Impact of long-term optimizing atrioventricular delay using device-based algorithms on cardiac resynchronization therapy.

Sub-optimal atrioventricular delay (AVD) is one of the main causes of non-responder for cardiac resynchronization therapy (CRT). Recently, device-based algorithms (DBAs) that provide optimal AVD based on intracardiac electrograms, have been developed. However, their long-term effectiveness is still unknown. This study aims to investigate the effect of optimizing AVD using DBAs over a long period, on the prognosis of patients undergoing CRT. A total of 118 patients who underwent CRT at our hospital between April 2008 and March 2018, were retrospectively reviewed; 61 of them with optimizing AVD using DBAs were classified into the treated group (group 1), and the remaining 57 were classified into the control group (group 2). The median follow-up period was 46.0 months. The responder and survival rate in group 1 were significantly better than those in group 2 (group 1 vs. group 2: responder rate = 64% vs. 46%, p = 0.046; survival rate: 85.2% vs. 64.9%, p = 0.02). Moreover, investigating only the non-responder population showed that group 1 had an improved survival rate compared to group 2 (group 1 vs. group 2 = 72.7% vs. 45.1%, p = 0.02). Optimizing AVD using DBAs was a significant contributor to the improved survival rate in CRT non-responders in multivariate analysis (HR 3.6, p = 0.01). In conclusion, the long-term optimizing AVD using DBAs improved the survival rate in CRT and the prognosis of CRT non-responders, as well.

Chest computer tomography is safe without additional interrogation or monitoring for modern cardiac implantable electrical devices.

INTRODUCTION: Whether diagnostic computed tomography (CT) scans to cardiac implantable electronic devices (CIED) is safe in recent models remains unknown. METHODS: A two-centers observational study. Over 14 years, consecutive 2362 chest CT scans (1666 pacemakers [PMs], 145 cardiac resynchronization therapy PM, 316 implantable cardioverter-defibrillator, and 233 cardiac resynchronization therapy defibrillator) were interrogated and monitored upon imaging. RESULTS: Electromagnetic interference occurred only in a few old models: InSync 8040 (n = 14), InSync III Marquis (n = 1), and Kappa (n = 4), which resulted no adverse events. CONCLUSION: CIEDs, especially recent ones, are confirmed safe on chest CT.

Ablation characteristics and incidence of steam pops with a novel, surface temperature-controlled ablation system in an ex vivo experimental model.

BACKGROUND: A novel irrigation catheter (QDOT MICRO™) has been introduced, which enables a surface temperature-controlled ablation combined with tip cooling. However, the detailed description of its complex behavior and effect on the incidence of pops and lesion formation remains elusive. This study aimed to systematically investigate the ablation characteristics, feedback behavior, and incidence of steam pops in a simplified ex vivo swine model. METHODS: Using swine ventricular tissue perfused with saline at 37°C, we systematically created lesions with 4×3 combinations of the wattage (20, 30, 40, and 50 W) and contact force (CF, 10, 30, and 50 g). Ablation was continued for either 120 s or until a steam pop occurred and repeated 10 times with each setting. The lesion geometry, ablation index, feedback dynamics, and conditions underlying the steam pops were measured and analyzed. RESULTS: Steam pops occurred particularly frequently in combinations of a low CF and high power (10 g vs. 30 g+50 g [p < .0001]; 40 W+50 W vs. 20 W+30 W [p < .0001]). Failure to activate a feedback process was associated with a 5.1 times higher incidence of steam pops (21/109 vs.11/11, [95% CI 3.499-7.716], p < .0001). The wattage feedback was particularly evident with a high CF (30 and 50 g) and high initial wattage (40 and 50 W). The average delivered wattage at 27 W predicted the occurrence of steam pops. CONCLUSION: The temperature-controlled ablation with the QDOT MICRO™ demonstrated a complex feedback behavior, which contributed to a reduced incidence of steam pops and prolonged lead time to the pops.

Characteristics and optimal ablation settings of a novel, contact-force sensing and local impedance-enabled catheter in an ex vivo perfused swine ventricle model.

BACKGROUND: Local impedance (LI) has emerged as a new technology that informs on electrical catheter-tissue coupling during radiofrequency (RF) ablation. Recently, IntellaNav StablePoint, a novel LI-enabled catheter that equips contact force (CF) sensing, has been introduced. Although StablePoint and its predecessor IntellaNav MiFi OI share the common technology that reports LI, distinct mechanics for LI sensing between the two products raise a concern that the LI-RF lesion formation relationship may differ. METHODS: In an ex vivo swine cardiac tissue model, we investigated the initial level and range of a reduction in LI during a 60-s RF ablation and the resultant lesion characteristics at nine combinations of three energy power (30, 40, and 50 W) and CF (10, 30, and 50 g) steps. Correlations and interactions between CF, LI, wattage, and formed lesions were analyzed. Incidence of achieving LI drop plateau and that of a steam pop were also determined. RESULTS: Positive correlations existed between CF and initial LI, CF and absolute/relative LI drop, CF and lesion volume, and LI drop and lesion volume. At the same LI drop, wattage-dependent gain in lesion volume was observed. Steam pops occurred in all CF steps and the prevalence was highest at 50 W. LI drop predicted a steam pop with a cutoff value at 89Ω. CONCLUSION: In StablePoint, wattage crucially affects LI drop and lesion volume. Because 30 W ablation may by underpowered for intramural lesion formation and 50 W often resulted in a steam pop, 40 W appears to achieve the balance between the safety and efficacy.

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.

Transvenous lead performance of implantable cardioverter-defibrillators and pacemakers.

BACKGROUND: After the reports of recalled leads, several technological improvements have been introduced and the durability of implantable cardioverter defibrillator (ICD) leads has improved. The incidence of lead failures is now less than in the previous studies. However, there are few reports that have shown the long-term durability of ICD leads as compared to pacemaker (PM) leads. This study analyzed the medium to long-term performance of transvenous ICD leads as compared to PM leads. METHODS: We retrospectively studied 1227 cases from April 2007 to December 2017 who underwent an initial transvenous ICD or PM implantation. The number of lead failures and patient background characteristics were analyzed. RESULTS: During a median 3-3.5 years follow up period, 1 (0.3%) ICD lead and 18 (2.4%) PM leads failed. The incidence of lead failures was significantly higher in the PM group than ICD group (p = .019). Males were associated with a higher incidence of lead failures in the PM group. CONCLUSION: Since the era of recalled ICD leads, the durability of ICD leads has remarkably improved and the incidence of lead failures with non-recalled ICD leads has been less than that for PM leads.

Erratum: Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation.

The errors in the following list appeared in the article entitled "Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation" by Mai Tahara, Ritsushi Kato, Yoshifumi Ikeda, Koji Goto, So Asano, Hitoshi Mori, Shiro Iwanaga, Toshihiro Muramatsu, and Kazuo Matsumoto (Vol. 61, No. 3, 503-509, 2020).

Differential Atrial Pacing to Detect Reconnection Gaps After Pulmonary Vein Isolation in Atrial Fibrillation.

High-resolution mapping is useful to identify reconnection gaps in the pulmonary vein after pulmonary vein isolation for atrial fibrillation. However, it is sometimes difficult to differentiate pulmonary vein potentials from far-field potentials because of very low amplitudes. Our purpose was to evaluate the usefulness of a novel differential atrial pacing method to differentiate reconnected pulmonary vein potentials from isolated pulmonary vein potentials. This retrospective observational study included 34 patients with atrial fibrillation (22 men; mean age, 64 ± 14 years; 28 with paroxysmal atrial fibrillation) who underwent radiofrequency or cryoballoon ablation. Following pulmonary vein isolation, we created a high-resolution activation map during pacing from both the coronary sinus and left atrial appendage. We compared the characteristics of the pulmonary vein potentials and the pattern of activation between the reconnected and isolated pulmonary veins. We analyzed 131 pulmonary veins and found reconnections in 41 pulmonary veins (R group); 90 pulmonary veins had no reconnection (NR group). The R group had a significantly shorter distance between the earliest pulmonary vein activation sites in both activation maps, compared with the NR group (5.22 ± 0.53 mm versus 17.08 ± 0.36 mm, respectively; P < 0.0001). The amplitude of the pulmonary vein potentials was higher in the R group versus the NR group (0.61 ± 0.05 mV versus 0.04 ± 0.03 mV, respectively; P < 0.0001). Six gaps (14%) in the R group that were unrecognized using a conventional method were identified using our novel method. In conclusion, differential atrial pacing was useful to identify pulmonary vein reconnection gaps during ablation using a novel high-resolution mapping system.

Percutaneous Simple Lead Traction Is a Feasible and Effective Method for Right Ventricular Lead Perforations.

Right ventricular (RV) lead perforations are relatively rare but a potentially life-threatening complication of surgical implantations of cardiac implantable electronic devices (CIEDs). The result of percutaneous simple lead traction after lead perforations in the Japanese population has not been well clarified.We retrospectively studied 1359 patients (pacemakers [PMs], 973 patients; implantable cardioverter defibrillators [ICD], 386 patients) from April 2007 to December 2018 who underwent initial CIED implantation. Fifteen patients (1.1%) were diagnosed with RV lead perforations. The clinical data were evaluated in those patients, and the baseline characteristics and echocardiographic data were compared between the lead perforation group and the non-perforation group. The success and complication rates of the simple traction and repositioning of the RV lead were also assessed.The number of perforated RV leads was seven ICD leads (1.8%) and eight PM leads (0.82%). They were diagnosed on a median seven days (5.5-36.0) after the CIED implantation. Twelve patients were asymptomatic but were detected by an increased capture threshold. Three patients had pericarditis and stimulation of the diaphragm. Only one patient in the ICD lead group who took anticoagulants had a cardiac tamponade and needed an urgent pericardiocentesis (0.07%). No one required a thoracotomy or other devices related to complications after repositioning the RV lead. There was no significant difference in the baseline characteristics and echocardiographic parameters between the groups.RV lead perforations were relatively rare complications of CIED implantations. Percutaneous simple lead traction and repositioning the perforated lead was feasible and effective if the patients did not receive anticoagulants.

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.

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.

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.

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.

Relationship between the ablation index, lesion formation, and incidence of steam pops.

BACKGROUND: The ablation index (AI) is reported to be useful for a durable pulmonary vein isolation (PVI). However, there have been no studies investigating the relationship between the power, contact force (CF), AI, and steam pops. METHODS: Using an in vitro model, ablation energy was delivered until a steam pop occurred and the time to the steam pop and AI when the steam pop occurred were measured. The experiment was performed with a combination of various powers (20, 30, 40, and 50 W) and contact forces (CFs) (10, 30, and 50 g) 20 times for each setting. The analysis consisted of two protocols. The first protocol was a comparison between the ablation power and several parameters under the same CF (10, 30, and 50 g). The second protocol was a comparison between the CF and several parameters under the same power (20, 30, 40, and 50 W). The correlation between the lesion formation and ablation parameters was evaluated. RESULTS: The AI value when steam pops occurred varied depending on the ablation settings. All AI median values were <500 under an ablation power of 50 W. On other hand, the median ablation time up to the steam pop was more than 46 seconds, but all median values of the AI were more than 550 under an ablation with 20 W. CONCLUSIONS: The AI cannot predict steam pops. A low power and long duration ablation could obtain a high AI value. However, high-power ablation could not obtain a high AI value because of an early occurrence of steam pops.

Establishment of a quantitative and qualitative analysis and isolation method for tetracyclic iridoids from Morinda lucida Bentham leaves.

A new high performance liquid chromatography (HPLC) method has been established for quantitative and qualitative analysis of three tetracyclic iridoids: ML-2-3 (1), molucidin (2), and ML-F52 (3), which are responsible for anti-trypanosomal and anti-leishmanial activities of Morinda lucida Bentham leaves. Separation of 1-3 from dried 80% aqueous (aq.) ethanol extract was achieved on a reversed-phase cholester column packed with cholesteryl-bonded silica using an acetonitrile-0.1% aq. formic acid mobile phase system. Ultraviolet-visible (UV-VIS) spectroscopy was employed for detection of compounds, and their contents were determined by measuring absorbance at 254 nm. Depending on the above system, several factors potentially affecting the concentration of tetracyclic iridoids were evaluated resulting in several variation on plant organs, seasonality, variation between individual trees, and branch positions within the trees. Moreover, we developed a simple, quick, and effective method for tetracyclic iridoid isolation from M. lucida leaves that consisted of extraction by sonication into 80% aq. ethanol, basic hydrolysis, acid neutralization, liquid-liquid extraction into an organic solvent, and reverse phase open column chromatography. Employing this method, we have succeeded to obtain 1 as a colorless crystal yielding of 0.23%, which was 28 times higher than that of previous isolation method. Setting up methodology in this paper may be important for future in vitro and in vivo studies of tetracyclic iridoids and moreover for their applications in new drug design and development.

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.