Understanding Antithrombotic Agents for Rehabilitation Therapy: A Comprehensive Narrative Review.

In rehabilitation medicine, attention must be paid to the medication. Among them, antithrombotic drugs are used for the initial treatment and secondary prevention of stroke, so as a basic knowledge, the pharmacological actions, characteristics, indications, and precautions for the use of antithrombotic drugs should be known. Antithrombotic agents are divided into antiplatelet agents and anticoagulants, and the appropriate antithrombotic agent is selected according to the main disease or condition. Antiplatelet agents include aspirin, clopidogrel, ticlopidine, prasugrel, ticagrelor, and cilostazol. Each antiplatelet agent has a different mechanism of action, characteristics, and indications, and should be prescribed with due consideration. Anticoagulants include heparin, synthetic Xa inhibitors, direct oral anticoagulants (DOACs), synthetic antithrombin agents, and warfarin. Knowledge of the mechanism of action, characteristics, and indications of each anticoagulant is necessary, as well as monitoring and dose adjustment. With regard to ischemic cerebrovascular disease (ICD) and antithrombotic agents, the first step is to classify cerebral infarction and to determine whether antiplatelet agents or anticoagulants should be used. Bleeding and recurrence prevention are important considerations in the selection of appropriate antithrombotic agents for the pathophysiology of ICD.

Right Atrial Septal Lead Enhances the Favorable Effects of the Adaptive Cardiac Resynchronization Therapy Algorithm.

The adaptive cardiac resynchronization therapy (CRT) algorithm provides synchronized left ventricular pacing (sLVP). However, ensuring a high sLVP rate is challenging. We assessed the association between the sLVP rate and pacing sites in the right atrium. We evaluated 71 patients who underwent CRT and in whom the adaptive CRT algorithm was applied (53 men; mean age, 66 ± 14 years; median follow-up period, 301 days; IQR: 212-596 days). The atrial pacing leads were positioned in the right atrial (RA) septum in 17 patients (septal group) and in the RA appendage in 54 patients (RA appendage group), with significantly higher sLVP rates in the septal group compared with the RA appendage group (81% ± 30% vs 63% ± 37%; P = 0.045). In patients with first-degree atrioventricular blocks, the sLVP rates tended to be higher in the septal group. Therefore, RA septal pacing increased sLVP rates in patients undergoing CRT.

Effect of adaptive cardiac resynchronization therapy in heart failure patients with pacemaker dependency.

BACKGROUND: An adaptive cardiac resynchronization therapy (aCRT) algorithm allows continuous adjustments of pacing timings of atrioventricular delays by periodic automatic evaluation of electrical conduction. This applies to patients with an atrioventricular block and is effective in cardiac resynchronization therapy (CRT) devices; however, whether this algorithm benefits patients with pacemaker dependency is uncertain. METHODS: This study examined the clinical impact of an aCRT algorithm in patients diagnosed with heart failure with reduced ejection fraction and pacemaker dependency. A total of 359 patients underwent CRT between January 2016 and December 2022. Patients undergoing pacemaker-dependent CRT with the aCRT algorithm function were selected. Sixty-four patients with pacemaker dependency (31 with aCRT algorithm and 33 without) were included. Pacemaker dependency was defined as the absence of spontaneous ventricular activity during the sensing test at VVI 30 bpm or prolonged atrioventricular delay (> 300 ms). The primary endpoint was the composite clinical outcome of all-cause death or hospitalization for heart failure. RESULTS: No significant differences were observed in baseline characteristics between groups. During a median follow-up of 1,067 days (interquartile range 553-1,776 days), aCRT reduced the risk of composite clinical outcomes in patients with pacemaker dependency (log-rank P = 0.028). In addition, using the aCRT algorithm was an independent predictor of the composite clinical outcomes in the multivariate analysis (hazard ratio 0.34, 95% confidence interval: 0.12-0.94, P = 0.038). CONCLUSION: The aCRT algorithm significantly reduced the risk of adverse clinical outcomes in patients with pacemaker dependency. This algorithm may be an important tool for managing such patients.

Long-term outcomes after catheter ablation for idiopathic atypical atrial flutter.

BACKGROUND: Idiopathic atypical (non-cavotricuspid isthmus-dependent) atrial flutter (IAAFL) may be seen in patients without structural heart disease and without previous cardiac surgery or ablation. OBJECTIVE: This study sought to determine the patient characteristics, electrophysiologic and electroanatomic properties, and clinical outcomes after ablation in patients with IAAFL. METHODS: We retrospectively compared IAAFL patients with cavotricuspid isthmus-dependent AFL (C-AFL) patients undergoing catheter ablation. The primary outcome was a composite of death from cardiovascular causes, ischemic stroke, and hospitalization for worsening of heart failure. RESULTS: Of 180 patients who underwent catheter ablation for AFL, 89 were included in this study (22 IAAFL and 67 C-AFL). Electrophysiologic study showed significantly longer intra-atrial conduction time and lower atrial voltage during sinus rhythm in the IAAFL group compared with the C-AFL group. The atrial scar was observed in all 22 IAAFL patients, with the most common sites being the posterior or lateral wall of the right atrium in 10 (45.5%) and the anterior wall of the left atrium in 8 (36.4%). During 3.5 ± 2.8 years of follow-up, the composite primary end point occurred significantly more frequently in the IAAFL group (hazard ratio [HR], 3.45; 95% confidence interval [CI], 1.20-9.89; P = .015). In multivariable analysis, brain natriuretic peptide levels (HR, 1.01; 95% CI, 1.00-1.01, per 1 pg/mL; P = .01) and IAAFL (HR, 4.14; 95% CI, 1.21-14.07; P = .02) were independently associated with the primary outcome. CONCLUSION: IAAFL in patients had distinct electrophysiologic features suggestive of atrial cardiomyopathy. These patients are at risk for development of cardiovascular adverse events after ablation.

Two Cases Showing That Cilostazol Administration Leads to an Increase in Cerebral Blood Flow and Has a Positive Effect on Rehabilitation.

Cilostazol is a drug that has both antiplatelet and vasodilatory effects. To examine the effects of cilostazol on cerebral blood flow and rehabilitation following stroke, cilostazol was administered to two patients with chronic atherothrombotic cerebral infarction. In both patients, cilostazol administration effectively increased cerebral blood flow and promoted rehabilitation. Therefore, cilostazol was considered to be a useful agent for improving the clinical condition of patients suffering from chronic cerebral infarction. Further clinical studies on the effective use of cilostazol for rehabilitation in stroke patients are needed.

Precordial ST-Segment Elevation: Anterior Myocardial Infarction or Something Else?

The differential diagnosis of ST-segment elevation on electrocardiogram is multifaceted. Particularly, in cases of precordial ST-segment elevation, considering anterior myocardial infarction is crucial. Herein, we present a case of precordial ST-segment elevation with normal left coronary arteries.

Human RFX6 regulates endoderm patterning at the primitive gut tube stage.

Transcriptional factor RFX6 is known to be a causal gene of Mitchell-Riley syndrome (MRS), an autosomal recessive neonatal diabetes associated with pancreatic hypoplasia and intestinal atresia/malformation. The morphological defects are limited to posterior foregut and mid-hindgut endodermal lineages and do not occur in the anterior foregut lineage; the mechanism remains to be fully elucidated. In this study, we generated RFX6+/eGFP heterozygous knockin and RFX6eGFP/eGFP homozygous knockin/knockout human-induced pluripotent stem cell (hiPSC) lines and performed in vitro endoderm differentiation to clarify the role of RFX6 in early endoderm development. RFX6 expression was found to surge at the primitive gut tube (PGT) stage in comparison with that in the undifferentiated or definitive endoderm stage. At the PGT stage, the expression of PDX1 and CDX2, posterior foregut and mid-hindgut master regulators, respectively, was decreased by the RFX6 deficit. PDX1+ and CDX2+ cells were mostly green fluorescent protein (GFP)+ in RFX6+/eGFP hiPSCs, but their cell number was markedly decreased in RFX6eGFP/eGFP hiPSCs. The expression of SOX2, an anterior foregut marker, was not affected by the RFX6 deficit. In addition, we found a putative RFX6-binding X-box motif using cap analysis of gene expression-seq and the motif-containing sequences in the enhancer regions of PDX1 and CDX2 bound to RFX6 in vitro. Thus, RFX6 regulates the ParaHox genes PDX1 and CDX2 but does not affect SOX2 in early endodermal differentiation, suggesting that defects in early stage endoderm patterning account for the morphological pathology of MRS.

Acute pulmonary vein stenosis during radiofrequency catheter ablation for atrial fibrillation.

We encountered acute pulmonary vein (PV) stenosis during radiofrequency catheter ablation. PV stenosis was not apparent before redo ablation (A). However, acute PV stenosis was observed after repeat ablation, including carina ablation (B, C). Computed tomography performed 6 months post-ablation revealed chronic PV stenosis (D).

Telehealth Follow-up Using a Real-Time Electrocardiogram Device Improves Electrocardiogram Monitoring Duration and Patient Satisfaction After Catheter Ablation.

Background: There is a strong demand for remote monitoring systems to gather health data. This study investigated the safety, usefulness, and patient satisfaction in outpatient care using telehealth with real-time electrocardiogram (ECG) monitoring after catheter ablation. Methods and Results: In all, 38 patients who underwent catheter ablation were followed up using telehealth. At the 3- and 6-month follow-up, a self-fitted Duranta ECG monitoring device was sent to the patient's home before the online consultation. Patients attached the devices themselves, and the doctors viewed the patients by video chat and performed real-time ECG monitoring. The frequency of hospital visits and the ECG monitoring duration were compared with conventional in-person follow-up data (n=102). The completion rate for telehealth follow-up was 32 of 38 patients (84%). The number of hospital visits during the 6 months was significantly lower with telehealth follow-up than with conventional follow-up (median [interquartile range] 1 [1-1] vs. 5 [3-5]; P<0.0001). However, the ECG monitoring duration was approximately 4-fold longer for the telehealth follow-up (median [interquartile range] 89 [64-117] vs. 24 [0.1-24] h; P<0.0001). No major adverse events were observed during the telehealth follow-up. Patient surveys showed high satisfaction with telehealth follow-up due to reduced hospital visits. Conclusions: A combination of telehealth follow-up with real-time ECG monitoring increased the ECG monitoring duration and patient satisfaction without any adverse events.

Noninvasive evaluation of donor and native pancreases following simultaneous pancreas-kidney transplantation using positron emission tomography/computed tomography.

It is crucial to develop practical and noninvasive methods to assess the functional beta-cell mass in a donor pancreas, in which monitoring and precise evaluation is challenging. A patient with type 1 diabetes underwent noninvasive imaging following simultaneous kidney-pancreas transplantation with positron emission tomography/computed tomography (PET/CT) using an exendin-based probe, [18 F]FB(ePEG12)12-exendin-4. Following transplantation, PET imaging with [18 F]FB(ePEG12)12-exendin-4 revealed simultaneous and distinct accumulations in the donor and native pancreases. The pancreases were outlined at a reasonable distance from the surrounding organs using [18 F]FB(ePEG12)12-exendin-4 whole-body maximum intensity projection and axial PET images. At 1 and 2 h after [18 F]FB(ePEG12)12-exendin-4 administration, the mean standardized uptake values were 2.96 and 3.08, respectively, in the donor pancreas and 1.97 and 2.25, respectively, in the native pancreas. [18 F]FB(ePEG12)12-exendin-4 positron emission tomography imaging allowed repeatable and quantitative assessment of beta-cell mass following simultaneous kidney-pancreas transplantation.

The relationship between the incision line and position of the latissimus dorsi muscle for subcutaneous implantable cardioverter-defibrillator intermuscular implantations.

INTRODUCTION: Intermuscular implantations of subcutaneous implantable cardioverter-defibrillators (S-ICD) have been recommended, but the position of the anterior border of the latissimus dorsi muscle (LDM) has not previously been evaluated in establishing an incision line to facilitate the intermuscular approach. The objective of this study is to evalua the position and trend of the anterior border of the LDM in patients who are candidates for implantable cardioverter-defibrillators. METHODS: The distance from the back to the anterior border of the LDM (A) and the anterior-posterior width of the chest wall (B) were measured on computed tomography retrospectively, and the ratio (=A/B) was used as the position of the anterior border of the LDM. In addition, the variability and factors affecting the values were evaluated. RESULTS: An analysis was performed on 78 patients, and the position of the anterior border of the LDM (=A/B) exhibited a normal distribution, with a mean value of 0.53 ± 0.062 (0.41-0.69). The position of the anterior border of the LDM tended to be more anterior in younger, taller, male, primary prevention, nonheart failure, low brain natriuretic peptide level, and nondiabetic patients. CONCLUSION: The position of the anterior border of the LDM varied from case to case with variable results. Conventional incisions on the midaxillary line may be inappropriate for intermuscular implantations, and the position of the anterior border of the LDM should be evaluated in each individual case to establish the incision line.

Elucidation of HHEX in pancreatic endoderm differentiation using a human iPSC differentiation model.

For pluripotent stem cell (PSC)-based regenerative therapy against diabetes, the differentiation efficiency to pancreatic lineage cells needs to be improved based on the mechanistic understanding of pancreatic differentiation. Here, we aimed to elucidate the molecular mechanisms underlying pancreatic endoderm differentiation by searching for factors that regulate a crucial pancreatic endoderm marker gene, NKX6.1. Unbiasedly screening an siRNA knockdown library, we identified a candidate transcription factor, HHEX. HHEX knockdown suppressed the expression of another pancreatic endoderm marker gene, PTF1A, as well as NKX6.1, independently of PDX1, a known regulator of NKX6.1 expression. In contrast, the overexpression of HHEX upregulated the expressions of NKX6.1 and PTF1A. RNA-seq analysis showed decreased expressions of several genes related to pancreatic development, such as NKX6.1, PTF1A, ONECUT1 and ONECUT3, in HHEX knockdown pancreatic endoderm. These results suggest that HHEX plays a key role in pancreatic endoderm differentiation.

Narrow QRS Complex Tachycardia With Variable R-R Intervals and Discrete P Waves.

Irregular narrow QRS complex tachycardia is associated with a wide range of differential diagnoses, including atrial fibrillation and atrial tachyarrhythmia with altered atrioventricular conduction. Here, we present a case of narrow QRS complex tachycardia with variable R-R intervals and discrete P waves. (Level of Difficulty: Intermediate.).

Predictors of recurrence in patients without non-inducibility of ventricular tachycardia at the end of ablation.

Background: Ventricular tachycardia (VT) non-inducibility at the end of ablation is associated with a less likely VT recurrence. However, it is not clear whether we should use VT non-inducibility as a routine end point of VT ablation. The aim of this study was to evaluate VT recurrence in patients in whom VT non-inducibility was not achieved at the end of the radiofrequency (RF) ablation and the factors attributing to the VT recurrence. Methods: We analyzed that 62 patients in whom VT non-inducibility was not achieved at the end of the RF ablation were studied. Results: Over 2 years, 22 (35%) of the cases had VT recurrences. A multivariate analysis showed that an LVEF ≥35% (HR: 0.19; 95% CI: 0.06-0.49; p < .01) and elimination of the clinical VT as an acute ablation efficacy (HR: 0.23; 95% CI: 0.04-0.81; p = .02) were independent predictors of fewer VT recurrences. RF ablation was associated with a 91.1% reduction in VT episodes. Conclusion: Even if VT non-inducibility was not achieved, patients with an LVEF ≥35% or in whom the clinical VT could be eliminated might be prevented from having VT recurrences. The validity of the VT non-inducibility of any VT should be evaluated considering each patient's background and the results of the procedure.

Prognostic Value of Left Atrial Calcification After Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Left atrial calcification (LAC) has occasionally been observed in patients who underwent catheter ablation for atrial fibrillation (AF) by chest computed tomography (CT). However, the evidence regarding the clinical impact of LAC in patients with AF is lacking. OBJECTIVES: This study aims to investigate the prevalence of LAC in AF patients and evaluate its clinical significance after AF ablation. METHODS: This observational registry included AF patients who received computed tomography and serial transthoracic echocardiography between January 2010 and November 2017. The primary composite outcome included cardiovascular death, hospitalization for worsening heart failure, and ischemic stroke. RESULTS: Among 534 patients (age 72 ± 13 years, 62.5% men) who met the inclusion criteria, 31 (5.8%) had LAC. In multivariable analysis, AF ablation was associated with an 11.8-fold (OR: 11.8; 95% CI: 2.03-227.65) increased risk of the development of LAC in AF patients. Among 218 patients with AF ablation, LAC was detected in 30 (13.8%) patients. Prior stroke (HR: 2.73; 95% CI: 1.08-6.93) and multiple ablation procedures (HR: 4.21; 95% CI: 1.63-10.87) were independently associated with the development of LAC in AF-ablation patients. During a median follow-up of 5.8 years, the primary composite outcome occurred in 11 patients in the LAC group (39.8 per 1,000 person-years) and 10 patients in the non-LAC group (8.9 per 1,000 person-years). The adjusted HR for the primary composite outcome in the LAC group, as compared with the non-LAC group, was 2.81 (95% CI: 1.16-6.84; P = 0.02). CONCLUSIONS: The presence of LAC was a significant and independent prognostic factor for identifying major adverse cardiovascular events after AF ablation.

The impact of the procedural parameters on the lesion characteristics associated with AF recurrence: Late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) analysis.

BACKGROUND: Lesion gaps assessed by late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) are associated with the atrial fibrillation (AF) recurrence after pulmonary vein isolation. Animal studies have demonstrated that the catheter-contact force (CF), stability, and orientation are strongly associated with lesion formation. However, the impact of those procedural factors on the lesion characteristics associated with AF recurrence has not been well discussed. METHODS: A total of 30 patients with paroxysmal AF who underwent catheter ablation were retrospectively enrolled. Radiofrequency (RF) applications were performed with 35 W for 30 s in a point-by-point fashion under esophageal temperature monitoring. The inter-lesion distance was 4 mm. The lesions were visualized by LGE-MRI 3 months postprocedure and assessed by the LGE volume (ml), gap number (GN), and average gap length (AGL [mm]). The gaps were defined as nonenhancement sites of >4 mm. The procedural factors including the catheter-CF, stability, and orientation were calculated on the NavX system. RESULTS: Six (20%) of 30 patients had AF recurrences 12 months postablation. A univariate analysis demonstrated that the AGL was associated with AF recurrence (hazard ratio [HR]: 1.20, confidence interval [CI]: 1.03-1.42, p = .02). All AF recurrence were found in patients with an AGL of >7 mm. The catheter-CF and stability were associated with an AGL of >7 mm, but not the orientation (CF-HR: 0.62, CI: 0.39-0.97, p = .038; stability-HR: 0.8, CI: 0.66-0.98, p = .027). CONCLUSIONS: RF ablation with a low CF and poor catheter stability has a potential risk of creating large lesion gaps associated with AF recurrence.

Effects of sodium bicarbonate bath on the quality of sleep: An assessor-blinded, randomized, controlled, pilot clinical trial.

BACKGROUND: Sleep is fundamental to a healthy life, and sleep disorders are an important health issue in healthcare. Whole-body warm water bathing is a non-pharmacological, safe (non-invasive), and widely used method for comforting. Here, we explored the feasibility and preliminary effectiveness of sodium bicarbonate bath (SBB) on sleep quality. METHODS: Healthy adults without sleep disturbances were randomly assigned to shower baths (SHB), tap-water baths (TWB, placebo tablets), or SBB. All participants took a bath (shower, tap-water, or SBB) once a day for 10 min, after dinner, for 7 days. Sleepscan-derived sleep parameters, including total sleep time (TST), symptom questionnaires, and salivary α-amylase concentration were evaluated as outcome measures. RESULTS: Forty participants were enrolled (14, 13, and 13 in SHB, TWB, and SBB groups, respectively) and 38 participants completed the trial (13, 12, and 13, respectively). The recruitment, adherence, and completion rates were 90.9% (40/44), 95.0% (38/40), and 95.0% (38/40), respectively. The SBB group showed a significant increase (12.35 [mean]±10.07 [standard deviation] min) in the mean TST at 1-week post-intervention (p = 0.0041) than the SHB (-1.81 ± 14.58 min; p = 0.0231) and TWB (4.54 ± 10.97 min; p = 0.0377) groups. The TST scores at 1-week post-intervention, sleep onset latency, wake after sleep onset, and sleep efficiency were significantly different between the groups. Sleep satisfaction by questionnaire was significantly improved with intervention in the SBB group than that in the SHB and TWB groups. Salivary α-amylase levels significantly improved in the SBB and TWB groups than in the SHB group, with the change being greater in the SBB group. CONCLUSIONS: SBB for 7 days had positive effects that improved sleep quality of adults. Further studies are needed to examine the efficacy and safety of SBB for prolonged usage in people diagnosed with insomnia, using objective sleep measurements, and to investigate potential sleep-enhancing mechanisms of action.

Ventricular arrhythmia events in heart failure patients with cardiac resynchronization therapy with or without a defibrillator for primary prevention.

Background: It is uncertain whether cardiac resynchronization therapy with a defibrillator (CRT-D) provides better survival benefits than a CRT-pacemaker (CRT-P) in heart failure patients with a reduced ejection fraction (≦35%, HFrEF) treated with contemporary HF therapy. Methods: We retrospectively analyzed the ventricular arrhythmia (VAs; sustained ventricular tachycardia/fibrillation) events in HFrEF patients who underwent CRT without a prior history of VAs or aborted sudden cardiac death before the CRT implantation. Between January/2010 and December/2020, a CRT device was implanted in 79 HFrEF patients (mean age: 69 ± 12 years, male: 57, ischemic cardiomyopathy: 16). CRT-D and CRT-P devices were implanted in 50 and 29 patients, respectively, at each physician's discretion. CRT-Ds were indicated in younger patients than were CRT-Ps (66 ± 12 vs. 73 ± 12 years, p = 0.03), but the gender distribution did not differ (female, 24% [12 of 50] vs. 35% [10 of 29], p = 0.44). The VA events during a median follow-up of 3.5-years (interquartile range [IQR]:1.6-5.5) and their predictors were analyzed. Results: VA events occurred in 9 patients with CRT-Ds (18%) and one with a CRT-P (3%, p = 0.08). The VA event rate was significantly lower in patients without a prior non-sustained ventricular tachycardia (NSVT: ≥3 beats; rate, ≥120 bpm; lasting <30 s, HR 0.05; 95% CI 0.01-0.30; p < 0.01) and females (HR 0.11; 95% CI 0.01-0.93; p = 0.04). Of note, no female patients without a prior history of NSVT experienced VA events. Conclusion: HFrEF CRT candidates without a prior history of NSVT and females may obtain less benefit from a primary preventive defibrillator indication.