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.

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.

The impact of sleep apnea on right atrial structural remodeling with atrial fibrillation.

BACKGROUND: Atrial remodeling associated with atrial fibrillation (AF) and sleep apnea is well known. Although sleep apnea is known to be associated with left atrial (LA) remodeling, its association with right atrial (RA) remodeling remains unclear. The study aimed to investigate the effect of sleep apnea on RA remodeling. METHODS: We enrolled 141 AF patients who had undergone ablation. Sleep study results were evaluated using a portable sleep apnea test device. RA and LA volumes were determined by computed tomography (CT), and atrial structural remodeling was defined as atrial volume on CT≥110mL according to previous reports. The atrial substrate was evaluated by three-dimensional electroanatomical mapping. RESULTS: After excluding 30 patients who received more than one catheter ablation or who could not receive enhanced CT, 111 patients were finally analyzed. The patients were classified into four groups according to the presence of RA and/or LA enlargement. Significant differences in AF type, N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and apnea-hypopnea index (AHI) were observed among the four groups. In univariate analysis, AHI values correlated with NT-proBNP levels (r=0.293, p=0.002), left ventricular ejection fraction (r=-0.198, p=0.044), LA volume (r=0.370, p<0.001), and RA volume (r=0.465, p<0.001). Multiple regression analysis showed that AHI was an independent predictor of increased RA volume, and LA was excluded as a multiple risk factor in AHI. AF type-adjusted AHI levels correlated with RA volume, and RA remodeling correlated with the percentage of LA low-voltage area. CONCLUSIONS: Sleep apnea was strongly associated with RA structural remodeling regardless of paroxysmal and non-paroxysmal AF, and this relationship was more prominent than the effect of LA. Our results suggest that the association between sleep apnea and RA dilatation should be given attention.

Decreased Defibrillation Threshold and Minimized Myocardial Damage With Left Axilla Implantable Cardioverter Defibrillator Implantation.

BACKGROUND: To reduce myocardial damage caused by implantable cardioverter defibrillator (ICD) shock, the left axilla was studied as an alternative pulse generator implantation site, and compared with the traditional implantation site, the left anterior chest. METHODS AND RESULTS: Computer simulation was used to study the defibrillation conduction pattern and estimate the simulated defibrillation threshold (DFT) and myocardial damage when pulse generators were placed in the left axilla and left anterior chest, respectively; pulse generators were also newly implanted in the left axilla (n=30) and anterior chest (n=40) to compare the corresponding DFT. On simulation, when ICD generators were implanted in the left axilla, compared with the left anterior chest, the whole heart may be defibrillated with a lower defibrillation energy (left axilla 6.4 J vs. left anterior chest 12.0 J) and thus the proportion of cardiac myocardial damage may be reduced (2.1 vs. 4.2%). Clinically, ventricular fibrillation was successfully terminated with a defibrillation output ≤5 J in 86.7% (26/30) of the left axillary group, and in 27.5% (11/40) of the left anterior group (P<0.001). CONCLUSIONS: Clinically and theoretically, the left axilla was shown to be an improved ICD implantation site that may reduce DFT and lessen myocardial damage due to shock. Lower DFT also facilitates less myocardial damage, as a result of the lower shock required.

Efficacy and Myocardial Injury With Subcutaneous Implantable Cardioverter Defibrillators　- Computer Simulation of Defibrillation Shock Conduction.

BACKGROUND: Subcutaneous implantable cardiac defibrillator (S-ICD) systems have a lower invasiveness than traditional ICD systems, and expand the indications of ICD implantations. The S-ICD standard defibrillation shock output energy, however, is approximately 4 times that of the traditional ICD system. This raises concern about the efficacy of the defibrillation and myocardial injury. In this study, we investigated the defibrillation efficacy and myocardial injury with S-ICD systems based on computer simulations. METHODS AND RESULTS: First, computer simulations were performed based on the S-ICD system configurations proposed in a previous study. Furthermore, simulations were performed by placing the lead at the left or right parasternal margin and the pulse generator in the superior and inferior positions (0-10 cm) of the recommended site. The simulated defibrillation threshold (DFT) for the 4 S-ICD system configurations were 30.1, 41.6, 40.6, and 32.8 J, which were generally similar to the corresponding clinical results of 33.5, 40.4, 40.1, and 34.3 J. CONCLUSIONS: The simulated DFT were generally similar to their clinical counterparts. In the simulation, the S-ICD system had a higher DFT but relatively less severe myocardial injury compared with the traditional ICD system. Further, the lead at the right parasternal margin may correspond to a lower DFT and cause less myocardial injury.

Recent trends among dental residents at Tokyo Dental College.

Trends among dental residents at Tokyo Dental College between 2006, at which time clinical residency became mandatory, and 2011 were analyzed and the following results obtained. Almost all the eligible students from our school participated in the orientation seminar on dental residency programs. Although the number varied slightly by year, approximately 70 to 150 students from other schools also participated in these orientation seminars. Almost all the students from our school and 60 to 80% of those from other schools participating in the orientation seminar each year applied to sit the dental residency entrance examination. The number of candidates was highest in 2006 (318) and lowest in 2010 (205) (average: 248), and the applicant-to-seat ratio for residency was 1.59. The examination pass rate was 59.02%. Approximately 10% of the students from other schools were admitted as dental residents.

Effect of emitted wavelength and light guide type on irradiance discrepancies in hand-held dental curing radiometers.

The purpose of this study was to determine any discrepancies in the outputs of five commercial dental radiometers and also to evaluate the accuracy of these devices using a laboratory-grade spectroradiometer. The power densities of 12 different curing light sources were repeatedly measured for a total of five times using each radiometer in a random order. The emission spectra of all of the curing light sources were also measured using the spectroradiometer, and the integral value of each spectrum was calculated to determine the genuine power densities, which were then compared to the displayed power densities measured by the dental radiometers. The displayed values of power density were various and were dependent on the brand of radiometer, and this may be because each radiometer has a different wavelength sensitivity. These results cast doubt upon the accuracy of commercially available dental radiometers.

The effects of three dry-field techniques on intraoral temperature and relative humidity.

BACKGROUND: The authors evaluated the effects of three dry-field techniques (rubber dam, Isolite i2 [Isolite Systems, Santa Barbara, Calif.] and Coolex [APT, Osaka, Japan]) on intraoral temperature and relative humidity (RH), compared with the effects of a nonisolated control on intraoral temperature and RH. METHODS: The authors measured the room's temperature and RH and then placed dry-field devices in five participants' mouths and measured the intraoral temperature and RH for 20 minutes. They then removed the devices or turned off the vacuum system and measured intraoral temperature for an additional five minutes. RESULTS: The authors found no significant differences in either intraoral temperature or RH at any time during the measurement period in the isolated control group (P > .05); the intraoral temperature was more than 30°C and RH was more than 95 percent. On the other hand, the use of dry-field techniques significantly reduced both intraoral temperature and RH when the rubber dam was in place or the vacuums were turned on (P > .05). The intraoral temperature and RH gradually increased after the authors removed the rubber dam or turned off the vacuums. CONCLUSIONS: The results of this study revealed that all three dry-field techniques could reduce both temperature and RH effectively. CLINICAL IMPLICATIONS: Both Isolite i2 and Coolex could provide environments similar to the room conditions used during in vitro specimen preparation for investigating the mechanical properties of dental restorative materials.

Clinical usefulness of "Isolite Plus" for oral environment of Japanese people.

The recent demand for dental devices which are easier to handle and offer higher levels of reliability and safety has led to the development in the US of Isolite Plus, a new oral support device. When placed in the oral cavity, Isolite Plus enables marking of the surgical field, secures the treatment space, ensures a vacuum, protects the cheek and tongue, assists in opening the mouth, prevents accidental ingestion/aspiration, ensures treatment without contamination and enhances comfort and safety during dental treatment. The present study was carried out to verify whether Isolite Plus can fit well in the mouth of Japanese people and to determine whether it performs adequately. Thirty resident dentists were required to wear Isolite Plus in their mouth and perform mutual simulation training using an air turbine handpiece. After the training, both subjects playing the role of surgeon and those playing the role of patient were asked to complete questionnaires. On the basis of the results, we discuss the clinical usefulness of Isolite Plus in Japanese people. In the present investigation, Isolite Plus was rated slightly better by surgeons than by patients. The supportive functions of the device were judged inadequate due to the poor fit of the mouthpiece portion of the device to subjects' mouth. For the distribution of Isolite Plus in the Japanese market, the mouthpiece portion of the device should be improved so that it can fit the mouth of Japanese people.