A 3-Dimensional In Silico Test Bed for Radiofrequency Ablation Catheter Design Evaluation and Optimization

Atrial fibrillation (AF) is the disordered activation of the atrial myocardium, which is a major cause of stroke. Currently, the most effective, minimally traumatic treatment for AF is percutaneous catheter ablation to isolate arrhythmogenic areas from the rest of the atrium. The standard in vitro evaluation of ablation catheters through lesion studies is a resource intensive effort due to tissue variability and visual measurement methods, necessitating large sample sizes and multiple prototype builds. A computational test bed for ablation catheter evaluation was built in SolidWorks® using the morphology and dimensions of the left atrium adjacent structures. From this geometry, the physical model was built in COMSOL Multiphysics®, where a combination of the laminar fluid flow, electrical currents, and bioheat transfer was used to simulate radiofrequency (RF) tissue ablation. Simulations in simplified 3D geometries led to lesions sizes within the reported ranges from an in-vivo ablation study. However, though the ellipsoid lesion morphologies in the full atrial model were consistent with past lesion studies, perpendicularly oriented catheter tips were associated with decreases of -91.3% and -70.0% in lesion depth and maximum diameter. On the other hand, tangentially oriented catheter tips produced lesions that were only off by -28.4% and +7.9% for max depth and max diameter. Preliminary investigation into the causes of the discrepancy were performed for fluid velocities, contact area, and other factors. Finally, suggestions for further investigation are provided to aid in determining the root cause of the discrepancy, such that the test bed may be used for other ablation catheter evaluations

Sex differences in efficacy of pharmacological therapies in heart failure with reduced ejection fraction:a meta-analysis

Aims: Recent studies have suggested potential sex differences in treatment response to pharmacological therapies in heart failure (HF). We performed a systematic review and meta-analysis of studies comparing treatment effects between men and women with HF and reduced ejection fraction (HFrEF) using established guideline-directed medical therapy and other emerging pharmacological treatments. Methods and results: Systematic search was performed on PubMed, Embase, and Cochrane Library for randomized controlled trials published in 1990–2021. Outcomes were all-cause mortality and combined outcome of all-cause mortality and/or hospitalization for HF. Of 618 articles identified, 25 articles and 100 213 patients (mean age 62 ± 1.7 years, women 23.1%, mean left ventricular ejection fraction 26.6 ± 1.3%) were included in the systematic review and meta-analysis. For the outcome of all-cause mortality, there was no evidence of treatment heterogeneity by sex for renin-angiotensin system inhibitors (RASi) [hazard ratio (HR) 0.86 (95% confidence interval 0.75–0.99) in men; HR 0.97 (0.77–1.23) in women; Pinteraction = 0.288], or for beta-blockers (BB) [HR 0.71 (0.59–0.86) in men; HR 0.87 (0.73–1.03) in women; Pinteraction = 0.345]. Similarly, for the composite outcome of death or HF hospitalization, there was no evidence of treatment heterogeneity by sex for RASi [HR 0.84 (0.77–0.93) in men; HR 0.94 (0.81–1.08) in women; Pinteraction = 0.210] or BB [HR 0.76 (0.64–0.90) in men; HR 0.72 (0.60–0.86) in women; Pinteraction = 0.650]. Results for mineralocorticoid receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) from previously published meta-analyses were included in the review. For the combined outcome of cardiovascular death or HF hospitalization, no significant interaction for sex was observed for MRA (Pinteraction = 0.78) or SGLT2i (Pinteraction = 0.37). Results for emerging pharmacological treatments, such as soluble guanylate cyclase stimulators and cardiac myosin activators, were included in the review and showed consistent treatment effects between men and women. Conclusions: Our meta-analysis showed no differences between sex in treatment effect for BB and RASi. Review on previously published trials for MRA, SGLT2i, and emerging therapies presented consistent treatment effects between men and women

Role of leptin as a biomarker for early detection of renal cell carcinoma? No evidence from a systematic review and meta-analysis

Renal cell carcinoma (RCC) is the commonest from of renal neoplasm. Although surgery is a successful curative treatment for localized RCC, most patients are diagnosed with advanced or metastatic RCC, which has poor prognosis. RCC is classified by stage and grade using tissue samples. Whilst these provide good prognostic information, they are not very useful for early detection. Proteins that are dysregulated in patient's serum can be a valuable alternative and less invasive biomarker for early detection of the disease. For this reason, a hypothesis was formed that leptin is a possible biomarker for early detection and prognostication of RCC. The literature has disparate results on the usefulness of leptin as a biomarker for the early detection of RCC. Hence, a systematic review and a meta-analysis was carried out to investigate whether serum leptin could be a reliable diagnostic and prognostic factor in RCC patients. Literature on the available cohort and case-control studies on serum leptin in RCC was searched in electronic databases and included to evaluate this adipokine in the progression of RCC. The relevant studies were evaluated for the diagnostic and prognostic value of leptin in RCC patients. Overall, only 6 original research studies matched selection criteria and were included for meta-analysis. This study was hypothesised that; leptin might be a useful biomarker for early detection and prognostication of RCC. However, the data were presented in this study did not support our hypothesis. Serum leptin levels in RCC patients do not strongly associate with the development or progression of RCC, thus cannot act as a biomarker for early detection in RCC in patients. Extending our hypothesis further to include levels of obesity and RCC development may be worthwhile, but studies are currently limited

Left atrial structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF):systematic review and meta-analysis

Left atrial (LA) structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF) is only established in small studies. Therefore, we conducted a systematic review of LA structure and function in order to find differences between patients with HFrEF and HFpEF. English literature on LA structure and function using echocardiography was reviewed to calculate pooled prevalence and weighted mean differences (WMD). A total of 61 studies, comprising 8806 patients with HFrEF and 9928 patients with HFpEF, were included. The pooled prevalence of atrial fibrillation (AF) was 34.4% versus 42.8% in the acute inpatient setting, and 20.1% versus 33.1% in the chronic outpatient setting when comparing between HFrEF and HFpEF. LA volume index (LAVi), LA reservoir global longitudinal strain (LAGLS(R)), and E/e' was 59.7 versus 52.7 ml/m(2), 9.0% versus 18.9%, and 18.5 versus 14.0 in the acute inpatient setting, and 48.3 versus 38.2 ml/m(2), 12.8% versus 23.4%, and 16.9 versus 13.5 in the chronic outpatient setting when comparing HFrEF versus HFpEF, respectively. The relationship between LAVi and LAGLS(R) was significant in HFpEF, but not in HFrEF. Also, in those studies that directly compared patients with HFrEF versus HFpEF, those with HFrEF had worse LAGLS(R) [WMD = 16.3% (22.05,8.61); p < 0.001], and higher E/e' [WMD = -0.40 (-0.56, -0.24); p < 0.05], while LAVi was comparable. When focusing on acute hospitalized patients, E/e' was comparable between patients with HFrEF and HFpEF. Despite the higher burden of AF in HFpEF, patients with HFrEF had worse LA global function. Left atrial myopathy is not specifically related to HFpEF

Epidemiology and Clinical Features of Heart Failure with Preserved Ejection Fraction

Heart failure (HF) with preserved ejection (HFpEF) constitutes a large and growing proportion of patients with HF around the world, and is now responsible for more than half of all HF cases in ageing societies. While classically described as a condition of elderly, hypertensive women, recent studies suggest heterogeneity in clinical phenotypes involving differential characteristics and pathophysiological mechanisms. Despite a paucity of disease-modifying therapy for HFpEF, an understanding of phenotypic similarities and differences among patients with HFpEF around the world provides the foundation to recognise the clinical condition for early treatment, as well as to identify modifiable risk factors for preventive intervention. This review summarises the epidemiology of HFpEF, its common clinical features and risk factors, as well as differences by age, comorbidities, race/ethnicity and geography

Readmissions, death and its associated predictors in heart failure with preserved versus reduced ejection fraction

BACKGROUND: Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF, <40%), in the multinational ASIAN‐HF (Asian Sudden Cardiac Death in Heart Failure) registry. METHODS AND RESULTS: Patients with symptomatic (stage C) chronic HF were followed up for death and recurrent HF hospitalizations for 1 year. Predictors of HF hospitalizations or all‐cause mortality were examined with Cox regression for time to first event and other methods for recurrent events analyses. Among 1666 patients with HF with preserved EF (mean age, 68±12 years; 50% women), and 4479 with HF with reduced EF (mean age, 61±13 years; 22% women), there were 642 and 2302 readmissions, with 28% and 45% attributed to HF, respectively. The 1‐year composite event rate for first HF hospitalization or all‐cause death was 11% and 21%, and for total HF hospitalization and all‐cause death was 17.7 and 38.7 per 100 patient‐years in HF with preserved EF and HF with reduced EF, respectively. In HF with preserved EF, consistent independent predictors of these clinical end points included enrollment as an inpatient, Southeast Asian location, and comorbid chronic kidney disease or atrial fibrillation. The same variables were predictive of outcomes in HF with reduced EF except atrial fibrillation, and also included Northeast Asian location, older age, elevated heart rate, decreased systolic blood pressure, diabetes, smoking, and non‐usage of beta blockers. CONCLUSIONS: One‐year HF rehospitalization and mortality rates were high among Asian patients with HF. Predictors of outcomes identified in this study could aid in risk stratification and timely interventions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01633398

Prevalence and Prognostic Significance of Frailty in Asian Patients With Heart Failure:Insights From ASIAN-HF

Background: Frailty is common in patients with heart failure (HF) and can adversely impact outcomes. Objectives: This study examined the prevalence of frailty among Asian patients with HF, its association with 1-year outcomes, and if race-ethnicity, HF subtypes, and sex modify this relationship. Methods: In the multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, a baseline frailty index (FI) was constructed using a cumulative deficits approach with 48 baseline variables, and patients were followed for the 1-year primary outcome of all-cause death or HF hospitalization. Results: Among 3,881 participants (age 61 ± 13 years, 27% female), the mean FI was 0.28 ± 0.11, and 69% were frail (FI &gt;0.21). Higher FI was associated with older age, Malay ethnicity, and Southeast Asian residency. While comorbidities were more frequent in frail patients (by definition), body mass index was not different across frailty classes. Compared with FI class 1 (&lt;0.21, nonfrail), FI class 2 (0.21-0.31) and FI class 3 (&gt;0.31) had increased risk of the 1-year composite outcome (hazard ratios of 1.84 [95% confidence interval (CI): 1.42-2.38] and 4.51 [95% CI: 3.59-5.67], respectively), even after multivariable adjustment (adjusted hazard ratios of 1.49 [95% CI: 1.13-1.97] and 2.69 [95% CI: 2.06-3.50], respectively). Race-ethnicity modified the association of frailty with the composite outcome (Pinteraction = 0.0097), wherein the impact of frailty was strongest among Chinese patients. The association between frailty and outcomes did not differ between men and women (Pinteraction = 0.186) or for HF with reduced ejection fraction versus HF with preserved ejection fraction (Pinteraction = 0.094). Conclusions: Most Asian patients with HF are frail despite relatively young age. Our results reveal specific ethnic (Malay) and regional (Southeast Asia) predisposition to frailty and highlight its prognostic importance, especially in Chinese individuals.</p

Satin associated lower cancer risk and related mortaity in patients with heart failure

Aims Patients with heart failure (HF) have an increased risk of incident cancer. Data relating to the association of statin use with cancer risk and cancer-related mortality among patients with HF are sparse. Methods and results Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (n = 87 102) from 2003 to 2015. Inverse probability of treatment weighting was used to balance baseline covariates between statin nonusers (n = 50 926) with statin users (n = 36 176). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of cancer and cancer-related mortality associated with statin use. Of all eligible subjects, the mean age was 76.5 +/- 12.8 years, and 47.8% was male. Over a median follow-up of 4.1 years (interquartile range: 1.6-6.8), 11 052 (12.7%) were diagnosed with cancer. Statin use (vs. none) was associated with a 16% lower risk of cancer incidence [multivariable adjusted subdistribution hazard ratio (SHR) = 0.84; 95% confidence interval (CI), 0.80-0.89]. This inverse association with risk of cancer was duration dependent; as compared with short-term statin use (3 months to = 6 years of use. Ten-year cancer-related mortality was 3.8% among statin users and 5.2% among nonusers (absolute risk difference, -1.4 percentage points [95% CI, -1.6% to -1.2%]; adjusted SHR= 0.74; 95% CI, 0.67-0.81). Conclusion Our study suggests that statin use is associated with a significantly lower risk of incident cancer and cancer-related mortality in HF, an association that appears to be duration dependent. [GRAPHICS]

Prevalence and Prognostic Significance of Frailty in Asian Patients With Heart Failure:Insights From ASIAN-HF

Background: Frailty is common in patients with heart failure (HF) and can adversely impact outcomes. Objectives: This study examined the prevalence of frailty among Asian patients with HF, its association with 1-year outcomes, and if race-ethnicity, HF subtypes, and sex modify this relationship. Methods: In the multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, a baseline frailty index (FI) was constructed using a cumulative deficits approach with 48 baseline variables, and patients were followed for the 1-year primary outcome of all-cause death or HF hospitalization. Results: Among 3,881 participants (age 61 ± 13 years, 27% female), the mean FI was 0.28 ± 0.11, and 69% were frail (FI &gt;0.21). Higher FI was associated with older age, Malay ethnicity, and Southeast Asian residency. While comorbidities were more frequent in frail patients (by definition), body mass index was not different across frailty classes. Compared with FI class 1 (&lt;0.21, nonfrail), FI class 2 (0.21-0.31) and FI class 3 (&gt;0.31) had increased risk of the 1-year composite outcome (hazard ratios of 1.84 [95% confidence interval (CI): 1.42-2.38] and 4.51 [95% CI: 3.59-5.67], respectively), even after multivariable adjustment (adjusted hazard ratios of 1.49 [95% CI: 1.13-1.97] and 2.69 [95% CI: 2.06-3.50], respectively). Race-ethnicity modified the association of frailty with the composite outcome (Pinteraction = 0.0097), wherein the impact of frailty was strongest among Chinese patients. The association between frailty and outcomes did not differ between men and women (Pinteraction = 0.186) or for HF with reduced ejection fraction versus HF with preserved ejection fraction (Pinteraction = 0.094). Conclusions: Most Asian patients with HF are frail despite relatively young age. Our results reveal specific ethnic (Malay) and regional (Southeast Asia) predisposition to frailty and highlight its prognostic importance, especially in Chinese individuals.</p