Comparison of the left ventricular dyssynchrony between stylet-driven and lumen-less lead technique in left bundle branch area pacing using myocardial perfusion scintigraphy.

Background: Left bundle branch area pacing (LBBAP) has emerged as a novel physiological pacing method to reduce left ventricular (LV) dyssynchrony due to ventricular pacing. Only lumen-less pacing leads (LLLs) with fixed helixes could achieve LBBAP previously, but recently, LBBAP has been performed using stylet-driven leads (SDLs). This study aimed to evaluate the LV dyssynchrony between SDLs and LLLs techniques in LBBAP. Methods: We retrospectively evaluated patients who underwent LBBAP with either SDLs or LLLs. We compared both groups' electrocardiogram (ECG) findings and LV dyssynchrony parameters derived from myocardial perfusion scintigraphy. LV dyssynchrony parameters consisted of phase analysis and regional wall motion analysis. We evaluated bandwidth, phase standard deviation (PSD), and entropy in the phase analysis. The time to the end-systolic frame (TES) was calculated in regional wall motion analysis using single-photon emission computed tomography (SPECT). We also evaluated the maximum differences between segmental TES (MDTES), the standard deviation of TES (SDTES), and the difference in the TES between the lateral wall and septum (DTES-LS). Results: In total, 97 patients were enrolled. The success rate of LBBAP did not differ between the groups [SDLs: 47/48 patients (98%) vs. LLLs: 47/51 patients (92%), P=0.36]. The paced QRS duration and the stimulus to the peak LV activation time (stim-LVAT) also did not differ between SDL and LLL groups (122±10 vs. 119±12 ms, P=0.206; 69±12 vs. 66±13 ms, P=0.31, respectively). There were no differences in bandwidth, PSD, and entropy between SDL and LLL groups (73°±37° vs. 86°±47°, P=0.18; 19°±8.5° vs. 21°±9.7°, P=0.19; 0.57±0.08 vs. 0.59±0.08, P=0.17, respectively). The regional wall motion analysis parameters MDTES, SDTES, and DTES-LS also did not differ between SDL and LLL groups (19%±10% vs. 20%±10%, P=0.885; 5.0%±2.5% vs. 5.0%±2.5%, P=0.995; 5.0%±3.7% vs. 4.8%±4.2%, P=0.78, respectively). Conclusions: LBBAP using SDLs was comparable to LV electrical and mechanical synchrony with LLLs.

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.

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.

Impact of the Degree of Wire Bias in the Vessel's Healthy Portion on Coronary Perivascular Trauma in Rotational Atherectomy.

BACKGROUND: In rotational atherectomy (RA), the risk of coronary perforation is considered to increase when the wire is in contact with the healthy portion of the vessel. However, the relationship between the extent of wire bias in the healthy portion of the vessel and the risk of coronary perivascular trauma (CPT) has not been reported. METHODS: We examined 90 consecutive cases wherein intravascular ultrasound (IVUS) was performed before and after RA. The IVUS catheter in contact with the healthy region of the vessel was defined as the healthy portion wire bias (HWB), of which we measured the bias diameter, defined as the media-to-media length between the site where the IVUS catheter was in contact and the opposite side of the vessel. The bias ratio was defined as the ratio of the bias diameter to the short diameter at the region where the wire bias was the strongest. The relationship between the bias ratio and the CPT risk was evaluated. RESULTS: CPT was significantly higher in the HWB group than in the non-HWB group (9% vs. 0%, P = 0.048). In the HWB group, the bias ratio was significantly greater in the CPT group than in the non-CPT group (1.31 ±â€¯0.09 vs. 1.06 ±â€¯0.06; P < 0.0001). The cutoff value of the bias ratio for CPT was 1.2, which was the maximum value of the sum of sensitivity 100% and specificity 97%. CONCLUSIONS: Lesions without HWB had no CPT. CPT risk increased when the bias ratio exceeded 1.2.

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.

Concomitant Pulmonary and Cerebral Tumor Embolism and Intracardiac Metastasis from Bladder Cancer.

An 82-year-old woman with a history of bladder cancer presented with dyspnea and loss of consciousness. Contrast-enhanced computed tomography revealed pulmonary embolism, and emergency thrombus aspiration therapy was performed, but the thrombus was not aspirated. Echocardiography showed mobile masses in the heart and a right-to-left shunt due to a patent foramen ovale (PFO). Magnetic resonance imaging showed multiple cerebral infarctions. Surgical thrombectomy and PFO closure were performed, and the patient was diagnosed with intracardiac metastasis of bladder cancer based on intraoperative histopathology. This is a rare case of concomitant pulmonary and cerebral tumor embolism and intracardiac metastasis from bladder cancer.

An Autopsy Case of Antibody-negative Immune-mediated Necrotizing Myopathy with Severe Cardiac Involvement.

A 41-year-old man was admitted with a chief complaint of dyspnea. Echocardiography showed diffuse severe hypokinesis in the left ventricle. Although his heart failure improved, high creatine kinase levels persisted. A muscle biopsy of the biceps brachii showed necrotic and regenerating fibers along with positive findings for major histocompatibility complex class I and membrane attack complex. He was diagnosed with antibody-negative immune-mediated necrotizing myopathy (IMNM). Steroid therapy was started, but he died due to ventricular fibrillation. Autopsy findings revealed CD68-positive macrophages in the myocardium and quadriceps. To our knowledge, this is the first case of antibody-negative IMNM with cardiac involvement.

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.

Impact of Hydrostatic Pressure Variations Caused by Height Differences in Supine and Prone Positions on Fractional Flow Reserve Values in the Coronary Circulation.

OBJECTIVES: To examine the influence of hydrostatic pressure on fractional flow reserve (FFR) in vivo. BACKGROUND: Systematic differences in FFR values have been observed previously in the left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). It has been suggested that as the hydrostatic pressure variations caused by the height differences between the catheter tip (mean aortic pressure (Pa)) and pressure-wire sensor (mean distal intracoronary pressure (Pd)) are small, intracoronary pressure need not be corrected. METHODS: Resting Pd/Pa and FFR values in 23 patients (27 lesions) were measured and compared in supine and prone positions. These values were corrected by hydrostatic pressure influenced by height levels and compared. Height differences between Pa and Pd were calculated using coronary computed tomography angiographies. RESULTS: In LAD, resting Pd/Pa and FFR values were significantly higher in the prone position than in the supine position (0.97 ± 0.05 vs 0.89 ± 0.04, P < 0.001 (resting Pd/Pa); 0.81 ± 0.09 vs 0.72 ± 0.07, P < 0.001 (FFR)). Conversely, in LCX and RCA, these values were significantly lower in the prone position (LCX: 0.93 ± 0.03 vs 0.98 ± 0.03, P < 0.001 (resting Pd/Pa); 0.84 ± 0.05 vs 0.89 ± 0.04, P < 0.001 (FFR); RCA: 0.91 ± 0.04 vs 0.98 ± 0.03, P=0.005 (resting Pd/Pa); 0.78 ± 0.07 vs 0.84 ± 0.07, P=0.019 (FFR)). FFR values corrected by hydrostatic pressure showed good correlations in the supine and prone positions (R 2 = 0.948 in LAD; R 2 = 0.942 in LCX; R 2 = 0.928 in RCA). CONCLUSIONS: Hydrostatic pressure variations due to height levels influence intracoronary pressure measurements and largely affect resting Pd/Pa and FFR, which might have caused systematic differences in FFR values between the anterior and posterior coronary territories.

Optical silencing of C. elegans cells with light-driven proton pumps.

Recent development of optogenetic techniques, which utilize light-driven ion channels or ion pumps for controlling the activity of excitable cells, has greatly facilitated the investigation of nervous systems in vivo. A new generation of optical silencers includes outward-directed proton pumps, such as Arch, which have several advantages over currently widely used halorhodopsin (NpHR). These advantages include the resistance to inactivation during prolonged illumination and the ability to generate a larger optical current from low intensity light. C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. In this article, we will outline the practical aspects of using of Arch and other proton pumps as optogenetic tools in C. elegans.

A blue-shifted light-driven proton pump for neural silencing.

Ion-transporting rhodopsins are widely utilized as optogenetic tools both for light-induced neural activation and silencing. The most studied representative is Bacteriorhodopsin (BR), which absorbs green/red light (∼570 nm) and functions as a proton pump. Upon photoexcitation, BR induces a hyperpolarization across the membrane, which, if incorporated into a nerve cell, results in its neural silencing. In this study, we show that several residues around the retinal chromophore, which are completely conserved among BR homologs from the archaea, are involved in the spectral tuning in a BR homolog (HwBR) and that the combination mutation causes a large spectral blue shift (λmax = 498 nm) while preserving the robust pumping activity. Quantum mechanics/molecular mechanics calculations revealed that, compared with the wild type, the ß-ionone ring of the chromophore in the mutant is rotated ∼130° because of the lack of steric hindrance between the methyl groups of the retinal and the mutated residues, resulting in the breakage of the π conjugation system on the polyene chain of the retinal. By the same mutations, similar spectral blue shifts are also observed in another BR homolog, archearhodopsin-3 (also called Arch). The color variant of archearhodopsin-3 could be successfully expressed in the neural cells of Caenorhabditis elegans, and illumination with blue light (500 nm) led to the effective locomotory paralysis of the worms. Thus, we successfully produced a blue-shifted proton pump for neural silencing.

An optogenetic application of proton pump ArchT to C. elegans cells.

Application of novel light-driven ion channel/pumps would benefit optogenetic studies of Caenorhabditis elegans. A recent study showed that ArchT, a novel light-driven outward proton pump, is >3 times more light-sensitive than the Arch proton pump. Here we report the silencing effect of ArchT in C. elegans cells. ArchT expressed by using a body-wall muscle or pan-neuronal-promoters caused a quick and reliable locomotion paralysis when worms were illuminated by green light. Unlike the report on mouse neurons, however, light sensitivity of ArchT is similar to that of Arch in C. elegans. ArchT-mediated acute silencing of serotonergic neurons quickly triggered backward locomotion. This response was abolished in the presence of exogenously added serotonin, suggesting that, in a normal situation, serotonin is secreted in a constitutive fashion to repress backward movement.

Optical silencing of C. elegans cells with arch proton pump.

BACKGROUND: Optogenetic techniques using light-driven ion channels or ion pumps for controlling excitable cells have greatly facilitated the investigation of nervous systems in vivo. A model organism, C. elegans, with its small transparent body and well-characterized neural circuits, is especially suitable for optogenetic analyses. METHODOLOGY/PRINCIPAL FINDINGS: We describe the application of archaerhodopsin-3 (Arch), a recently reported optical neuronal silencer, to C. elegans. Arch::GFP expressed either in all neurons or body wall muscles of the entire body by means of transgenes were localized, at least partially, to the cell membrane without adverse effects, and caused locomotory paralysis of worms when illuminated by green light (550 nm). Pan-neuronal expression of Arch endowed worms with quick and sustained responsiveness to such light. Worms reliably responded to repeated periods of illumination and non-illumination, and remained paralyzed under continuous illumination for 30 seconds. Worms expressing Arch in different subsets of motor neurons exhibited distinct defects in the locomotory behavior under green light: selective silencing of A-type motor neurons affected backward movement while silencing of B-type motor neurons affected forward movement more severely. Our experiments using a heat-shock-mediated induction system also indicate that Arch becomes fully functional only 12 hours after induction and remains functional for more than 24 hour. CONCLUSIONS/SGNIFICANCE: Arch can be used for silencing neurons and muscles, and may be a useful alternative to currently widely used halorhodopsin (NpHR) in optogenetic studies of C. elegans.