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Author(s): M. Fulchignoni [1, 2]; F. Ferri (corresponding author) [3]; F. Angrilli [3]; A. J. Ball [4]; A. Bar-Nun [5]; M. A. Barucci [1]; C. Bettanini [3]; G. Bianchini [3]; [...]

The purpose of this study is to clarify the efficacy and safety of bepridil for persistent atrial fibrillation (AF).Method Bepridil (100-200mg/day) was administered to 159 patients (141 males, 58 years) with persistent AF. The effects of conversion and maintenance of sinus rhythm (SR) were evaluated. If sinus restoration was not obtained until 3 months observation, DC cardioversion was performed. Results In 87 of 159 patients (55%), SR was restored within an average 2.1 months following administration of bepridil. 74 of those 87 patients (85%) have been maintained in SR for the average follow-up of 16 months. The 31 out of remaining 72 patients failed pharmacological conversion were performed DC cardioversion. All of patients restored SR, and 18 of them (58%) could be maintained SR for an average of 20 months. Although ECG revealed significant prolongation of QT interval from 0.38 to 0.42 sec, QTc was unchanged and no serious adverse complications including torsade de pointes were recognized. Conclusion Bepridil is clinically safe and useful with favorable efficacy for conversion and maintenance of SR in patients with persistent AF. [ABSTRACT FROM PUBLISHER]

A 14 year-old boy was admitted for evaluation of recurrent syncope. His ECG on admission revealed a sinus rhythm with an undetermined QRS axis, T wave inversion in leads V3, V4 and abnormal q leads I, aVL, V5 and V6. However, no underlying disease could be detected by any morphological examination. Programmed ventricular stimulation also induced no ventricular tachycardia or fibrillation (VF). Only signal-averaged ECG showed ventricular late potential and the cause of syncope was not clarified. As his brother with similar ECG had died suddenly, he was prophylactically treated with an ICD. However, 14 month later he died suddenly after playing a video game. The ICD recorded VF, which was not converted despite 6 cardioversion attempts by the ICD with 30 J. Progression of myocardial damages and/or elevation of defibrillation threshold may have been the cause of unsuccessful cardioversion. [ABSTRACT FROM PUBLISHER]

We have observed 3 cases of Brugada like ECG findings after the resection of esophageal cancer. Case 1. A 63 years-old male who had atrial fibrillation (AF) was diagnosed as affected byesophageal cancer and underwent the resection of esophagus with subsequent reconstruction using stomach into retro-sternum. Post-operative ECG showed coved type ST elevation in lead V1-4. This finally gradually reverted in ten days after operation and normalized within 2 weeks. Case 2. A 69 year-old male, who had paroxysmal AF and esophageal cancer, received the same procedure as in case 1. His ECG revealed abnormal ST elevation in V1. In thoracic CT image, right ventricle (RV) was compressed by the reconstructed stomach. Case 3. A 68 year-old male underwent the same operation as described above. His post-operative ECG showed Brugada like ST elevation in V1-3. This ST change disappeared within 3 weeks. In none of these 3 cases, there was a family history of sudden death or syncope, and the previous ECG showed no ST segment elevation. The compression of the RV by lifted stomach was considered to induce the precordial ST elevation mimicking Brugada syndrome. [ABSTRACT FROM PUBLISHER]

Endovascular therapy (EVT) utilizing self-expanding stent grafts has shown promising clinical outcomes for femoropopliteal lesions. However, restenosis and thrombotic occlusion remain significant concerns with unclear underlying mechanisms. This is the case of a 53-year-old male with diabetic nephropathy requiring hemodialysis. He presented with left lower limb intermittent claudication and underwent EVT, resulting in subsequent restenosis 12 months post-implantation and recurrence of symptoms. Intravascular imaging revealed neointimal proliferation and stent-edge restenosis, with segments of neointima not in contact with the stent. A second EVT procedure was performed successfully with the endograft extension. Our case highlights the challenges in diagnosing and managing stent graft restenosis. Intravascular imaging modalities such as optical coherence tomography (OCT) were crucial in identifying the etiology and guiding treatment decisions. The presence of neointima not in contact with the stent suggests a potential mechanism for thrombus formation and underscores the importance of tailored treatment strategies. This case underscores the utility of OCT in evaluating stent graft restenosis and guiding therapeutic interventions. Further research is warranted to elucidate optimal treatment strategies for this challenging complication., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abe et al.)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes., Methods: A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values., Results: In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was - 1.07 (95% confidence interval [CI] - 1.29 to - 0.86; P < 0.001). The change in the number of appropriate device discharges during and before treatment was 0.06 in the empagliflozin group and 0.27 in the placebo group, with no significant difference between the groups (P = 0.204). Empagliflozin was associated with an increase in blood ketones and hematocrit and a decrease in blood brain natriuretic peptide and body weight., Conclusions: In patients with type 2 diabetes treated with ICD/CRT-D, empagliflozin reduces the number of ventricular arrhythmias compared with placebo. Trial registration jRCTs031180120., (© 2024. The Author(s).)

Whether malnutrition during the early phase of recovery from acute myocardial infarction (AMI) could be a predictor of mortality or morbidity has not been ascertained. We examined 289 AMI patients. All-cause mortality and composite endpoints (all-cause mortality, nonfatal stroke, nonfatal acute coronary syndrome, and hospitalization for acute decompensated heart failure) during the follow-up duration (median 39 months) were evaluated. There were 108 (37.8%) malnourished patients with GNRIs of less than 98 on arrival; however, malnourished patients significantly decreased to 91 (31.4%) during the convalescence period ( p < 0.01). The incidence rates of mortality and primary composite endpoints were significantly higher in the malnourished group than in the well-nourished group both on arrival and during the convalescence period (All p < 0.05). Nutrition guidance significantly improved GNRI in a group of patients who were undernourished (94.7 vs. 91.0, p < 0.01). Malnourished patients on admission who received nutritional guidance showed similar all-cause mortality with well-nourished patients, whereas malnourished patients without receiving nutritional guidance demonstrated significantly worse compared to the others ( p = 0.03). The assessment of GNRI during the convalescence period is a useful risk predictor for patients with AMI. Nutritional guidance may improve the prognoses of patients with poor nutritional status.

Atherosclerosis is a major cause of cerebral and cardiovascular diseases. Intravascular plaques, a well-known pathological finding of atherosclerosis, have a necrotic core composed of macrophages and dead cells. Intraplaque macrophages, which are classified into various subtypes, play key roles in maintenance of normal cellular microenvironment. Excessive uptake of oxidized low-density lipoprotein causes conversion of macrophages to foam cells, and consequent progression/exacerbation of atherosclerosis. G-protein-coupled receptor 55 (GPR55) signaling has been reported to associate with atherosclerosis progression. We demonstrated recently that lysophosphatidylglucoside (lysoPtdGlc) is a specific ligand of GPR55, although in general physiological ligands of GPR55 are poorly understood. Phosphatidylglucoside is expressed on human monocytes and can be converted to lysoPtdGlc. In the present study, we examined possible involvement of lysoPtdGlc/GPR55 signaling in foam cell formation. In monocyte-derived M2c macrophages, lysoPtdGlc/GPR55 signaling inhibited translocation of ATP binding cassette subfamily A member 1 to plasma membrane, and cholesterol efflux. Such inhibitory effect was reversed by GPR55 antagonist ML193. LysoPtdGlc/GPR55 signaling in M2c macrophages was involved in excessive lipid accumulation, thereby promoting foam cell formation. Our findings suggest that lysoPtdGlc/GPR55 signaling is a potential therapeutic target for inhibition of atherosclerosis progression., (© 2023. Springer Nature Limited.)

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) requires a large amount of economic and human resources. The presence of bystander cardiopulmonary resuscitation (CPR) was focused on selecting appropriate V-A ECMO candidates., Result: This study retrospectively enrolled 39 patients with V-A ECMO due to out-of-hospital cardiac arrest (CA) between January 2010 and March 2019. The introduction criteria of V-A ECMO included the following: (1) < 75 years old, (2) CA on arrival, (3) < 40 min from CA to hospital arrival, (4) shockable rhythm, and (5) good activity of daily living (ADL). The prescribed introduction criteria were not met by 14 patients, but they were introduced to V-A ECMO at the discretion of their attending physicians and were also included in the analysis. Neurological prognosis at discharge was defined using The Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories of Brain Function (CPC). Patients were divided into good or poor neurological prognosis (CPC ≤ 2 or ≥ 3) groups (8 vs. 31 patients). The good prognosis group had a significantly larger number of patients who received bystander CPR (p = 0.04). The mean CPC at discharge was compared based on the combination with the presence of bystander CPR and all five original criteria. Patients who received bystander CPR and met all original five criteria showed significantly better CPC than patients who did not receive bystander CPR and did not meet some of the original five criteria (p = 0.046)., Conclusion: Considering the presence of bystander CPR help in selecting the appropriate candidate of V-A ECMO among out-of-hospital CA cases., (© 2023. The Author(s).)

Aims: Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF-PH inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF-PH inhibitor, in patients with HF and renal anaemia., Methods and Results: We designed a pilot, multi-centre, open-label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m 2 , and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF-PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment., Conclusion: Considering the hypothetical upside and downside of using HIF-PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: This study investigated whether the age of patients undergoing pacemaker implantation is increasing., Methods and results: This study retrospectively reviewed the consecutive cases of 3,582 patients who underwent an initial pacemaker implantation at our hospitals because of symptomatic bradyarrhythmias between 1970 and 2019. The exclusion criteria were: patients with AV block due to cardiac surgery or AV junction ablation, and patients aged <20 years. The patients were divided into 5×10-year groups: those treated in the 1970s (1970-1979), 1980s (1980-1989), 1990s (1990-1999), 2000s (2000-2009), and 2010s (2010-2019). A total of 3,395 patients satisfied the study criteria. The average age at which the patients underwent a first pacemaker implantation increased across the 10-year periods: 63.7±13.2 years in the 1970s, 66.2±12.6 years (1980s), 69.1±12.4 years (1990s), 72.0±11.1 years (2000s), and 75.8±10.0 years (2010s) and advanced significantly in the 1990s, 2000s, and 2010s compared to the 1970s (all P<0.001). The ratio of patients aged ≥80 and ≥90 years increased from 10.6% and 0% in the 1970 s to 38.2% (P<0.001) and 5.2% (P= 0.017) in the 2010s, respectively., Conclusions: The average age at initial pacemaker implantation increased by 12.1 years over the last 50 years in Japan. In particular, the ratios of ≥80 and ≥90 years as the patients age increased significantly.

Rhodopsin phosphodiesterase (Rh-PDE) is an enzyme rhodopsin belonging to a recently discovered class of microbial rhodopsins with light-dependent enzymatic activity. Rh-PDE consists of the N-terminal rhodopsin domain and C-terminal phosphodiesterase (PDE) domain, connected by 76-residue linker, and hydrolyzes both cAMP and cGMP in a light-dependent manner. Thus, Rh-PDE has potential for the optogenetic manipulation of cyclic nucleotide concentrations, as a complementary tool to rhodopsin guanylyl cyclase and photosensitive adenylyl cyclase. Here we present structural and functional analyses of the Rh-PDE derived from Salpingoeca rosetta. The crystal structure of the rhodopsin domain at 2.6 Å resolution revealed a new topology of rhodopsins, with 8 TMs including the N-terminal extra TM, TM0. Mutational analyses demonstrated that TM0 plays a crucial role in the enzymatic photoactivity. We further solved the crystal structures of the rhodopsin domain (3.5 Å) and PDE domain (2.1 Å) with their connecting linkers, which showed a rough sketch of the full-length Rh-PDE. Integrating these structures, we proposed a model of full-length Rh-PDE, based on the HS-AFM observations and computational modeling of the linker region. These findings provide insight into the photoactivation mechanisms of other 8-TM enzyme rhodopsins and expand the definition of rhodopsins.

Photosystem II (PSII) is a multiprotein complex that has a function of light-driven water oxidation. The catalytic site of water oxidation is the Mn 4 CaO 5 cluster, which is bound to the lumenal side of PSII through amino acid residues from the D1 and CP43 proteins and is further surrounded by the extrinsic proteins. In this study, we have for the first time visualized the structural dynamics of the lumenal region of a PSII core complex using high-speed atomic force microscopy (HS-AFM). The HS-AFM images of a PSII membrane fragment showed stepwise dissociation of the PsbP and PsbO extrinsic proteins. Upon subsequent destruction of the Mn 4 CaO 5 cluster, the lumenal domain of CP43 was found to undergo a conformational fluctuation. The observed structural flexibility and conformational fluctuation of the CP43 lumenal domain are suggested to play important roles in the biogenesis of PSII and the photoassembly of the Mn 4 CaO 5 cluster.

The bacterial flagellum is an organelle responsible for motility and has a rotary motor comprising the rotor and the stator. Flagellar biogenesis is initiated by the assembly of the MS-ring, a supramolecular complex embedded in the cytoplasmic membrane. The MS-ring consists of a few dozen copies of the transmembrane FliF protein, and is an essential core structure which is a part of the rotor. The number and location of the flagella are controlled by the FlhF and FlhG proteins in some species. However, there is no clarity on the factors initiating MS-ring assembly, and contribution of FlhF/FlhG to this process. Here, we show that FlhF and a C-ring component FliG facilitate Vibrio MS-ring formation. When Vibrio FliF alone was expressed in Escherichia coli cells, MS-ring formation rarely occurred, indicating the requirement of other factors for MS-ring assembly. Consequently, we investigated if FlhF aided FliF in MS-ring assembly. We found that FlhF allowed GFP-fused FliF to localize at the cell pole in a Vibrio cell, suggesting that it increases local concentration of FliF at the pole. When FliF was co-expressed with FlhF in E. coli cells, the MS-ring was effectively formed, indicating that FlhF somehow contributes to MS-ring formation. The isolated MS-ring structure was similar to the MS-ring formed by Salmonella FliF. Interestingly, FliG facilitates MS-ring formation, suggesting that FliF and FliG assist in each other's assembly into the MS-ring and C-ring. This study aids in understanding the mechanism behind MS-ring assembly using appropriate spatial/temporal regulations. Importance Flagellar formation is initiated by the assembly of the FliF protein into the MS-ring complex, embedded in the cytoplasmic membrane. The appropriate spatial/temporal control of MS-ring formation is important for the morphogenesis of the bacterial flagellum. Here, we focus on the assembly mechanism of Vibrio FliF into the MS-ring. FlhF, a positive regulator of the number and location of flagella, recruits the FliF molecules at the cell pole and facilitates MS-ring formation. FliG also facilitates MS-ring formation. Our study showed that these factors control flagellar biogenesis in Vibrio, by initiating the MS-ring assembly. Furthermore, it also implies that flagellar biogenesis is a sophisticated system linked with the expression of certain genes, protein localization and a supramolecular complex assembly., (Copyright © 2020 American Society for Microbiology.)

A 35-year-old Japanese man was emergently admitted to our hospital with chief complaints of palpitation and dyspnea. He has been treated for Basedow's disease. He was diagnosed with acute decompensated heart failure, atrial fibrillation and thyrotoxicosis. We started anti-thyroid agents and a treatment for heart failure with beta blockers and diuretics under anti-coagulation therapy. His B-type natriuretic peptide levels remained high, although the heart failure had been compensated and the heart rate was well controlled while hyperthyroidism still existed. We should bear in mind that a discrepancy can exist between the clinical course and the B-type natriuretic peptide level in heart failure patients complicated with hyperthyroidism.

Background: In pacemaker-dependent patients, the risk of asystole must be managed during device replacement. This study aimed to examine whether we could predict the indication for temporary pacing (TP) during the generator replacement., Methods: We studied 105 consecutive patients who underwent pacemaker replacement due to battery depletion at Juntendo Nerima Hospital between September 2005 and December 2016. We examined the relationship between the stability of the intrinsic rhythm (IR) during pacemaker replacement and several clinical factors including age, gender, sick sinus syndrome or atrioventricular (AV) block, duration of pacing, structural heart disease, use of anti-arrhythmic drugs, and the presence/absence of a stable IR (>40 bpm) at the outpatient clinic (OPC) just before pacemaker replacement., Results: Of the 105 patients, we excluded 1 patient who required TP because of bradycardia-dependent torsades de points. Therefore, we evaluated 104 patients for the indication for TP. TP was underwent in 19 patients (18%) because of an absence or instability of the IR during pacemaker replacement. The indication for TP was significantly correlated with AV block (84% vs 48%, P = .0044) and the absence of a stable IR at the last OPC visit (89% vs 24%, P < .0001). For predicting the indication for TP, the following values of no stable IR at the last OPC visit were obtained: 89% sensitivity, 77% specificity, 46% positive predictive value, and 97% negative predictive value., Conclusions: The presence of a stable IR at the last OPC visit was a good predictor (97%) of no indication for TP during pacemaker replacement.

Background: Paroxysmal atrioventricular block (P-AVB) is a well-known cause of syncope; however, its underlying mechanism is difficult to determine. This study aimed to evaluate a new ECG index, the "vagal score (VS)," to determine the mechanism of P-AVB., Methods: We evaluated the VS in 20 patients with P-AVB (13 men, 7 women; aged 25-78 years [mean, 59.3 years]). The VS was developed by assigning 1 point each for the following: (1) no AVB or intraventricular conduction disturbance on the baseline ECG, (2) PR prolongation immediately before P-AVB, (3) sinus slowing immediately before P-AVB, (4) initiation of P-AVB by PP prolongation, (5) sinus slowing during ventricular asystole, and (6) resumption of AV conduction with PP shortening, and by assigning -1 point each for (7) the initiation of P-AVB by a premature beat, and (8) resumption of AV conduction by an escape beat. Based on the clinical situations and electrophysiologic findings, we considered the mechanism of P-AVB as vagally mediated or intrinsic conduction disease (ICD)., Results: The VS ranged from 5 to -2 points for each patient. Five patients with a definite vagally mediated P-AVB had high VSs (3-5 points). We observed characteristic ECG findings of ICD consisting of changes in AV conduction by an extrasystole and/or escape beat in only 5 of the 6 patients (83%) with a low VS (1 to -2)., Conclusions: The VS is simple and potentially useful for determining the mechanism of P-AVB. P-AVB with a VS ≥3 strongly suggested a vagally mediated mechanism.