Reversible complete atrioventricular block caused by aortic bicuspid valve calcification with severe aortic stenosis: a case report.

Background: The aetiology of secondary complete atrioventricular blocks includes ischaemia, cardiac sarcoidosis, electrolyte imbalance, drug use, rheumatic fever, and infections such as Lyme disease and endocarditis. Diagnosis is important since some of these causes are reversible. Although several studies have reported on aortic valve calcification causing complete atrioventricular blocks, no study has described improvement of complete atrioventricular blocks by removal of the calcification. Case summary: A 42-year-old man with syncope had a Mobitz type II atrioventricular block, an alternating bundle branch block, and severe aortic stenosis. We identified a 10 s paroxysmal complete atrioventricular block with pre-syncope and performed pacemaker implantation. Electrocardiography-gated computed tomography confirmed that the calcification had reached the muscular septum. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed significant FDG uptake with high CT value of calcification in basal interventricular septum. The calcification in the septum was removed carefully, and aortic valve replacement was performed. The atrioventricular conduction capacity improved post-surgery. During the 1-year follow-up, the patient reported dramatic improvement in exercise capacity. We also noted an improvement of <0.1% in the right ventricular pacing burden. Discussion: Complete atrioventricular blocks occur in patients with aortic stenosis accompanied by severe calcification of the aortic valve, which are visualized comprehensively by echocardiography. Electrocardiography-gated computed tomography and FDG-PET enabled detailed evaluation of the extent of calcification and pre- and post-operative tissue inflammation. Hence, we suspected that the calcification in the septum was causing complete atrioventricular block. Moreover, clinicians should recognize that aortic valve calcification with aortic stenosis can cause complete atrioventricular blocks.

Efficacy of Computed Tomography-Based Evaluation of Myocardial Extracellular Volume Combined With Red Flags for Early Screening of Concealed Cardiac Amyloidosis in Patients With Atrial Fibrillation.

BACKGROUND: The prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) in atrial fibrillation (AF) patients remains unclear. We explored the efficacy of computed tomography-based myocardial extracellular volume (CT-ECV) combined with red flags for the early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.Methods and Results: Patients referred for AF ablation at Oita University Hospital were prescreened using the red-flag signs defined by echocardiographic or electrocardiographic findings, medical history, symptoms, and blood biochemical findings. Myocardial CT-ECV was quantified in red flag-positive patients using routine pre-AF ablation planning cardiac CT with the addition of delayed-phase cardiac CT scans. Patients with high (>35%) ECV were evaluated using technetium pyrophosphate (99 mTc-PYP) scintigraphy. A cardiac biopsy was performed during the planned AF ablation procedure if 99 mTc-PYP scintigraphy was positive. Between June 2022 and June 2023, 342 patients were referred for AF ablation. Sixty-seven (19.6%) patients had at least one of the red-flag signs. Myocardial CT-ECV was evaluated in 57 patients because of contraindications to contrast media, revealing that 16 patients had high CT-ECV. Of these, 6 patients showed a positive 99 mTc-PYP study, and 6 patients were subsequently diagnosed with wild-type ATTR-CM via cardiac biopsy and genetic testing. CONCLUSIONS: CT-ECV combined with red flags could contribute to the systematic early screening of concealed ATTR-CM in AF patients undergoing catheter ablation.

Quality of epicardial adipose tissue predicts major adverse cerebral and cardiovascular events following transcatheter aortic valve implantation.

Epicardial adipose tissue (EAT) have been shown to be associated with several heart disease, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). It is reported that the quality of EAT, represented by fat attenuation determined using computed tomography (CT) imaging, can detect the histologically-assessed remodeled EAT. We tested the hypothesis that quality of EAT would predict major adverse cerebral and cardiovascular events (MACCE) following transcatheter aortic valve implantation (TAVI) in patients with aortic stenosis (AS). A total of 125 consecutive severe AS patients who underwent TAVI were enrolled (39 male, mean 85.4 ± 4.0 years). Using CT imaging before TAVI, we measured the average CT fat attenuation of EAT (EAT attenuation) and investigated the association with MACCE. During the mean follow up period of 567 ± 371 days, 21 cases of MACCE were observed. Patients with MACCE had greater levels of EAT attenuation compared to those without (- 74 ± 3.7 Hounsfield Units (HU) vs - 77 ± 5.5 HU, p = 0.010). Based on the ROC curves, the high EAT attenuation was defined as > - 74.3 HU. According to this cut-off index, 44 patients were classified into the high EAT attenuation group (28 female, mean age 87 ± 3.6 years), whereas 81 patients were classified into the low EAT attenuation group (13 female, 85 ± 4.1 years). Kaplan-Meier survival curve demonstrated that the patients in the high EAT attenuation group showed greater prevalence of MACCE (log-rank 6.64, p = 0.010). Cox proportional hazards regression analysis revealed that EAT attenuation and Logistic EuroSCORE were independently associated with the incidence of MACCE. Our results suggest that quality of EAT, assessed by EAT attenuation detected by CT imaging, can predict the cerebral and cardiovascular events after TAVI in patients with AS.

Cardiomyopathy with an LMNA Genetic Variant Affecting Three Consecutive Generations: A Case Series.

We report the case of a family afflicted with cardiac laminopathy who showed atrial fibrillation (AF) and complete atrioventricular block across three generations. Implantable cardioverter defibrillators (ICDs) implantation, or cardiac resynchronization therapy (CRT) were delivered to the three patients (proband; 61 years old, proband's mother: 84 years old, and proband's daughter; 38 years old) to prevent sudden cardiac death or suppress heart failure progression. A novel frameshift mutation (LMNA Exon 9: c.1550dupA;p. N518Efs*34) was found in all three cases through genetic testing, and this mutation may potentially result in the relatively late appearance of a phenotype of left ventricular systolic dysfunction.

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan part 3: Inappropriate internal processing in the automatic diagnosis of electrocardiograms and its problems.

Computer diagnosis of electrocardiograms is widely used to provide useful information in clinical practice and medical checkups. However, it is common for users to be confused by the inappropriate diagnosis. We illustrate some examples of inappropriate automatic diagnoses and discuss the actual situation of inappropriate automatic processing and its problems.

Impact of the COVID-19 Pandemic on the Long-Term Prognosis of Acute Myocardial Infarction in Japan.

Background During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a global reduction in hospitalizations for acute myocardial infarction (AMI) was observed. Generally, patients experienced increased severity of AMI with delays in time from symptom onset to treatment during the pandemic. However, the impact of the COVID-19 pandemic on in-hospital mortality among patients with AMI remains unclear. This study aimed to compare the long-term prognosis of patients with AMI during the COVID-19 pandemic to that observed in the pre-pandemic period and to evaluate the influence of the COVID-19 pandemic on the prognosis of patients with AMI. Methods We reviewed the data of patients admitted to our hospital for AMI treatment between April 1, 2018, and March 31, 2021. The time from admission to major adverse cardiac events (MACE), as well as the time from admission to all-cause death, were examined between the pandemic period (April 1, 2020, to March 31, 2021) and the pre-pandemic period (April 1, 2018, to March 31, 2020). Results Eighty patients were included in the study, and those admitted during the pandemic exhibited a higher likelihood of advanced age, lower levels of LDL-cholesterol, and a reduced prevalence of hypertension. The 2.5-year MACE-free survival and overall survival rates between the patients during the pre-pandemic and pandemic periods were not significantly different. Conclusion The long-term prognosis of patients with AMI during the COVID-19 pandemic remains unclear. In this study, we reported that the 2.5-year MACE-free survival and overall survival rates of the patients with AMI admitted during the COVID-19 pandemic were not significantly different from those during the pre-pandemic period. The impact of the COVID-19 pandemic on the prognosis of patients with AMI appears to vary according to the study population.

R-R' interval in the left bundle branch block predicts long-term outcomes after cardiac resynchronization therapy by estimating greater mechanical dyssynchrony and viable myocardium.

BACKGROUND: Typical left bundle branch block (LBBB) shows 2 peaks of the R wave, which reflect activation reaching the interventricular septum (R) and posterolateral wall (R') sequentially. OBJECTIVE: The purpose of this study was to investigate the relationship among R-R' interval (RR'), mechanical dyssynchrony, extent of viable myocardium, and long-term outcomes in cardiac resynchronization therapy (CRT) candidates. METHODS: The study enrolled 49 patients (34 men; mean age: 69 ± 11 years) with LBBB who received CRT. The LBBB definition used requires the presence of mid-QRS notching in leads V1, V2, V5, V6, I, and aVL. Baseline evaluations were QRS duration (QRSd) and RR' measured from the 12-lead electrocardiogram; eyeball dyssynchrony (apical rocking and septal flash) and opposing-wall delay by speckle tracking from echocardiography, and extent of viable myocardium assessed by thallium-201 single-photon emission computed tomography. Primary outcomes included the combination of all-cause death and heart failure-related hospitalization. RESULTS: RR' predicted volumetric response better than QRSd (area under the curve 0.73 vs 0.67, respectively). The long RR' group (≥48 ms) revealed more frequent eyeball dyssynchrony and significantly greater radial (SL) and circumferential dyssynchrony (AP and SL) and %viable segment than the short RR' group. In multivariate regression analysis, only RR' ≥48 ms was independently associated with higher event-free survival rates following CRT (hazard ratio 0.21; P = .014). CONCLUSION: These findings suggest that RR' in complete LBBB was associated with mechanical dyssynchrony, extent of viable myocardium, and long-term outcomes following CRT.

A Heart Failure Smartphone Application That Nudges Patients/Physicians Toward Optimal Medical Therapy　- Development and Usability Study.

Background: The low implementation rate of guideline-directed medical therapy for heart failure (HF) remains a problem worldwide. To address this issue, we hypothesized that a smartphone application (app) based on behavioral economics that nudges physicians and patients towards optimal medical therapy would be a scalable approach. Methods and Results: The app prototype was developed, and its usability was tested with 5 HF patients in the outpatient setting. Adherence to the app was outstanding, with a high usability rating from the patients. Conclusions: It appears feasible to further study our app in a larger cohort to evaluate its efficacy.

Remission of Cardiac Sarcoidosis after the Administration of Methotrexate as First-line Drug Therapy.

A 54-year-old woman developed new-onset heart failure and was diagnosed with cardiac sarcoidosis. An implantable cardioverter-defibrillator with biventricular pacing was implanted before immunosuppressive therapy to prevent sudden death. The patient refused oral steroids because she disliked their specific side effects and potential adverse events with long-term use; therefore, methotrexate was chosen as an alternative first-line drug. Nine months after starting oral therapy, 18F-fluorodeoxyglucose-positron emission tomography revealed remission of sarcoidosis, disappearance of heart failure symptoms, marked improvement in cardiac contractility, and a reduced frequency of ventricular arrhythmias.

Innovations in online classes introduced during the COVID-19 pandemic and their educational outcomes in Japan.

BACKGROUND: The novel coronavirus disease (COVID-19) pandemic emerged in Japan in February 2020, forcing the adoption of online education by university medical schools across Japan. The advantages and disadvantages of online education have been studied in Japan; however, the educational outcome of online classes conducted during the COVID-19 pandemic has not been completely evaluated. In this study, we examined the relationship between lecture format (e.g., face-to-face or online) and performance of third-year university students in their organ-specific cardiovascular course examination. METHODS: This retrospective, nonclinical, and noninterventional comparative educational study included 550 third-year medical students who took a cardiovascular course between April 2018 and May 2022. Cardiovascular coursework was conducted in-person in 2018 and 2019, online in 2020 and 2021, and again in-person in 2022. The course comprised 62 lecture and 2 problem-based learning (PBL) sessions. A quiz was set up in advance on Moodle based on all lectures conducted in 2021 and 2022. A written examination was administered at the end of the course to evaluate the knowledge of students. The student online course evaluation questionnaires were administered in 2020 and 2021. Examination scores and proportion of failures in each year were compared. RESULTS: The mean examination scores were significantly higher in 2021 and 2022 than in 2018, 2019, and 2020 (p < 0.05). Univariate and multivariate analyses adjusted for the class type, online quiz, and PBL revealed that only online quiz was significantly associated with better examination results (p < 0.05). A student course evaluation survey indicated that the online format did not interfere with the students' learning and was beneficial. CONCLUSIONS: The introduction of online classes into medical education due to the COVID-19 pandemic was as effective as face-to-face classes owing to learning management system and other innovations, such as online quizzes. Online education may confer more benefits when provided in a combination with face-to-face learning after COVID-19 pandemic.

Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce epicardial adipose tissue (EAT) in humans, enhancing cardioprotective effects on heart failure and atrial fibrillation. We investigated the direct effect of the SGLT2 inhibitor empagliflozin on human primary epicardial adipocytes and preadipocytes. SGLT2 is primarily expressed in human preadipocytes in the EAT. The expression levels of SGLT2 significantly diminished when the preadipocytes were terminally differentiated. Adipogenesis of preadipocytes was attenuated by empagliflozin treatment without affecting cell proliferation. The messenger RNA levels and secreted protein levels of interleukin 6 and monocyte chemoattractant protein 1 were significantly decreased in empagliflozin-treated adipocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes pretreated with or without empagliflozin revealed that empagliflozin significantly suppressed reactive oxygen species. IL6 messenger RNA expression in human EAT showed significant clinically relevant associations. Empagliflozin suppresses human epicardial preadipocyte differentiation/maturation, likely inhibiting epicardial adipogenesis and improving the paracrine secretome profile of EAT, particularly by regulating IL6 expression.

Usefulness of Prehospital 12-Lead Electrocardiography System in ST-Segment Elevation Myocardial Infarction Patients in Oita　- Comparison Between Urban and Rural Areas, Weekday Daytime and Weekday Nighttime/Holidays.

BACKGROUND: We have reported that a prehospital 12-lead electrocardiography system (P-ECG) contributed to transport of suspected acute coronary syndrome (ACS) patients to appropriate institutes and in this study, we compared its usefulness between urban and rural areas, and between weekday daytime and weekday nighttime/holiday.Methods and Results: Consecutive STEMI patients who underwent successful primary percutaneous coronary intervention after using P-ECG were assigned to the P-ECG group (n=123; 29 female, 70±13 years), and comparable STEMI patients without using P-ECG were assigned to the conventional group (n=117; 33 females, mean age 70±13 years). There was no significant difference in door-to-reperfusion times between the rural and urban cases (70±32 vs. 69±29 min, P=0.73). Door-to-reperfusion times in the urban P-ECG group were shorter than those in the urban conventional group for weekday nighttime/holiday (65±21 vs. 83±32 min, P=0.0005). However, there was no significance different between groups for weekday daytime. First medical contact to reperfusion time (90±22 vs. 105±37 min, P=0.0091) in the urban P-ECG group were significantly shorter than in the urban conventional groups for weekday nighttime/holiday, but were not significantly different between the groups for weekday daytime. CONCLUSIONS: P-ECG is useful even in urban areas, especially for patients who develop STEMI during weekday nighttime or while on a holiday.

Cardiac Reversibility and Survival After Transcatheter Aortic Valve Implantation in Patients With Low-Gradient Aortic Stenosis.

Background Prognostic implications of transcatheter aortic valve implantation (TAVI) in low-gradient (LG) aortic stenosis (AS) remain controversial. The authors hypothesized that differences in cardiac functional recovery may solve this ongoing controversy. The aim was to evaluate clinical outcomes and the response of left ventricular (LV) function following TAVI in patients with LG AS. Methods and Results This multicenter retrospective study included 1742 patients with severe AS undergoing TAVI between January 2015 and March 2019. Patients were subdivided into low-flow (LF) LG, normal-flow (NF) LG, LF high-gradient, and NF high-gradient AS groups according to the mean gradient of the aortic valve (LG <40 mm Hg) and LV stroke volume index (LF <35 mL/m2). Outcomes and changes in echocardiographic parameters after TAVI were compared between the groups. A total of 227 patients (13%) had reduced ejection fraction, and 486 patients (28%) had LG AS (LF-LG 143 [8%]; NF-LG 343 [20%]). During a median follow-up period of 747 days, 301 patients experienced a composite end point of cardiovascular death and rehospitalization for cardiovascular events, which was higher in the LF-LG and NF-LG groups than in the high-gradient groups. LG AS was independently associated with the primary outcome (hazard ratio, 1.69; P<0.001). Among 1239 patients with follow-up echocardiography, LG AS showed less improvement in the LV mass index and LV end-diastolic volume compared with high-gradient AS after 1 year, while LV recovery was similar between the LF AS and NF AS groups. Conclusions LG AS was associated with poorer outcomes and LV recovery, regardless of flow status after TAVI. Careful evaluation of AS severity may be required in LG AS to provide TAVI within the appropriate time and advanced care afterward.

Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR).

BACKGROUND: The overactivation of mineralocorticoid receptor (MR) plays a key pathological role in the progression of cardiovascular and renal diseases by promoting pro-inflammatory and pro-fibrotic signaling. Recently, it has been found that finerenone, a novel nonsteroidal selective MR antagonist, can robustly improve cardiorenal outcomes in patients with type 2 diabetes (T2D) and a wide spectrum of chronic kidney disease (CKD). However, the mechanisms underlying the cardiorenal benefits of finerenone are poorly understood. Further, whether the clinical benefits are mediated by an improvement in vascular stiffness is not confirmed. Therefore, the current study aims to evaluate the effects of finerenone on vascular stiffness as assessed using cardio ankle vascular index (CAVI) and relevant cardiorenal biomarkers in patients with T2D and CKD. METHODS: The Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR) is an ongoing, investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized clinical trial in Japan. Its target sample size is 100 subjects. Recruitment will be performed from September 2023 to July 2024. After obtaining informed consent, eligible participants with T2D and CKD (25 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 90 mL/min/1.73 m2 and 30 mg/g Cr ≤ urinary albumin-to-creatinine ratio [UACR] < 3500 mg/g Cr) will be equally randomized to receive 24-week treatment with either finerenone (starting dose at 10 mg once daily in participants with a baseline eGFR < 60 mL/min/1.73 m2 or at 20 mg once daily in those with a baseline eGFR ≥ 60 mL/min/1.73 m2) or dose-matched placebo. The primary endpoint is the change from baseline in CAVI at 24 weeks. The secondary endpoints are changes from baseline in UACR at 12 and 24 weeks and relevant serum and urinary biomarkers at 24 weeks. As an exploratory endpoint, proteomic analysis using the Olink® Target 96 panels will be also performed. DISCUSSION: FIVE-STAR is the first trial evaluating the therapeutic impact of finerenone on vascular stiffness and relevant cardiorenal biomarkers in patients with T2D and CKD. This study will provide mechanistic insights on the clinical benefits of finerenone based on recent cardiovascular and renal outcome trials. Trial registration Unique Trial Number, NCT05887817 ( https://clinicaltrials.gov/ct2/show/NCT05887817 ) and jRCTs021230011 ( https://jrct.niph.go.jp/latest-detail/jRCTs021230011 ).

Histological validation of atrial structural remodelling in patients with atrial fibrillation.

BACKGROUND AND AIMS: This study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation. METHODS AND RESULTS: Patients undergoing atrial fibrillation ablation and endomyocardial atrial biopsy were included (n = 230; 67 ± 12 years old; 69 women). Electroanatomic mapping was performed during right atrial pacing. Voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and the proportion of points with fractionated electrograms defined as ≥5 deflections in each electrogram (%Fractionated EGM) were evaluated. SCZtotal was calculated as the total width of slow conduction zones, defined as regions with a conduction velocity of <30 cm/s. Histological factors potentially associated with electroanatomic characteristics were evaluated using multiple linear regression analyses. Ultrastructural features and immune cell infiltration were evaluated by electron microscopy and immunohistochemical staining in 33 and 60 patients, respectively. Fibrosis, intercellular space, myofibrillar loss, and myocardial nuclear density were significantly associated with Vbiopsy (P = .014, P < .001, P < .001, and P = .002, respectively) and VGLA (P = .010, P < .001, P = .001, and P < .001, respectively). The intercellular space was associated with the %Fractionated EGM (P = .001). Fibrosis, intercellular space, and myofibrillar loss were associated with SCZtotal (P = .028, P < .001, and P = .015, respectively). Electron microscopy confirmed plasma components and immature collagen fibrils in the increased intercellular space and myofilament lysis in cardiomyocytes, depending on myofibrillar loss. Among the histological factors, the severity of myofibrillar loss was associated with an increase in macrophage infiltration. CONCLUSION: Histological correlates of atrial structural remodelling were fibrosis, increased intercellular space, myofibrillar loss, and decreased nuclear density. Each histological component was defined using electron microscopy and immunohistochemistry studies.

Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study.

Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.

Role of epicardial adipose tissue in human atrial fibrillation.

A recent meta-analysis among which four reports were conducted in Japan demonstrated that epicardial adipose tissue (EAT) is closely associated with an increased risk of atrial fibrillation (AF) recurrence after catheter ablation. We previously investigated the role of EAT in AF in humans. Left atrial (LA) appendage samples were obtained from AF patients during cardiovascular surgery. Histologically, the severity of fibrotic EAT remodeling was associated with LA myocardial fibrosis. Total collagen in the LA myocardium (i.e., LA myocardial fibrosis) was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α, in EAT. Human peri-LA EAT and abdominal subcutaneous adipose tissue (SAT) were obtained by autopsy. EAT- or SAT-derived conditioned medium was applied to the rat LA epicardial surface using an organo-culture system. EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium. The profibrotic effect of EAT was greater than that of SAT. The fibrotic area of the organo-cultured rat atrium treated with EAT from patients with AF was greater than in patients without AF. Treatment with human recombinant angiopoietin-like protein 2 (Angptl2) induced fibrosis in organo-cultured rat atrium, which was suppressed by concomitant treatment with anti-Angptl2 antibody. Finally, we attempted to detect fibrotic EAT remodeling on computed tomography (CT) images, which demonstrated that the percent change in EAT fat attenuation was positively correlated with EAT fibrosis. Based on these findings, we conclude that the percent change in EAT fat attenuation determined using CT non-invasively detects EAT remodeling.