Association between Mobility of Residual Left Atrial Thrombus and Stroke Severity in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The differences in the characteristics of ischemic stroke associated with a mobile versus nonmobile residual left atrial thrombus (LAT) are unclear. We investigated whether the mobility of an LAT detected by transthoracic echocardiography is associated with the clinical features of stroke. METHODS: This study included 20 consecutive patients with nonvalvular atrial fibrillation who were admitted to our hospital for treatment of acute ischemic stroke and then found to have an LAT on transthoracic echocardiography. The patients were divided into two groups: those with a mobile LAT (Group M) and those with a nonmobile LAT (Group N). The clinical, neuroradiological, and echocardiographic variables were assessed. RESULTS: The LAT was mobile in 11 patients (Group M) and nonmobile in nine patients (Group N). The median National Institutes of Health Stroke Scale score on admission was higher in Group M than N (17 vs. 7, respectively; p=0.196). Four patients in Group M and one in Group N developed in-hospital stroke recurrence (36% vs. 11%, respectively; p=0.319). The prevalence of large vessel occlusion (15 events in Group M and 10 events in Group N, including in-hospital recurrent events) was significantly higher in Group M than N (73% vs. 30%, respectively; p=0.049), which seemed to lead to poorer functional outcomes in Group M than N (ratio of modified Rankin scale score of 0-2 at discharge: 18% vs. 44%, respectively; p=0.336). CONCLUSIONS: The mobility of LAT may affect stroke severity in patients with nonvalvular atrial fibrillation.

Cardioembolic Stroke: Past Advancements, Current Challenges, and Future Directions.

Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke.

Supra-normal and mildly reduced ejection fraction in women -An overlooked vulnerable subpopulation in heart failure.

BACKGROUND: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients. METHODS: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge. RESULTS: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and ß-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037). CONCLUSIONS: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management.

Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation.

OBJECTIVES: Several studies have reported the effects of Fusobacterium nucleatum stimulation on oral cancer cells. However, given that these studies typically span a stimulation period of three days to eight days, the in vitro studies conducted to date may not fully mimic the oral cancer environment, which involves constant exposure to oral commensal bacteria. This study aimed to elucidate the effects of prolonged and persistent Fusobacterium nucleatum infection on oral cancer cells. METHODS: Human tongue squamous cell carcinoma (SCC) cells were continuously stimulated with Fusobacterium nucleatum for two or four weeks, then experimentally evaluated. RESULTS: Prolonged, persistent Fusobacterium nucleatum stimulation increased the cells' proliferative, invasive, and migratory capacities, decreased their expression of epithelial markers, and increased their expression of mesenchymal markers progressively with time. The cells also adopted a spindle-shaped morphology and cell-to-cell contact dependence was progressively lost, suggesting time-dependent occurrence of epithelial-mesenchymal transition. Furthermore, mRNA levels of CD44, a cancer stem cell marker, were time-dependently upregulated. When SCC cells were stimulated with Fusobacterium nucleatum for four weeks in the presence of dexamethasone, Fusobacterium nucleatum induced epithelial-mesenchymal transition was inhibited. CONCLUSIONS: Epithelial-mesenchymal transition in human tongue SCC cells was time-dependently induced by prolonged, persistent Fusobacterium nucleatum stimulation and inhibited by dexamethasone. Routine decontamination of the oral cavity may be crucial for controlling tumor invasion and metastasis.

Postoperative intravenous patient-controlled analgesia improves pain management after subcutaneous implantable defibrillator implantation.

Objective: Postoperative pain is a major issue with subcutaneous implantable cardioverter defibrillators (S-ICD). In 2020, we introduced intravenous patient-controlled analgesia (IV-PCA) in addition to the conventional, request-based analgesia for postoperative pain control in S-ICD. To determine the effect and safety, we quantitatively assessed the effect of IV-PCA after S-ICD surgery over conventional methods. Methods: During the study period, a total of 113 consecutive patients (age, 50.1 ± 15.5 years: males, 101) underwent a de novo S-ICD implantation under general anesthesia. While the postoperative pain was addressed with either request-based analgesia (by nonsteroid anti-inflammatory drugs, N = 68, dubbed as "PCA absent") or fentanyl-based IV-PCA in addition to the standard care (N = 45, dubbed as "PCA present"). The degree of postoperative pain from immediately after surgery to 1 week were retrospectively investigated by the numerical rating scale (NRS) divided into four groups at rest and during activity (0: no pain, 1-3: mild pain, 4-6: moderate pain, 7-10: severe pain). Results: Although IV-PCA was removed on Day 1, it was associated with continued better pain control compared to PCA absent group. At rest, the proportion of patients expressing pain (mild or more) was significantly lower in the PCA present group from Day 0 to Day 4. In contrast to at rest, a better pain control continued through the entire study period of 7 days. No serious adverse events were observed. A few patients experienced nausea in both groups and the inter-group difference was not found significant. Conclusion: IV-PCA suppresses postoperative pain in S-ICD without major safety concerns.

Rationale and protocol of the LAQUA-HF trial: a factorial randomised controlled trial evaluating the effects of neurohormonal and diuretic agents on health-status reported outcomes in heart failure patients.

INTRODUCTION: The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects. METHODS AND ANALYSIS: In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint. ETHICS AND DISSEMINATION: The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses. TRIAL REGISTRATION NUMBER: UMIN000045229.

In-Hospital Mortality in Patients With Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation With Concomitant Use of Impella vs. Intra-Aortic Balloon Pump　- A Retrospective Cohort Study Using a Japanese Claims-Based Database.

BACKGROUND: Patients with refractory cardiogenic shock (CS) necessitating peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) often require an intra-aortic balloon pump (IABP) or Impella for unloading; however, comparative effectiveness data are currently lacking.Methods and Results: Using Diagnosis Procedure Combination data from approximately 1,200 Japanese acute care hospitals (April 2018-March 2022), we identified 940 patients aged ≥18 years with CS necessitating peripheral VA-ECMO along with IABP (ECMO-IABP; n=801) or Impella (ECPella; n=139) within 48 h of admission. Propensity score matching (126 pairs) indicated comparable in-hospital mortality between the ECPella and ECMO-IABP groups (50.8% vs. 50.0%, respectively; P=1.000). However, the ECPella cohort was on mechanical ventilator support for longer (median [interquartile range] 11.5 [5.0-20.8] vs. 9.0 [4.0-16.8] days; P=0.008) and had a longer hospital stay (median [interquartile range] 32.5 [12.0-59.0] vs. 23.0 [6.3-43.0] days; P=0.017) than the ECMO-IABP cohort. In addition, medical costs were higher for the ECPella than ECMO-IABP group (median [interquartile range] 9.09 [7.20-12.20] vs. 5.23 [3.41-7.00] million Japanese yen; P<0.001). CONCLUSIONS: Our nationwide study could not demonstrate compelling evidence to support the superior efficacy of Impella over IABP in reducing in-hospital mortality among patients with CS necessitating VA-ECMO. Further investigations are imperative to determine the clinical situations in which the potential effect of Impella can be maximized.

Does the same lesion index mean the same efficacy and safety profile: influence of the differential power, time, and contact force on the lesion size and steam pops under the same lesion index.

BACKGROUND: The lesion index (LSI) helps predict the lesion size and is widely used in ablation of various types of arrhythmias. However, the influence of the ablation settings on the lesion formation and incidence of steam pops under the same LSI value remains unclear. METHODS: Using a contact force (CF) sensing catheter (TactiCath™) in an ex vivo swine left ventricle model, RF lesions were created with a combination of various power steps (30 W, 40 W, 50 W) and CFs (10 g, 20 g, 30 g, 40 g, 50 g) under the same LSI values (5.2 and 7.0). The correlation between the lesion formation and ablation parameters was evaluated. RESULTS: Ninety RF lesions were created under a target LSI value of 5.2, and eighty-four were developed under a target LSI value of 7.0. In the LSI 5.2 group, the resultant lesion size widely varied according to the ablation power, and a multiple regression analysis indicated that the ablation energy delivered was the best predictor of the lesion formation. To create a lesion depth > 4 mm, an ablation energy of 393 J is the best cutoff value, suggesting a possibility that ablation energy may be used as a supplemental marker that better monitors the progress of the lesion formation in an LSI 5.2 ablation. In contrast, such inconsistency was not obvious in the LSI 7.0 group. Compared with 30 W, the 50-W ablation exhibited a higher incidence of steam pops in both the LSI 5.2 and 7.0 groups. CONCLUSIONS: The LSI-lesion size relationship was not necessarily consistent, especially for an LSI of 5.2. To avoid any unintentional, weak ablation, the ablation energy may be a useful supportive parameter (393 J as a cutoff value for a 4-mm depth) during ablation with an LSI around 5.2. Thanks to a prolonged ablation time, the LSI-lesion size relationship is consistent for an LSI of 7.0. However, it is accompanied by a high incidence of steam pops. Care should be given to the ablation settings even when the same LSI value is used.

Temporal Trends in Heart Failure Management and Outcomes: Insights From a Japanese Multicenter Registry of Tertiary Care Centers.

Background The management of heart failure (HF) has markedly changed, due to changes in demographics and the emergence of novel pharmacotherapies. However, detailed analyses on the temporal trends in characteristics and outcomes among patients with HF are scarcely available. This study aimed to assess the temporal trends over 11 years in clinical management and outcomes in patients with HF. Methods and Results We analyzed data from a multicenter registry of hospitalized patients with acute HF, including 6877 patients registered from 2011 to 2021. Age-adjusted mortality was calculated using standardized mortality ratios. During the study period, mean age increased from 75.2 years in 2011 to 2012 to 76.4 years in 2020 to 2021 (P for trend <0.001). The proportion of HF with reduced ejection fraction (HFrEF, left ventricular ejection fraction <40%) remained constant (from 43.4% to 42.7%, P for trend=0.38). The median duration of hospital stays (from 15 to 17 days, P for trend<0.001) had increased. As for the implementation of guideline-directed medical therapy, the use of mineralocorticoid receptor antagonist at discharge increased in patients with HFrEF (from 44.3% to 60.2%, P for trend<0.001). There was also an increase in the use of sodium-glucose cotransporter-2 inhibitors following their approval for use. The age-adjusted 1-year mortality decreased in patients with HFrEF (from 18.0% to 9.3%, P for trend<0.001) but not in patients with non-HFrEF (left ventricular ejection fraction ≥40%; from 9.2% to 9.5%, P for trend=0.79). Conclusions Hospitalized patients with HF have been aging over the past decade. Their long-term outcomes after discharge have improved predominantly because of decreased mortality in patients with HFrEF.

Initiation and Up-Titration of Guideline-Based Medications in Hospitalized Acute Heart Failure Patients　- A Report From the West Tokyo Heart Failure Registry.

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (ß-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Age-dependent contribution of intrinsic mechanisms to sinoatrial node function in humans.

Average beat interval (BI) and beat interval variability (BIV) are primarily determined by mutual entrainment between the autonomic-nervous system (ANS) and intrinsic mechanisms that govern sinoatrial node (SAN) cell function. While basal heart rate is not affected by age in humans, age-dependent reductions in intrinsic heart rate have been documented even in so-called healthy individuals. The relative contributions of the ANS and intrinsic mechanisms to age-dependent deterioration of SAN function in humans are not clear. We recorded ECG on patients (n = 16 < 21 years and n = 23 41-78 years) in the basal state and after ANS blockade (propranolol and atropine) in the presence of propofol and dexmedetomidine anesthesia. Average BI and BIV were analyzed. A set of BIV features were tested to designated the "signatures" of the ANS and intrinsic mechanisms and also the anesthesia "signature". In young patients, the intrinsic mechanisms and ANS mainly contributed to long- and short-term BIV, respectively. In adults, both ANS and intrinsic mechanisms contributed to short-term BIV, while the latter also contributed to long-term BIV. Furthermore, anesthesia affected ANS function in young patients and both mechanisms in adult. The work also showed that intrinsic mechanism features can be calculated from BIs, without intervention.

Association of pre-hospital precipitating factors with short- and long-term outcomes of acute heart failure patients: A report from the WET-HF2 registry.

BACKGROUND: Interest in clinical course preceding heart failure (HF) exacerbation has grown, with a greater emphasis placed on patients' clinical factors including precipitant factor (PF). Large-scale studies with precise PF documentation and temporal-outcome variation remain limited. METHODS: We reviewed prospectively collected 2412 consecutive patient-level records from a multicenter Japanese registry of hospitalized patients with HF (West Tokyo Heart Failure2 Registry: 2018-2020). Patients were categorized based on PFs: behavioral (i.e., poor adherence to physical activity, medicine, or diet regimen), treatment-required (i.e., anemia, arrhythmia, ischemia, infection, thyroid dysfunction or other conditions as suggested exacerbating factors), and no-PF. The composite outcomes of HF rehospitalization and death within 1 year after discharge and HF rehospitalization were individually assessed. RESULTS: Median patient age was 78 years (interquartile range: 68-85 years), and 1468 (61%) patients had documented PFs, of which 356 (15%) were considered behavioral. The behavioral PF group were younger, more male and had past HF hospitalization history compared to those in the other groups (all p < 0.05). Although risk of in-hospital death was lower in the behavioral PF group, their risk of composite outcome was not significantly different from the treatment-required group (hazard ratio [HR] 1.19 [95% confidence interval {CI} 0.93-1.51]) and the no-PF group (HR 1.28 [95%CI 1.00-1.64]). Furthermore, the risk of HF rehospitalization was higher in the behavioral PF group than in the other two groups (HR 1.40 [95%CI 1.07-1.83] and HR 1.39 [95%CI 1.06-1.83], respectively). CONCLUSION: Despite a better in-hospital prognosis, patients with behavioral PFs were at significantly higher risk of HF rehospitalization.

Progression of coronary artery calcification after radiation therapy for esophageal cancer.

BACKGROUND: Advances in cancer treatment have resulted in increased attention toward potential cardiac complications, especially following treatment for esophageal cancer, which is associated with a risk of coronary artery disease. As the heart is directly irradiated during radiotherapy, coronary artery calcification (CAC) may progress in the short term. Therefore, we aimed to investigate the characteristics of patients with esophageal cancer that predispose them to coronary artery disease, CAC progression on PET-computed tomography and the associated factors, and the impact of CAC progression on clinical outcomes. METHODS: We retrospectively screened 517 consecutive patients who received radiation therapy for esophageal cancer from our institutional cancer treatment database between May 2007 and August 2019. CAC scores were analyzed clinically for 187 patients who remained by exclusion criteria. RESULTS: A significant increase in the Agatston score was observed in all patients (1 year: P  = 0.001*, 2 years: P  < 0.001*). Specifically for patients receiving middle-lower chest irradiation (1 year: P  = 0.001*, 2 years: P  < 0.001*) and those with CAC at baseline (1 year: P  = 0.001*, 2 years: P  < 0.001*), a significant increase in the Agatston score was observed. There was a trend for a difference in all-cause mortality between patients who had irradiation of the middle-lower chest ( P  = 0.053) and those who did not. CONCLUSION: CAC can progress within 2 years after the initiation of radiotherapy to the middle or lower chest for esophageal cancer, particularly in patients with detectable CAC before radiotherapy initiation.

Which congestion presentation pattern on the physical findings is associated with future adverse events? A cluster analysis in the multicenter acute heart failure registry.

BACKGROUND: Clinical congestion is the most frequent reason for hospital admission in patients with acute heart failure (AHF). However, few studies have investigated the patterns and prognostic implication of the physical congestion using unbiased and robust statistical methods. METHODS: A hierarchical agglomerative clustering analysis was performed in the multicenter Japanese AHF registry (N = 3151) with the distance calculated by Jaccard's distance for jugular vein distention (JVD), leg edema, S3, crackles, and orthopnea. The primary outcome was a composite of cardiac death and heart failure readmission within 1-year. RESULTS: At the time of admission, the median number of prevalent congestive signs was 2. We identified three phenogroups: 'no physical congestions' (N = 251); 'congestion without JVD' (N = 1415); and 'congestion with JVD' (N = 1495). Patients in 'no physical congestion' were the youngest (median 75 [62, 83] years) with the lowest systolic blood pressure (122 [106, 142] mmHg). Patients in 'congestion without JVD', and 'congestion with JVD' were similar in terms of age (77 [67, 84] vs. 78 [69, 84] years) and systolic blood pressure (138 [118, 160] vs. 137 [118, 158] mmHg). While 30-day mortality was similar (4.0%, 3.7%, and 4.3% in 'no physical congestion,' 'congestion without JVD,' and 'congestion with JVD', respectively), the patients in 'congestion with JVD' were at the highest risk for the primary outcome (adjusted hazard ratio 1.79, 95% CI 1.26-2.55 when 'no physical congestion' was a reference). CONCLUSIONS: Our clustering analysis demonstrated that congestion signs, particularly JVD, allowed identification of AHF phenogroups with distinct clinical characteristics and long-term outcomes.

Detailed investigation of the lesion formation with a novel contact force sensing catheter with a mesh-shaped irrigation tip.

Background: Recently, a novel contact force (CF) sensing catheter with mesh-shaped irrigation tip (TactiFlex SE, Abbott) was invented and is expected to be useful for safe and effective radiofrequency ablation. However, this catheter's detailed characteristics of the lesion formation are unknown. Methods: With an in vitro model, TactiFlex SE and its predecessor, FlexAbility SE, were used. A cross-sectional analysis of 60 s lesions (combination of various energy power settings [30, 40, and 50 W], and CFs [10, 30, and 50 g]) and longitudinal analysis (combination of various powers [40 or 50 W], CFs [10, 30, and 50 g] and ablation times [10, 20, 30, 40, 50, and 60 s]) of both catheters were analyzed and compared. Results: One hundred eighty RF lesions were created in protocol 1 and 300 in protocol 2. The lesion formation, impedance changes, and steam pops characteristics were similar between the two catheters. Higher CFs were related to higher incidences of steam pops. A nonlinear, time-dependent increase in the lesion depth and diameter was observed for all power and CF settings, and linear, positive correlations between the RF delivery time and lesion volume were observed for all power settings. Compared with 40 W, a 50 W ablation created greater lesions. Longer durations with higher CF settings had a higher steam pop incidence. Conclusions: The lesion formation and incidence of steam pops with TactiFlex SE and FlexAbility SE were similar. A 40 or 50 W ablation with careful CF control not to exceed 30 g in addition to monitoring impedance drops was required to safely create transmural lesions.

Diagnostic and Therapeutic Strategies for Stable Coronary Artery Disease Following the ISCHEMIA Trial.

Until recently, coronary revascularization with coronary artery bypass grafting or percutaneous coronary intervention has been regarded as the standard choice for stable coronary artery disease (CAD), particularly for patients with a significant burden of ischemia. However, in conjunction with remarkable advances in adjunctive medical therapy and a deeper understanding of its long-term prognosis from recent large-scale clinical trials, including ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), the approach to stable CAD has changed drastically. Although the updated evidence from recent randomized clinical trials will likely modify the recommendations for future clinical practice guidelines, there are still unresolved and unmet issues in Asia, where prevalence and practice patterns are markedly different from those in Western countries. Herein, the authors discuss perspectives on: 1) assessing the diagnostic probability of patients with stable CAD; 2) application of noninvasive imaging tests; 3) initiation and titration of medical therapy; and 4) evolution of revascularization procedures in the modern era.

Detailed analysis of the lesion formation using a diamond tip catheter in an ex vivo experimental model.

BACKGROUND: A novel Diamond Temp™ (DT; Medtronic, Minneapolis, MN, USA) catheter has enabled performing a surface temperature-controlled ablation. The chemical vapor deposition diamond of the ablation catheter acts as a thermal radiator and is useful for effective cooling of the ablation catheter tip. However, a detailed analysis of the lesion formation with this catheter remains unknown. METHODS: DT catheters were used in an excised swine heart experimental model. A cross-sectional analysis of 60-s lesions [a combination of various energy power settings (30, 40, and 50 W), and various contact forces (CF) (10, 30, and 50 g)] and a longitudinal analysis [a combination of various powers (40 W or 50 W), various CFs (10, 30, and 50 g), and various ablation times (5 s, 10 s, 15 s, 20 s, 25 s, 30 s, and 60 s)] of the DT catheter were analyzed. RESULTS: The maximum lesion depth, maximum diameter, and lesion volume with a 10 g ablation were significantly lower than those with a 30 g or 50 g ablation. There were no significant differences in the lesion formation between the 30 g ablation and 50 g ablation under each radiofrequency (RF) power setting. The impedance drops with steam pops were significantly greater than those without steam pops (pop (+) vs. pop (-), 26.2 ±â€¯6.6 Ohm vs. 18.4 ±â€¯7.1 Ohm, p = 0.0001). A non-linear, time-dependent increase in the lesion depth and diameter was observed for all power and CF settings. Comparing the lesion depth and diameter between 40 W and 50 W under the same CF setting and same ablation time, most of the settings had no significant difference. CONCLUSION: Ablation lesions created with the DT catheter were similar to other catheters. Similar ablation lesions were created with the 40 W or 50 W ablation under the same CF setting and same ablation time. Regardless of the ablation power, monitoring the general impedance during the RF application was indispensable for a safe procedure.

Geriatric Nutritional Risk Index at Hospital Admission or Discharge in Patients with Acute Decompensated Heart Failure.

Geriatric Nutritional Risk Index (GNRI) is known both as a reliable indicator of nutritional status and a predictor of long-term survival among patients with acute decompensated heart failure (ADHF). However, the optimal timing to evaluate GNRI during hospitalization remains unclear. In the present study, we retrospectively analyzed patients hospitalized with ADHF in the West Tokyo Heart Failure (WET-HF) registry. GNRI was assessed at hospital admission (a-GNRI) and discharge (d-GNRI). Out of 1474 patients included in the present study, 568 (40.1%) and 796 (57.2%) patients had lower GNRI (<92) at hospital admission and discharge, respectively. After the follow-up (median 616 days), 290 patients died. The multivariable analysis showed that all-cause mortality was independently associated with d-GNRI (per 1 unit decrease, adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.09, p < 0.001), but not with a-GNRI (aHR: 0.99, 95% CI: 0.97-1.01, p = 0.341). The predictability of GNRI for long-term survival was more pronounced when evaluated at hospital discharge than at hospital admission (area under the curve 0.699 vs. 0.629, DeLong's test p < 0.001). Our study suggested that GNRI should be evaluated at hospital discharge, regardless of the assessment at hospital admission, to predict the long-term prognosis for patients hospitalized with ADHF.

Prognosis of Patients with Acute Kidney Injury due to Type 1 Cardiorenal Syndrome Receiving Continuous Renal Replacement Therapy.

INTRODUCTION: The prognosis of patients with acute kidney injury (AKI) caused by type 1 cardiorenal syndrome (CRS) requiring continuous renal replacement therapy (CRRT) is unclear. We investigated the in-hospital mortality and prognostic factors in these patients. METHODS: We retrospectively identified 154 consecutive adult patients who received CRRT for AKI caused by type 1 CRS between January 1, 2013, and December 31, 2019. We excluded patients who underwent cardiovascular surgery and those with stage 5 chronic kidney disease. The primary outcome was in-hospital mortality. Cox proportional hazards analysis was performed to analyze independent predictors of in-hospital mortality. RESULTS: The median age of patients at admission was 74.0 years (interquartile range: 63.0-80.0); 70.8% were male. The in-hospital mortality rate was 68.2%. Age ≥80 years (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.21-2.87; p = 0.004), previous hospitalization for acute heart failure (HR, 1.67; 95% CI, 1.13-2.46; p = 0.01), vasopressor or inotrope use (HR, 5.88; 95% CI, 1.43-24.1; p = 0.014), and mechanical ventilation at CRRT initiation (HR, 2.24; 95% CI, 1.46-3.45; p < 0.001) were associated with in-hospital mortality. CONCLUSION: In our single-center study, the use of CRRT for AKI due to type 1 CRS was associated with high in-hospital mortality.

Correlation of UGT1A1 Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101).

The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.