Associations among Plasma Concentrations of Edoxaban and M-4, Prothrombin Time, and the SLCO1B1*15 Haplotype in Patients With Nonvalvular Atrial Fibrillation.

INTRODUCTION: The authors aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, the hepatic uptake transporter organic anion transporter protein 1B1, cytochrome P450 ( CYP ) 3A5, and carboxylesterase-1 ( CES1 ) on the steady-state dose-adjusted trough concentrations of edoxaban (C Edo /D) and M-4 (C M-4 /D). They also investigated whether C M-4 and C Edo affect prothrombin time (PT). METHODS: The analyses included 152 patients with nonvalvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3 ; CES1 c.1168-33A>C, c.257+885T>C; SLCO1B1 c.388A>G, c.521T>C; and ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T genotypes were determined. RESULTS: Stepwise selection multiple linear regression analyses demonstrated that creatinine clearance (Ccr), concomitant use of amiodarone, and SLCO1B1*15 haplotype status were independent factors influencing C M-4 /D (partial R2 = 0.189, 0.098, 0.067, respectively, all P values < 0.005). Ccr and concomitant use of amiodarone were independent factors influencing C Edo /D (partial R2 = 0.260, 0.117, respectively, both P value < 0.001). C Edo and C M-4 showed a weak correlation with PT (ρ = 0.369 and 0.315, both P values < 0.001). CONCLUSIONS: Although information concerning Ccr, concomitant use of amiodarone, and SLCO1B1*15 haplotype may be useful in assessing the pharmacokinetics of edoxaban, further studies are needed to clarify the requirement of PT monitoring at the trough level for dose adjustment of edoxaban in patients with NVAF.

Incidence, Predictors, and Outcome Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

BACKGROUND: The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown.Methods and Results: Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.3%, and 75% of cases occurred by the end of PCI. Independent predictors associated with VT/VF occurrence by the end of PCI and after PCI, respectively, were identified. Additionally, the differences between patients with VT and VF were examined, which revealed that the characteristics of patients and predictors for VT and VF were clearly different. Additionally, the QRS duration during VT was measured, which demonstrated the possible involvement of Purkinje fibers for VT in the acute phase of AMI. Of the patients with VT/VF, 12% required ECMO support due to refractory VT/VF despite intravenous antiarrhythmic agents such as ß-blockers, amiodarone, and nifekalant. Among the patients discharged alive, 1,690 were followed up for a mean of 3.7 years. VT/VF occurrence during hospitalization did not affect the mid-term clinical outcomes even in patients with VT. CONCLUSIONS: The results clearly indicated that VT/VF is still a serious complications of AMI. We need to identify patients at high risk of developing VT/VF for careful observation and appropriate intervention.

Impacts of pregnane X receptor and cytochrome P450 oxidoreductase gene polymorphisms on trough concentrations of apixaban in patients with non-valvular atrial fibrillation.

PURPOSE: We examined the impact of polymorphisms in genes encoding cytochrome P450 (CYP) 3A5 (gene code CYP3A5), P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), cytochrome P450 oxidoreductase (POR), and pregnane X receptor (PXR; NR1I2) on the daily dose-adjusted steady-state trough concentrations (C0h/D) of apixaban. METHODS: The analyses included 104 patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation. The CYP3A5*3; ABCG2 421C > A; ABCB1 1236C > T, 2677G > A/T, 3435C > T, and 2482-2236G > A; NR1I2 11156A > C, 11193T > C, and 8055C > T; and POR*28 genotypes were determined. The combination of the noted NR1I2 genotypes determined the PXR*1B haplotype. RESULTS: Multiple linear regression analyses demonstrated that decreased creatinine clearance (Ccr) and the PXR*1B/*1B haplotype correlated with increased C0h/D of apixaban, while the presence of the POR*28 allele correlated with decreased C0h/D of apixaban (partial R2 = 0.168, 0.029, and 0.044, all P < 0.05). The mean (95% CI) of estimated marginal means of apixaban C0h/D calculated using Ccr as a covariate was the highest in POR*28 noncarriers with PXR*1B/*1B (23.5 [21.0-25.9] ng/mL/[mg/day]) and lowest in POR*28 carriers with other haplotypes (16.6 [15.5-17.7] ng/mL/[mg/day]). CONCLUSION: The PXR*1B haplotype and POR*28 genotype statuses, which involve genes that impact the expression of multiple drug-metabolizing enzymes and drug-transporters, may have modest effects on the C0h/D of apixaban, but these effects were found to be small.

Diltiazem Inhibits Coronary Spasm via Inhibition of Cav1.2Phosphorylation and Protein Kinase C Activation in a Mouse Model of Coronary Spastic Angina.

Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.

Trends in Prevalence of Non-Valvular Atrial Fibrillation and Anticoagulation Therapy in a Japanese Region　- Analysis Using the National Health Insurance Database.

BACKGROUND: Direct oral anticoagulants (DOACs) are effective in reducing thromboembolism events in patients with non-valvular atrial fibrillation (NVAF). However, little is known about trends in NVAF prevalence and DOAC prescriptions in daily clinical practice. This study investigated the current status and trends in NVAF prevalence and DOAC prescriptions in a region of Japan.Methods and Results:Annual data for the 4 years from May 2014 to May 2017 in the Tsugaru region of Aomori Prefecture, Japan, were obtained for analysis from the Japanese National Health Insurance database ("Kokuho" database [KDB]). The prevalence of NVAF in subjects aged 40-74 years increased gradually over the 4-year study period (1,094/57,452 [1.90%] in 2014, 1,055/56,018 [1.88%] in 2015, 1,072/54,256 [1.98%] in 2016, and 1,154/52,341 [2.20%] in 2017). The proportion of NVAF patients prescribed warfarin decreased (42%, 33%, 24%, and 21% in 2014, 2015, 2016, and 2017, respectively), the proportion of those prescribed DOACs increased (30%, 42%, 50%, and 57%, respectively), and the proportion not prescribed an oral anticoagulant (OAC) decreased (28%, 25%, 26%, and 22%, respectively). However, 17% of patients with a CHADS2score ≥2 were not prescribed an OAC in 2017. CONCLUSIONS: By using the KDB we found that the prevalence of NVAF has increased gradually from 2014 to 2017. In the Tsugaru region in Japan, DOACs prescriptions increased and warfarin prescriptions decreased over the 4-year period.

Safety and Efficacy of Subcutaneous Cardioverter Defibrillator in Patients at High Risk of Sudden Cardiac Death　- Primary Japanese Experience.

BACKGROUND: The entirely subcutaneous implantable cardioverter defibrillator (S-ICD) was introduced as a new alternative to conventional transvenous ICD (TV-ICD) in Japan in February 2016, but its safety and efficacy are unclear.Methods and Results:A total of 60 patients (48 men, median age, 60 years; IQR, 44-67 years; primary prevention, n=24) underwent S-ICD implantation between February 2016 and August 2017. The device pocket was formed in the intermuscular space between the serratus anterior muscle and the latissimus dorsi muscle, and the parasternal S-ICD lead was placed according to pre-implant screening. Defibrillation test was performed in 56 patients (93%). Ventricular fibrillation (VF) was induced in 55 patients and terminated by a single 65-J shock in all patients. The median time to shock therapy was 13.4 s (IQR, 12.1-14.9 s) and the median post-shock impedance of the S-ICD lead was 64 Ω (IQR, 58-77 Ω). There were no operation-related complications or subsequent infectious complications. During follow-up (median, 275 days; IQR, 107-421 days), 1 patient (1.7%) had appropriate shock for VF with successful termination, whereas 5 patients (8.3%) had inappropriate shock due to oversensing of myopotential (n=3) or T-wave (n=1), and detection of supraventricular tachycardia (n=1). CONCLUSIONS: S-ICD is a safe and effective alternative to conventional TV-ICD. The long-term safety and efficacy of the S-ICD need further investigation.

Long Postpacing Interval After Entrainment of Tachycardia Including a Slow Conduction Zone Within the Circuit.

BACKGROUNDS: Postpacing interval (PPI) measured after entrainment pacing describes the distance between pacing site and reentrant circuit. However, the influential features to PPI remain to be elucidated. METHODS AND RESULTS: This study included 22 cases with slow/fast atrioventricular (AV) nodal reentrant tachycardia (AVNRT), 14 orthodromic AV reciprocating tachycardia (AVRT) using an accessary pathway, 22 typical atrial flutter (AFL), and 18 other macroreentrant atrial tachycardia (atypical AFL). Rapid pacing at a pacing cycle length (PCL) 5% shorter than tachycardia cycle length (TCL) was done from a site on or close to the reentry circuit. Pacing sites included the coronary sinus ostium in AVNRT, earliest atrial activation site in AVRT, and cavotricuspid isthmus in typical AFL. In atypical AFL, tachycardia circuit was determined on the basis of CARTO mapping, and then the pacing site was. TCL was significantly longer in AVNRT and AVRT than in typical AFL and atypical AFL (both P < 0.05). PCL minus TCL value was similar among the 4 groups. PPI minus TCL value (milliseconds) was significantly longer in AVNRT (median, 40 [IQR, 29-60.8]) and AVRT (34 [20-47]) than in typical AFL (0 [0-4]) and atypical AFL (3.5 [0-8]) (both P < 0.05). Furthermore, PPI minus TCL was prolonged with shortening of PCL in AVNRT and AVRT (both P < 0.05), whereas it was unchanged in typical AFL (P = 0.50). CONCLUSION: PPI after concealed entrainment is prolonged compared with TCL when the reentry circuit involves a slow conduction zone with a decremental conduction property such as the AV node.

Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression.

Enhanced renin-angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1-7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of blood pressure, and evaluated the potential mechanisms. The 3- to 4-month-old male mice overexpressing renin in the liver (Ren-Tg) were given Olm (5 mg/kg/d) and hydralazine (Hyd) (3.5 mg/kg/d) orally for 2 months. Systolic blood pressure was higher in the Ren-Tg mice than in wild-type littermates. Olm and Hyd treatments lowered systolic blood pressure to the same degree. However, cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression, was inhibited by only Olm treatment, but not by Hyd. Olm treatment reversed decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibited enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species, whereas Hyd treatment had no influence on them. These findings indicate that Olm treatment inhibits cardiac hypertrophy independently of blood pressure, not only through its original AT1R blockade but partly through enhancement of ACE2/Ang(1-7)/Mas axis and suppression of Nox4 expression.

Reduced residual conduction gaps and favourable outcome in contact force-guided circumferential pulmonary vein isolation.

AIMS: Although contact force (CF)-guided circumferential pulmonary vein isolation (CPVI) for paroxysmal atrial fibrillation (PAF) is useful, AF recurrence at long-term follow-up still remains to be resolved. The purpose of this study was to assess safety and efficacy of CF-guided CPVI and to compare residual conduction gaps during CPVI and long-term outcome between the conventional (non-CF-guided) and the CF-guided CPVI. METHODS AND RESULTS: We studied the 50 consecutive PAF patients undergoing CPVI by a ThermoCool EZ Steer catheter (conventional group, mean age 61 ± 10 years) and the other 50 consecutive PAF patients by a ThermoCool SmartTouch catheter (CF group, 65 ± 11 years). The procedure parameters and residual conduction gaps during CPVI, and long-term outcome for 12 months were compared between the two groups. Circumferential pulmonary vein isolation was successfully accomplished without any major complications in both groups. Total procedure and total fluoroscopy times were both significantly shorter in the CF group than in the conventional group (160 ± 30 vs. 245 ± 61 min, P < 0.001, and 17 ± 8 vs. 54 ± 27 min, P < 0.001, respectively). Total number of residual conduction gaps was significantly less in the CF group than in the conventional group (2.7 ± 1.7 vs. 6.3 ± 2.7, P < 0.05). The AF recurrence-free rates after CPVI during 12-month follow-up were 96% (48/50) in the CF group and 82% (41/50) in the conventional group (P = 0.02 by log rank test). Multivariate Cox regression analysis further supported this finding. CONCLUSION: Contact force-guided CPVI is safe and more effective in reducing not only the procedure time but also the AF recurrence than the conventional CPVI, possibly due to reduced residual conduction gaps during CPVI procedure.

NF-κB-dependent increase in tissue factor expression is responsible for hypoxic podocyte injury.

BACKGROUND: Fibrin deposition within glomeruli is commonly seen in kidney biopsy specimens, suggesting enhanced coagulant activity. Tissue factor (TF) is a coagulation factor which is also related to various biological effects, and TF is upregulated by hypoxia in cancer cells. Recently, hypoxic podocyte injury has been proposed, therefore, we investigated TF expression in hypoxia. METHODS: Conditionally immortalized human podocytes were differentiated and treated under hypoxic or normoxic conditions. mRNA expressions of TF and tissue factor pathway inhibitor (TFPI) were analyzed by quantitative RT-PCR. Protein levels of TF and TFPI were tested by enzyme-linked immunosorbent assay. We employed small interfering RNA (siRNA) to temporary knockdown early growth response protein 1 (Egr-1), hypoxia-inducible factor-1α (HIF-1α) and TF. The expression of CD2-associated protein (CD2AP) mRNA and phalloidin staining was examined to assess podocyte injury. RESULTS: Hypoxia increased mRNA expression of TF (6 h: 2.3 ± 0.05 fold, p < 0.001, 24 h: 5.6 ± 2.4 fold, p < 0.05) and suppressed TFPI (6 h: 0.54 ± 0.04 fold, p < 0.05, 24 h: 0.24 ± 0.06 fold, p < 0.001) compared with normoxia. Similarly, protein levels of TF were increased and TFPI were decreased. Egr-1 siRNA did not change TF mRNA expression. Pyrrolidine dithiocarbamate (PDTC), a nuclear factor kappa B (NF-κB) inhibitor, significantly reduced hypoxia induced TF expression, and HIF-1α knockdown further increased TF. Hypoxia resulted in decreased CD2AP and actin reorganization in podocytes, and these changes were attenuated by TF siRNA. CONCLUSION: Hypoxia increased the expression of TF in human podocytes NF-κB dependently. TF may have a critical role in the hypoxic podocyte injury.

Dual tachyarrhythmia: Ventricular fibrillation induced by atrial tachyarrhythmia in a patient with hypertrophic cardiomyopathy.

A patient with hypertrophic cardiomyopathy experienced cardiopulmonary arrest. An automated external defibrillator administered defibrillation for ventricular fibrillation (A). The pacemaker recorded atrial tachycardia with a rapid ventricular response before the patient collapsed (B). After a few minutes, the pacemaker records dual tachyarrhythmia, characterized by the simultaneous presence of ventricular fibrillation (VF) and atrial fibrillation (AF) (C). This case demonstrates that VF induced by atrial tachyarrhythmia could contribute to AF-related sudden cardiac death.

Complete remission of giant cell myocarditis by prednisolone monotherapy: A case with mild inflammation demonstrated by mismatch between T2-high intensity areas and late gadolinium enhancement.

Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with prednisolone monotherapy. The patient had a fever and shortness of breath and was referred to our hospital. Laboratory test results revealed elevated troponin I levels. Cardiac magnetic resonance (CMR) showed high intensity in the inferoseptal segment of the left ventricle on T2-weighted short tau inversion recovery imaging without late gadolinium enhancement (LGE), suggesting predominant edema rather than necrosis. The patient was diagnosed with GCM based on an endomyocardial biopsy, which revealed lymphocyte infiltration and multinucleated giant cells in the absence of granuloma formation. Subsequently, the patient received intravenous methylprednisolone at 1000 mg/day for 3 days followed by oral prednisolone at 30 mg/day, which normalized troponin levels. Follow-up CMR revealed improved cardiac inflammation; therefore, the patient was discharged without prescribing another immunosuppressive agent. Prednisolone was tapered and terminated three years after discharge. The patient went one year without medication and had no recurrence of GCM on follow-up. This case highlights the presence of mild GCM, successfully treated by steroid monotherapy, in which the mismatch between high-intensity T2 areas and LGE suggests mild inflammation. Learning objective: Giant cell myocarditis (GCM) is potentially lethal and usually requires multiple immunosuppressive agents. Here, we report a patient with GCM with preserved left ventricular ejection fraction. Cardiac magnetic resonance revealed focal high T2 signal intensity areas without late gadolinium enhancement, indicating myocardial edema without necrosis. The patient remained in remission with prednisolone monotherapy for 2 years. Our report indicates that "mild" GCM may be treated with prednisolone monotherapy.

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.

Validation of accuracy of three-dimensional left atrial CartoSound™ and CT image integration: influence of respiratory phase and cardiac cycle.

BACKGROUND: CartoSound™ (CS) module is useful in integrating 3-dimensional (3D) left atrial (LA) image with CT image. Integration method, however, has not been established. We reported the accuracy of LA electroanatomical (EA) and CT image integration by registering LA roof (LAR) and posterior wall (LAPW). METHODS: The consecutive 56 atrial fibrillation patients undergoing pulmonary vein isolation were studied. In the initial 29 patients, before the transseptal puncture, 3D CS LAR and LAPW image was created by registering a mean of 10 contour lines between the right and left pulmonary veins. After transseptally inserting a mapping catheter into LA, 3D EA image of LAR and LAPW was obtained by sampling a mean of 40 points. LA CT image was taken at the full-inspiratory position and 0% of R-R interval. After visual alignment of CS or EA and LA CT image, the 2 images were integrated with surface registration program. In the latter 27 patients, both CT and CS images were taken while matching the respiratory phase at the end-tidal position and cardiac cycle at 50% of R-R interval. RESULTS: In the initial 29 patients, the mean distances between EA and CT images and between CS and CT images were 1.53 ± 0.27 and 1.59 ± 0.23 mm, respectively (P = NS). In the latter 27, the mean distance was decreased to 1.08 ± 0.14 mm (P < 0.0001). CONCLUSIONS: CS system is useful in image integration with 3D CT. Matching both respiratory phase and cardiac cycle between CS and CT image acquisition improves the image integration accuracy.

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.

The usefulness of balloon occlusive left ventricular lead delivery in combination with the quadripolar active fixation lead for a patient with complex coronary venous morphology.

Complex coronary vein morphology impedes the insertion of the left ventricular (LV) lead and reduces the effectiveness of cardiac resynchronization therapy (CRT). A 77-year-old woman underwent dual-chamber pacemaker implantation via the left subclavian approach for a complete atrioventricular block 17 years previously. She was hospitalized due to decompensated heart failure, and her cardiac rhythm completely depended on ventricular pacing at that time. Transthoracic echocardiography showed thinning of the ventricular septum in the basal region and pacing-induced dyssynchrony. She was clinically diagnosed with cardiac sarcoidosis with severe LV systolic dysfunction. She was referred for an upgrade to CRT. Given that prior contrast venography showed occlusion of the left subclavian vein, an additional LV lead was inserted through the right subclavian vein. Coronary venography showed a lateral vein that branched from the great cardiac vein with an acute angle and had multiple tortuosities in the peripheral branches. Since the LV lead placement was unsuccessful with the conventional method, we attempted the lead placement using the balloon occlusion technique (BOT). Lead delivery into the anatomical optimal lateral vein was successful by using BOT, and LV pacing from the most delayed basal region was achieved in combination with the active fixation LV lead. .

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.

Impact of gene polymorphisms in drug-metabolizing enzymes and transporters on trough concentrations of rivaroxaban in patients with atrial fibrillation.

Rivaroxaban is excreted from the body via multiple pathways involving glomerular filtration, drug-metabolizing enzymes and transporters. In this study, we aimed to examine the impact of single nucleotide polymorphisms in P-glycoprotein, breast cancer resistance protein, cytochrome P450 (CYP) 3A5 and CYP2J2 on the pharmacokinetics of rivaroxaban. Eighty-six patients with non-valvular atrial fibrillation (NVAF) undergoing AF catheter ablation were enrolled in this study. In these analyses, the dose-adjusted plasma trough concentration ratio (C0h /D) of rivaroxaban was used as the pharmacokinetic index. The median (quartile range) rivaroxaban C0h /D was 3.39 (2.08-5.21) ng/mL/mg (coefficient of variation: 80.5%). The C0h /D did not differ significantly among ABCB1 c.3435C>T, c.2677G>A/T, c.1236C>T, ABCG2 c.421C>A, CYP3A5*3 and CYP2J2*7 genotypes. Stepwise selection multiple linear regression analysis showed that the estimated glomerular filtration rate was the only independent factor influencing the C0h /D of rivaroxaban (R2  = 0.152, P < 0.001). There was a significant correlation between the C0h of rivaroxaban and prothrombin time (PT) (rho = 0.357, P = 0.001). In patients with NVAF, pharmacokinetic genotype tests are unlikely to be useful for prediction of the C0h of rivaroxaban.

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.