Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm.

INTRODUCTION: Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS. METHODS: The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES. RESULTS: Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients. CONCLUSIONS: ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES.

Tacrolimus treatment in women with repeated implantation failures.

Background: Tacrolimus is an immunosuppressive drug that works as a calcineurin inhibitor to improve the reproductive outcomes for women who have experienced multiple implantation failures (RIF) and show elevated type 1 helper T (Th1)/Th2 cell ratios. Methods: In the first part of this review, we indicate how we re-evaluated the cut-off index for selecting the participants in a tacrolimus regimen via transferred euploid blastocysts. In the second part, we cite cases where tacrolimus has improved the live birth rate for women who have experienced recurrent pregnancy losses (PRL) and we introduce the utility of tacrolimus treatment to prevent obstetrical complications. Main Findings: After reconsideration of the cut-off index (Th1/Th2 ≥ 11.8), however, the pregnancy rates of women with tacrolimus were significantly higher than those of women without tacrolimus. The PRL women treated with tacrolimus showed significantly lower rates of biochemical pregnancy, but higher live-birth rates compared with women who were not treated with tacrolimus. Moreover, prior severe obstetrical complications could be controlled via the administration of tacrolimus during pregnancy. Conclusion: Tacrolimus has become indispensable in the field of solid-organ transplantation, and in the near future, it should become an essential agent in the reproductive field, as well.

Temporary balloon occlusion test can overestimate the risk of acute pulmonary edema after transcatheter atrial septal defect closure.

BACKGROUND: Atrial septal defect (ASD) closure can cause acute pulmonary edema. Before transcatheter closure is performed, temporary balloon occlusion test (BOT) is recommended in patients with left ventricular dysfunction to predict the risk of pulmonary edema. However, the accuracy of BOT has not been verified. This study aimed to compare hemodynamic differences between BOT and transcatheter closure. METHODS: A total of 42 patients with a single ASD over age 18 years who underwent BOT before transcatheter ASD closure between October 2010 and May 2020 were analyzed. Pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter placed in the pulmonary artery at baseline, after 10 min of BOT, and after transcatheter closure. Amplatzer septal occluder was used for all transcatheter closures. RESULTS: Mean patient age was 64 ± 18 years (range, 18-78). Mean ASD diameter and pulmonary to systemic flow ratio were 18 ± 5 and 2.8 ± 1.0 mm, respectively. Mean PCWP at baseline, during BOT, and after transcatheter closure was 8.9 ± 2.9, 13.5 ± 4.2, and 9.5 ± 2.6 mmHg, respectively. The difference between BOT and after transcatheter closure values was significant (p < 0.001). During BOT, PCWP increased ≥18 mmHg in 7 patients, whereas after ASD closure, PCWP was <18 mmHg in all 7 and none developed acute pulmonary edema. CONCLUSION: Temporary balloon occlusion of an ASD and transcatheter ASD closure result in different hemodynamic change. BOT overestimates increase of PCWP after transcatheter ASD closure and requires careful interpretation. Well-designed, larger studies in higher-risk patients are warranted to verify the clinical implications of BOT in more detail.

Hyaluronan-enriched transfer medium (HETM) can improve the implantation rate in morphologically poor euploid blastocyst transfer.

PURPOSE: Hyaluronan-enriched transfer medium (HETM) could improve the clinical pregnancy rate (CPR) for patients with repeated implantation failures (RIF). In contrast, there have been seldom reports addressing the potentially beneficial effects of HETM for morphologically poor blastocysts (MPBLs). Our study aimed to evaluate whether the use of HETM would improve the CPR for the patients who were transferred with euploid MPBLs. METHODS: Patients who underwent single euploid blastocyst transfer between July 2020 and June 2022 were enrolled. We included only those blastocysts confirmed as euploid by PGT-A, and those blastocysts were transferred after thawing. The natural ovulatory cycle or hormone replacement cycle (HRC) protocol were used for endometrial preparation for frozen embryo transfer (FET). A total of 1,168 FET cycles were performed in the study period, including 954 cycles of morphologically good blastocysts (≥ 4BB in Gardner's classification), and 85 cycles of MPBLs, of which 47 were transferred using HETM in FET (the HETM group), and the remaining 38 were transferred with the medium without hyaluronan (the control group). We compared the CPR between these two groups. RESULTS: The characteristics of patients were similar between the HETM and control groups. The CPR in the HETM group was significantly higher than the control group (47.4% and 21.5%, respectively, p = 0.019). The multiple logistic regression analysis found that the use of HETM was a predictive factor of positive pregnancy outcomes (OR = 5.08, 95% CI = 1.62-16.0, p = 0.019). CONCLUSION: Our data suggests that HETM used in the euploid blastocyst transfer can improve the clinical pregnancy rates of morphologically poor blastocysts.

Transcriptomic profiling analysis of human endometrial stromal cells treated with autologous platelet-rich plasma.

Purpose: To clarify the mechanisms of intrauterine platelet-rich plasma (PRP) infusion that support embryo implantation in in vitro fertilization treatment. Methods: Blood and endometrial samples were collected from four infertile women. Human endometrial stromal cells (HESCs) were cultured and passaged equally into four cell culture dishes in each patient. Two were treated with PRP twice, and the other two were treated with vehicle. Subsequently, two cultures with and without PRP were decidualized with 8-bromoadenosine 3',5'-cyclic AMP and progesterone for 5 days. Results: The gene expression in undifferentiated or decidualized HESCs with and without PRP was compared. In the microarray analysis, 381 and 63 differentially expressed genes were detected in undifferentiated and decidualized HESCs, respectively. In the undifferentiated HESCs, PRP was found to promote the gene expression associated with cell growth, tissue regeneration, proinflammatory response, and antibiotic effects. In decidualized HESCs, PRP was found to attenuate the gene expression involved in cell proliferation and inflammation by inhibiting the expression of phosphoinositide 3-kinase signaling. Conclusions: Platelet-rich plasma regulates the reprogramming of cell proliferation and inflammation depending on menstrual cycle phases in an appropriate manner, suggesting that PRP has the potential to increase endometrial thickness in the proliferative phase and improve immune tolerance in the secretory phase.

Therapeutic efficacy of gentle endometrial curettage on antibiotic-resistant chronic endometritis in infertile women.

Purpose: To identify the efficacy of endometrial curettage on antibiotic-resistant chronic endometritis (CE) in infertile women. Methods: Of 1580 women with CE, 87 with antibiotic-resistant CE after two to five cycles of antibiotic treatment were recruited between 2019 and 2021. The women who underwent endometrial curettage without applying any force and, in the subsequent menstrual cycle, endometrial sampling for CD138 immunostaining without antibiotic use. Pregnancy outcomes after in vitro fertilization treatment were analyzed in women who did not desire endometrial curettage and in those with cured and persistent CE after endometrial curettage. Results: In 64 women who underwent endometrial curettage, the number of CD138-positive cells decreased from 28.0 ± 35.3 to 7.7 ± 14.0 (p < 0.0001), and CE in 41 women (64.1%) was cured (<5 CD138-positive cells). The pathological findings detected 3.1% of endometrial hyperplasia and 1.6% of endometrial cancer. The ongoing pregnancy rates in women aged ≤42 without endometrial curettage were significantly lower than those of women with cured and persistent CE (26.7%, 67.6%, and 57.1%, respectively, p = 0.03). Conclusions: Gentle endometrial curettage for antibiotic-resistant CE significantly decreased the number of CD138-positive cells, resulting in improved pregnancy outcomes regardless of remaining CE. Endometrial curettage is also important as a screening for endometrial malignancy.

Therapeutic efficacy of the optimization of thyroid function, thrombophilia, immunity and uterine milieu (OPTIMUM) treatment strategy on pregnancy outcomes after single euploid blastocyst transfer in advanced age women with recurrent reproductive failure.

Purpose: To clarify the efficacy of the OPtimization of Thyroid function, Thrombophilia, IMmunity and Uterine Milieu (OPTIMUM) treatment strategy on pregnancy outcomes after euploid blastocyst transfer in advanced age women with recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL). Methods: Between January 2019 and May 2022, 193 consecutive women aged ≥40 years with RIF and/or RPL received single euploid blastocyst transfer. Before embryo transfer, 127 women underwent RIF/RPL testing. Chronic endometritis was treated with mainly antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. We compared pregnancy outcomes in the women who did and did not receive the OPTIMUM treatment strategy. Results: Women with RIF/RPL in the OPTIMUM group had significantly higher clinical pregnancy and livebirth rates than did those in the control group (clinical pregnancy rate of 71.7% and 45.5%, p < 0.001; livebirth rate of 64.6% and 39.4%, p = 0.001, respectively). However, preimplantation genetic testing for aneuploidy with and without OPTIMUM promoted low miscarriage rates with no significant difference between them (9.9%, and 13.3%, respectively; p = 0.73). Conclusions: The OPTIMUM treatment strategy improved clinical pregnancy rates after single euploid blastocyst transfer; but not miscarriage rates.

Overview of the 86th Annual Scientific Meeting of the Japanese Circulation Society　- Cardiology Spreading Its Wings.

The 86thAnnual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.

Risk factors for infertility treatment-associated harassment among working women: a Japan-Female Employment and Mental health in assisted reproductive technology (J-FEMA) study.

PURPOSE: This study aims to elucidate the risk factors of infertility treatment-associated harassment (I-harassment) among Japanese working women. METHODS: The study participants were 1103 female patients who enrolled in the Japan-Female Employment and Mental Health in artificial reproductive technology (J-FEMA) study. Of the 1727 female patients, 1103 female patients were working during the initiation of infertility treatment and were still working during the survey. Risk factors for I-harassment were analyzed using a multivariable logistic regression model. RESULTS: In this study, 82 female patients (7.4%) experienced I-harassment. The risk was significantly higher in those who had more in vitro fertilization (IVF) cycles than those who had fewer IVF cycles (OR, 1.06; 95% CI, 1.01-1.10). Similarly, those who disclosed their infertility treatment to their workplace were at significantly higher risk for I-harassment than those who did not (OR, 1.80; 95% CI, 1.03-3.15). CONCLUSION: This study found that 7.4% of female patients experienced I-harassment after infertility treatment initiation. Those female patients who "experienced more IVF cycles," and "disclosed their infertility treatment in their workplace" should be carefully followed up by healthcare professionals to prevent I-harassment.

Therapeutic effects of an oral gonadotropin-releasing hormone receptor antagonist, relugolix, on preventing premature ovulation in mild ovarian stimulation for IVF.

PURPOSE: Can relugolix, a novel oral gonadotropin-releasing hormone receptor (GnRH) antagonist, function as an alternative ovulation inhibitor to GnRH antagonist injections? METHODS: This single-center, cross-sectional retrospective study compared premature ovulation rates and clinical outcomes in IVF treatment after mild ovarian stimulation with 40 mg of relugolix (relugolix group) or 0.25-mg injections of ganirelix acetate or cetrorelix acetate (injection group) between March 2019 and January 2020. Of 247 infertile women (256 IVF cycles) aged ≤42 years, 223 women (230 cycles) were evaluated. In the relugolix and injection groups, we compared 104 and 85 cycles after GnRH antagonist use before the LH surge (LH levels <10 mIU/ml) and 22 and 19 cycles during the LH surge (LH levels ≥10 mIU/ml), respectively. RESULTS: Before the LH surge, the ovulation rates in the two groups were very low (p = 0.838), however; during the LH surge, the cycles using relugolix had a high ovulation rate of 40.9% compared with no ovulation in the injection group (p = 0.002). There were no significant differences in embryo culture findings and pregnancy outcomes between the two groups. CONCLUSIONS: Although relugolix had a high ovulation suppressive effect, when the LH surge occurred, its effect was insufficient.

Feasibility of transcatheter closure for absent aortic rim in patients with atrial septal defect.

OBJECTIVES: This study aimed to assess the feasibility of transcatheter atrial septal defect (ASD) closure in patients with absent aortic rim. BACKGROUND: The indication of transcatheter closure for ASD with absent aortic rim is controversial. METHODS: We enrolled 547 patients with ASD who were scheduled for transcatheter closure. Morphologies of aortic rim were evaluated using transesophageal echocardiography (TEE). RESULTS: Aortic rim of <5 mm was observed in 396 (72%) patients; 128 (23%) had absent aortic rim of 0 mm, and 268 (49%) had deficient aortic rim of >0 to <5 mm. Patients with absent aortic rim frequently had aortic rim absence at an angle of 0° on TEE and septal malalignment. Of the 128 patients with absent aortic rim, 126 (98%) successfully underwent transcatheter closure, while 2 (2%) failed transcatheter closure due to a large defect with severe septal malalignment. The success rate of transcatheter closure was similar between patients with absent aortic rim and those with deficient aortic rim (98% vs. 99%, p = .45). After the procedure, no patients had erosion or device embolization during a median follow-up of 24 months. CONCLUSIONS: Transcatheter closure was successfully performed without adverse events in patients with absent aortic rim, as well as in those with deficient aortic rim. Our findings can be valuable to determine the indication of transcatheter closure in patients with ASD.

Morphological assessments of deficient posterior-inferior rim for transcatheter closure of atrial septal defect.

OBJECTIVES: This study aimed to determine morphological characteristics of deficient posterior-inferior rim for transcatheter atrial septal defect (ASD) closure success. BACKGROUND: The feasibility of transcatheter closure of ASD with deficient posterior-inferior rim remains unclear. METHODS: Of 869 patients with ASD who were scheduled transcatheter closure, 121 with posterior-inferior rim of <5 mm were included. Posterior-inferior rim morphologies were evaluated by transesophageal echocardiography. RESULTS: One hundred six patients successfully underwent transcatheter closure, while 15 patients failed. These 15 patients had complete deficient posterior-inferior rim of 0 mm and/or a large defect of ≥38 mm. Multivariate logistic regression analysis showed that transcatheter closure failure was independently related to complete deficient posterior-inferior rim and a large defect of ≥38 mm. Incomplete deficient posterior-inferior rim of >0 to <5 mm was observed in 84 patients. All these patients successfully underwent transcatheter closure, except two patients with a large defect of ≥38 mm. Complete deficient posterior-inferior rim was observed in 37 patients. The frequency of complete deficient posterior-inferior rim was higher in patients who failed transcatheter closure (87% vs. 23%, p < .01), but transcatheter closure was performed successfully if the range of complete deficient rim was ≤30°. After the procedure, no adverse events occurred during a median follow-up of 24 months. CONCLUSIONS: Most patients with deficient posterior-inferior rim successfully underwent transcatheter closure. Transcatheter closure could be performed even in patients with complete deficient posterior-inferior rim if the range was partial. Our findings can help to identify candidates for transcatheter closure.

Efficacy and safety of atrial septal defect closure using Occlutech Figulla Flex II compared with Amplatzer Septal Occluder.

Few studies have reported the efficacy of Occlutech Figulla Flex II (FFII) device compared with Amplatzer Septal Occluder (ASO) device. The aim of this study was to examine the efficacy and safety of FFII compared with ASO for transcatheter atrial septal defect (ASD) closure. We retrospectively evaluated 190 patients using FFII and 190 patients using ASO who underwent transcatheter ASD closure. ASD characteristics were evaluated by transesophageal echocardiography. The prevalence of procedural complications, including erosion, device embolization, stroke, and new-onset atrial arrhythmia, and the presence of a residual shunt were evaluated between the two groups during 12-month follow-up. FFII was used more frequently than ASO in patients with a deficient aortic rim or septal malalignment (P = 0.02, P < 0.01, respectively). The procedural complications of erosion, device embolization, and stroke did not occur in any patients. New-onset atrial arrhythmia occurred in 3 patients of the FFII group and 4 patients of the ASO group, and the difference between the two groups was not significant (P = 0.70). A large residual shunt (≥ 3 mm) was observed in 6 patients of the FFII group and 5 patients of the ASO group, and the difference between the two groups was not significant (P = 0.76). FFII was used frequently in patients with high-risk ASD morphology; however, there was no difference in the prevalence of procedural complications or efficacy between patients using FFII and those using ASO.

Importance of direct right-to-left shunt as high-risk patent foramen ovale associated with cryptogenic stroke.

BACKGROUND: Because transcatheter closure of patent foramen ovale (PFO) has become effective for preventing cryptogenic stroke (CS), it is necessary to determine high-risk PFO associated with CS. This study aimed to clarify the importance of direct right-to-left (RL) shunt through the PFO for identifying high-risk PFO. METHODS: We analyzed 137 patients with and without CS who were confirmed to have PFO. The timing of RL shunt through the PFO was evaluated by cardiac cycles after right atrium (RA) opacification on saline contrast transesophageal echocardiography. Direct RL shunt was defined as microbubbles crossing the PFO before and at the same time of RA opacification. RESULTS: Cardiac cycles of microbubbles crossing the PFO were shorter in patients with CS than in those without CS (2.0 ± 2.2 vs .5 ± 1.1, p < 0.01). Direct RL shunt was more frequently observed in patients with CS than in those without CS (77% vs 29%, p < 0.01), with a sensitivity of 79% and a specificity of 71% for the association with CS. Multivariate analysis revealed that direct RL shunt was related to atrial septal aneurysm and low-angle PFO. Regarding functional features of PFO, the detection rate of CS was 50% for large RL shunt alone, and was increased to 83% when direct RL shunt was added. CONCLUSION: Direct RL shunt was associated with CS and had the incremental value in detecting PFO associated with CS for large RL shunt. The timing of RL shunt can be valuable for identifying high-risk PFO.

Analysis of severe psychological stressors in women during fertility treatment: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study.

PURPOSE: To identify risk factors for severe psychological stress in women undergoing fertility treatment. METHODS: This cross-sectional, multi-center study was conducted from August to December 2018. We recruited 1672 subjects who completed an anonymous, self-reported questionnaire regarding fertility treatment, conditions at work and home, and psychological stress using K6 score, which estimates psychological distress during the previous 30 days. We further focused our analysis on 1335 subjects who were working when starting fertility treatment. RESULTS: Of 1672 women, mean K6 score (range 0-24) was 4.8 ± 4.4, including 103 women (6.2%) with K6 score ≥ 13 (high K6), and classified as probable severe psychological distress. Multivariate logistic regression analysis showed that high K6 was strongly associated with low annual family income of ≤ USD55,700 (JPY6 million) (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.04-3.42), infertility duration of ≥ 2 years (OR 1.87, 95% CI 1.08-3.25), and no experience of childbirth (OR 2.04, 95% CI 1.05-3.97). Focusing on 1335 working women, 266 (19.9%) experienced resignation from work. High K6 was strongly associated with low family income (OR 2.83, 95% CI 1.52-5.28), cessation of professional duties (OR 2.08, 95% CI 1.05-4.14), infertility-related harassment in the workplace (OR 2.07, 95% CI 1.08-3.98), and perceived difficulties to continue working during fertility treatment (OR 2.94, 95% CI 1.15-7.50). CONCLUSION: Severe psychological stressors in women during fertility treatment included low family income, long infertility duration, childlessness, infertility-related harassment, and perceived difficulty in working conditions or cessation from work. Establishment of mental health care support systems is urgently required in this population.

Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy.

PURPOSE: Does the OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy, developed for treating repeated implantation failure (RIF), contribute to improving pregnancy outcomes in patients with a history of recurrent pregnancy loss (RPL)? METHODS: Between 2018 and 2019, women with RPL after two or more clinical pregnancy losses underwent RPL testing. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 168 consecutive women aged ≤43 years, 115 underwent RPL testing. We compared 100 pregnancies (90 women) and 46 pregnancies (41 women) with and without the OPTIMUM treatment strategy, respectively. RESULTS: RPL testing identified intrauterine abnormalities in 66 (57.4%), elevated Th1/Th2 cell ratios in 50 (43.5%), thyroid dysfunction in 33 (28.7%), and thrombophilia in 33 (28.7%). The live birth rate in the OPTIMUM group was significantly higher than that in the control group among women aged <40 years (78.1% and 42.3%, respectively; p = 0.002), but no significant difference was observed in women aged ≥40 years (55.6% and 30.0%, respectively; p = 0.09). CONCLUSIONS: The OPTIMUM treatment strategy improved pregnancy outcomes in patients with not only RIF but also RPL.

Clinical Significance of Septal Malalignment for Transcatheter Closure of Atrial Septal Defect.

BACKGROUND: Septal malalignment is related to erosion and device embolization in transcatheter closure of atrial septal defect (ASD), but limited information is available. OBJECTIVES: This study aimed to assess clinical significance of septal malalignment and to determine appropriate evaluation of ASD diameter, including the selection of device size. METHODS: Four hundred and seventeen patients with ASD who underwent transcatheter closure were enrolled. Septal malalignment was defined as separation between the septum primum and the septum secundum on transesophageal echocardiography. RESULTS: One hundred and eighty-four patients had septal malalignment. The frequency of septal malalignment increased with age reaching around 50% in adult patients. Septal malalignment was related to aortic rim deficiency. The distance of separation between the septum primum and the septum secundum was 5 ± 2 mm (range, 1-11 mm). In patients with septal malalignment, the ASD diameter measured at the septum primum was 19 ± 6 mm, while the ASD diameter measured at the septum secundum was 16 ± 6 mm. There was a difference of 4 ± 2 mm (range, 0-8 mm) between the ASD diameter measured at the septum primum and that measured at the septum secundum. For transcatheter closure, the Amplatzer Septal Occluder device size 2-3 mm larger and the Occlutech Figulla Flex II device size 4-7 mm larger than the ASD diameter measured at the septum primum were frequently used. During the study period, erosion or device embolization did not occur in all of the patients. CONCLUSIONS: Septal malalignment is highly prevalent in adult patients with aortic rim deficiency. The measurement of ASD diameter at the septum primum can be valuable for the selection of device size in patients with septal malalignment.

Impact of Right Ventricular Dilatation in Patients with Atrial Septal Defect.

OBJECTIVE: The aim of this study was to examine the relationship between right ventricular (RV) volume and exercise capacity in adult patients with atrial septal defect (ASD) and to determine the degree of RV dilatation for transcatheter ASD closure. BACKGROUND: RV dilatation is an indication of transcatheter ASD closure; however, few studies have reported the clinical significance of RV dilatation. METHODS: We enrolled 82 consecutive patients (mean age, 49 ± 18 years; female, 68%) who underwent cardiac magnetic resonance imaging and symptom-limited cardiopulmonary exercise test before ASD closure. The relationship between RV volume and peak oxygen uptake (VO2) was evaluated. RESULTS: The mean RV end-diastolic volume index was 108 ± 27 ml/m2 (range, 46 to 180 ml/m2). The mean peak VO2 was 24 ± 7 ml/min/kg (range, 14 to 48 ml/min/kg), and the mean predicted peak VO2 was 90 ± 23%. There were significant negative relationships of RV end-diastolic volume index with peak VO2 (r = -0.28, p < 0.01) and predicted peak VO2 (r = -0.29, p < 0.01). The cutoff value of RV end-diastolic volume index <80% of predicted peak VO2 was 120 ml/m2, with the sensitivity of 49% and the specificity of 89%. CONCLUSIONS: There was a relationship between RV dilatation and exercise capacity in adult patients with ASD. RV end-diastolic volume index ≥120 ml/m2 was related to the reduction in peak VO2. This criterion of RV dilatation may be valuable for the indication of transcatheter ASD closure.

Indication and prognostic significance of programmed ventricular stimulation in asymptomatic patients with Brugada syndrome.

AIMS: To establish the indication for programmed ventricular stimulation (PVS) for asymptomatic patients with Brugada syndrome (BrS), we evaluated the prognostic significance of PVS based on abnormal electrocardiogram (ECG) markers. METHODS AND RESULTS: One hundred and twenty-five asymptomatic patients with BrS were included. We performed PVS at two sites of the right ventricle with up to three extrastimuli [two pacing cycle lengths and minimum coupling interval (MCI) of 180 ms]. We followed the patients for 133 months and evaluated ventricular fibrillation (VF) events. Fragmented QRS (fQRS) and Tpeak-Tend (Tpe) interval were evaluated as ECG markers for identifying high-risk patients. Fragmented QRS and long Tpe interval (≥100 ms) were observed in 66 and 37 patients, respectively. Ventricular fibrillation was induced by PVS in 60 patients. During follow-up, 10 patients experienced VF events. Fragmented QRS, long Tpe interval, and PVS-induced VF with an MCI of 180 ms or up to two extrastimuli were associated with future VF events (fQRS: P = 0.015, Tpe ≥ 100 ms: P = 0.038, VF induction: P < 0.001). However, PVS-induced VF with an MCI of 200 ms was less specific (P = 0.049). The frequencies of ventricular tachyarrhythmia events during follow-up were 0%/year with no ECG markers and 0.1%/year with no VF induction. The existence of two ECG factors with induced VF was strongly associated with future VF events (event rate: 4.4%/year, P < 0.001), and the existence of one ECG factor with induced VF was also associated (event rate: 1.3%/year, P = 0.011). CONCLUSION: We propose PVS with a strict protocol for asymptomatic patients with fQRS and/or long Tpe interval to identify high-risk patients.

New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Multiple spikes in the QRS complex (fragmented QRS [fQRS]) on 12-lead electrocardiography have been associated with ventricular arrhythmic events (VAEs) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess the association between new appearances of fQRS and cardiac events in patients with HCM.Methods and Results:The association between baseline fQRS and cardiac events, namely VAEs, heart failure-related hospitalization, and all-cause death, was evaluated retrospectively in 146 HCM patients (46 patients with fQRS, 100 without fQRS). The median follow-up was 5.3 years. Cardiac events occurred in 29 patients with baseline fQRS and 32 patients without baseline fQRS (63% vs. 32%; P<0.001). VAEs occurred in a significantly larger percentage of patients with than without baseline fQRS (54% vs. 23%, respectively; P<0.001). Of the 100 patients without baseline fQRS, 33 had a new appearance of fQRS during the 4.6-year follow-up, whereas 67 did not. VAEs occurred more frequently in the 33 patients with the appearance of fQRS than in those without (42% vs. 13%, respectively; P=0.001). Multivariable analysis showed that the new appearance of fQRS documented before VAEs was associated with VAEs (hazard ratio 4.29, 95% confidence interval 1.81-10.2; P=0.001). CONCLUSIONS: The new appearance of fQRS was associated with an increased risk of VAEs in HCM patients.