Impact of left ventricular diastolic function and direct oral anticoagulant use for predicting embolic events in patients with heart failure and atrial fibrillation.

Background: Patients with atrial fibrillation (AF) and heart failure (HF) have high stroke risk owing to left atrial dysfunction. However, anticoagulation is a concern in patients with high bleeding risk. We aimed to identify independent predictors of stroke in HF patients with AF. Methods: We retrospectively examined 320 patients (mean age 79 ± 12 years, 163 women) hospitalized with acute HF complicated by AF between January 2014 and December 2018. Patients were followed from admission until ischemic stroke or systemic embolism (SSE) onset or death or were censored at the last contact date or September 2023. Results: SSE occurred in 40 patients (median follow-up of 528 days). Multivariate Cox regression analysis identified age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.00-1.07, p = .034), direct oral anticoagulant (DOAC) use (HR 0.26, 95% CI 0.11-0.60, p = .002), and early diastolic peak flow velocity to early diastolic peak annular velocity (E/e'; HR 1.05, 95% CI 1.02-1.08, p < .001) to be independent predictors of SSE, whereas left atrial reservoir strain was not. After determining an appropriate E/e' cutoff by receiver-operating characteristic curve analysis and adjusting the multivariate Cox model, E/e' ≥17.5 (HR 3.30, 95% CI 1.56-6.83, p = .001) independently predicted SSE. The results were consistent with no interaction in the subanalysis except for gender. Conclusion: Elderly patients not on DOACs with elevated E/e' may be at higher risk of stroke, suggesting that DOACs should be the first choice for patients with elevated E/e' and aggressive additional prophylaxis and careful follow-up are needed.

Impact of High-Voltage Device Implantation in Elderly Japanese Patients With Heart Failure as Primary Prevention　- Post Hoc Analysis of HINODE.

BACKGROUND: Despite an increased incidence of chronic heart failure (HF) and sudden cardiac death (SCD), the use of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) is much lower in Japan than in Western countries. The HF Indication and SCD Prevention Trial Japan (HINODE) prospectively assessed the mortality rate, appropriately treated ventricular arrhythmias (VA), and HF in Japanese patients with a higher risk of HF. METHODS AND RESULTS: HINODE consisted of ICD, CRT-defibrillator (CRT-D), pacing, and non-device treatment cohorts. This subanalysis evaluated the impact of the implantation of high-voltage devices (HVD; ICD and CRT-D) in 171 Japanese patients. We compared all-cause mortality, VA, and HF events between elderly (age >70 years at study enrollment) and non-elderly HVD recipients. The estimated survival rate through 24 months in the HVD cohort was 85.8% (97.5% lower control limit 77.6%). The risk of all-cause mortality was increased for the elderly vs. non-elderly (hazard ratio [HR] 2.82; 95% confidence interval [CI] 1.01-7.91; P=0.039), but did not differ after excluding ICD patients with CRT-D indication (HR 2.32; 95% CI 0.79-6.78; P=0.11). There were no differences in VA and HF event-free rates between elderly and non-elderly HVD recipients (P=0.73 and P=0.55, respectively). CONCLUSIONS: Although elderly patients may have a higher risk of mortality in general, the benefit of HVD therapy in this group is comparable to that in non-elderly patients.

A Case of Ventricular Fibrillation in Masked Long-QT Syndrome Coexisting with Coronary Vasospasm.

Although long-QT syndrome (LQTS) with a normal range QT interval at rest leads to fatal ventricular arrhythmias, it is difficult to diagnose. In this article, we present a rare case of a patient who suffered a cardiac arrest and was recently diagnosed with LQTS and coronary vasospasm. A 62-year-old man with no syncopal episodes had a cardiopulmonary arrest while running. During coronary angiography, vasospasm was induced and we prescribed coronary vasodilators, including calcium channel blockers. An exercise stress test was performed to evaluate the effect of medications and accidentally unveiled exercise-induced QT prolongation. He was diagnosed with LQTS based on diagnostic criteria. Pharmacotherapy and an implantable cardioverter defibrillator were used for his medical management. It is extremely rare for LQTS and coronary vasospasm to coexist. In cases of exercise-induced arrhythmic events, the exercise stress test might be helpful to diagnose underlying disease.

Impact of Preprocedural Frailty Status in Elderly Transvenous Pacemaker Recipients.

The number of TV-PM implantations in elderly people is increasing. Although frailty syndrome is common in elderly patients, the relationship between the pre-procedural frailty status and clinical outcomes has not been fully elucidated in elderly TV-PM recipients.This study included 103 consecutive patients over 80 years old who were newly implanted with a TV-PM (age 85.7 ± 4.2, 41.7% male). We assessed the relationship between the clinical outcome and predictive factors, especially for the pre-procedural frailty status after the TV-PM implantation. The pre-procedural frailty status was retrospectively assessed from the medical records and classified on the basis of impairments in 3 domains (walking, cognition, and activities of daily living). The primary endpoint was defined as a heart failure admission.During the follow-up period (4.1 ± 2.3 years), 20 patients (19.4%) met the primary endpoint. Frailty syndrome was identified in 40 patients (38.8%). In univariate analysis, the LVEF (HR 0.97, 95% CI 0.96-1.00 P = 0.0492), an RV pacing burden over 40% (HR 1.58, 95% CI 1.00-2.54 P = 0.0473), and presence of a frailty status (HR 1.82, 95% CI 1.13-2.87 P = 0.0134) were found to be statistically significant predictors for the study endpoint. In multivariate analysis, having frailty syndrome was the only predictive factor for a heart failure admission (HR 1.83, 95% CI 1.12-2.93 P = 0.0157).The presence of frailty syndrome and incidence of clinical events were high and a pre-procedural frailty status assessment was key in determining the clinical outcomes in TV-PM recipients over 80 years old.

Graves' Disease after mRNA COVID-19 Vaccination, with the Presence of Autoimmune Antibodies Even One Year Later.

A 45-year-old man who had received his second mRNA COVID-19 vaccination one week earlier was presented to the emergency department with chest discomfort. Therefore, we suspected post-vaccination myocarditis; however, the patient showed no signs of myocarditis. After 2 weeks, he revisited the hospital complaining of palpitations, hand tremors, and weight loss. The patient exhibited high free thyroxine (FT4) (6.42 ng/dL), low thyroid-stimulating hormone (TSH) (<0.01 µIU/mL), and high TSH receptor antibody (17.5 IU/L) levels, and was diagnosed with Graves' disease. Thiamazole was administered, and the patient's FT4 levels normalized after 30 days. One year later, the patient's FT4 is stable; however, their TSH receptor antibodies have not become negative and thiamazole has continued. This is the first case report to follow the course of Graves' disease one year after mRNA COVID-19 vaccination.

Risk of Mortality Prediction Involving Time-Varying Covariates for Patients with Heart Failure Using Deep Learning.

Heart failure (HF) is challenging public medical and healthcare systems. This study aimed to develop and validate a novel deep learning-based prognostic model to predict the risk of all-cause mortality for patients with HF. We also compared the performance of the proposed model with those of classical deep learning- and traditional statistical-based models. The present study enrolled 730 patients with HF hospitalized at Toho University Ohashi Medical Center between April 2016 and March 2020. A recurrent neural network-based model (RNNSurv) involving time-varying covariates was developed and validated. The proposed RNNSurv showed better prediction performance than those of a deep feed-forward neural network-based model (referred as "DeepSurv") and a multivariate Cox proportional hazard model in view of discrimination (C-index: 0.839 vs. 0.755 vs. 0.762, respectively), calibration (better fit with a 45-degree line), and ability of risk stratification, especially identifying patients with high risk of mortality. The proposed RNNSurv demonstrated an improved prediction performance in consideration of temporal information from time-varying covariates that could assist clinical decision-making. Additionally, this study found that significant risk and protective factors of mortality were specific to risk levels, highlighting the demand for an individual-specific clinical strategy instead of a uniform one for all patients.

A Possibility of Vasospastic Angina after mRNA COVID-19 Vaccination.

We report a case of vasospastic angina (VSA) following COVID-19 mRNA vaccination. Despite the widespread occurrence of myocarditis, there have been few reports of post-vaccinal VSA. A 41-year-old male patient was referred for chest pain at rest following mRNA vaccination; he had never experienced chest pain prior to vaccination. He was diagnosed by an acetylcholine (Ach) provocation test that showed multivessel vasospasm. After the initiation of treatment with a calcium channel blocker and nitrate, no further exacerbation of chest pain was observed. To our knowledge, this constitutes the first reported case of VSA proven by Ach provocation test after COVID-19 vaccination. The vaccination may increase coronary artery spasticity. VSA should be ruled out in post-vaccine new onset resting chest pain.

MitraClip procedure assisted with 3-dimensional electro anatomical mapping system.

Percutaneous mitral annuloplasty is widely used for the treatment of functional mitral regurgitation. There are limited imaging options to guide MitraClip procedure (Abbott Vascular, Santa Clara, CA, USA) in patients intolerant to transesophageal echocardiography. We describe a case using a 3-dimensional electro anatomical mapping system to facilitate the successful MitraClip procedure. Learning objectives: There are situations in which percutaneous mitral valve repair (MitraClip) for mitral regurgitation is difficult to perform under transesophageal echocardiography due to esophageal disease.3D mapping system may be useful when performing MitraClip under transthoracic echocardiography.

What Should We Do after the COVID-19 Vaccination? Vaccine-Associated Diseases and Precautionary Measures against Adverse Reactions.

COVID-19 vaccines have been used to counteract the global COVID-19 pandemic. While these are effective, adverse reactions have been reported, such as injection-site pain, muscle ache, fever, palpitation, and chest discomfort. The release of inflammatory cytokines, such as interleukin (IL)-6 and IL-1ß, is a potential mechanism for post-vaccine side-effects. Chest discomfort after the vaccination, including myocarditis and acute coronary syndrome, is a particularly serious adverse reaction. It is important to be familiar with the differential diagnoses of chest discomfort and organ-specific diseases associated with COVID-19 vaccines as the preparation for booster shots and vaccinations among children aged 5-11 years begins. High-intensity exercise, alcohol, tobacco smoking, and baths promote inflammatory cytokines, such as IL-6, which may exacerbate the adverse reactions after vaccination. Japanese data show that deaths during baths are the most common for several days after mRNA vaccination. Additionally, alcohol and tobacco smoking were identified as predictive factors of lower antibody titers after vaccination. In this review, we aimed to provide a few recommendations to prevent vaccine-associated disease.

Exploring and Identifying Prognostic Phenotypes of Patients with Heart Failure Guided by Explainable Machine Learning.

Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was applied to explore phenotypes of patients in a derivation dataset (n = 562) based on their medical records. Thereafter, supervised ML models were trained on the derivation dataset to classify these identified phenotypes. Then, the trained classifiers were further validated on an independent validation dataset (n = 168). Finally, Shapley additive explanations were used to interpret decision making of phenotype classification. Three patient phenotypes corresponding to stratified mortality risk (high, low, and intermediate) were identified. Kaplan−Meier survival curves among the three phenotypes had significant difference (pairwise comparison p < 0.05). Hazard ratio of all-cause mortality between patients in phenotype 1 (n = 91; high risk) and phenotype 3 (n = 329; intermediate risk) was 2.08 (95%CI 1.29−3.37, p = 0.003), and 0.26 (95%CI 0.11−0.61, p = 0.002) between phenotype 2 (n = 142; low risk) and phenotype 3. For phenotypes classification by random forest, AUCs of phenotypes 1, 2, and 3 were 0.736 ± 0.038, 0.815 ± 0.035, and 0.721 ± 0.03, respectively, slightly better than the decision tree. Then, the classifier effectively identified the phenotypes for new patients in the validation dataset with significant difference on survival curves and hazard ratios. Finally, age and creatinine clearance rate were identified as the top two most important predictors. ML could effectively identify patient prognostic phenotypes, facilitating reasonable management and treatment considering prognostic condition.

Deep Learning-Based Recurrence Prediction of Atrial Fibrillation After Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). However, it the problem of AF recurrence remains. This study investigates whether a deep convolutional neural network (CNN) can accurately predict AF recurrence in patients with AF who underwent RFCA, and compares CNN with conventional statistical analysis.Methods and Results:Three-hundred and ten patients with AF after RFCA treatment, including 94 patients with AF recurrence, were enrolled. Nine variables are identified as candidate predictors by univariate Cox proportional hazards regression (CPH). A CNNSurv model for AF recurrence prediction was proposed. The model's discrimination ability is validated by a 10-fold cross validation method and measured by C-index. After back elimination, 4 predictors are used for model development, they are N-terminal pro-BNP (NT-proBNP), paroxysmal AF (PAF), left atrial appendage volume (LAAV) and left atrial volume (LAV). The average testing C-index is 0.76 (0.72-0.79). The corresponding calibration plot appears to fit well to a diagonal, and the P value of the Hosmer-Lemeshow test also indicates the proposed model has good calibration ability. The proposed model has superior performance compared with the DeepSurv and multivariate CPH. The result of risk stratification indicates that patients with non-PAF, higher NT-proBNP, larger LAAV and LAV would have higher risks of AF recurrence. CONCLUSIONS: The proposed CNNSurv model has better performance than conventional statistical analysis, which may provide valuable guidance for clinical practice.

Safety and feasibility of implanting a transvenous implantable cardioverter defibrillator (TV-ICD) in the left axilla.

BACKGROUND: Transvenous implantable cardioverter defibrillator (TV-ICD) systems are commonly implanted in the left anterior chest because of an easier implantation and better defibrillation threshold. This study aimed to evaluate the safety and feasibility of left axillary implantations of TV-ICD systems. METHODS: We performed left axillary TV-ICD implantations and compared that to the major complication rate and operation time of the conventional TV-ICD implantation site (left anterior chest). The electrical parameter trends were also assessed in the left axilla group. RESULTS: Seventy-six consecutive patients were evaluated for the analysis. Thirty-one patients had their system implanted in the left axilla and the reasons for the implantations included 29 patients for cosmetic reasons and two for post-infection conditions. The operation time and major complication rate were similar between the two groups (left anterior chest vs. left axilla: 134±62.4 min vs. 114±33.5 min, p = .11, 1/45 patient, 2.2% [pocket hematoma] vs. 1/31 patient, 3.2% [lead dislodgement], p = .77). During the follow up period (4.9±2.3years), no lead interruptions were observed in either group. The electrical lead parameters at the time of the implantation and follow up were similar in the study group (R wave sensing 20.8±33.4 vs. 11.2±7.42 mv, p = .34; lead impedance 464±64.7 vs. 418±135ohm, p = .22; pacing threshold [at 0.4 ms] 1.0±0.76 vs. 1.21±0.93V, p = .49). CONCLUSION: TV-ICD implantations in the left axilla were performed safely without increasing the operation time as compared to the conventional ICD implantation site. ICD implantations in the left axilla are an alternative in those not suitable for implanting TV-ICDs in the conventional implantation site.

Impact of right atrial structural remodeling on recurrence after ablation for atrial fibrillation.

BACKGROUND: Recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) is associated with left atrial (LA) remodeling; however, its association with right atrial (RA) remodeling remains unclear. OBJECTIVE: This study aimed to identify whether RA structural remodeling could predict recurrence of AF after PVI. METHODS: This study prospectively analyzed 245 patients with AF who had undergone PVI. RA and LA volumes were determined by contrast-enhanced computed tomography. Atrial structural remodeling was defined as an atrial volume of ≥110 mL according to previous reports and receiver operating characteristic curve analysis. RESULTS: After excluding 32 patients, 213 patients were analyzed. During a follow-up period of 12 months, 41 patients (19%) demonstrated atrial arrhythmia recurrence after PVI. With the Cox proportional-hazards model, RA structural remodeling was the only predictor of arrhythmia recurrence (hazard ratio, 1.012; 95% confidence interval 1.003-1.021; P = .009). Kaplan-Meier analysis showed that arrhythmia recurrence was more frequent in the RA structural remodeling group compared with the group without RA remodeling (log-rank, P < .001), and the arrhythmia-free survival rates in these groups at 12 months were 68.0% and 91.4%, respectively. Additionally, there was a significant difference in recurrence-free survival after RA structural remodeling in each type of AF (log-rank, P < .001). CONCLUSIONS: RA structural remodeling is a useful predictor of clinical outcome after PVI regardless of the type of AF. Our results suggest that patients without RA structural remodeling may be good candidates for successful ablation with PVI.

Impact of atrial mitral and tricuspid regurgitation on atrial fibrillation recurrence after ablation.

BACKGROUND: Atrial fibrillation (AF) induces functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) during atrial remodeling. FMR and FTR are associated with AF prognosis, but the effects for AF recurrence after ablation have not been determined conclusively. METHODS: Two hundred thirty nine patients who underwent AF ablation were enrolled. Forty five patients were excluded. In total, 194 patients were analyzed. FMR and FTR were assessed by echocardiography. The left atrial volume index (LAVI) was evaluated by contrast-enhanced computed tomography. RESULTS: Significant FMR and moderate FTR were observed in 15 (7.7%) and in 25 (12.9%) patients, respectively. The severity of tricuspid regurgitation (TR) significant correlated with age, NT-proBNP, and LAVI. During a 13.4 month follow-up period of, 39 patients (20.1%) demonstrated AF recurrence. In the Cox proportional-hazards model, E/e', FTR, and LAVI, were termed as predictor factors of AF recurrence (E/e'. hazard ratio [HR] = 1.117; P = 0.019, significant FTR. HR = 4.679; P = 0.041, LAVI. HR = 1.057; P = 0.003). Kaplan-Meier analysis showed that AF recurrence was more frequent in FTR compared with the nonsignificant FTR cases (log-rank, P = 0.001). Although survival analysis showed no difference with or without FMR, the presence of FMR and FTR was strongly associated with high-AF recurrence (log-rank, P = 0.004). CONCLUSIONS: AF recurrence was associated with E/e', LAVI, and extensive FTR. Specifically, the combination of FTR and FMR markedly worsens the AF prognosis.

Lesion size and adjacent tissue damage assessment with high power and short duration radiofrequency ablation: comparison to conventional radiofrequency ablation power setting.

There is increased interest in creating high-power short duration (HPSD) ablation lesions in the field of atrial fibrillation (AF) radiofrequency ablation (RFA). We evaluated the lesion characteristics and collateral damage using two separate RFA protocols setting (HPSD: 50 W and 7 s vs control: 25 W and 30 s) in vitro model. Sixteen freshly killed porcine hearts were obtained, and the atrium and ventricle slabs were harvested for ablation. The each slabs were placed in a tissue bath with circulating 0.9% NaCl at maintained temperature 37 °C. RFA was performed with 4 mm tip irrigated force sensing catheter. All lesions were ablated under recording the electrical parameters using with Ensite Navx system (St. Jude Medical, St. Paul, Minnesota). After RFA, lesion characteristics were assessed for each lesion. Thirty-five lesions were made for each ablation protocol (total 70 lesions for analysis). Ablation parameters were similar between two groups (HPSD vs control; impedance drop (Ω): 34.2 ± 13.1 vs 36.1 ± 8.65 P = 0.49, contact force (g): 13.9 ± 4.37 vs 14.6 ± 5.09, P = 0.51, lesion size index: 4.8 ± 0.52 vs 4.73 ± 0.59, P = 0.62). Although the lesion volume was similar, the HPSD ablation creates wider but more shallower lesions compared to control group (HPSD vs control; lesion volume: 29.6 ± 18.1 mm3 vs 35.5 ± 17.1 mm3 P = 0.16, lesion diameter: 4.98 ± 0.91 mm vs 4.45 ± 0.74 mm P = 0.0095, lesion depth: 2.2 ± 0.76 mm vs 2.8 ± 1.56 mm P = 0.046). Of these, 38 lesions were assessed for adjacent tissue damage and adjacent tissue damages were more frequent seen in control group (HPSD vs control; 1/19 (5.26%) vs 6/19 (31.5%), P = 0.036). Effective lesions were made with HPSD, thereby reducing RFA procedure time. Although the lesion volume was similar between two groups, collateral damage was less seen in HPSD group attributed by lesion characteristics.

The Association of Cardio-Ankle Vascular Index (CAVI) with Biatrial Remodeling in Atrial Fibrillation.

AIM: Arterial stiffness results in elevated left ventricular filling pressure and can promote atrial remodeling due to chronic pressure overload. However, the impact of arterial stiffness on the process of atrial remodeling in association with atrial fibrillation (AF) has not been fully evaluated. METHODS: We enrolled 237 consecutive patients diagnosed with AF who had undergone ablation; data from 213 patients were analyzed. Cardio-ankle vascular index (CAVI) was used as a marker of arterial stiffness. The left atrial (LA) and right atrial (RA) volumes were determined by computed tomography imaging; atrial conduction and voltage amplitude were evaluated using a three-dimensional electromapping system used to guide the ablation procedure. RESULT: In univariate analysis, CAVI significantly correlated with atrial structural and electrical remodeling (LA volume index, r=0.297, P=0.001; RA volume index, r=0.252, P=0.004; LA conduction velocity, r=0.254, P= 0.003; LA mean voltage, r=-0.343, P=0.001, RA mean voltage; r=-0.245, P=0.015). Multivariate regression analysis revealed that CAVI and plasma levels of N-terminal B-type natriuretic peptide were independent determinants of LA and RA remodeling, respectively. On the other hand, age and LA conduction velocity were independent variables with respect to CAVI. Age-adjusted CAVI was highest in long-standing persistent AF when compared with measures of persistent or paroxysmal AF. CONCLUSION: CAVI was closely associated with biatrial remodeling in patients diagnosed with AF. These results suggest that arterial stiffness may play a significant role with respect to disease progression.