Late life-threatening arrhythmia in patients with Brugada syndrome: Results from long-term follow-up in a large Japanese cohort.

INTRODUCTION: Most patients with Brugada syndrome (BrS) are first diagnosed in their 40s, with sudden cardiac death (SCD) often occurring in their 50s. Ventricular fibrillation (VF) may occur in some patients with BrS despite having been asymptomatic for a long period. This study aimed to assess the incidence and risk factors for late life-threatening arrhythmias in patients with BrS. METHODS: Patients with BrS (n = 523; mean age, 51 ± 13 years; male, n = 497) were enrolled. The risk of late life-threatening arrhythmia was investigated in 225 patients who had experienced no cardiac events (CEs: SCD or ventricular tachyarrhythmia) for at least 10 years after study enrollment. The incidence of CEs during the follow-up period was examined. RESULTS: During the follow-up of the 523 patients, 59 (11%) experienced CEs. The annual incidences of CEs were 2.87%, 0.77%, and 0.09% from study enrollment to 3, 3-10, and after 10 years, respectively. Among 225 patients who had experienced no CEs for at least 10 years after enrollment, four patients (1.8%) subsequently experienced CEs. Kaplan-Meier analysis revealed significant differences in the incidence of late CEs between patients with and without a history of symptoms (p = .032). The positive and negative predictive values of late CEs for the programmed electrical stimulation (PES) test were 2.9% and 100%, respectively. CONCLUSION: Our results suggest that patients with BrS who are asymptomatic and have no ventricular tachycardia/VF inducibility by PES are at extremely low risk of experiencing late life-threatening arrhythmias.

The utility of combining continuous wavelet transform analysis and high-density voltage map in predicting the long-term outcomes after ablation of persistent atrial fibrillation.

BACKGROUND: Continuous wavelet transform (CWT) analysis is a frequency analysis to detect areas of stable high-frequent activity (stable pseudo frequency [sPF]) during atrial fibrillation (AF). As previously reported, patients with the highest sPF area in pulmonary veins (PV) showed better short-term outcomes after PV isolation (PVI). This study sought to evaluate the efficacy of CWT analysis in predicting the long-term (2 years) outcomes after PVI. We also combined the left atrial (LA) voltage map with CWT analysis to further predict the outcome. METHODS: Persistent AF patients (n = 109, age 65 ± 10) underwent a CWT analysis at PVs and 8 LA sites during AF for pre-PVI analysis. After PVI during AF, CWT analysis was performed again in the LA as post-PVI analysis and was compared with pre-PVI analysis. A sinus voltage map of LA was created after cardioversion. RESULTS: Seventy patients had the highest sPF within PVs (PV-dominant group), while 39 patients had the highest sPF outside PVs (LA-dominant group). The global frequency in the LA showed a significant decrease after PVI only in PV-dominant group (6.55 ± 0.27 to 6.43 ± 0.37, P < 0.01). AF-free survival was better in PV-dominant group than LA-dominant group at 2-year follow-up (87.1% vs. 64.3%, P < 0.002). This trend was recognized throughout all degrees of low voltage area in the LA (LA-LVA), and AF-free survival was well predicted by combining CWT analysis and LA-LVA. CONCLUSIONS: By combining CWT analysis and sinus LA-LVA, the long-term AF-free survival after PVI was well stratified and predicted.

Electrogram characteristics at successful cryoablation sites in slow-fast atrioventricular nodal reentrant tachycardia.

PURPOSE: Cryoablation is a safe alternative to radiofrequency (RF) ablation for slow-fast atrioventricular reentrant tachycardia (AVNRT); however, optimal electrogram parameters for site selection remain unknown. We retrospectively investigated local electrograms for slow pathway (SP) modification in cryoablation. METHODS: Forty-five consecutive patients with slow-fast AVNRT who underwent cryoablation using a 6-mm-tip catheter were enrolled. Electrogram parameters for sites of successful SP modification (success-sites) were investigated; these included the interval between atrial activation at His and the last deflection of SP potential, defined as the His(A)-SPP interval. In 8 patients, 3-dimensional mapping by multi-electrode catheter was performed pre-ablation for more detailed SP assessment. RESULTS: Twenty-seven of 45 patients had successful SP modification by 1 cycle of freeze-thaw-freeze cryoablation at a single site with a low amplitude and fragmented SP potential. Among a total of 76 cryoablation sites in all patients, the His(A)-SPP interval at success-sites (45 sites) was significantly longer than that at unsuccess-sites (31 sites) (86 ± 9 vs.78 ± 10 msec, p < 0.0001). The AV amplitude ratio was not significantly different between success-and unsuccess-sites (0.21 ± 0.22 vs.0.25 ± 0.23, p = 0.429). The cutoff value of the His(A)-SPP interval for successful cryoablation was 82 msec with a sensitivity of 0.67 and specificity of 0.71 (AUC: 0.739; 95%CI: 0.626-0.852; p < 0.0001). Three-dimensional mapping in all 8 patients showed that sites with the most delayed atrial activation and the last deflection of the fragmented SP potential within the Koch's triangle coincided with success-sites. CONCLUSION: A longer His(A)-SPP interval and fractionated SP potential were characteristics of successful cryoablation for SP modification in slow-fast AVNRT.

Leiomyosarcoma arising from the ovarian vein as a gynecologic malignancy: Two case reports and a review of the literature.

Leiomyosarcoma arising from the ovarian vein has rarely been reported. Herein, we report two cases from a single institute. Given their direct connections to ovarian vessels, both leiomyosarcomas were initially suspected to be gynecological malignancies. In one case, leiomyosarcoma was discovered incidentally without any clinical symptoms; it had a close connection with the ovarian vein, was removed surgically, and the patient has survived for over 12 years. In another case, bowel obstruction caused by the tumor helped to identify metastatic leiomyosarcoma. Blood flow was supplied by the ovarian artery and grew into the lumen of the ovarian vein without invading adjacent organs. After surgical resection, the patient underwent 18 months of chemotherapy prior to palliative care. We propose that leiomyosarcoma arising from the ovarian vein should be treated as a gynecologic malignancy, especially if it develops in the lower abdomen.

A new biomarker of cardiac resynchronization therapy response: cGMP to mature BNP ratio.

BACKGROUND: Biomarkers that can predict cardiac resynchronization therapy (CRT) response have not yet been identified. The purpose of this study was to assess whether individual measurements of four brain/B-type natriuretic peptide (BNP) forms, coupled with cyclic guanosine monophosphate (cGMP) might contribute to the prediction of echocardiographic CRT responders. METHODS: A BNP precursor (proBNP) and total BNP (= proBNP + mature BNP) were measured with newly developed kits, while an N-terminal fragment of proBNP (NT-proBNP) and cGMP were measured with commercial kits on the day before CRT implantation. Estimated mature BNP (emBNP = total BNP-proBNP), and the ratio of cGMP to each BNP form, as well as the concentrations of three other BNP forms, were prospectively investigated for their capability in predicting a response to CRT. A CRT responder was defined as an improvement in left ventricular ejection fraction >10% and/or a reduction in left ventricular end-systolic volume >15% at 6-month follow-up. RESULTS: Out of 77 patients, 46 (60%) were categorized as CRT responders. Among the measurement parameters, only the highest quartile of the cGMP to emBNP ratio was an independent predictor of CRT responders (odds ratio 4.87, 95% confidence interval 1.25-18.89, p = 0.02). The cGMP to emBNP ratio was associated with the cumulative events of heart failure hospitalization within one year following CRT implantation (log-rank p = 0.029). CONCLUSIONS: The cGMP to emBNP ratio could be utilized as a predictive biomarker of CRT responders. (Clinical Study on Responder Prediction in Cardiac Resynchronization Therapy Using Individual Molecular Measurement of Natriuretic Peptide: UMIN R000038927).

A Case of Undifferentiated Carcinoma in a 2-Month Postpartum Reproductive Tract with a Rapid and Fulminant Course.

Advanced carcinoma of the lower female reproductive tract is rare during pregnancy and the postpartum period. We here present a case of a 32-year-old Japanese woman, whose entire lower reproductive tract had been invaded by carcinomas as of 2 months after childbirth. She had been infertile, and pregnancy had been established by repeated embryo transfer. The gynecological cancer screening, which included Pap smear tests, was negative during the periods she underwent infertility treatment or during the first trimester. At 26 gestational weeks, the patient noticed uterine contractions concomitant with genital bleeding. Labor progressed slowly and steadily; thus, the pregnancy was ended by cesarean section at 29 weeks. At 2 months after childbirth, the patient experienced increased left abdominal pain and underwent a pelvic examination, revealing multiple pelvic masses and diffuse vaginal tumors causing stenosis. Vaginal tumors were biopsied, and histochemical analysis showed undifferentiated carcinoma with possible adenocarcinoma. Imaging modalities including CT, MRI, and PET-CT suggest that the carcinoma had invaded the entire reproductive tract, especially the uterine body, metastasized into the lungs and the ischial bones, and disseminated onto the peritoneum. She received multiple rounds of chemotherapy but died 6 months after childbirth. Taking into consideration the clinical feature and immunohistochemical profiles of the cancer cells, the endometrium is the most likely origin.

Pulmonary Vein Isolation and Pacemaker Implantation in a Patient with Dextrocardia Situs Inversus.

A 70-year-old female with dextrocardia with situs inversus (DSI) totalis and inferior vena cava occlusion underwent radiofrequency catheter ablation because she had symptomatic paroxysmal atrial fibrillation (AF). Careful preoperative examination made successful pulmonary vein isolation through the left jugular vein approach. One-year later, however, AF recurred, and symptomatic sinus bradycardia or junctional bradycardia often occurred. Then, the pacemaker was implanted. We here reported a rare case of congenital abnormality, DSI with inferior vena cava occlusion who had undergone successful pulmonary vein isolation and pacemaker implantation without any complications.

Complications Associated With Catheter Ablation in Patients With Atrial Fibrillation: A Report From the JROAD-DPC Study.

Background Aging is one of the major concerns and determinants of the indications for catheter ablation (CA) for atrial fibrillation. This study aimed to assess the safety of CA in older patients with atrial fibrillation undergoing CA. Methods and Results The JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination) is a nationwide claims database using data from the Japanese Diagnosis Procedure Combination/Per Diem Payment System. Among 6 632 484 records found between April 2012 and March 2018 from 1058 hospitals, 135 299 patients with atrial fibrillation (aged 65±10 years, 38 952 women) who underwent CA in 456 hospitals were studied and divided into the following age groups: <60, 60 to 64, 65 to 69, 70 to 74, 75 to 79, 80 to 84, and ≥85 years. The overall in-hospital complication rate was 3.4% (cardiac tamponade 1.2%), and in-hospital mortality was 0.04%. Older patients had a higher prevalence of women, lower body mass index, and a higher burden of comorbidities such as hypertension, and all of those characteristics were predictors for complications in multivariate analysis. A multivariate adjusted odds ratio revealed that increased age was independently and significantly associated with overall complications (60-64 years, 1.19; 65-69 years, 1.29; 70-74 years, 1.57; 75-79 years, 1.63; 80-84 years, 1.90; and ≥85 years, 2.86; the reference was <60 years). Conclusions The nationwide JROAD-DPC database demonstrated that the frequency of complications following CA in patients with atrial fibrillation increased according to age.

Long-term prognosis in patients with non-type 1 Brugada electrocardiogram: Results from a large Japanese cohort of idiopathic ventricular fibrillation.

BACKGROUND: Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with spontaneous, drug-induced, or fever-induced type 1 morphology. Prognosis in type 2 or 3 Brugada electrocardiogram (Br-ECG) patients remains unknown. The purpose of this study is to evaluate long-term prognosis in non-type 1 Br-ECG patients in a large Japanese cohort of idiopathic ventricular fibrillation (The Japan Idiopathic Ventricular Fibrillation Study [J-IVFS]). METHODS: From 567 patients with Br-ECG in J-IVFS, a total of 28 consecutive non-type 1 patients who underwent programmed electrical stimulation (PES) (median age: 58 years, all male, previous sustained ventricular tachyarrhythmias [VTs] 1, syncope 11, asymptomatic 16) were enrolled. Cardiac events (CEs: sudden cardiac death or sustained VT/ventricular fibrillation) during the follow-up period were examined. RESULTS: During a median follow-up of 136 months, four patients (14%) had CEs. None of patients with PES- have experienced CEs. There was no statistically significant clinical risk factor for the development of CEs. Using the Kaplan-Meier method, the event-free rate significantly decreased in a group with all 3 risk factors (symptom, wide QRS complex in lead V2 , and positive PES) (p = .01). CONCLUSIONS: Our study revealed long-term prognosis in patients with non-type 1 Br-ECG. The combination analysis of these risk factors may be useful for the risk stratification of CEs in non-type 1 Br-ECG patients. The present study suggests that the patients with all these parameters showed high risk for CEs and need to be carefully followed.

New metabolites produced by endophyte Clonostachys rosea B5 - 2.

The endophytic fungus, Clonostachys rosea B5-2 was isolated from mangrove plants and subjected to the one strain many compounds (OSMAC) methodology. By this approach, it was found that modification of the culture media enhanced the production of secondary metabolites by C. rosea B5-2. The apple juice supplemented solid rice media led to significant changes in the secondary metabolism of the fungus, C. rosea B5-2, and induced the production of four new compounds, (-)-dihydrovertinolide (2), and clonostach acids A (3), B (4), and C (5) together with the known compound, (-)-vertinolide (1). The new compound (-)-dihydrovertinolide (2) exhibited phytotoxicity against lettuce seedlings at a concentration of 50 mg L-1.

Risk stratification in asymptomatic patients with Brugada syndrome: Utility of multiple risk factor combination rather than programmed electrical stimulation.

BACKGROUND: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. Asymptomatic BrS patients generally have a better prognosis than those with symptoms. The purpose of this study was to evaluate the value of nonaggressive PES with up to two extra stimuli and predict clinical factors for risk stratification in asymptomatic BrS patients. METHODS: The study enrolled 193 consecutive asymptomatic BrS patients with type 1 ECG (mean age: 50 ± 13 years, 180 males) who underwent PES using a nonaggressive uniform protocol. Cardiac events (CEs: sudden cardiac death or ventricular tachyarrhythmia) during the follow-up period were examined. RESULTS: During a mean follow-up of 101 ± 48 months, seven asymptomatic patients (3.6%) had a CE. The incidence of CEs was not different between patients with and without inducible ventricular tachyarrhythmia by PES (p = .51). The clinical significance of risk factor combinations, including spontaneous type 1 ECG, family history of sudden cardiac death, QRS duration in lead V2 , and presence of J wave, was evaluated. Using the Kaplan-Meier method according to the number of risk factors, the prevalence of CE in patients with three or four risk factors was determined to be significantly higher than in those with one risk factor (p = .02 and p = .004, respectively). CONCLUSIONS: The present study suggests that inducibility of ventricular tachyarrhythmia does not predict future CEs in asymptomatic BrS patients. Combination analysis of the other four clinical risk parameters may be effective for risk assessment.

Subcutaneous and transvenous implantable cardioverter defibrillator in high-risk long-QT syndrome type 3 associated with Val411Met mutation in SCN5A.

Congenital long-QT syndrome type 3 (LQT3) with SCN5A-V411M mutation has been reported as a malignant case of LQT3 with highest risk for sudden cardiac death (SCD). Here, we present two cases of LQT3 with SCN5A-V411M who had been implanted with subcutaneous (S-) or transvenous (TV-) implantable cardioverter defibrillators (ICD). Case 1, a 2-year-old boy, although he had no symptoms, was diagnosed as having LQT3 (V411M-SCN5A) due to family history. The QTc interval was still longer than 500 ms during follow-up even under oral mexiletine. Case 2 (his aunt) diagnosed as LQT3 suffered from syncope caused by ventricular fibrillation at 35-years-old despite taking mexiletine. Furthermore, case 1's father and half-brother, both had the V411M mutation with LQT3, had suddenly died. Thus, case 1 was recommended S-ICD when he was 15-years-old for primary prevention of SCD but not necessary for pacing therapy, while, case 2 had been implanted TV-ICD for secondary prevention of SCD. They had no event after ICD implantation, however, case 2 had to have added an extra ICD-lead due to lead failure when she was 44-years-old. The S-ICD may be a potent therapeutic option for high-risk LQTS when patients are younger and do not need pacing therapy. .

Mobile mural thrombus and spontaneous echo contrast in ascending aorta after postoperative adjuvant cisplatin-based chemotherapy.

A 70-year-old asymptomatic male who had undergone a right nephrectomy for renal pelvic cancer was referred to us with a thrombus in the ascending aorta detected by contrast-enhanced computed tomography after chemotherapy with gemcitabine/cisplatin. Transesophageal echocardiography revealed a 4-cm mobile mural thrombus in the ascending aorta. An emergency thoracotomy for planned aortic root replacement was performed, but the intraoperative epi-aortic ultrasound indicated that the thrombus had disappeared, and it showed prominent spontaneous-echo contrast (SEC) in the ascending aorta. We speculate that vascular endothelium damage due to the cisplatin-based chemotherapy induced the thrombus and SEC in the ascending aorta.

Oral Supplementation Using Gamma-Aminobutyric Acid and Whey Protein Improves Whole Body Fat-Free Mass in Men After Resistance Training.

BACKGROUND: Oral gamma-aminobutyric acid (GABA) supplementation increases growth hormone (GH) serum levels and protein synthesis. Therefore, post-exercise supplementation using GABA and protein may help enhance training-induced muscle hypertrophy. We evaluated whether GABA with whey protein enhanced muscular hypertrophy in men after progressive resistance training. METHODS: Twenty-one healthy men (26 - 48 years) were randomized to receive whey protein (WP; 10 g) or whey protein + GABA (WP + GABA; 10 g + 100 mg) daily for 12 weeks. Both groups performed resistance training twice per week (three sets of 12 repetitions at 60% of maximal strength; leg press, leg extension, leg curl, chest press, and pull down). Body composition was assessed using dual-energy X-ray absorptiometry. RESULTS: In the WP + GABA group, resting plasma GH concentrations were significantly elevated at 4 and 8 weeks, compared to baseline. However, resting plasma GH concentrations in the WP group were only significantly elevated at 8 weeks. After 12 weeks, the WP + GABA group exhibited significantly greater increase in whole body fat-free mass than the WP group. CONCLUSIONS: The GABA and whey protein combination was more effective for increasing whole body fat-free mass; daily GABA supplementation may help enhance exercise-induced muscle hypertrophy.

Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction.

BACKGROUND: Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threatening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refractory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. METHODS: We conducted a multicenter, retrospective observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary outcome was in-hospital and long-term mortalities. Univariate logistic regression and Cox proportional-hazards analysis were used to evaluate clinical characteristics associated with in-hospital and long-term mortalities, respectively. RESULTS: One hundred ten patients were enrolled (age, 65±11years; 92 men; left ventricular ejection fraction, 31±10%). VF storm occurred at the acute phase of MI (4.5±2.5 days after the onset of MI during the index hospitalization for MI) in 43 patients (39%), the subacute phase (>1 week) in 48 (44%), and the remote phase (>6 months) in 19 (17%). The focal triggers were found to originate from the scar border zone in 88 patients (80%). During in-hospital stay after ablation, VF storm subsided in 92 patients (84%). Overall, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mortality (odds ratio for each 1-day increase, 1.11 [95% CI, 1.03-1.20]; P=0.008). During follow-up after discharge from hospital, only 1 patient developed recurrent VF storm. However, 29 patients (36%) died, with a median survival time of 2.2 years (interquartile range, 1.2-5.5 years). Long-term mortality was associated with left ventricular ejection fraction <30% (hazard ratio, 2.54 [95% CI, 1.21-5.32]; P=0.014), New York Heart Association class ≥III (hazard ratio, 2.68 [95% CI, 1.16-6.19]; P=0.021), a history of atrial fibrillation (hazard ratio, 3.89 [95% CI, 1.42-10.67]; P=0.008), and chronic kidney disease (hazard ratio, 2.74 [95% CI, 1.15-6.49]; P=0.023). CONCLUSIONS: In patients with MI presenting with focally triggered VF storm, catheter ablation of culprit triggers is lifesaving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over the long-term follow-up is associated with the severity of underlying cardiovascular disease and comorbidities in this specific patient population.