Impact of cryoballoon application abortion due to phrenic nerve injury on reconnection rates: a YETI subgroup analysis.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures. METHODS AND RESULTS: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence. CONCLUSION: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577.

Feasibility of energy-guided short duration protocol of laser balloon based pulmonary vein isolation for atrial fibrillation (EG-Laser Study).

BACKGROUND: Laser balloon-based pulmonary vein isolation (LB-PVI) is available for atrial fibrillation (AF) ablation. The lesion size depends on laser energy; however, the default protocol is not an energy-based setting. We hypothesized that an energy-guided (EG) short-duration protocol may be an alternative to shorten the procedure time without affecting efficacy and safety. METHODS: We evaluated the efficacy and safety of the EG short-duration protocol (EG group) (target energy 120 J/site [12W/10s; 10W/12s; 8.5W/14s; 5.5W/22s]) compared with the default protocol (control group) (12W/20s; 10W/20s; 8.5W/20s; 5.5W/30s). RESULTS: A total of 52 consecutive patients (EG: n = 27 [103veins] and control: n = 25 [91veins]) undergoing LB-PVI (64 ± 10 years, 81% male, 77% paroxysmal) were enrolled. The EG group had a shorter total time in the pulmonary vein (PV) (43.0 ± 13.9 min vs. 61.1 ± 16.0 min, p < .0001), a shorter total laser application time (1348 ± 254 sec vs. 2032 ± 424 sec, p < .0001), and lower total laser energy (12455 ± 2284J vs. 18084 ± 3746J, p < .0001). There was no difference in the total number of laser applications (p = 0269) or first-pass isolation (p = .725). Acute reconduction was identified only in one vein in the EG. No significant differences were observed in the incidence of pinhole rupture (7.4% vs. 4%, p = 1.000) or phrenic nerve palsy (3.7% vs. 12%, p = .341). During a mean follow-up of 13.5 ± 6.1 months, Kaplan-Meier analysis revealed no significant difference in atrial tachyarrhythmia recurrence (p = .227). CONCLUSION: LB-PVI with the EG short-duration protocol may be achieved in a shorter procedure time to avoid deterioration of efficacy and safety. The EG protocol is feasible as a novel point-by-point manual laser-application approach.

Assessing cardiac mechanical dyssynchrony in left bundle branch area pacing and right ventricular septal pacing using myocardial perfusion scintigraphy in the acute phase of pacemaker implantation.

INTRODUCTION: Left bundle branch area pacing (LBBAP) has recently been reported to be a new, clinically feasible and safe physiological pacing strategy. The present study aims to investigate the usefulness of LBBAP in reducing mechanical dyssynchrony compared with right ventricular septal pacing (RVSP). METHODS AND RESULTS: A total of 39 LBBAP patients, 42 RVSP patients, and 93 healthy control participants were retrospectively evaluated. We compared phase analysis- (bandwidth, phase standard deviation [PSD], entropy) and regional wall motion analysis parameters. Wall motion analysis parameters included the time to the end-systolic frame (TES) assessed using single-photon emission computed tomography analysis. The maximum differences between segmental TES (MDTES), the standard deviation of TES (SDTES), and the TES difference between the lateral and septal segments (DTES-LS) were obtained. All phase analysis parameters were significantly smaller in the LBBAP group than in the RVSP group (bandwidth: LBBAP, 74 ± 31° vs. RVSP, 102 ± 59°, p = .009; PSD: LBBAP, 19 ± 6.7° vs. RVSP, 26 ± 15°, p = .007; entropy: LBBAP, 0.57 ± 0.07 vs. RVSP, 0.62 ± 0.11 p = .009). The regional wall motion analysis parameters were also smaller in the LBBAP group than in the RVSP group (MDTES:LBBAP, 17 ± 7.1% vs. RVSP, 25 ± 14%, p = .004; SDTES:LBBAP, 4.5 ± 1.7% vs. RVSP, 6.0 ± 3.5%, p = .015; DTES-LS: LBBAP, 4.1 ± 3.4% vs. RVSP, 7.1 ± 5.4%, p = .004). All phase analysis and wall motion analysis parameters were same in the LBBAP and control groups. CONCLUSION: LBBAP may reduce mechanical dyssynchrony and achieve greater physiological ventricular activation than RVSP.

Four-dimensional flow magnetic resonance imaging visualizes reverse vortex pattern and energy loss increase in left bundle branch block.

AIMS: This study aimed to investigate the intraventricular blood flow pattern of patients with left bundle branch block (LBBB) using four-dimensional flow magnetic resonance imaging (4D-flow MRI). METHODS AND RESULTS: We performed 4D-flow MRI for 16 LBBB patients (LBBB group) and 16 propensity score-matched patients with a normal QRS duration (non-LBBB group). The energy loss (EL) in the left ventricle was evaluated. In both groups, blood flow from the mitral valve to the apex of the heart and left ventricular (LV) outflow tract during LV diastole were observed. Vortices were also observed in both groups. There were two patterns of vortices: unidirectional clockwise rotation and counterclockwise rotation taking place from the mid-diastole to the systole (reverse pattern). The reverse pattern was observed significantly more frequently in the LBBB group (LBBB 94% vs. non-LBBB 19%, P < 0.001). The interobserver agreement for the streamline analysis was good (kappa = 0.68). The maximum EL was significantly higher in the LBBB group [LBBB 12 (11-15) mW vs. non-LBBB 8.0 (6.2-9.7) mW, P < 0.001]. CONCLUSION: Left bundle branch block patients may suffer from inefficient LV haemodynamics reflected by non-physiological counterclockwise vortices and increased EL. Thus, the shape of the vortices and EL in the left ventricle can serve as markers of LV mechanical dyssynchrony in LBBB patients and could be investigated as predictors of response to cardiac resynchronization therapy.

Usefulness of P-wave peak time as an electrocardiographic parameter in predicting left ventricular diastolic dysfunction in patients with mitral regurgitation.

INTRODUCTION: Conventional Doppler measurements have limitations in predicting left ventricular diastolic dysfunction (LVDD) in patients with mitral regurgitation (MR). Recently, electrocardiographic P-wave peak time (PWPT) has been proposed as a parameter of detecting LVDD. This study aimed to evaluate the association between PWPT and left ventricular end-diastolic pressure (LVEDP) in patients with MR. METHODS: We performed echocardiography and cardiac catheterization in 82 patients with moderate or severe MR. We classified patients into two groups: low LVEDP group (L-LVEDP) (LVEDP <16 mmHg, n = 40) and high LVEDP group (H-LVEDP) (LVEDP ≥16 mmHg, n = 42). We evaluated LVDD and PWPT based on echocardiographic and electrocardiographic findings in both groups. RESULTS: The PWPT in lead II (PWPTII ) was significantly longer in patients in the H-LVEDP group than in those in the L-LVEDP group (67 vs. 47 ms, p < .001). Using correlation analysis, LVEDP was positively correlated with PWPTII (r = .577, p < .001). Using multivariate analysis, PWPTII was found to be an independent predictor of increased LVEDP (95% CI: 0.1030-0.110; p < .001). Using receiver operating characteristic (ROC) curve analysis, the optimal cutoff value of PWPTII for predicting elevated LVEDP was 58.9 ms, with a sensitivity of 80.0% and a specificity of 73.8% (area under curve: 0.809, 95% CI: 0.713-0.905). CONCLUSION: To the best of our knowledge, this is the first study to assess the effect of a significant valvular disease on PWPT in lead II. These findings suggest that prolonged PWPTII may be an independent predictor of increased LVEDP in patients with moderate or severe MR.

Distribution of evoked delayed potential and delayed potential in a patient with subendocardial inferior infarction and transmural postero-lateral infarction: A case report.

A 47-year-old man with transmural posterolateral myocardial infarction (MI) and subendocardial inferior MI underwent catheter ablation for monomorphic ventricular tachycardia (VT). Right ventricular extra stimulation could unmask evoked delayed potentials in the subendocardial infarction area without delayed potentials in the sinus rhythm. Extra stimulation mapping for VT is useful for hidden VT substrates, particularly in the subendocardial infarction area.

Safety of a Cardiac Resynchronization Therapy Device Implantation in a Patient with Unstable Heart Failure Who Require Impella-Device Assistance.

Implantation of a cardiac resynchronization therapy (CRT) device is usually scheduled in the compensated phase of heart failure; however, procedural safety may be sometimes disturbed in the decompensated phase. We report a case of a successful semi-urgent implantation of a CRT device temporary assisted with Impella in a patient with the decompensated phase of severe heart failure dependent on inotropic agents and who cannot maintain the supine position. Impella assistance with left ventricular (LV) unloading and maintenance of end-organ perfusion contributed to early recovery from acute heart failure. Furthermore, an acute effect of mechanical resynchronization by biventricular pacing plays an important role in weaning from the mechanical support or inotropic dependence. These mutual effects of mechanical support and CRT might contribute to a decrease in LV end-diastolic pressure and to a remarkable early recovery from a severely decompensated condition.

The usefulness of a delivery catheter system for right ventricular "true" septal pacing.

Right ventricular (RV) septum is an alternate site for the placement of RV lead tip instead of RV apex. Recent studies have demonstrated that less than half of the RV leads targeted for septal implantation are placed on the RV septum using a conventional stylet system; new guiding catheter systems have become available for RV lead placement. This study aimed to investigate the usefulness of the delivery catheter system in lead placement on the RV septum when compared with the stylet system. We retrospectively evaluated 198 patients who underwent fluoroscopically guided pacemaker implantation with RV leads targeted to be placed in the RV septum and in whom computed tomography was incidentally and subsequently performed. A delivery catheter was used in 16 patients, and a stylet in 182 patients. The primary endpoint of this study was the success rate of RV lead placement on the RV septum. The proportion of RV lead placement on the RV septum was higher in the delivery catheter group than in the stylet group (100% vs. 44%; p < 0.001). In the stylet group, the lead tips were placed at the hinge in 92 cases (51%) and on the free wall in 9 cases (5%). Paced QRS duration was narrower in the delivery catheter group than in the stylet group (128 ± 16 vs. 150 ± 21 ms, p < 0.01). The delivery catheter system designated for pacing leads may aid in selecting RV septal sites and achieve good physiologic ventricular activation.

Clinical feasibility of pulmonary vein orifice pacing for the prediction of phrenic nerve injury during cryoballoon ablation of atrial fibrillation.

INTRODUCTION: Phrenic nerve (PN) injury is a well-known complication of cryoballoon ablation (CBA) for pulmonary vein (PV) isolation in patients with atrial fibrillation. However, it is still insufficient to practically predict phrenic nerve injury (PNI) before freezing. We hypothesized that phrenic nerve capture (PNC) with phrenic nerve orifice pacing (PVOP) might be a surrogate sign of the close proximity of the PN, and that might predict PNI and changes in the compound motor action potential (CMAP) amplitude. METHODS: Seventy patients (60 ± 12 years, male 80%, paroxysmal 56%) underwent PVOP with a 20-electrode ring catheter before the CBA. The clinical outcome was the occurrence of transient and persistent PNI. In addition, the PV position and pacing threshold during PNC with PVOP, and changes in the CMAP amplitude were recorded. We compared these measurements between patients with and without PNC (PNC/non-PNC group) with PVOP. RESULTS: PNC with PVOP occurred in 39 (56%) patients and was localized only to the right superior PV. Transient PNI occurred in seven (10%) patients and permanent in none. The CMAP amplitude decreased significantly more in the PNC group (PNC 33% vs non-PNC 16%, P = .027). PNC group had a higher risk of the composite outcome of transient PNI or ≥30% decrease in the CMAP amplitude (PNC 54% vs non-PNC 13%; P < .001). CONCLUSIONS: This PVOP technique could be feasible and contribute to predicting transient PNI and CMAP amplitude reductions before cryoapplications. Further studies are necessary to elucidate the additional efficacy of PVOP over CMAP monitoring alone.

Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy.

BACKGROUND: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels. CONCLUSIONS: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

Eicosapentaenoic acid ameliorates palmitate-induced lipotoxicity via the AMP kinase/dynamin-related protein-1 signaling pathway in differentiated H9c2 myocytes.

BACKGROUND: Emerging evidence suggested the preferable effects of eicosapentaenoic acid (EPA; n-3 polyunsaturated fatty acid) against cardiac lipotoxicity, which worsens cardiac function by means of excessive serum free fatty acids due to chronic adrenergic stimulation under heart failure. Nonetheless, the precise molecular mechanisms remain elusive. In this study, we focused on dynamin-related protein-1 (Drp1) as a possible modulator of the EPA-mediated cardiac protection against cardiac lipotoxicity, and investigated the causal relation between AMP-activated protein kinase (AMPK) and Drp1. METHODS AND RESULTS: When differentiated H9c2 myocytes were exposed to palmitate (PAL; saturated fatty acid, 400µM) for 24h, these myocytes showed activation of caspases 3 and 7, enhanced caspase 3 cleavage, depolarized mitochondrial membrane potential, depleted intracellular ATP, and enhanced production of intracellular reactive oxygen species. These changes suggested lipotoxicity due to excessive PAL. PAL enhanced mitochondrial fragmentation with increased Drp1 expression, as well. EPA (50µM) restored the PAL-induced apoptosis, mitochondrial dysfunction, and mitochondrial fragmentation with increased Drp1 expression by PAL. EPA activated phosphorylation of AMPK, and pharmacological activation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide ameliorated the PAL-induced apoptosis, mitochondrial dysfunction, and downregulated Drp1. An AMPK knockdown via RNA interference enhanced Drp1 expression and attenuated the protective effects of EPA against the PAL-induced lipotoxicity. CONCLUSION: EPA ameliorates the PAL-induced lipotoxicity via AMPK activation, which subsequently suppresses mitochondrial fragmentation and Drp1 expression. Our findings may provide new insights into the molecular mechanisms of EPA-mediated myocardial protection in heart failure.

Intra-left ventricular flow dynamics in patients with preserved and impaired left ventricular function: Analysis with 3D cine phase contrast MRI (4D-Flow).

PURPOSE: To examine how left ventricular (LV) volume and function affect flow dynamics by analyzing 3D intra-LV vortex features using 4D-Flow. MATERIALS AND METHODS: Twenty-one patients with preserved (LVEF > 60%) and 14 with impaired LV function (LVEF < 40%) underwent 4D-Flow (at 3T). RESULTS: In patients with preserved LV function, the intra-LV vortices developed in both the early and late diastolic phases. The shift of inflow vectors at the basal LV toward the posterior-lateral side of the LV and the mid-ventricular turn of inflow vectors toward the LV outflow could explain clearer vortex formation in the late diastolic phase. In patients with impaired LV function, the intra-LV vortices during the diastolic phase located at the more apical LV were larger and more spherically shaped. Both the distance to the vortex core and the vortex area correlated significantly with LV end-diastolic volume (r = 0.66 and 0.73), LVEF (r = -0.74 and -0.68), LV sphericity index (r = -0.60 and -0.65), and peak filling rate (r = -0.61 and -0.64), respectively (P < 0.01). The intra-LV vortices developed during the systolic phase in 10 cases. In those, some of the particles at the apical LV rotated within the LV, whereas in patients with preserved LV function, all of the particles were directed straight to the ascending aorta with accelerated flow velocity (256.8 ± 120.2 cm/s vs. 414.3 ± 88.2 cm/s, P < 0.01). CONCLUSION: Vortex formation during the diastolic phase may be critical for both LV filling and ejection. 4D-Flow showed the 3D alterations of intra-LV flow dynamics by LV dilatation and dysfunction in a noninvasive and comprehensive manner. J. Magn. Reson. Imaging 2016;44:1493-1503.

Characteristics of intra-left atrial flow dynamics and factors affecting formation of the vortex flow ­ analysis with phase-resolved 3-dimensional cine phase contrast magnetic resonance imaging.

BACKGROUND: The intra-left atrial (LA) blood flow from pulmonary veins (PVs) to the left ventricle (LV) changes under various conditions and might affect global cardiac function. By using phase-resolved 3-dimensional cine phase contrast magnetic resonance imaging (4D-Flow), the intra-LA vortex formation was visualized and the factors affecting the intra-LA flow dynamics were examined. METHODS AND RESULTS: Thirty-two patients with or without organic heart diseases underwent 4D-Flow and transthoracic echocardiography. The intra-LA velocity vectors from each PV were post-processed to delineate streamline and pathline images. The vector images revealed intra-LA vortex formation in 20 of 32 patients. All the vortices developed during the late systolic and early diastolic phases and were directed counter-clockwise when viewed from the subjects' cranial side. The flow vectors from the right PVs lengthened predominantly toward the mitral valves and partly toward the LA appendage, whereas those from the left PVs directed rightward along the posterior wall and joined the vortex. Patients with vortex had less organic heart diseases, smaller LV and LA volume, and greater peak flow velocity and volume mainly in the left PVs, although the flow directions from each PV or PV areas did not differ. CONCLUSIONS: 4D-Flow can clearly visualize the intra-LA vortex formation and analyze its characteristic features. The vortex formation might depend on LV and LA volume and on flow velocity and volume from PVs.

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance.

PURPOSE: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. METHODS AND RESULTS: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨm) depolarization, exhibited attenuated insulin signaling and 2-deoxy-d-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H2O2), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨm depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H2O2-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨm depolarization and impaired 2-DG uptake, however they improved insulin signaling. CONCLUSIONS: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance.

Characteristics and clinical relevance of late gadolinium enhancement in cardiac magnetic resonance in patients with systemic sclerosis.

Cardiac involvement in systemic sclerosis (SSc) is considerably frequent in autopsy, but the early identification is clinically difficult. Recent advantages in cardiac magnetic resonance (CMR) enabled to detect myocardial fibrotic scar as late gadolinium enhancement (LGE). We aimed to examine the prevalence and distribution of LGE in patients with SSc, and associate them with clinical features, electrocardiographic abnormalities and cardiac function. Forty patients with SSc (58 ± 14 years-old, 35 females, limited/diffuse 25/15, disease duration 106 ± 113 months) underwent serological tests, 12-lead electrocardiogram (ECG) and CMR. Seven patients (17.5 %) showed LGE in 26 segments of left ventricle (LV). LGE distributed mainly in the basal to mid inter-ventricular septum and the right ventricular (RV) insertion points, but involved all the myocardial regions. More patients with LGE showed NYHA functional class II and more (71 vs. 21 %, p < 0.05), bundle branch blocks (57 vs. 6 %, p < 0.05), LV ejection fraction (LVEF) < 50 % (72 vs. 6 %, p < 0.01), LV asynergy (43 vs. 0 %, p < 0.01) and RVEF < 40 % (100 vs. 39 %, p < 0.01). There was no difference in disease duration, disease types, or prevalence of positive autoimmune antibodies or high serum NT-proBNP level (>125 pg/ml). When cardiac involvement of SSc was defined as low LVEF, ECG abnormalities or high NT-proBNP, the sensitivity, specificity positive and negative predictive values of LGE were 36, 92, 71 and 72 %, respectively. We could clarify the prevalence and distribution of LGE in Japanese patients with SSc. The presence of LGE was associated with cardiac symptom, conduction disturbance and impaired LV/RV contraction.

Microtubule disorganization affects the mitochondrial permeability transition pore in cardiac myocytes.

BACKGROUND: Microtubule (MT) disorganization is related to cardiac disorders. To elucidate the mechanism by which disorganization of the MT network deteriorates cardiac function, the relationship between MT disorganization and mitochondrial permeability transition pore (mPTP) in cardiac myocytes was investigated. METHODS AND RESULTS: The effects of MT stabilization (by paclitaxel) and MT disruption (by nocodazole) on mitochondrial membrane potential (ΔΨm) and the opening of mPTP were measured in permeabilized Sprague-Dawley rat myocytes. Both paclitaxel and nocodazole depolarized ΔΨm and opened mPTP. When isolated mitochondria were exposed to paclitaxel or nocodazole, there were no changes in ΔΨm. The effects of paclitaxel or nocodazole on ΔΨm depolarization and mPTP were inhibited by cyclosporin A. Treatment of myocytes with 0Ca+BAPTA or inhibition of sarcoplasmic reticulum (SR) Ca(2+) uptake by thapsigargin prevented the effect of paclitaxel on mPTP, but not that of nocodazole. Inhibition of the mitochondrial Ca(2+) uniporter by Ru360 did not alter the effect of paclitaxel on mPTP. Paclitaxel reduced the expression of the mitochondrial fusion protein, mitofusin-2, and induced mitochondrial fragmentation. CONCLUSIONS: Disruption of the MT network by nocodazole might destroy the MT-mitochondria connection and alter mitochondrial function. MT disorganization by paclitaxel could regulate mPTP through the outer mitochondrial membrane complex and the Ca(2+)-sensitive signaling pathway, which also interacts with the mitochondrial fusion protein, mitofusin-2.

Mitochondrial dysfunction caused by saturated fatty acid loading induces myocardial insulin-resistance in differentiated H9c2 myocytes: a novel ex vivo myocardial insulin-resistance model.

Heart failure (HF) is often accompanied with metabolic disorders and insufficient energy production. Some previous studies have suggested an elevated serum free fatty acid (FA) due to chronic adrenergic stimulation induces myocardial insulin-resistance, which further impairs myocardial energy production. Because little is known about the pathogenesis of FA-induced cardiac insulin-resistance, we established an ex vivo cardiac insulin-resistant model and investigated the relationship between insulin-resistance and mitochondrial dysfunction. The ex vivo insulin-resistant myocytes, which was produced by treating differentiated H9c2 myocytes with palmitate (saturated FA; 0.2mM) for 24h, exhibited insulin-signaling deficiency and attenuated 2-deoxy-d-glucose (2-DG) uptake. When myocytes were pretreated with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP, a ROS scavenger; 200 µM), the insulin-signaling deficiency by palmitate was restored, whereas the attenuated 2-DG uptake was remained. In contrast to TMPyP, the pretreatment with perhexiline (a mitochondrial FA uptake inhibitor; 2 µM) restored the insulin-signaling deficiency and the attenuated 2-DG uptake by palmitate. Perhexiline restored the depolarized mitochondrial membrane potential (ΔΨm) and the reduced intracellular ATP by palmitate, and thereby improved the impaired GLUT4 recruitment to plasma membrane after insulin, whereas TMPyP failed to do so. These results suggested that the mitochondrial dysfunction by saturated FA loading and consequent intracellular energy shortage induced myocardial insulin-resistance in our ex vivo insulin-resistant model.

Evaluation and comparison of impedance and amplitude changes in lesion index-guided pulmonary vein isolation.

Background: The lesion index (LSI) has been used to estimate lesion formation after radiofrequency catheter ablation. However, the impedance drop and decrease in bipolar amplitude of intracardiac electrograms, which are parameters that are traditionally used to predict effective ablation lesions, are not used to calculate LSI. Therefore, we aimed to investigate the association between LSI and traditional parameters. Methods: We retrospectively investigated 1355 ablation points from 31 patients who underwent LSI-guided pulmonary vein isolation (PVI) using TactiCath. All points were classified into 3 groups based on the impedance drop: (i) <10 Ω (n = 67), (ii) 10-20 Ω (n = 909), and (iii) >20 Ω (n = 379). The LSI targets were 4.5 for the posterior left atrium and 5.2 for the anterior left atrium. After excluding 583 points at which it was difficult to measure the amplitude, 772 ablation points during sinus rhythm were included in the analysis of bipolar amplitude. Results: The target LSI was achieved at 1177 points (86.9%). The median total impedance drop and amplitude just after ablation were 16.0 [13.0-20.0] Ω and 0.21 [0.14-0.30] mV, respectively. There were significant differences among the 3 groups in the impedance and amplitude before ablation, power, target LSI, final LSI, contact force, and interlesion distance. An impedance drop of >10 Ω or an amplitude reduction of >50% was achieved at 95% and 82% of the study points, respectively. There were no major complications at any of the ablation points. Conclusion: LSI-guided PVI seemed to be useful for making sufficient ablation lesions, as assessed by the conventional parameters of impedance and amplitude change.

Pregnancy-related acute myocardial infarction in Japan: a review of epidemiology, etiology and treatment from case reports.

BACKGROUND: Pregnancy-related acute myocardial infarction (AMI) is uncommon, but can result in maternal and/or fetal death. This study retrospectively reviews pregnancy-related AMI reported from medical institutions in Japan. METHODS AND RESULTS: We electronically or manually searched the literature for reports of pregnancy-related AMI between 1981 and 2011. In total, 62 patients were described and the numbers increased in accordance with the rising average age of the mothers. AMI occurred frequently in women aged 30-34 years (mean age, 33), in the third trimester and postpartum (n=11 and n=28, respectively). The prevalence of conventional risk factors was relatively low (n=21). On the other hand, 29 patients had obstetric and/or non-obstetric complications, and 24 received medication. Only 8 AMI were caused by atherosclerosis, while coronary dissection, thrombus and spasm were the cause in 14, 9 and 12 cases, respectively. All patients with atherosclerosis had conventional risk factors, and some patients with spasm had a history of smoking. Medication with ergot derivatives was associated mostly with spasm, whereas ritodrine was potentially related to dissection. CONCLUSIONS: The prevalence of pregnancy-related AMI in Japan seems lower than in Western countries, and the etiology differs considerably. However, as the trend of later childbearing continues, more pregnant women have more risk factors, complications, and require medication. Cardiologists and obstetricians must consider the increased risk of AMI.

Ultrasound analysis of the relationship between right internal jugular vein and common carotid artery in the left head-rotation and head-flexion position.

Common carotid artery (CCA) injury is a serious complication of internal jugular vein (IJV) cannulation. To minimize unintentional CCA puncture, the anatomic relationship between the IJV and the CCA and the size of IJV were compared under different head positions. Ultrasound analyses of the IJV and the CCA were performed in 103 consecutive patients. Overlapping angle (OA), real puncture angle (RPA) and diameter of IJV (D IJV) were evaluated with 30° and 60° left rotation and with 30° left flexion. When the head position was changed from 30° left rotation to 60° left rotation, OA increased significantly from 6.5° ± 7.7° to 14.5° ± 7.4° at the cricoid cartilage level (Cricoid-level) and from 14.4° ± 8.4° to 20.6° ± 6.9° at the middle triangle level (Triangle-level), whereas RPA decreased significantly at these levels (from 49.7° ± 11.9° to 43.5° ± 13.1° and from 51.1° ± 14.4° to 44.3° ± 13.9°, respectively; P < 0.01 for both). When the head position was changed from 30° left rotation to 30° left flexion, neither OA nor RPA significantly changed (OA: 6.3° ± 6.1° and 15.0° ± 7.2°, RPA: 48.5° ± 12.4° and 51.8° ± 13.6°, P not significant vs 30° left rotation). There was no difference in D IJV when comparing 30° left rotation and 30° left flexion, although D IJV was largest at 60° left rotation. RPA positively correlated with age, and D IJV positively correlated with body mass index. In conclusion, excessive left rotation should be avoided to minimize the probability of unintentional CCA puncture during IJV cannulation. When 30° left rotation is not feasible, the head-flexion position should be utilized.