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Arterial thromboembolism is a life-threatening condition in COVID-19 patients; however, the mechanism of hypercoagulopathy remains unknown. A 62-year-old man with a history of obesity was diagnosed with COVID-19 pneumonia. After hospitalisation, unfractionated heparin was administered because of increased D-dimer levels; nevertheless, an arterial embolism in the left lower limb developed on the following day. Enhanced computed tomography revealed an occluded left iliac artery and intra-aortic thrombus at the juxtarenal level. Urgent thrombectomy was performed. On post-operative day 6, coumadin was initiated to treat the remaining thrombus. The patient was discharged without any complications. The removed thrombus pathologically presented platelet aggregation and degenerated neutrophils that were in various time axes; some neutrophils had clear margins of nuclear membrane, whereas others had pyknotic and fragment nuclei. We believe that the platelet formation and the neutrophils in several time axes could be key factors in promoting thrombus formation in COVID-19 patients.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Superficial angiomyxoma is a rare, benign, multilobulated cutaneous tumor composed of stellate and spindle cells, a prominent myxoid matrix, and numerous blood vessels. Superficial angiomyxoma may be indistinguishable from cutaneous lesions of the Carney complex, although superficial angiomyxoma can occur independently of the complex. In this article, we present the case of a 39-year-old Japanese woman with a 40 × 30 mm, focally ulcerated, polypoid superficial angiomyxoma on the left nipple without any evidence of Carney complex. The development of superficial angiomyxoma on the nipples in a patient without the Carney complex is extremely rare. Indeed, only 3 cases of superficial angiomyxoma arising on the nipple have been reported to date, and this is the first such report in Japan. In such cases, the majority of superficial angiomyxoma of the nipples develop in premenopausal women. The possibility of superficial angiomyxoma should be considered for all polypoid nipple lesion, particularly in premenopausal women, and complete excision with follow-up observation should be performed.

A well-established preclinical model of pancreatic cancer needs to be established to facilitate research on new therapeutic targets. Recently established animal models of pancreatic cancer, including patient-derived tumor models and organoid models, are used for pre-clinical drug testing and biomarker discovery. These models have useful characteristics over conventional xenograft mouse models based on cell lines in preclinical studies, but still cannot accurately predict the clinical outcomes of new treatments and have not yet been broadly implemented in research. We employed pancreatic cancer organoid culture methods using the pancreatic cancer cell line S2-013, and performed pathological and immunohistochemical analyses to characterize tumor xenografts obtained from a mouse model implanted with S2-013 cell line-derived organoids. Serum levels of the pancreatic cancer tumor marker CA19-9 were measured by ELISA. We generated human pancreatic cancer organoids using a co-culture of S2-013 cells, human endothelial cells derived from human umbilical vein endothelial cells, and human mesenchymal stem cells, and established a mouse model with subcutaneously transplanted human pancreatic cancer organoids (S2-013-organoid model). Although blood clotting crater-like formation developed in the middle of subcutaneous xenografts in the S2-013-conventional model, created by subcutaneously injecting S2-013 cells into the right flank of nude mice, the size of xenografts in the S2-013-organoid model gradually increased without crater-like formation. Importantly, tumor xenografts obtained from the S2-013-organoid model exhibited a clinical human pancreatic cancer tissue-like cellular morphology, tissue architecture, and polarity, and actively formed cancer stroma containing mature blood vessels with the high expression of the vascular tight junction marker CD31. In subcutaneous xenografts of S2-013-conventional mice, no blood vessel density or widely expanding areas of necrotic regions were present. Consequently, serum levels of CA19-9 in the S2-013-organoid model correlated with tumor volumes. In addition, epithelial–mesenchymal transition, the conversion of epithelial cells to the mesenchymal phenotype, was observed in tumor xenografts of the S2-013-organoid model. The S2-013-organoid model provides tumor xenografts consisting of clinical human pancreatic cancer-like tissue formation with the effective development of vascularized stroma, and may be valuable for facilitating studies on pre-clinical drug testing and biomarker discovery.

We previously showed that hindlimb ischemia-reperfusion (IR) enhanced glucose uptake in the liver through the activation of the parasympathetic nervous system. Although we suggested that the key glucose transporter (GLUT) in this hepatic glucose uptake was GLUT4 by western blotting, the molecular weight of GLUT4 was nearly the same as that of GLUT2, which is predominantly expressed in the liver. We primarily conducted a histological evaluation to determine whether IR specifically accelerates the overexpression of GLUT4, rather than GLUT2, in the hepatocytes in vitro and in vivo.A total of 54 male C57BL/6J mice were used and subjected to 3 min hindlimb ischemia repeated three times with 3 min interval. Focusing on the area connecting portal and central veins, the GLUT4 and GLUT2 expression in the hepatocytes were examined by real-time PCR and immunohistochemically. Moreover, the alteration of GLUT4 and GLUT2 expression by acetylcholine in the primary hepatocytes were examined by immunofluorescence.IR significantly upregulated the GLUT4, rather than GLUT2, expression in both mRNA and protein in the liver. Histological examination revealed marked glycogen storage in zone1, the periportal area, coincident with the enhanced GLUT4 immunoreactivity, in the IR-treated liver. Incubation of primary hepatocytes with acetylcholine induced the appearance of GLUT4 on the membrane peripheries.The overexpression of GLUT4 on the membrane peripheries contributed to increasing glucose uptake found in IR-treated livers. This acceleration of glucose uptake via GLUT4 may induce marked glycogen storage in zone1 through energy production linked with increased glucose preference.

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Profunda femoris artery aneurysm (PFAA) is rare and has a high incidence of rupture. Herein, we report the case of an 80-year-old man who developed sarcopenia after gastric surgery. The patient presented to our hospital with a reddish thigh and was diagnosed with PFAA rupture. We performed aneurysmectomy and graft interposition in emergency. Postoperative enhanced computed tomography revealed an interposed graft, and the patient was discharged on postoperative Day 7. We considered that the PFAA patients with sarcopenia has a high risk of rupture because the muscles surrounding the profunda femoris artery became weak, and should be followed-up closely.

Limb ischemia caused by tumor embolus is rare. In this study, we report the case of a 77-year-old woman who suffered from acute ischemic limb. Computed tomography showed a tumor in the right bronchus invading the left atrium. The tumor fragments scattered resulting in the occlusion of the right iliac artery. The excluded embolus was revealed as a squamous cell carcinoma. Regarding the popliteal venous thrombus, Trousseau's syndrome was complicated. The patient was discharged without any complications. We believe that advanced lung cancer is a differential diagnosis of acute ischemic limbs and that successful limb rescue contributed to a patient's quality of life.

A 39-year-old man with severe mitral regurgitation was referred to our institution for surgical evaluation. During preoperative workup, a coronary–pulmonary artery fistula was incidentally found by computed tomography. After multidisciplinary cardiac team discussion, the decision was made to proceed with coronary–pulmonary artery fistula ligation and mitral valve repair through a mini-thoracotomy approach. Cardiopulmonary bypass was initiated with femoral vessels. A mini-thoracotomy was made in the fourth intercostal space. First, mitral valve repair with posterior leaflet folding and ring annuloplasty was done. The coronary–pulmonary artery fistula was running on the roof of the left atrium and was ligated with metal clips under thoracoscopic vision. Postoperative computed tomography showed no residual fistula.

Background The pathologic assessments of tumor response after neoadjuvant chemoradiotherapy (NACRT) are critical to improving the prognostic stratification for patients with pancreatic ductal adenocarcinoma (PDAC). Here we clarified the utility of our new grading system based on the area of residual tumor (ART) as compared to existing systems, such as the College of American Pathologists (CAP) and MD Anderson (MDA) score. Methods: Eight reviewers individually evaluated the tumor regression grade of 30 patients with PDAC based on three types of grading systems. The interobserver concordance and clinicopathological characteristics were compared between the three systems. Results: The interobserver concordance (kappa value) of the ART, CAP, and MDA score were 0.61, 0.48, and 0.53, respectively. Discrepant cases, which were 27% of the cases, exhibited smaller tumor and tumor bed sizes than concordant cases. The reduction in tumor size evaluated by microscopy showed a correlation with the rate of change in carcinoembryonic antigen (CEA) level, CA19-9 level, and tumor size on computed tomography (CT). The ART score was correlated with the tumor size on CT before and after NACRT and disease-free survival. The CAP and MDA scores were not associated with prognosis. Conclusion: The ART grading system may be the most practical system to assess the tumor response in post-NACRT resections of PDAC.

Ventricular septal rupture (VSR) is a serious and fatal mechanical complication after acute myocardial infarction. Emergent or urgent, surgical/transcatheter intervention is necessary to treat VSR, though the outcome is not favorable. We performed temporary pulmonary artery banding (PAB) in an 85-year-old man who presented with chest pain to adjust the shunt flow through the VSR, which prevented further pulmonary edema and delayed the timing of surgical repair. There has been no report showing successful PAB performed for VSR after myocardial infarction.

Aims Hindlimb ischemia-reperfusion (IR) was previously demonstrated by our group to decrease blood sugar levels by suppressing hepatic gluconeogenesis and enhancing glucose uptake using activation of the parasympathetic nervous system. While IR attenuated hyperglycemia in diabetic mice, it was unclear whether IR regulated energy metabolism in the liver. We investigated the mechanisms by which IR regulates energy metabolism in the liver from type1 diabetic mice. Main methods Streptozotocin-induced diabetic male C57BL/6J mice were used to determine the effect of IR on the factors involved in energy metabolism in the liver (i.e., activation levels of AMP-activated protein kinase, aconitase and pyruvate dehydrogenase; adenosine triphosphate and fumarate concentrations; sirtuin (Sirt) 1 expression). These various signaling pathways and key enzyme activities were examined using western blot analysis and a biochemical technique including a colorimetric assay. Key findings Under feeding conditions (free access to normal murine chow and water), blood glucose levels and serum ketone body levels were significantly suppressed by IR, whereas phospho-AMP-activated protein kinase and its activity, pyruvate dehydrogenase, aconitase activity, and Sirt 1expression were upregulated. In contrast, peroxisome proliferator-activated receptor γ coactivator-1, which accelerated fatty acid use, was suppressed by IR. Significance These results indicated that in the IR-treated diabetic liver, energy production was promoted through acceleration of the tricarboxylic acid cycle linked with increased glucose preference rather than fatty acid under feeding conditions. Therefore, IR may be beneficial against diabetic hyperglycemia, but also ketoacidosis.

Background: The aim of this study is to evaluate severe mitral regurgitation caused by so called atrial leaflet “pseudoprolapse” and verify the effect of simple annular stabilization. Methods: One-hundred-twenty-two patients underwent surgery for severe mitral regurgitation at our institute between January 2015 to July 2018. Of those, 32 cases diagnosed as anterior leaflet prolapse that underwent mitral repair were analyzed. Ten cases with pseudoprolapse, which is defined as anterior leaflet prolapse without dropping into the left atrium beyond the annular line causing eccentric regurgitation flow directed to the posterior atrium, were classified as the Pseudoprolapse Group. The other 22 cases had obvious anterior leaflet prolapse dropping into the left atrium; these cases were classified as the True Prolapse Group. We compared clinical findings between the 2 groups and reviewed pseudoprolapse cases. Results: Patients in the Pseudoprolapse Group had lower ejection fraction and lower regurgitation volume than those in the True Prolapse Group. A2 lesion as main inflow of regurgitation was more included in the Pseudoprolapse Group. All but one patient in the Pseudoprolapse Group received only simple annuloplasty, and all patients in the True Prolapse Group received leaflet repair and annuloplasty. In both groups, mid-term regurgitation grade and the reoperation rate were satisfactory. In the Pseudoprolapse Group, 6 cases were clarified as atrial functional mitral regurgitation, and 4 cases were considered to have focal posterior leaflet tethering. Conclusions: Pseudoprolapse cases could be characterized by low ejection fraction, low regurgitation volume, and A2 prolapse. For most cases with pseudoprolapse, simple annuloplasty may be enough, however further study is needed.

Aims Our previous study revealed that cyclic hindlimb ischaemia–reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Methods Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. Results IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. Conclusions IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism.

Background We have previously reported the usefulness of our newly developed visual aortic stenosis (AS) score in screening for AS using pocket-sized echocardiography. The objective of this study was to investigate whether the visual AS score and/or conventional aortic valve calcification score derived from pocket-sized echocardiography can be used to predict AS-related events. Methods One hundred and nine patients with systolic ejection murmur (SEM) or known AS (64 males, age 75 ± 9 years) were enrolled and a visual AS score and an aortic valve calcification score were assessed using pocket-sized echocardiography. The primary endpoint was defined as AS-related events, including cardiac death and aortic valve replacement, during the follow-up period. Results In a multivariate Cox proportional hazards analysis, AS-related events were independently predicted by an aortic valve calcification score ≥3 (HR, 3.5; 95% CI, 1.1–11; p = 0.033) and a visual AS score ≥3 (HR, 15; 95% CI, 1.8–125; p = 0.013). During 18 ± 9 months of follow-up, the event-free survival rate was 98% in patients with both a visual AS score

A rare case of adult PHACE syndrome with a distal aortic arch aneurysm was treated surgically. The patient had several anomalies including uneven cerebral blood flow, a small left common carotid artery and a narrowed transverse aorta. Under deep hypothermic circulatory arrest, aortic replacement with reconstruction of the left subclavian artery was performed uneventfully. Cystic degeneration of the tunica media was observed in the aneurysm wall.

The first case of late thoracic wall bleeding after minimally invasive mitral valve repair treated by endovascular therapy is reported. A 55-year-old woman underwent mitral valve repair and tricuspid annuloplasty through a mini-thoracotomy approach. Her postoperative course was uneventful until she had anemia one week after the surgery. Contrast-enhanced computed tomography showed right hemothorax due to bleeding from a branch of the right lateral thoracic artery. Endovascular coil embolization and gelatin sponge injection were performed. The patient was discharged without any complications on postoperative day 20.

Pulmonary artery sarcoma is a rare and highly malignant neoplasm. Early diagnosis and a multidisciplinary approach including surgical treatment and optimal medical therapy could prolong survival. Since the clinical symptoms and imaging findings of pulmonary artery sarcoma mimic pulmonary embolism, definitive diagnosis and surgical intervention are often delayed. In this report, a case of pulmonary artery sarcoma that was initially misdiagnosed as pulmonary embolism is presented.

Brachiocephalic artery dissection complicated by acute type A aortic dissection occasionally causes cerebral malperfusion. Although immediate central aortic repair has been the standard treatment for aortic dissection, dissection in supra-aortic vessels frequently remains after the surgery. The residual brachiocephalic artery dissection is reported to be associated with late neurological events. Therefore, additional intervention for brachiocephalic artery dissection during central aortic repair should be considered in selected cases. In this report, we describe two cases requiring open brachiocephalic artery stenting simultaneous with central aortic repair. There were no neurological or stent induced complications at latest follow-up.

The purpose of the present study is to evaluate the vital prognoses of elderly people in their mid-eighties living in a group home (GH) compared to age- and sex-matched outpatient clinic (OPC) in an observational study conducted over 6 years. We investigated the association between mortality and general, cardiac, and nutritional parameters, including eicosapentaenoic acid (EPA) in 54 GH residents (83 ± 8 years old) and 57 OPC attendees (83 ± 5 years old). Kaplan–Meier curves and Cox proportional hazard ratio analyses were used to assess the association between EPA drug administration and mortality in the GH residents and OPC attendees, respectively. The 54 GH residents had higher mortality and poorer nutritional states, as indicated by lower EPA/arachidonic acid values (median 0.20 vs 0.55, p

AIM In the present study, we analyzed the severity of white matter hyperintensities detected on magnetic resonance imaging of the brain in older Japanese adults who were aged in their mid 80s, and examined its relationships with the clinical parameters. METHODS To identify factors related to the severity of white matter hyperintensities in 33 older adult attendees of our outpatient clinic and 17 older adults living in a group home, we carried out logistic regression analyses and/or correlation analyses. RESULTS Cognitive function and activities of daily living were significantly correlated with the severity of white matter hyperintensities. Multivariate analysis identified activities of daily living, but not cognitive function, as being independently associated with the severity of white matter hyperintensities. Several hemodynamic and cardiac parameters, including diastolic blood pressure, hemoglobin, serum level of N-terminal pro-brain natriuretic peptide, cardiothoracic ratio on the chest X-ray, severity of supraventricular arrhythmias on a Holter electrocardiogram and serum levels of docosahexaenoic acid, were significantly correlated with the severity of white matter hyperintensities. In contrast, the serum cholesterol, glycosylated hemoglobin value and systolic blood pressure were not correlated with the severity of white matter hyperintensities. CONCLUSIONS The severity of white matter hyperintensities detected on magnetic resonance imaging of the brain in older Japanese patients aged in their mid 80s was significantly correlated with activities of daily living, hemodynamic and cardiac parameters, and the serum level of docosahexaenoic acid.

Aim As altered blood flow in the cerebral perforating arteries (PA) might be related to development of cerebral white matter hyperintensities, we examined whether the hemodynamic relationship of the PA and middle cerebral artery (MCA) is altered in rat models of diabetes, compared with normal rats and a rat model of sinoatrial denervation (blood pressure fluctuation model). Methods We used microangiography with monochromatic synchrotron radiation to measure the diameters of the PA and MCA at 4.5 μm resolution in five groups of rats: (i) Long-Evans Tokushima Otsuka (LETO); (ii) Otsuka Long-Evans Tokushima Fatty (a model of type 2 diabetes with obesity); (iii) LETO with sinoaortic denervation (LETO + SAD); (iv) F344; and (v) F344 + streptozotocin (a model of type 1 diabetes). Results Compared with LETO, Otsuka Long-Evans Tokushima Fatty rats showed a significant reduction in the diameter of both PA and MCA, though the PA/MCA diameter ratio was unchanged. In contrast, compared with LETO, LETO + SAD rats showed an increased MCA diameter, and the PA/MCA diameter ratio was decreased. Compared with F344 rats, the MCA diameter was increased in F344 + streptozotocin rats, and the PA/MCA diameter ratio was decreased. Scatter diagrams showed that the diameters of the PA and MCA were essentially independent of each other in the two types of diabetic models. Conclusion PA were consistently visualized at high resolution by means of microangiography using synchrotron radiation. The present results show that rat diabetic models exhibit changes in PA diameter and PA/MCA diameter ratio, which might be related to the development of diabetes-associated cerebral white matter hyperintensities. Geriatr Gerontol Int 2015; 15 (Suppl. 1): 74–80.

The purpose of this study is to support zoo visitors’ scientific observations through the picture-story show. The evaluation methods included interviews to assess whether zoo visitors acquire as viewpoints for observing animals through a picture-story show, video research to assess whether zoo visitors observe animals’ behavioral and morphological characteristics. The results of this study indicate that thirty percent of all families acquired the behavioral and morphological characteristics of animals as viewpoints by watching a picture-story show. The results suggest that it is possible to offer zoo visitors viewpoints for observing animals scientifically by performing picture-story shows.

Conventional angiography is insufficient for evaluating the therapeutic effect of cardiac regeneration therapy. A microangiographic X-ray system using a cerium anode was developed. Cerium has a characteristic X-ray with a peak at 34.6 keV, which allows visualization of tiny amounts of iodine. The performance of the cerium anode X-ray system was evaluated in two excised normal canine hearts and in excised ischemic canine hearts treated with c-kit-positive cardiac stem cells (5 canines) or without cells (5 control canines). In the normal canines, branches penetrating from the left anterior descending artery into the myocardium were visualized, down to third-order branches. In just the treated hearts treated with stem cells, small vessels characterized by irregular vessel walls were observed. The cerium anode X-ray system allowed visualization of microvessels in excised ischemic canine hearts, and may evaluate the effect of cardiac stem cell therapy.

Background The mechanism of persistent atrial fibrillation (AF) is multifactorial, and arrhythmogenic foci (AMF) might be involved in the occurrence of persistent AF. In this study, we examined the electrophysiological features of AMF during and immediately after ablation, and evaluated the relationship between the presence and number of residual AMF on the risk of AF recurrence after a vigorous sinus rhythm restoration ablation in patients with long-standing persistent AF. Methods The study consisted of 117 consecutive patients with persistent AF who underwent catheter ablation (CA). We performed direct cardioversion to restore sinus rhythm before the pulmonary vein (PV) isolation and at the end of the CA. Then we evaluated the features of the AMF inducible with isoproterenol and the pacing-based AF inducibility. Results After the completion of ablation, AF could still be induced in 37 of 117 patients (31.6%). Spontaneous PV AMF during CA were observed in 104 of 117 patients (91%), and non-PV AMF in 63 of 117 (54%). Residual non-PV AMF were significantly associated with the pacing-based AF inducibility and an enlarged left atrial volume. In the multivariate analysis, the AF duration (1.01 [range, 1.00-1.02] months; P = 0.012), left atrial volume (1.01 [range, 1.01-1.02] mm; P = 0.006), and residual AMF (3.95 [range, 1.32-11.8] yes, no; P = 0.004) were independent risk factors for recurrent AF. Conclusions Residual AMF are associated with an increased long-term AF recurrence after sinus rhythm restoration ablation for long-standing persistent AF.