Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. METHODS: We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS ≥ 12 months). RESULTS: Fifty patients (76.9%) received ≥ 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9 months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4 months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of ≥ 1 dose of pegfilgrastim, or either ≥ 5 doses of filgrastim or ≥ 1 dose of pegfilgrastim). CONCLUSIONS: G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC.

Incremental value of diastolic wall strain in predicting heart failure events in patients with atrial fibrillation.

Diastolic wall strain (DWS), an echocardiographic index based on linear elasticity theory, has been identified as a predictor of heart failure (HF) in patients with sinus rhythm. However, its effectiveness in atrial fibrillation (AF) patients remains uncertain. This study aims to assess DWS as a predictor of HF in AF patients with preserved ejection fraction. We analysed a prospective database of AF patients undergoing transthoracic echocardiography. AF patients with reduced left ventricular ejection fraction (< 50%), posterior wall motion abnormality, hypertrophic cardiomyopathy, valvular heart disease, pericardial disease, congenital heart disease, or history of pacemaker/implantable cardioverter-defibrillator implantation or cardiac surgery were excluded. The study followed patients until HF development, death, or last visit. Follow-up for patients who underwent catheter ablation was censored on the date of their procedure. HF was ascertained based on the Framingham criteria. DWS was calculated using a validated formula: DWS = (PWs -PWd)/PWs, where PWs is the posterior wall thickness at end-systole and PWd is the posterior wall thickness at end-diastole. Among 411 study patients (mean age 69.6 years, 66% men), 20 (5%) was underwent catheter ablation and 57 (14%) developed HF during a mean follow-up of 82 months. Cox-proportional hazards demonstrated that low DWS (≤ 0.33) significantly predicted HF events (hazard ratio [HR] 3.28, 95% confidence interval [CI]) 1.81-5.94, P < 0.0001), independent of age (per 10 years; HR 1.99, 95% CI 1.35-2.93, P < 0.001), indexed left ventricular mass (per 10 g/m2; HR 1.16, 95% CI 1.05-1.27, P < 0.01), and indexed left atrial volume (per 10 mL/m2; HR 1.14, 95% CI 1.04-1.24, P < 0.01). Additionally, global log-likelihood ratio chi-square statistics indicated that DWS incrementally predicts HF development beyond age, indexed left ventricular mass, and left atrial volume (P < 0.001).

H2ARDD score as a feasible predictor of heart failure events in patients with atrial fibrillation: a validation study.

It was reported that the H2ARDD score (organic heart diseases = 2 points, anemia = 1 point, renal dysfunction = 1 point, diabetes = 1 point, and diuretic use = 1point; range 0 to 6 points) may help identify patients with AF at high risk for HF events. However, this score has not been externally validated. The objective of this study was to evaluate the usefulness of H2ARDD score in predicting HF events in patients with AF. We used a prospective database of patients with AF, and Cox-proportional hazards models were used to assess the risk of HF events. The outcome of interest was defined as HF events including new-onset HF and death from HF. Of 562 AF patients, 518 (mean 69.7 ± 9.7 years-old, 64.9% men) met study criteria, and 84 (16.2%) developed HF events during a mean follow-up of 54 ± 42 months. In multivariable analyses, H2ARDD score was shown as a significant predictor for HF events [hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.36-1.79], independent of age (per 10 years, HR: 1.35, 95% CI: 1.03-1.78). In the Kaplan-Meier analyses stratified by H2ARDD score categories (0-2, 3-4, 5-6), the patients with higher H2ARDD scores had significantly worse HF event-free survival (log-rank P < 0.0001). The area under the ROC curve was 0.71 (95% CI: 0.65-0.77, P < 0.0001). The sensitivity and specificity at a cut-off score of ≥ 3 were 60% and 71%, respectively. In conclusion, the H2ARDD score may be feasible for HF risk stratification in patients with AF.

Atrial fibrillation and stroke: importance of left atrium as assessed by echocardiography.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which has been increasing dramatically. AF has unfavorable consequences, such as stroke, heart failure, and cardiovascular death. Of these, stroke has been considered to be the serious complication. Recently, direct oral anticoagulation or new technologies, such as the WATCHMAN left atrium (LA) appendage closure device, have emerged to prevent stroke. Therefore, the accurate estimation of thromboembolic risk and appropriate prevention are essential for high-risk patients with AF. Although CHADS2 and CHA2DS2-VASc scores has been widely used to predict the risk of stroke in patients with AF, some researchers showed that there was no relationship between CHADS2 and CHA2DS2-VASc scores and LA appendage thrombus formation. Recent studies have reported that combination of echocardiographic parameters to CHADS2 or CHA2DS2-VASc scores can stratify high risk groups for LA appendage thrombus formation and onset of stroke. In this review, we focus on the epidemiological, pathophysiological, and prognostic associations between AF and stroke, and review the clinical and echocardiographic predictors for stroke in patients with AF.

Predictors of in-hospital mortality in patients with infective endocarditis.

BACKGROUND: Infective endocarditis is a serious septic disease, and the epidemiological profile has changed over the last decade. However, there is a paucity of data regarding the current outcome and predictor of in-hospital mortality in patients with infective endocarditis. METHODS: Consecutive patients diagnosed as infective endocarditis based on the modified Duke criteria at Kansai Medical University hospital from January 2006 to June 2019 were prospectively included. The primary outcome was in-hospital mortality. Cox proportional hazards modelling was used to assess risk factors of in-hospital mortality. RESULTS: Of 137 consecutive patients with infective endocarditis (age 60 ± 17 years-old, 62% men, 65% underlying cardiac disease, 11% chronic haemodialysis), 18 (13%) died during hospitalisation. Age and sex were not associated with in-hospital mortality. Patients on chronic haemodialysis exhibited significantly higher in-hospital mortality rate than those without (47 vs. 9%). After adjusting for comorbidities in a multivariate Cox proportional hazards model, chronic haemodialysis was a significant predictor of in-hospital mortality [hazard ratio (HR) 4.22, 95% confidential interval (CI): 1.49-12.0, p < 0.01], independently of C-reactive protein (per 1 mg/dl; HR 1.07, 95%CI: 1.02-1.12, p < 0.05). CONCLUSIONS: Infective endocarditis in patients on chronic haemodialysis is a serious life-threatening condition that requires early diagnosis and an effective therapeutic approach.

Heart Failure in Atrial Fibrillation　- An Update on Clinical and Echocardiographic Implications.

Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and has unfavorable consequences such as stroke, heart failure (HF), and death. HF is the most common adverse event following AF and the leading cause of death. Therefore, identifying the association between AF and HF is important to establish risk stratification for HF in AF. Recent studies suggested that left atrial and ventricular fibrosis is an important link between AF and HF, and the prognostic impact may differ with respect to HF subtype, stratified with left ventricular ejection fraction (EF). Mortality risk in patients with concurrent AF and HF with reduced EF (HFrEF) appears slightly higher compared with those with concurrent AF and HF with preserved EF (HFpEF). On the other hand, the prognostic impact of HF in AF is similar between HFrEF and HFpEF. Further, left atrial size, as well as left atrial and left ventricular functional assessment, are reported to be useful for the prediction of HF in AF, incremental to the conventional risk factors. In this review, we focus on the epidemiological, pathophysiological, and prognostic associations between AF and HF, and review the clinical and echocardiographic predictors for HF in AF.

Usefulness of Left Atrial Volume as an Independent Predictor of Development of Heart Failure in Patients With Atrial Fibrillation.

Left atrial (LA) volume is known as a robust predictor of heart failure (HF) development in patients with sinus rhythm. However, among patients with atrial fibrillation (AF), the utility of LA volume for prediction of HF development has not been determined. The objective of this study was to investigate the utility of LA volume for prediction of HF development in patients with AF. Among adult patients who were referred for transthoracic echocardiography, those with AF at the baseline echocardiography were included and prospectively followed up to new-onset HF events. Patients who had significant valvular heart disease, congenital heart disease, or reduced left ventricular (LV) ejection fraction were excluded. Cox-proportional hazards models were used to assess the risk of HF development. Of a total of 562 patients, 422 (mean age 69.6 ± 9.7 years, 66.1% men) met study criteria, and 52 (12.3%) developed HF during a mean follow-up of 55 ± 43 months. Patients with HF events had larger indexed LA volume, compared with those without HF events (69 ± 46 vs 50 ± 23 ml/m2, p <0.0001). In a multivariable analysis adjusted for other co-morbidities, LA volume was a significant predictor for HF development [per 10 ml/m2; hazard ratio (HR) 1.14, 95% confidence interval (CI) 1.06 to 1.22, p <0.001], independently of age (per 10 years; HR 1.71, 95% CI 1.16 to 2.52, p <0.01), LV ejection fraction (per 10%; HR 0.67, 95% CI 0.52 to 0.86, p <0.01), and indexed LV mass (per 10 g/m2; HR 1.13, 95% CI 1.03 to 1.24, p <0.05). Also, LA volume had an incremental effect for prediction of HF development to these conventional risk factors (p <0.0001). In conclusion, LA volume provides prognostic information for the prediction of future HF events in patients with AF.