Mast Cells Play an Important Role in the Pathogenesis of Hyperglycemia-Induced Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Recently, it was reported that mast cells (MCs) could underlie the mechanisms of several cardiovascular diseases. However, the role of MCs in diabetes-induced atrial fibrillation (AF) has not been notably investigated. We tested the hypothesis that MC deficiency attenuates hyperglycemia-induced AF in mice. METHODS AND RESULTS: Mast cell-deficient W/W(v)  mice, and congenic +/+ littermates (WT) were divided into either the vehicle (VEH)-injection group or the streptozotocin (STZ)-injection group (MCKO-VEH, MCKO-STZ, WT-VEH, and WT-STZ groups). On day 28 of our studies, we observed that (1) STZ-induced hyperglycemia increased MC infiltration in the left atrium (LA) in WT mice (P < 0.01), (2) atrium isolated from the WT-STZ group showed inhomogeneous interstitial fibrosis, abundant infiltration of macrophages, and enhanced apoptosis compared to the WT-VEH group (P < 0.01, P < 0.01, P < 0.05, respectively). However, the changes observed in the WT-STZ group were significantly attenuated in the MCKO-STZ mice. In addition, we observed that (3) messenger RNA levels of tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, transforming growth factor-ß, and collagen-1 in the LA were increased in the WT-STZ group, but not in the MCKO-STZ group, (4) STZ-induced hyperglycemia increased AF induction and prolonged interatrial conduction time in the WT mice, which were not observed in the MCKO mice, and that (5) hyperglycemia-enhanced atrial production of reactive oxygen species (ROS) was equally observed in the WT and MCKO mice. CONCLUSIONS: Our results suggest that MCs contribute to the pathogenesis of hyperglycemia-induced AF via enhancement of inflammation and fibrosis.

Endothelial Function Predicts New Hospitalization due to Heart Failure Following Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been established as a treatment for patients with chronic heart failure (HF). We tested the hypothesis that assessment of peripheral endothelial function is associated with the long-term outcome of CRT and its linkage to coronary flow reserve (CFR) was also investigated. METHODS: From 2010, a total of 34 consecutive patients implanted with CRT for the treatment of advanced HF were evaluated at baseline (immediately before CRT) and 6-8 months after CRT. Endothelial function was evaluated by measurement of reactive hyperemia peripheral arterial tonometry (RH-PAT). In 24 of 34 patients, CFR was determined by transthoracic echocardiography. RESULTS: Based on the receiver-operating characteristic curves, depressed RH-PAT index (RHI) was defined as ≤1.5. Accurate follow-up information during the mean of 343 ± 120 days was obtained in 20 preserved RHI group (mean age 66 ± 1.8 years) and 14 depressed RHI group (71 ± 2.2 years). Kaplan-Meier survival analysis demonstrated that depressed RHI group had higher prevalence of new hospitalization due to HF progression (log-rank 5.40). Cox proportional hazards regression analysis revealed that the baseline log brain natriuretic peptide (hazard ratio 5.95) and the baseline RHI value (hazard ratio 0.066) were independently associated with the incidence of new hospitalization due to HF progression. The baseline RHI values were positively correlated with the 6-8 months change of CFR (R = 0.434, P = 0.0343). CONCLUSIONS: Our results suggest that the baseline peripheral endothelial function could predict the long-term outcome of CRT. The results also suggest that improvement of coronary microcirculation might be associated with the better baseline endothelial function.

Cardiac autonomic dysfunction in patients with head-up tilt test-induced vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is the result of an autonomic reflex that has a final effect of reducing sympathetic drive and increasing vagal activity. However, whether syncopal symptoms are associated with pathological cardiac autonomic modulation is not fully known. We tested the hypothesis that cardiac autonomic function is impaired in patients with VVS. METHODS: Eighty-four consecutive patients (59 males; 48.8 ± 20.9 years) with recurrent unexplained syncope were enrolled. The head-up tilt test (HUTT) was positive in 38 patients and negative in 46 patients. Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability, plasma concentrations of norepinephrine, and (123) I-metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: BRS indices were significantly lower in the HUTT-positive group than in the HUTT-negative group (6.1 ± 5.5 mm Hg/s vs 9.8 ± 7.6 mm Hg/s, P = 0.02). With regard to cardiac (123) I-MIBG scintigraphy, the mean heart-to-mediastinum ratio at the delayed phase tended to be lower in HUTT-positive than in HUTT-negative individuals, but this difference was not significant (2.75 ± 0.55 vs 3.02 ± 0.49, P = 0.08).The percent washout rate of (123) I-MIBG was significantly higher in the positive group compared with the negative group (40.7 ± 13.1% vs 31.5 ± 13.3%, P = 0.02). Multivariate logistic analysis revealed that the appearance of HUTT-induced VVS was predicted independently by a high percent washout rate of (123) I-MIBG (odds ratio, 0.954; 95% confidence interval, 0.903-0.998; P = 0.048). CONCLUSIONS: Our results suggest that pathological autonomic cardiac modulation may play a role in the appearance of syncope in VVS patients.

Impact of Mobile Cloud Electrocardiography System on Door-to-Balloon Time in Patients With Acute Coronary Syndrome in Oita Prefecture.

Background: The mobile cloud electrocardiography (C-ECG) system is useful for reducing door-to-balloon (DTB) time in patients with acute coronary syndrome (ACS), but few studies have reported the usefulness of the C-ECG system across a wide provincial prefecture, such as Oita, in Japan. Methods and Results: On 17 April 2017, the C-ECG system was integrated into the Oita remote image transmission system, in 10 ambulances of 10 respective fire departments in Oita Prefecture. During 6 months, 162 ECG indicating suspected ACS were transmitted to 18 hospitals using the C-ECG system. Of 162 patients, 17 who received emergency percutaneous coronary intervention (PCI) were assigned to the cloud group (mean age, 71±11 years). The control group consisted of 29 consecutive ACS patients who were transported to Oita University Hospital without using the C-ECG system (mean age, 66±12 years). Another 40 consecutive patients were diagnosed with ACS before transportation to Oita University Hospital, and were assigned to the diagnosed group (mean age, 70±14 years). DTB time (70±26 min vs. 96±24 min, P<0.005) and door-to-catheterization laboratory time (33±20 min vs. 53±22 min, P<0.0001) were shorter in the cloud group than in the control group, respectively. Conclusions: C-ECG system integration in Oita Prefecture was useful to appropriately transfer ACS patients to hospital and to facilitate earlier PCI than in the conventional diagnostic system.

CORRIGENDUM: Impact of Mobile Cloud Electrocardiography System on Door-to-Balloon Time in Patients With Acute Coronary Syndrome in Oita Prefecture.

[This corrects the article DOI: 10.1253/circrep.CR-19-0020.].

Interleukin 10 Treatment Ameliorates High-Fat Diet-Induced Inflammatory Atrial Remodeling and Fibrillation.

BACKGROUND: Obesity, characterized by systemic low-grade inflammation, is considered a well-known risk for atrial fibrillation. In fact, IL-10 (interleukin 10), which is a potent anti-inflammatory cytokine, has been reported to decrease in obese and diabetic patients. We tested the hypotheses forwarding that genetic deletion of IL-10 exacerbates high-fat diet (HFD)-induced obesity-caused atrial inflammation, lipidosis, fibrosis, and fibrillation and that IL-10 therapy inhibits this pathology. METHODS: Eight- to 10-week-old male CL57/B6 (wild-type) mice and IL-10 knockout mice were divided into a 12-week HFD group and a 12-week normal-fat diet (NFD) group, respectively. In addition, the effect of IL-10 administration was also investigated. RESULTS: HFD-induced obesity for 12 weeks significantly depressed serum levels of IL-10 but were found to increase several proinflammatory cytokines in wild-type mice. Adverse atrial remodeling, including atrial inflammation, lipidosis, and fibrosis, was induced in both wild-type and IL-10 knockout mice by HFD. Vulnerability to atrial fibrillation was also significantly enhanced by HFD. With regard to epicardial and pericardial adipose tissue, the total amount of epicardial adipose tissue+pericardial adipose tissue volume was increased by HFD. Besides, proinflammatory and profibrotic cytokines of epicardial adipose tissue+pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by HFD. These HFD-induced obesity-caused adverse effects were further exaggerated in IL-10 knockout mice in comparison to wild-type mice. Systemic IL-10 administration markedly ameliorated HFD-induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation, in addition to improving the quality of epicardial adipose tissue+pericardial adipose tissue. CONCLUSIONS: Our results highlight IL-10 treatment as a potential therapeutic approach to limit the progression of HFD-induced obesity-caused atrial fibrillation.

A case of Type-C Wolff-Parkinson-White syndrome with severe left ventricular dysfunction: Efficacy of catheter ablation.

The present case report describes a 59-year-old female with manifest Wolff-Parkinson-White syndrome and severe left ventricular (LV) dysfunction, however, there was no indication of heart palpitations. The polarity of delta is consistent with the features of the right anteroseptal accessory pathways (APs). The echocardiography showed a remarkable dyssynchrony of the LV wall motion. To circumvent the cardiac dysfunctions, radiofrequency catheter ablation (RFCA) was successfully performed to disconnect the AP. Thereafter, the dyssynchrony disappeared, and the clinical reports observed 6 months following RFCA showed that the LV ejection fraction had been improved from 13% up to 48%, in addition to the improvement in other parameters. The RFCA prevented her from receiving a cardiac resynchronization therapy defibrillator as well as a heart transplantation. .

Combination therapy of cilostazol and bepridil suppresses recurrent ventricular fibrillation related to J-wave syndromes.

BACKGROUND: Brugada syndrome and idiopathic ventricular fibrillation (VF) associated with inferolateral early repolarization patterns are termed "J-wave syndromes." In such patients, an implantable cardioverter-defibrillator (ICD) is first-line therapy for prevention of sudden cardiac death. However, frequent ICD shocks due to recurrent VF remain serious problems. OBJECTIVE: The purpose of this study was to ascertain if combination therapy of cilostazol and bepridil could suppress recurrent VF. METHODS: We enrolled 7 patients with J-wave syndromes who experienced ICD shocks due to recurrent VF after ICD implantation. At first, cilostazol was instituted. In all subjects, palpitations due to sinus tachycardia caused by cilostazol were symptomatic. Addition of bepridil attenuated cilostazol-induced palpitations and maintained the suppressive effect of cilostazol against VF (87 ± 12 bpm to 66 ± 7 bpm, P < .01). RESULTS: Six patients remained free of VF. Three patients underwent replacement of the ICD generator 4-5 years after ICD placement. Cilostazol was discontinued 2 days before replacement because of its antiplatelet effects. In all 3 patients, temporary discontinuation of cilostazol led to the reappearance of J waves, culminating in VF and an appropriate ICD shock in 1 patient. J waves disappeared with reinstitution of cilostazol. CONCLUSION: These data suggest that combination therapy of cilostazol and bepridil may be effective and safe in suppressing VF recurrence in some cases of J-wave syndromes.