to discharge and for planning postoperative rehabilitation programs.

The expression of matrix metalloproteinase-12 in the peritoneum of rats with continuous peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is an important alternative treatment for end-stage renal disease. Continuous exposure to non-physiological fluids during PD is associated with pathological responses, such as sustained microinflammation, leading to tissue fibrosis and angiogenesis. However, the effect of PD fluid on submesothelial cells has not yet been investigated in detail. METHODS: We investigated the association between macrophages and the expression of matrix metalloproteinase-12 (MMP-12), an elastin proteinase secreted by macrophages, in the peritoneal tissue of rats undergoing continuous PD. RESULTS: Morphological data revealed that the submesothelial layer of the peritoneum in PD model rats was markedly thickened, with fibrosis and angiogenesis. In the fibrillization area, elastin was disorganized and fragmented, and macrophages accumulated, which tended to have M2 characteristics. The expression of MMP-12 was enhanced by continuous exposure to PD fluid, suggesting that MMP-12 expression may be involved in PD fluid-induced peritoneal damage. CONCLUSIONS: The results of this study may lead to a better understanding of the mechanisms underlying fibrosis in PD.

SGLT2 Inhibitors Improve Cardiac Failure by Reducing Whole-Body Oxygen Demand: A Hypothesis.

Beyond the effects of lowering glycated hemoglobin, recent evidence for sodium-glucose cotransporter 2 (SGLT2) inhibitors has revolutionarily impacted the management of patients with heart failure. However, the mechanism of SGLT2 inhibitors that can explain the following features has not been clarified. First, SGLT2 inhibitors significantly reduced the risk of heart failure in the early stage. Second, SGLT2 inhibitors are effective in treating heart failure without increasing cardiac output. Third, the effects of SGLT2 inhibitors are incremental and complementary to those of conventional therapies for heart failure. Fourth, SGLT2 inhibitors can improve prognosis in patients with heart failure independent of the ejection fraction. Fifth, SGLT2 inhibitors show consistent effects on heart failure, irrespective of etiology. Based on the perspective of Guyton's physiology and clinical experiences that SGLT2 inhibitors reduced oxygen consumption of the whole body, we provided a demand-reducing theory that SGLT2 inhibitors alleviate the imbalance between oxygen demand and supply not by increasing cardiac output but by reducing oxygen consumption of the whole body, which can explain several unique characteristics of SGLT2 inhibitors.

Efficacy of pressure gradient measurement using peripheral fractional flow reserve in common femoral artery: a case report.

Background: The severity of peripheral artery disease (PAD) is usually diagnosed by physiological assessments, such as the ankle brachial index (ABI) or peak systolic velocity (PSV) on ultrasonography. We examined peripheral fractional flow reserve (pFFR: distal mean pressure divided by proximal mean pressure) measured by a pressure wire and pressure gradient to diagnose PAD patients who do not have lowered ABI or high PSV on ultrasonography. Case summary: An 84-year-old woman with intermittent claudication in her left leg had severe calcification in the left common femoral artery (CFA) on angiography. The exercise-stress ABI of pre-endovascular therapy (EVT) was 1.05/0.98. In addition, the PSV of the left CFA on ultrasonography was 230 cm/s. However, the pFFR using papaverine and alprostadil in the left CFA was 0.86, which was a significant score. In addition, the systolic pressure gradient between the distal and proximal regions was >20 mmHg. We performed EVT for the lesion, and the pFFR improved to 0.96. The systolic pressure gradient was only 1 mmHg at the lesion. Discussion: Symptomatic PAD patients whose ABI or PSV on ultrasonography is insufficient for EVT could be diagnosed with ischaemia using a pressure gradient and pFFR.

The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure.

Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.

Prediction of PR interval prolongation after catheter ablation of incisional atrial tachycardia.

A three-dimensional (3D) mapping system is safe and effective for catheter ablation of incisional atrial tachycardia (IAT). Prolongation of the PR interval is occasionally observed after this procedure. Although a first-degree atrioventricular block is typically benign, an excessively prolonged PR interval can indicate a worse prognosis. Currently, a method to predict the PR interval after ablation therapy for IAT is lacking. We report the case of a 70-year-old woman with paroxysmal atrial tachycardia, in which our maneuver using a 3D mapping system and the electrophysiological findings enabled us to preoperatively predict the post-ablation PR interval. We believe that this method is useful for determining treatment strategies for IAT. Learning objective: Three-dimensional (3D) mapping systems can clearly visualize macro-reentrant circuits and enable the creation of precise ablation lines. When creating ablation lines for incisional atrial tachycardia, attention should be paid to the prolongation of the PR interval, because an excessively prolonged PR interval may indicate a worse prognosis. Herein, we have presented a method for predicting the post-ablation PR interval using a 3D mapping system and electrophysiological findings.

Spread of infection and treatment interruption among Japanese workers during the COVID-19 pandemic: A cross-sectional study.

Background: The COVID-19 pandemic has resulted in treatment interruption for chronic diseases. The scale of COVID-19 in Japan has varied greatly in terms of the scale of infection and the speed of spread depending on the region. This study aimed to examine the relationship between local infection level and treatment interruption among Japanese workers. Methods: Cross-sectional internet survey was conducted from December 22 to 26, 2020. Of 33,302 participants, 9,510 (5,392 males and 4,118 females) who responded that they required regular treatment were included in the analysis. The infection level in each participant's prefecture of residence was assessed based on the incidence rate (per 1,000 population) and the number of people infected. Age-sex and multivariate adjusted odds ratios (ORs) of regional infection levels associated with treatment interruption were estimated by multilevel logistic models, nested by prefecture of residence. The multivariate model was adjusted for sex, age, marital status, equivalent household income, educational level, occupation, self-rated health status and anxiety. Results: The ORs of treatment interruption for the lowest and highest levels of infection in the region were 1.32 [95 % confidence interval (CI) were 1.09-1.59] for the overall morbidity rate (per 1,000) and 1.34 (95 % CI 1.10-1.63) for the overall number of people infected. Higher local infection levels were linked to a greater number of workers experiencing treatment interruption. Conclusions: Higher local infection levels were linked to more workers experiencing treatment interruption. Our results suggest that apart from individual characteristics such as socioeconomic and health status, treatment interruption during the pandemic is also subject to contextual effects related to regional infection levels. Preventing community spread of COVID-19 may thus protect individuals from indirect effects of the pandemic, such as treatment interruption.