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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.

Background The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). Conclusions In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.

Malnutrition in real-world patients hospitalized for heart failure with preserved ejection fraction and its potential impact on generalizability of EMPEROR-Preserved trial.

BACKGROUND: Despite the benefits of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin, its suitability for patients with heart failure (HF) in the real-world setting remains unclear. Considering the unique pharmacological profile of SGLT2i (e.g., glucose excretion leading to calorie loss) and increasingly aging patients with HF, applicability of trials' finding in patients with malnutrition is important. METHODS: We examined 1633 consecutive patients with a preserved left ventricular ejection fraction (LVEF; >40%) enrolled in a multicenter-based acute HF registry. After applying the EMPEROR-Preserved eligibility criteria, we compared the baseline characteristics of trial-eligible and actual trial participants, and patients with and without malnutrition among the trial-eligible group. Malnutrition was assessed by the geriatric nutritional risk index (GNRI). The trial-eligible patients were divided into high (GNRI≥92) and low (GNRI<92) nutritional groups, and a composite endpoint comprising all-cause death and HF rehospitalization was evaluated. RESULTS: Majority (70.2%) of the analyzed patients were eligible for the EMPEROR-Preserved trial (age: 77 ± 12 years and body mass index [BMI]: 22.0 ± 4.1 kg/m2), but were older and had lower BMIs than the actual trial participants. Notably, 51.9% of the eligible patients were at high risk for malnutrition and had a higher rate of the composite endpoint than non-malnourished counterparts (HR 1.27, 95%CI 1.04-1.56, P = 0.020). The difference in outcomes was predominantly due to mortality from non-cardiac causes. CONCLUSIONS: Mostly patients with HF in a real-world setting met the EMPEROR-Preserved criteria; however, approximately half were at high risk for malnutrition with poorer outcomes owing to non-cardiac-related causes.

Low blood pressure and guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

BACKGROUND: Patients with heart failure (HF) presenting with low blood pressure (BP) have been underrepresented in large-scale clinical trials. We investigated the characteristics and implementation of conventional guideline-directed medical therapy (GDMT; renin-angiotensin system inhibitors and ß-blockers) in patients with low BP hospitalized for HF with systolic dysfunction. METHODS: Conventional GDMT was evaluated by discharge BP among 2043 consecutive patients with HF and left ventricular ejection fraction (LVEF) < 50% in the WET-HF registry. Among the 708 (34.7%) patients with lower discharge BP (≤ 100 mmHg; the lower tertiles), exploratory subgroups included patients with previous HF hospitalization, inotrope use, New York Heart Association (NYHA) III-IV class, and lower estimated glomerular filtration rate (eGFR) and LVEF (lower than median value). We evaluated the risk-adjusted association between GDMT implementation and 2-year adverse events (all-cause mortality or HF rehospitalization). RESULTS: Among the 2043 patients (age 74 [63-82] years), the median systolic BP was 108 (98-120) mmHg. Among patients with lower BP, GDMT prescription rate was 62.7%, and GDMT use was associated with decreased adverse events (HR:0.74, 95%CI:0.58-0.94). GDMT prescription rates were lower among higher-NYHA class and lower-eGFR subgroups compared with their reference subgroups, and directionally similar outcomes were noted in all subgroups (favoring GDMT use); however, this association was somewhat attenuated in the lower-eGFR group (HR:0.87, 95%CI:0.64-1.17). CONCLUSIONS: Conventional GDMT use was associated with decreased adverse outcomes in most patients with HF compounded by systolic dysfunction and low BP, albeit caution is warranted in patients with renal dysfunction.