Comparing cryoballoon and contact-force guided radiofrequency ablation in pulmonary vein isolation for atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Pulmonary vein isolation (PVI) employing cryoballoon (CB) or contact force-guided radiofrequency (CF-RF) catheter ablation has been established as an effective strategy for managing atrial fibrillation (AF). However, its efficacy in hypertrophic cardiomyopathy (HCM) remains to be further explored. METHODS: This retrospective study analyzed 60 consecutive AF patients with HCM (average age 67 ± 10 years; 41 men) who were consecutively admitted to our hospital from January 2014 to December 2022 and underwent initial PVI. RESULTS: The patients were treated with CB (26 patients) or CF-RF (34 patients). Successful PVI was achieved in both groups without significant complications. In the CF-RF group, additional ablations were performed on the cavotricuspid isthmus (14.7% of patients) and the anterior line (2.9%). The CB group benefited from reduced procedural times (93 ± 31 vs. 165 ± 60 min, p < 0.05) and decreased saline irrigation requirements (77.5 ± 31.4 vs. 870 ± 281.9 mL, p < 0.0001). Using a contrast medium was exclusive to the CB group (33.8 ± 4.2 mL). In a 12-month follow-up, the atrial tachyarrhythmia recurrence-free rates in the CB and CF-RF groups were comparable (77% and 76%, respectively; p = 0.63 according to the log-rank test). Notably, pulmonary vein reconnection was prevalent in most (7 out of 8) patients requiring a secondary ablation procedure. CONCLUSION: PVI is feasible as a strategy for AF in patients with HCM employing either CB or CF-RF techniques. While the recurrence-free rates were comparable in both groups, differences were noted in procedure duration, saline usage, and the need for a contrast medium.

Application of transition-edge sensors for micro-X-ray fluorescence measurements and micro-X-ray absorption near edge structure spectroscopy: a case study of uranium speciation in biotite obtained from a uranium mine.

In this study, we successfully applied a transition-edge sensor (TES) spectrometer as a detector for microbeam X-ray measurements from a synchrotron X-ray light source in the hard X-ray region to determine uranium (U) distribution at the micro-scale and its chemical species in biotite obtained from a U mine. It is difficult to separate the fluorescent X-ray of the U Lα1 line at 13.615 keV from that of the Rb Kα line at 13.395 keV in the X-ray fluorescence spectrum with an energy resolution of approximately 220 eV using a conventional silicon drift detector (SDD). Meanwhile, the fluorescent X-rays of U Lα1 and Rb Kα were fully separated by a TES with 50 eV energy resolution at an energy of around 13 keV. The successful peak separation by the TES led to an accurate mapping analysis of trace U in micro-X-ray fluorescence measurements and a decrease in the signal-to-background ratio in micro-X-ray absorption near edge structure spectroscopy. Thus, it could be a powerful tool for studying the U distribution and speciation in various environmental samples.

Landiolol, an intravenous ß1-selective blocker, is useful for dissociating a fusion of atrial activation via accessory pathway and atrioventricular node.

Introduction: During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. Objective: We tested the hypothesis that landiolol, an ultra-short-acting intravenous ß1-blocker, could dissociate a fusion of atrial activation. Methods: We conducted a prospective before-and-after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Results: Six patients exhibited a fusion of atrial activation. After landiolol administration (10 µg/kg/min), the effective refractory period was unchanged in AP (280 [240-290] ms vs. 280 [245-295] ms, p = .91), whereas that of the AV node was prolonged (275 [215-380] ms vs. 332 [278-445] ms, p = .03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140-200] beats per minute [bpm] vs. 140 [120-180] bpm, p = .02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160-200] bpm vs. 140 [128-155] bpm, p = .007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Conclusion: Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate.

High-sensitive XANES analysis at Ce L2-edge for Ce in bauxites using transition-edge sensors: Implications for Ti-rich geological samples.

Accurate determination of cerium (Ce) valence state is important for interpreting the Ce anomaly in geological archives for (paleo)redox reconstruction. However, the routine application of Ce L3-edge X-ray absorption near-edge structure (XANES) spectroscopy for detecting trace Ce in geological samples can often be restricted by coexisting titanium (Ti) due to the proximity of their fluorescence emission lines. Therefore, the signal-to-noise ratio of Ce L3-edge XANES spectra may not be sufficiently high for high-quality spectroscopic analysis. This study introduces a semi-quantitative approach appropriate for Ti-rich, Ce-dilute geological materials by synchrotron-based X-ray measurement at the Ce L2-edge. First, the results confirm that Ce L2-edge XANES spectra are able to avoid overlapping Ti Kß emissions and provide more reliable information on the Ce valence state in Ti-rich materials relative to L3-edge XANES. Moreover, the application of transition-edge sensor (TES) could reach the higher sensitivity with better energy resolution than conventional silicon drift detector (SDD) to detect fluorescence X-ray (Ce Lß1). The investigation on bauxites developed from the Columbia River Basalts shows that combining Ce L2-edge XANES and TES allows for resolving weak Ce fluorescence lines at the L2-edge from Ti-rich, Ce-dilute samples (Ti/Ce mass ratio up to ∼6000, tens of ppm Ce). The outcome emphasizes the practical possibility of investigating Ce redox state in Ti-rich geological samples.

Characterization of the PRAETORIAN score in Japanese patients undergoing subcutaneous implantable cardioverter-defibrillator implantation.

BACKGROUND: The PRAETORIAN score was developed to evaluate the implant position and predict defibrillation success in patients implanted with a subcutaneous implantable cardioverter-defibrillator (S-ICD). However, usefulness of the PRAETORIAN score for Japanese patients is unknown. METHODS: We evaluated usefulness of this score, which was determined by width of sub-coil fat, sub-generator fat, and anterior positioning of the S-ICD generator by post-operative chest X-ray, in consecutive 100 Japanese S-ICD implanted patients [78 men, median age 59 (IQR 46.5-67.0) years, median body mass index (BMI) 24.2 (21.3-27.2) kg/m2]. RESULTS: The median PRAETORIAN score was 30 (30-45) and 93 patients were classified as a low risk of conversion failure. The remaining seven were at an intermediate risk. Almost all patients were classified as an optimal pulse-generator position in the second and third steps of the PRAETORIAN score. The only difference observed was in the width of sub-coil fat in the first step. To further evaluate its significance, patients were divided into the Thicker group (sub-coil fat >1 coil width, n = 19) and the Thinner group (sub-coil fat ≤1 coil width, n = 81). BMI and post-shock impedance were both higher in the Thicker group than in the Thinner group [27.1 (25.6-31.6) versus 23.1 (20.9-25.7) kg/m2, p < 0.001, and 75 (68-88) versus 63 (55-74) Ω, p = 0.003, respectively]. During the median follow-up periods of 888 (523-1418) days, 7 patients experienced appropriate shock therapy for spontaneous ventricular tachyarrhythmias, who were all at a low risk. No conversion failure was observed. Inappropriate shock (IAS) occurred in 11 patients, and there was no difference in IAS rate between the Thicker group (n = 2) and the Thinner group (n = 9) (p = 0.747 by log-rank test). CONCLUSIONS: Most Japanese patients were classified as at low risk of conversion failure. The PRAETORIAN score may be useful for the evaluation of conversion failure in Japanese S-ICD implanted patients.

Enhanced ß-adrenergic response in mice with dominant-negative expression of the PKD2L1 channel.

Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure in humans. Among the various PKD-related molecules, PKD2L1 forms cation channels, but its physiological importance is obscure. In the present study, we established a transgenic mouse line by overexpressing the dominant-negative form of the mouse PKD2L1 gene (i.e., lacking the pore-forming domain). The resulting PKD2L1del-Tg mice exhibited supraventricular premature contraction, as well as enhanced sensitivity to ß-adrenergic stimulation and unstable R-R intervals in electrocardiography. During spontaneous atrial contraction, PKD2L1del-Tg atria showed enhanced sensitivity to isoproterenol, norepinephrine, and epinephrine. Action potential recording revealed a shortened action potential duration in PKD2L1del-Tg atria in response to isoproterenol. These findings indicated increased adrenergic sensitivity in PKD2L1del-Tg mice, suggesting that PKD2L1 is involved in sympathetic regulation.

Decreased cardiac pacemaking and attenuated ß-adrenergic response in TRIC-A knockout mice.

Changes in intracellular calcium levels in the sinus node modulate cardiac pacemaking (the calcium clock). Trimeric intracellular cation (TRIC) channels are counterion channels on the surface of the sarcoplasmic reticulum and compensate for calcium release from ryanodine receptors, which play a major role in calcium-induced calcium release (CICR) and the calcium clock. TRIC channels are expected to affect the calcium clock in the sinus node. However, their physiological importance in cardiac rhythm formation remains unclear. We evaluated the importance of TRIC channels on cardiac pacemaking using TRIC-A-null (TRIC-A-/-) as well as TRIC-B+/-mice. Although systolic blood pressure (SBP) was not significantly different between wild-type (WT), TRIC-B+/-, and TRIC-A-/-mice, heart rate (HR) was significantly lower in TRIC-A-/-mice than other lines. Interestingly, HR and SBP showed a positive correlation in WT and TRIC-B+/-mice, while no such correlation was observed in TRIC-A-/-mice, suggesting modification of the blood pressure regulatory system in these mice. Isoproterenol (0.3 mg/kg) increased the HR in WT mice (98.8 ±â€…15.1 bpm), whereas a decreased response in HR was observed in TRIC-A-/-mice (23.8 ±â€…5.8 bpm), suggesting decreased sympathetic responses in TRIC-A-/-mice. Electrocardiography revealed unstable R-R intervals in TRIC-A-/-mice. Furthermore, TRIC-A-/-mice sometimes showed sinus pauses, suggesting a significant role of TRIC-A channels in cardiac pacemaking. In isolated atrium contraction or action potential recording, TRIC-A-/-mice showed decreased response to a ß-adrenergic sympathetic nerve agonist (isoproterenol, 100 nM), indicating decreased sympathetic responses. In summary, TRIC-A-/-mice showed decreased cardiac pacemaking in the sinus node and attenuated responses to ß-adrenergic stimulation, indicating the involvement of TRIC-A channels in cardiac rhythm formation and decreased sympathetic responses.

Blockade of PAR-1 Signaling Attenuates Cardiac Hypertrophy and Fibrosis in Renin-Overexpressing Hypertensive Mice.

Background Although PAR-1 (protease-activated receptor-1) exerts important functions in the pathophysiology of the cardiovascular system, the role of PAR-1 signaling in heart failure development remains largely unknown. We tested the hypothesis that PAR-1 signaling inhibition has protective effects on the progression of cardiac remodeling induced by chronic renin-angiotensin system activation using renin-overexpressing hypertensive (Ren-Tg) mice. Methods and Results We treated 12- to 16-week-old male wild-type (WT) mice and Ren-Tg mice with continuous subcutaneous infusion of the PAR-1 antagonist SCH79797 or vehicle for 4 weeks. The thicknesses of interventricular septum and the left ventricular posterior wall were greater in Ren-Tg mice than in WT mice, and SCH79797 treatment significantly decreased these thicknesses in Ren-Tg mice. The cardiac fibrosis area and monocyte/macrophage deposition were greater in Ren-Tg mice than in WT mice, and both conditions were attenuated by SCH79797 treatment. Cardiac mRNA expression levels of PAR-1, TNF-α (tumor necrosis factor-α), TGF-ß1 (transforming growth factor-ß1), and COL3A1 (collagen type 3 α1 chain) and the ratio of ß-myosin heavy chain (ß-MHC) to α-MHC were all greater in Ren-Tg mice than in WT mice; SCH79797 treatment attenuated these increases in Ren-Tg mice. Prothrombin fragment 1+2 concentration and factor Xa in plasma were greater in Ren-Tg mice than in WT mice, and both conditions were unaffected by SCH79797 treatment. In isolated cardiac fibroblasts, both thrombin and factor Xa enhanced ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation, and SCH79797 pretreatment abolished this enhancement. Furthermore, gene expression of PAR-1, TGF-ß1, and COL3A1 were enhanced by factor Xa, and all were inhibited by SCH79797. Conclusions The results indicate that PAR-1 signaling is involved in cardiac remodeling induced by renin-angiotensin system activation, which may provide a novel therapeutic target for heart failure.

Relapsing polychondritis coupling with cerebral amyloid deposit inducing cerebral amyloid angiopathy-related inflammation.

Cerebral amyloid angiopathy-related inflammation is a syndrome of reversible encephalopathy with cerebral amyloid angiopathy, however the pathology is not well understood. We clear a part of the pathology through the first case of an 80-year-old man with cerebral amyloid angiopathy-related inflammation induced by relapsing polychondritis (RP) analysis. An 80-year-old man was diagnosed with RP by auricular cartilage biopsy. Almost no abnormality including intracranial microbleeding was detected by cranial magnetic resonance image (MRI) at diagnosis. However, he developed a headache and hallucination after five months. Seven-month cranial MRI showed novel, multiple, intracranial microbleeding, especially in the bilateral but asymmetry posterior, temporal, and parietal lobes. 123I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography showed increased cerebral blood flow in the bilateral posterior lobes. After treatment, both of his neurological symptoms and increased cerebral blood flow improved to mild. Photon emission computed tomography using Pittsburgh compound B (PiB) for evaluation of brain amyloidosis at 12 months after onset showed an amyloid deposit in the bilateral frontal lobes, but a lack of uptake corresponded to the RP lesions. Our case suggests that inflammation coupled with an amyloid deposit, induced the multiple intracranial bleeding, and resulted in the lack of PiB uptake. Findings from our case show that inflammation including excess blood flow coupled with an amyloid deposit synergistically facilitate intracranial bleeding.

A novel screening test for inappropriate shocks due to myopotentials from the subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is effective in preventing sudden cardiac death. Compared with transvenous ICDs, S-ICDs have a lower rate of inappropriate shocks (IASs) for supraventricular arrhythmias, but such shocks for T-wave oversensing (TWO) and extracardiac myopotentials are more common. No screening tests to identify patients at risk for IAS due to myopotential interference (MPI) currently are available. OBJECTIVE: The purpose of this study was to assess the efficacy of a tube exercise test (TET) developed to detect MPI post S-ICD implantation. METHODS: TET includes 3 different maneuvers using an exercise tube. S-ICD electrograms were recorded to assess MPI while patients performed each of the maneuvers. RESULTS: TET was performed in 43 patients, and MPI was observed in 12 patients (28%). In 10 of the 12 TET-positive patients, the positive vector corresponded with a vector that did not show TWO on standard S-ICD preoperative screening. During median follow-up of 672 days (interquartile range 465-805 days), 3 patients (7%) experienced IAS due to MPI. Importantly, the vector at the time of IAS in all 3 patients passed standard preoperative screening for TWO but was positive with TET. Sensitivity and specificity of TET were 100% and 78%, respectively, and positive and negative predictive values were 25% and 100%, respectively. CONCLUSION: Postimplant screening for MPI identified patients at increased risk for IAS. TET may be helpful for guiding optimal programming to prevent IAS.

D-dimer and C-reactive Protein as Potential Biomarkers for Diagnosis of Trousseau's Syndrome in Patients with Cerebral Embolism.

BACKGROUND: Differentiating stroke due to Trousseau's syndrome from other types of cerebral embolism is challenging, especially in patients with occult cancer. The current study aimed to determine predicting factors and biomarkers of stroke due to Trousseau's syndrome. METHODS: This retrospective study comprised 496 consecutive patients with acute cerebral embolism, including 19, 85, 310, and, 82 patients with stroke due to Trousseau's syndrome, artery-to-artery embolism, cardioembolic stroke, and embolic stroke with undetermined source, respectively. All patients were evaluated within 72 hours of onset. The clinical characteristics, laboratory findings, and patterns on diffusion-weighted magnetic resonance imaging (DWI) were compared among the groups. RESULTS: Plasma D-dimer and C-reactive protein (CRP) levels were significantly higher in the Trousseau's syndrome than in the other causes of cerebral embolism. Multivariate analyses demonstrated that female sex, multiple lesions on DWI, high D-dimer and CRP levels, and low platelet and low brain natriuretic peptide levels were independent predictors that could distinguish Trousseau's syndrome from the other causes of cerebral embolism. The cutoff values of D-dimer and CRP to identify stroke due to Trousseau's syndrome was 2.68 µg/mL fibrinogen equivalent units and .29 mg/dL, respectively. CONCLUSIONS: The elevated D-dimer and CRP levels on admission in addition to specific clinical features may be useful for diagnosis of Trousseau's syndrome in patients with cerebral embolism.

Novel Electrocardiographic Criteria for the Diagnosis of Left Ventricular Hypertrophy in the Japanese General Population.

Although there are several diagnostic criteria for left ventricular hypertrophy (LVH), their sensitivity remains low. A recent study reported that the sum of the amplitude of the deepest S wave in any lead (SD) and the S wave in lead V4 (SV4) (SD + SV4) improved sensitivity compared with commonly used criteria. To test whether this new formula improves sensitivity in the Japanese general population, we analyzed 12-lead electrocardiograms for Japanese residents participating in the Iwaki Health Promotion Project (n = 866). Left ventricular mass was calculated by echocardiography, indicating that 156 (18%) of the study population had LVH. In receiver operating characteristic analyses, the sum of the R wave in limb lead Ι (RLΙ) and the S wave in V4 (SV4) (RLΙ + SV4) showed a higher area under the curve (AUC = 0.76) than the Sokolow-Lyon voltage criteria (0.61) and the SD + SV4 criteria (0.63), and almost the same AUC as the Cornell voltage criteria (0.74) and the Cornell product criteria (0.76). The validation study also showed similar results. The cutoff values of RLΙ + SV4 criteria were ≥1.6 mV in men and ≥1.4 mV in women with a sensitivity of 39% and a specificity of 89%, whereas the sensitivity and specificity calculated based on SD + SV4 criteria were 21% and 94%, respectively. Thus, the diagnostic criterion of RLΙ + SV4 seems to be more useful than the previous criteria for diagnosing LVH in the Japanese general population.

Medaka as a model for ECG analysis and the effect of verapamil.

The heart of the medaka, a small fish native to East Asia, has electrophysiological aspects similar to mammalian hearts. We found that the heart rates of medaka were more similar to humans than mice or rats. Medaka exhibited similar electrocardiogram patterns to those of humans, suggesting a similarity in cardiac impulse formation and propagation. Their hearts also exhibited similar responsiveness to verapamil, a calcium channel antagonist; atropine, a parasympathetic nerve blocker; propranolol, a sympathetic ß-adrenergic blocker; and isoproterenol, a sympathetic ß-adrenergic agonist. We successfully analyzed action potentials and cardiac contractile forces in vivo. Verapamil affected action potential duration and reduced heart rate, suggesting the importance of voltage-dependent calcium channels in determining the heart rhythm of medaka. We also analyzed the expression of the voltage-dependent calcium channel ß2 subunit, which participates in channel formation in cardiac myocytes, and found that splice variant type-2 was the only major transcript in the heart. Our results indicate that medaka could be an appropriate animal model for studying cardiovascular pharmacology.