Ultrahigh density atrio-ventricular dual-chamber mapping as a next generation tool for ablation of accessory pathways.

INTRODUCTION: Detailed three-dimensional (3D) mapping has been useful for effective radiofrequency catheter ablation. The Rhythmia system can create atrio-ventricular dual-chamber mapping, which reveals the atrial and ventricular potentials all at once in the same map. The aim of this study was to investigate the utility of mapping the atrium and ventricle simultaneously with a high-density 3D mapping system for the ablation of accessory pathways (AP). METHODS: From July 2015 to August 2020, 111 patients underwent ablation of APs. Dual-chamber maps were created in 50 patients (median age 15 [10-54], 32 male [64.0%]), while 61 patients underwent radiofrequency (RF) ablation with conventional single-chamber 3D maps. The background characteristics and procedural details were compared between the dual-chamber mapping group and the conventional single-chamber mapping group. RESULTS: The number of RF applications (median [IQR]; 1.0 [1.0-3.0] vs. 3.0 [1.0-6.0], p = .0023), RF time (median [IQR], s; 9.2 [2.0-95.7] vs. 95.6 [4.1-248.7], p = .0107), and RF energy (median [IQR], J; 248.4 [58.7-3328.2] vs. 2867.6 [134.2-7728.4], p = .0115) were significantly lower in the dual-chamber group. The fluoroscopy time (median [IQR], min; 19.9 [14.2-26.1] vs. 26.5 [17.7-43.4], p = .0025) and fluoroscopy dose (median [IQR], mGy; 52.5 [31.3-146.0] vs. 119.0 [43.7-213.5], p = .0249) were also significantly lower in the dual-chamber than single-chamber mapping group. CONCLUSION: The dual-chamber mapping was useful for ablating accessory pathways and reducing the number of RF applications, total RF energy, and radiation exposure as compared with traditional mapping techniques.

Uterine intravenous leiomyomatosis with an isolated large metastasis to the right atrium: a case report.

BACKGROUND: An intravenous leiomyomatosis is a special type of uterine leiomyoma characterized by the formation of benign leiomyomatous tissue within the vascular wall. Although histologically benign, intracardiac metastasis can lead to circulatory failure, and death, if untreated. Herein, we report on a case of a uterine intravenous leiomyomatosis with an isolated large adherent metastasis in the right atrium of the heart. CASE PRESENTATION: A 52-year-old Japanese woman sought medical attention at our hospital for lower abdominal pain. A 27-cm uterine mass was detected on clinical imaging, with a 78 × 47-mm mass in the right atrium detected on preoperative echocardiography. Intracardiac mass resection and tricuspid annuloplasty were performed as the first-stage surgery. The pedicle of the tumor was adherent to the wall of the atrium. On histological examination, the tumor was found to consist of spindle-shaped cells with eosinophilic cytoplasm, without atypia, but with a myxoid change, and rich microvascularization of the pedicle. Total abdominal hysterectomy was performed as the second-stage surgery, with confirmation of the diagnosis as uterine intravenous leiomyomatosis with an isolated metastasic lesion to the right atrium. There has been no evidence of tumor recurrence in the 15 months since surgery. CONCLUSION: We report a unique case in which a large right atrial leiomyoma was identified following a uterine intravenous leiomyomatosis. Our case exemplifies that intravenous leiomyomatosis metastatic tumors have the potential to grow via their vascularization.

Influence of various energy settings and overlap ratios on size and continuity of lesions in a laser balloon ablation in vitro model.

INTRODUCTION: The influence of power (Watt [W]) and total energy (Joule [J]) on lesion size and the optimal overlap ratio remain unclear in laser balloon (LB) ablation for atrial fibrillation. We aimed to evaluate lesion size and visible gaps after LB ablation with various energy settings and different overlap ratios in vitro model. METHODS AND RESULTS: Chicken muscles were cauterized using the first-generation LB with single applications of full and a half duration of six energy settings (5.5 W/30 seconds [165 J] to 12 W/20 seconds [240 J]) and varying power (5.5-12 W) at the constant total energy (160 J). Three overlapped ablations with different ratios (25% and 50%) for each energy setting were also performed to evaluate the visible gap degree categorized from 1 (perfect) to 3 (poor). Twenty lesions were evaluated for each energy setting. In single applications of full duration, lesion depth, lesion volume, and maximum lesion diameter increased according to the total energy (all, P < .001) and were greater than in those of half duration in each energy setting (all, P < .05). However, applications with larger power created larger lesion volume and maximum lesion diameter at constant total energy (P < .05). The visible gap degree was better in all energy settings with 50% overlapped ablation than in those with 25% (all, P < .001). CONCLUSION: Lesion size depends not only on power but also on total energy in the LB ablation. Sufficiently overlapped ablations allow continuous lesion formation.

Real-time observation of pathophysiological processes during murine experimental Schistosoma japonicum infection using high-resolution ultrasound imaging.

BACKGROUND: Hepatosplenic lesion formation is one of the typical clinical symptoms of schistosomiasis japonica. Although it is established that circum-oval granuloma formation mediated by T lymphocytes is the key event triggering the formation of hepatic lesions, the time-course kinetics of disease progression remains to be fully elucidated. METHODS: The real-time process of the pathophysiology of schistosomiasis japonica from the early to late clinical phase was non-invasively observed in a murine experimental infection model using high-resolution ultrasonography. Together with clinical parameters, including body weight and the levels of serum markers of hepatic damage or fibrosis, ultrasonography was used to assess changes in the liver parenchyma and diameter of the portal vein and portal blood flow velocity. In parallel, parasitological parameters were observed, including egg number in the feces and maturation of parasites. RESULTS: Abnormal high-echo spot patterns in the liver parenchyma, reflecting hepatic fibrosis in ultrasonography, appeared in the liver at 4 weeks post-infection and the pattern became more enlarged and severe over time. This finding was concordant with parasite maturation and initial egg excretion. The serum M2BPGi level markedly increased from 8 weeks post-infection, suggesting sharp deterioration of hepatic fibrosis. At the same time, the diameter of the portal vein, reflecting portal hypertension, became enlarged and reached the peak level at 8 weeks post-infection. Ascites were apparent around the spleen at 9 weeks post-infection, and dilatation of the splenic vein was noted at 10 weeks post-infection. Live adult worms seemed to be detected in the portal vein at 4 weeks post-infection by ultrasonography. CONCLUSIONS: We obtained real-time imaging of the development of hepatosplenic lesions of schistosomiasis japonica in mice. The time-course kinetics of the onset, development, and modulation of each symptom was uncovered. These results are expected to provide new clues for understanding the pathophysiology of human schistosomiasis japonica.

Analysis of the heart rate variability during cryoballoon ablation of atrial fibrillation.

Aims: Vagal responses such as marked bradycardia or a rapid blood pressure decrease are often observed during pulmonary vein (PV) isolation of atrial fibrillation (AF) using a cryoballoon (CB). However, the relationship between the marked vagal response and change in the heart rate variability (HRV) as a marker of the autonomic tone is not well understood. Methods and results: Fifty-four paroxysmal AF patients underwent CB ablation. The CB ablation was started from the right sided PVs in 25 patients (R group) and left sided PVs in 29 (L group). The HRV and haemodynamic status during the procedure were analysed. A vagal response was observed in 16 L group patients (61.5%) during the ablation of the different PVs (RSPV:1, RIPV:5, LSPV:15, LIPV:5), while it was observed in only 2 R group patients (9.5%) (RSPV:0, RIPV:0, LSPV:1, LIPV:1) (P = 0.0002). The HRV in the L group was significantly higher than that in the R group just after the CB ablation especially for the left sided PVs (L group vs. R group, total power of the HRV, median; RSPV, 11184.7 vs. 4360.0, P = 0.21; RIPV, 9044.3 vs. 2115.1, P = 0.01; LSPV, 21186.0 vs. 1314.2, P = 0.0002; LIPV 10265.9 vs. 1236.2, P = 0.0007). Conclusion: A marked increase in the HRV parameters was observed just after the CB ablation. An initial CB ablation of the right PVs decreased the change in the autonomic tone during the right PV ablation and subsequent left PV ablation. It prevented an excessive vagal response during the CB ablation and might be a safe procedure.

Nuclear hormone receptor LXRα inhibits adipocyte differentiation of mesenchymal stem cells with Wnt/beta-catenin signaling.

Nuclear hormone receptor liver X receptor-alpha (LXRα) has a vital role in cholesterol homeostasis and is reported to have a role in adipose function and obesity although this is controversial. Conversely, mesenchymal stem cells (MSCs) are suggested to be a major source of adipocyte generation. Accordingly, we examined the role of LXRα in adipogenesis of MSCs. Adult murine MSCs (mMSCs) were isolated from wild-type (WT) and LXR-null mice. Using WT mMSCs, we further generated cell lines stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) or GFP alone (mMSC/GFP) by retroviral infection. Confluent mMSCs were differentiated into adipocytes by the established protocol. Compared with MSCs isolated from WT mice, MSCs from LXR-null mice showed significantly increased adipogenesis, as determined by lipid droplet accumulation and adipogenesis-related gene expression. Moreover, mMSCs stably overexpressing GFP-LXRα (mMSC/LXRα/GFP) exhibited significantly decreased adipogenesis compared with mMSCs overexpressing GFP alone (mMSC/GFP). Since Wnt/beta-catenin signaling is reported to inhibit adipogenesis, we further examined it. The LXR-null group showed significantly decreased Wnt expression accompanied by a decrease of cellular beta-catenin (vs WT). The mMSC/LXRα/GFP group exhibited significantly increased Wnt expression accompanied by an increase of cellular beta-catenin (vs mMSC/GFP). These data demonstrate that LXRα has an inhibitory effect on adipogenic differentiation in mMSCs with Wnt/beta-catenin signaling. These results provide important insights into the pathophysiology of obesity and obesity-related consequences such as metabolic syndrome and may identify potential therapeutic targets.

A rare case of fungal endocarditis caused by Candida glabrata after completion of antibiotic therapy for Streptococcus endocarditis.

We present the rare case of a 76-year-old female with infective endocarditis (IE) caused by Candida glabrata. Immediately before developing the present infection, she developed IE with vegetation on the mitral annular calcification, which was caused by Streptococcus mitis and successfully treated with penicillin-G and gentamicin. However, her fever recurred, and she developed disseminated intravascular coagulation. Blood culture revealed C. glabrata, and echocardiography revealed new vegetation on the mitral valve. After 4 weeks of treatment with micafungin, prosthetic valve replacement was performed, followed by additional administration of micafungin for 4 weeks (total of 8 weeks). No relapse at 9 months after surgery has been observed. C. glabrata endocarditis is extremely rare and difficult to manage. Our case and review of past reported cases suggest that early diagnosis and initiation of treatment contribute to good prognosis of C. glabrata endocarditis.

Bioprosthetic tricuspid valve replacement in carcinoid heart disease from primary ovarian carcinoid tumor.

Carcinoid heart disease (CHD) commonly occurs in association with primary gastrointestinal tract carcinoid tumors with hepatic metastases. Unlike primary gastrointestinal tract carcinoid tumors, primary ovarian carcinoid tumors may cause CHD without hepatic metastases, accounting for only 0.3 % of all carcinoid tumors. Only 37 cases of CHD from primary ovarian carcinoid tumors have been reported. We present a case of CHD in which tricuspid valve thickening and shortening led to reduced valve mobility with the resulting severe tricuspid regurgitation. Considering these characteristics of an abnormal tricuspid valve, we suspected CHD, but prosthetic valve replacement was performed without sufficient systemic examination before surgery. Two years after valve replacement, the patient underwent excision of a mass in the lower abdomen, which was diagnosed as an ovarian carcinoid tumor by histopathological examination. The patient has been observed for more than 3 years after tricuspid valve replacement. She has not experienced bioprosthetic valve leaflet degeneration or dysfunction, although it has been reported that bioprosthetic valves may degenerate in patients with carcinoid tumors. Sufficient systemic examinations should be performed to explore the cause of disease.

Prediction of improvement in left atrial function index after catheter ablation for atrial fibrillation.

PURPOSE: Although left atrial function index is reportedly a possible predictor of hospitalization for heart failure and of stroke irrespective of the presence or not of atrial fibrillation (AF), the effects of catheter ablation on left atrial function index have not yet been reported. METHODS: We performed catheter ablation on 55 patients (age 56.6 ± 9.6 years; 44 men; 30 with paroxysmal and 25 with persistent, long-standing AF) and evaluated them by transthoracic echocardiography preoperatively and 3 monthly for 12-24 months after catheter ablation. We then compared clinical characteristics and echocardiographic variables before catheter ablation between two groups: the 42 subjects with the most recent left atrial function index <30 and the 13 in which it was ≥30. RESULTS: Left atrial function index improved after catheter ablation in both groups, plateauing 6 months after the procedure. Univariate analysis showed statistically significant differences in the prevalence of chronic AF and left atrial emptying fraction, diameter, and maximum and minimum volume (prevalence of chronic AF, p < 0.05; others, p < 0.01) between the groups. Multivariate analysis showed that only maximum left atrial volume predicts left atrial function index after catheter ablation (p < 0.05). In addition, we used ROC analysis to calculate a cutoff value for LA maximum volume as a good predictor and found that a good cutoff value was 63.5 mL, the sensitivity and specificity being 0.75 and 0.75, respectively. CONCLUSIONS: Catheter ablation improves left atrial function index. However, in patients with left atrial maximum volume of over 63.5 mL on echocardiography, the index did not recover to within the normal range after catheter ablation.

Isolated accessory mitral valve tissue in an asymptomatic elderly patient.

Accessory mitral valve tissue is a membranous or tumor-like structure observed in the left ventricular outflow tract. This congenital anomaly has been reported in more than 100 cases since 1842; however, most of them were found in patients with complex cardiac malformations. We report a 72-year-old Asian woman with isolated accessory mitral valve tissue incidentally found during the evaluation of hypertension and arrhythmia. Her left ventricular outflow tract obstruction was mild. Because worsening of the left ventricular outflow tract obstruction was reported in patients without significant obstruction at the time of diagnosis, periodical echocardiographic follow-up is necessary.

Effect of lesional differences in prolapsed leaflets on clinical outcomes in patients with mitral valve prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is usually benign, although serious complications may occur. It remains unclear whether the region of prolapsed mitral leaflets might affect prognosis. The aim of this study was to investigate lesional differences of clinical courses of MVP. METHODS AND RESULTS: We retrospectively investigated 128 MVP patients who had been followed up for for a mean of 56.4 months. They were classified into prolapse of the anterior mitral leaflet (AML, n = 59), posterior mitral leaflet (PML, n = 47), or both leaflets (AML & PML, n = 22). Echocardiographic and clinical data were examined from medical records. Average time to clinical events; MV surgery, new onset of atrial fibrillation (AF), echocardiographic evidence of new chordal rupture, and worsening of mitral regurgitation severity were all significantly shorter in PML prolapse than in those with AML or AML & PML prolapses. Increases in the left ventricular dimensions and estimated pulmonary arterial systolic pressures were significantly larger in PML prolapse, compared with AML or AML & PML prolapses. A subanalysis of PML prolapse revealed that new chordal rupture tended to be more frequent in middle scallop prolapse (48%) compared with lateral and medial scallops (18%). In contrast, new onset of AF tended to occur in lateral and medial scallop prolapses (44%) compared with middle scallop prolapse (20%). CONCLUSIONS: PML prolapse patients had a poor outcome, compared with AML or AML & PML prolapse patients. Precise regional evaluation of the prolapsed leaflets may predict cardiac complications in MVP.

Reconstruction of the free margin of the anterior mitral leaflet with autologous pericardium in active infected endocarditis.

In patients with active infective endocarditis mitral valve repair is better than mitral valve replacement, but it remains a challenge when there has been massive destruction of the rough zone of the anterior leaflet. We report a technical modification of mitral valve repair for advanced active infective endocarditis in which a widely infected rough zone and the chordae were successfully replaced with autologous pericardium and multiple artificial chordae. The procedure described here is capable of improving the prospects of mitral valve repair in advanced infective endocarditis.

Mesenchymal stem cells differentiate into renin-producing juxtaglomerular (JG)-like cells under the control of liver X receptor-alpha.

Renin is a key enzyme for cardiovascular and renal homeostasis and is produced by highly specialized endocrine cells in the kidney, known as juxtaglomerular (JG) cells. The nature and origin of these cells remain as mysteries. Previously, we have shown that the nuclear hormone receptor liver X receptor-alpha (LXRalpha) is a major transcriptional regulator of the expression of renin, c-myc, and other genes involved with growth/differentiation. In this study we test the hypothesis that LXRalpha plays an important role not only in renin expression but also in renin-containing cell differentiation, specifically from the mesenchymal stem cell (MSC), which may be the origin of the JG cell. Indeed, our data demonstrated that LXRalpha activation by its ligands or cAMP stimulated renin gene expression in both murine and human MSCs. Furthermore, sustained cAMP stimulation of murine MSCs overexpressing LXRalpha led to their differentiation into JG-like cells expressing renin and alpha-smooth muscle actin. These MSC-derived JG-like cells contained renin in secretory granules and released active renin in response to cAMP. In conclusion, the activation of LXRalpha stimulates renin expression and induces MSCs differentiation into renin-secreting, JG-like cells. Our results suggest that the MSC may be the origin of the juxtaglomerular cell and provide insight into novel understanding of pathophysiology of the renin-angiotensin system.

Extrinsic compression of the left main coronary artery by atrial septal defect.

On rare occasions, extrinsic compression of the coronary artery can cause significant stenosis. We report a 42-year-old woman who was referred to our hospital for surgical repair of atrial septal defect. Cardiac 64-slice multi-detector computed tomography before the operation revealed the extrinsic compression of the proximal left main coronary artery by the marked dilatation of pulmonary trunk. The patient eventually underwent atrial septal defect closure and coronary artery bypass simultaneously. Four months after the operation, multi-detector computed tomographic scan revealed reduction of pulmonary trunk diameter and resolution of left main coronary artery narrowing.

A case report of surgical correction for congenital mitral regurgitation with subvalvular apparatus abnormality.

We report a successful complex mitral valve plasty using port access minimally invasive cardiac surgery for congenital mitral regurgitation that presented as an abnormality of the subvalvular apparatus. A 16-year-old male patient received a diagnosis of mitral regurgitation resulting from tethering of the anterior mitral leaflet and posterior mitral leaflet caused by an abnormality in papillary muscle insertion and a hypoplastic chordae tendineae. The posterior leaflet was closely tethered to the tips of the papillary muscle with essentially no chordae tendineae. The flexibility of the leaflet was restored by surgically removing the abnormal chordae, and reconstruction of chordae tendinae of the anterior leaflet was carried out using three loops and of the posterior leaflet using one loop with a loop technique method. As an additional procedure for persistent regurgitation, an edge-to-edge technique to the posterior commissure side was performed, after which the mitral regurgitation disappeared.

Interleukin-6/soluble interleukin-6 receptor complex reduces infarct size via inhibiting myocardial apoptosis.

Apoptosis of cardiomyocytes plays an important role in reperfusion injury following myocardial infarction. Conversely, interleukin-6 (IL-6)--a potent cytokine--inhibits myeloma cell apoptosis by activating GP130 through the IL-6 receptor (IL-6R). We hypothesized that the IL-6/soluble IL-6R complex can inhibit myocardial apoptosis, and limit infarct size in reperfused acute myocardial infarction. Anesthetized rats were randomly divided into five groups: sham, coronary occlusion and reperfusion rats administered IL-6/soluble IL-6R complex, IL-6 alone, soluble IL-6R (sIL-6R) alone, or a control vehicle. Rats were subjected to 30 min occlusion of the left coronary artery followed by 3 h reperfusion. After reperfusion, the hearts were excised. For detection and quantification of apoptosis, gel electrophoresis of extracted genomic DNA and TUNEL method of paraffin sections were performed. The percentage of the infarct area was measured using tetrazolium chloride staining. The cardiomyocyte apoptosis analysis revealed that apoptosis in the reperfused myocardium was inhibited only in the complex group. Furthermore, the percentage of the infarct area out of the area at risk was remarkably reduced in the complex group (23.8+/-1.8%), compared with that in the vehicle (37.9+/-3.7%), the IL-6 (40.7+/-1.0%), or the sIL-6R (37.5+/-2.4%) groups (P=0.0002). No significant differences were observed among the vehicle, IL-6, and sIL-6R groups. The IL-6/soluble IL-6 receptor complex inhibits cardiomyocyte apoptosis in reperfused acute myocardial infarction. It possibly reduces irreversible reperfusion injury.

Targeted deletion or pharmacological inhibition of MMP-2 prevents cardiac rupture after myocardial infarction in mice.

MMPs are implicated in LV remodeling after acute myocardial infarction (MI). To analyze the role of MMP-2, we generated MI by ligating the left coronary artery of MMP-2-KO and WT mice, the latter of which were administered orally an MMP-2-selective inhibitor or vehicle (TISAM). The survival rate was significantly higher in MMP-2-KO and TISAM-treated mice than in control WT mice. The main cause of mortality in control WT mice was cardiac rupture, which was not observed in MMP-2-KO or TISAM-treated mice. Control WT mice, but not MMP-2-KO or TISAM-treated mice, showed activation of the zymogen of MMP-2, strong gelatinolytic activity, and degradation of ECM components, including laminin and fibronectin, in the infarcted myocardium. Although infarcted cardiomyocytes in control WT mice were rapidly removed by macrophages, the removal was suppressed in MMP-2-KO and TISAM-treated mice. Macrophage migration was induced by the infarcted myocardial tissue from control WT mice and was inhibited by treatment of macrophages with laminin or fibronectin peptides prior to migration assay. These data suggest that inhibition of MMP-2 activity improves the survival rate after acute MI by preventing cardiac rupture and delays post-MI remodeling through a reduction in macrophage infiltration.

Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene.

EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1 alpha promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 -- possible heterodimeric partners for EAT in the anti-apoptotic process -- were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.