Examining the interim proposal for name change to steatotic liver disease in the US population.

BACKGROUND AND AIMS: Fatty liver is the commonest liver condition globally and traditionally associated with NAFLD. A consensus meeting was held in Chicago to explore various terminologies. Herein, we explore the proposed changes in nomenclature in a population data set from the US. APPROACH AND RESULTS: Statistical analysis was conducted using survey-weighted analysis. Assessment of fatty liver was conducted with vibration-controlled transient elastography. A controlled attenuation parameter of 288 dB/m was used to identify hepatic steatosis. Patients were classified into nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease. Liver stiffness measures at ≥8.8, ≥11.7, and ≥14 kPa were used to identify clinically significant fibrosis, advanced fibrosis, and cirrhosis, respectively. A total of 5102 individuals were included in the analysis. Using a survey-weighted analysis, a total of 25.43%, 6.95%, and 0.73% of the population were classified as nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, respectively. A sensitivity analysis at controlled attenuation parameter of 248 dB/m and fatty liver index found similar distribution. In a comparison between nonalcoholic steatotic liver disease, alcohol-associated steatotic liver disease, and viral hepatitis steatotic liver disease, there was no significant difference between the odds of advanced fibrosis and cirrhosis between groups. However, viral hepatitis steatotic liver disease individuals were found to have a significantly higher odds of clinically significant fibrosis (OR: 3.76, 95% CI, 1.27-11.14, p =0.02) compared with nonalcoholic steatotic liver disease. CONCLUSIONS: The current analysis assessed the proposed changes based on discussions from the consensus meeting. Although the definitions are an interim analysis of discussions, steatotic liver disease respects the underlying liver etiology and reduces stigma while increasing awareness of FL among viral and alcohol-associated steatosis/steatohepatitis.

Effectiveness of an Artificial Intelligence-Assisted App for Improving Eating Behaviors: Mixed Methods Evaluation.

BACKGROUND: A plethora of weight management apps are available, but many individuals, especially those living with overweight and obesity, still struggle to achieve adequate weight loss. An emerging area in weight management is the support for one's self-regulation over momentary eating impulses. OBJECTIVE: This study aims to examine the feasibility and effectiveness of a novel artificial intelligence-assisted weight management app in improving eating behaviors in a Southeast Asian cohort. METHODS: A single-group pretest-posttest study was conducted. Participants completed the 1-week run-in period of a 12-week app-based weight management program called the Eating Trigger-Response Inhibition Program (eTRIP). This self-monitoring system was built upon 3 main components, namely, (1) chatbot-based check-ins on eating lapse triggers, (2) food-based computer vision image recognition (system built based on local food items), and (3) automated time-based nudges and meal stopwatch. At every mealtime, participants were prompted to take a picture of their food items, which were identified by a computer vision image recognition technology, thereby triggering a set of chatbot-initiated questions on eating triggers such as who the users were eating with. Paired 2-sided t tests were used to compare the differences in the psychobehavioral constructs before and after the 7-day program, including overeating habits, snacking habits, consideration of future consequences, self-regulation of eating behaviors, anxiety, depression, and physical activity. Qualitative feedback were analyzed by content analysis according to 4 steps, namely, decontextualization, recontextualization, categorization, and compilation. RESULTS: The mean age, self-reported BMI, and waist circumference of the participants were 31.25 (SD 9.98) years, 28.86 (SD 7.02) kg/m2, and 92.60 (SD 18.24) cm, respectively. There were significant improvements in all the 7 psychobehavioral constructs, except for anxiety. After adjusting for multiple comparisons, statistically significant improvements were found for overeating habits (mean -0.32, SD 1.16; P<.001), snacking habits (mean -0.22, SD 1.12; P<.002), self-regulation of eating behavior (mean 0.08, SD 0.49; P=.007), depression (mean -0.12, SD 0.74; P=.007), and physical activity (mean 1288.60, SD 3055.20 metabolic equivalent task-min/day; P<.001). Forty-one participants reported skipping at least 1 meal (ie, breakfast, lunch, or dinner), summing to 578 (67.1%) of the 862 meals skipped. Of the 230 participants, 80 (34.8%) provided textual feedback that indicated satisfactory user experience with eTRIP. Four themes emerged, namely, (1) becoming more mindful of self-monitoring, (2) personalized reminders with prompts and chatbot, (3) food logging with image recognition, and (4) engaging with a simple, easy, and appealing user interface. The attrition rate was 8.4% (21/251). CONCLUSIONS: eTRIP is a feasible and effective weight management program to be tested in a larger population for its effectiveness and sustainability as a personalized weight management program for people with overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04833803; https://classic.clinicaltrials.gov/ct2/show/NCT04833803.

Correction: Effectiveness of an Artificial Intelligence-Assisted App for Improving Eating Behaviors: Mixed Methods Evaluation.

[This corrects the article DOI: 10.2196/46036.].

An Observational Data Meta-analysis on the Differences in Prevalence and Risk Factors Between MAFLD vs NAFLD.

BACKGROUND & AIMS: The shift to redefine nonalcoholic fatty liver disease (NAFLD) as metabolic associated fatty liver disease (MAFLD) can profoundly affect patient care, health care professionals, and progress within the field. To date, there remains no consensus on the characterization of NAFLD vs MAFLD. Thus, this study sought to compare the differences between the natural history of NAFLD and MAFLD. METHODS: Medline and Embase databases were searched to include articles on prevalence, risk factors, or outcomes of patients with MAFLD or NAFLD. Meta-analysis of proportions was conducted using the generalized linear mix model. Risk factors and outcomes were evaluated in conventional pairwise meta-analysis. RESULTS: Twenty-two articles involving 379,801 patients were included. Pooled prevalence of MAFLD was 39.22% (95% confidence interval [CI], 30.96%-48.15%) with the highest prevalence in Europe and Asia, followed by North America. The current MAFLD Definition only accounted for 81.59% (95% CI, 66.51%-90.82%) of NAFLD diagnoses. Patients had increased odds of being diagnosed with MAFLD compared with NAFLD (odds ratio, 1.37; 95% CI, 1.16-1.63; P < .001). Imaging modality resulted in a significantly higher odds of being diagnosed with MAFLD compared with NAFLD, but not biopsy. MAFLD was significantly associated with males, higher body mass index, hypertension, diabetes, lipids, transaminitis, and greater fibrosis scores compared with NAFLD. CONCLUSIONS: There were stark differences in the prevalence and risk factors between MAFLD and NAFLD. However, in the use of the MAFLD Definition, a greater emphasis on the management of concomitant metabolic diseases and a collaborative effort is required to explore the complex pathophysiologic mechanisms underlying the disease.

Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis.

INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM. MATERIALS AND METHODS: The current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events. RESULTS: 6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001). CONCLUSIONS: The identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.

Echocardiographic assessment of cardiovascular function and clinical outcomes in liver transplant recipients.

BACKGROUND & AIMS: Cardiovascular disease contributes to a high rate of morbidity and mortality after liver transplantation (LT). However, the progression of cardiac function and cardiac remodeling in LT recipients remains poorly understood. This study sought to evaluate the progression of cardiac function and structure in LT recipients and identify independent predictors of prognosis using echocardiography. METHODS: From 2009 to 2019, 178 adult LT recipients at a tertiary academic transplant center were retrospectively studied. Transthoracic echocardiograms 1-year pre- and post-LT were assessed. Primary outcomes were progression of systolic and diastolic function. Secondary outcomes included left ventricular remodeling, all-cause mortality, and heart failure readmission post-LT. Subgroup analyzes were performed for etiology of native liver disease. A multivariable model was constructed to examine independent predictors of outcomes. RESULTS: Systolic function significantly worsened, with reduction in stroke volume (45-37 ml/m2 , p < .001), left ventricular ejection fraction (LVEF) (65%-62%, p < .001) and cardiac index (3.00-2.60 L/min/m2 , p < .001). Conversely, there were significant improvements in diastolic indices, including tricuspid regurgitation Vmax (228-215 cm/s, p = .017), left atrial volume index (LAVI) (32-26 ml/m2 , p < .001) and right ventricular systolic pressure (RVSP) (31-28 mmHg, p = .001). Additionally, patients had increased relative wall thickness (RWT) (p < .001) and decreased left ventricular end-diastolic dimension/body surface area (p < .001) post-LT. The independent predictors for all-cause mortality and heart failure were increased pre-LT mitral annular early diastolic velocity (HR 1.11, CI 1.02-1.22, p = .018), LAVI (HR 1.06, CI 1.02-1.11, p = .007) and decreased LVEF (HR .89, CI .82-.97, p = .006). The effect of non-alcoholic steatohepatitis on cardiovascular outcomes post-LT was largely comparable to that of Hepatitis B. CONCLUSION: This study showed reduced systolic and improved diastolic function in LT recipients and highlighted the utility of pre-LT echocardiogram in the prognostication and risk stratification of LT candidates.

Clinical and echocardiographic characteristics associated with the development of infective endocarditis in patients with significant mitral stenosis.

BACKGROUND: Infective endocarditis (IE) confers significant mortality and morbidity in patients with underlying mitral stenosis (MS), with both diseased native valves and after valvular procedures. PURPOSE: We examined the clinical and echocardiographic parameters in association with the development of IE on patients with significant MS. METHODS: A total of 478 consecutive patients with index echocardiographic diagnosis of significant mitral stenosis (mitral valve area <1.5 cm2 ) were included. Patients were grouped into those with or without IE on at least 5 years of follow-up. Baseline clinical, echocardiographic profile and clinical outcomes were compared. RESULTS: IE was observed in 4.4% (n = 21) of the cohort. These patients were younger (45.3 ± 14.6 vs. 53.2 ± 15.5 years, p = 0.022) at the time of MS diagnosis. NT-proBNP was higher in patients who developed IE (13529 ± 12230 vs. 4381 ± 5875 pg/ml, p < 0.001), with larger left atrial diameter (54.4 ± 10.1 vs. 49.9 ± 9.5 mm, p = 0.040) and elevated pulmonary artery systolic pressure (PASP, 62.3 ± 17.2 vs. 47.2 ± 16.5 mmHg, p = 0.026). There was no significant difference in terms of MS severity, other concomitant valvulopathies, or etiology (rheumatic or degenerative) of MS. Patients who smoked had higher incidence of IE (33.3% vs. 14.2%, log-rank 7.27, p = 0.007). After adjusting for age, valve procedure and PASP, patients who smoked remained at elevated risk of IE (adjusted hazards ratio 2.99, 95% confidence interval 1.18-7.56, p = 0.021). CONCLUSION: IE occurs in a proportion of patients with MS. Smoking, younger age of diagnosis of MS as well as dilated left atria with elevated PASP may be associated with an elevated risk of this complication.

Impact of the COVID-19 Pandemic on Door-to-Balloon Time for Primary Percutaneous Coronary Intervention　- Results From the Singapore Western STEMI Network.

BACKGROUND: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029). CONCLUSIONS: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.

Has the first year of the COVID pandemic impacted the trends in obesity-related CVD mortality between 1999 and 2019 in the United States?

Background: During the covid-19 pandemic there was a marked rise in the number of cardiovascular deaths. Obesity is a well-known modifiable risk factor for cardiovascular disease and has been identified as a factor which leads to poorer covid-19 related outcomes. In this study we aimed to analyse the impact of covid-19 on obesity-related cardiovascular deaths compared to trends seen 20 years prior. We also analysed the influence different demographics had on mortality. Methods: Multiple Cause of Mortality database was accessed through CDC WONDER to obtain the obesity-related and general cardiovascular crude mortality and age adjusted mortality rates (AMMR) between 1999 and 2020 in the US. The obesity-related sample was stratified by demographics and cardiovascular mortality was subdivided into ischemic heart disease, heart failure, hypertension and cerebrovascular disease. Joinpoint Regression Program (Version 4.9.1.0) was used to calculate the average annual percent change (AAPC) in AAMR, and hence projected AAMR. Excess mortality was calculated by comparing actual AAMR in 2020 to projected values. Results and discussion: There were an estimated 3058 excess deaths during the early stages of the pandemic impacting all cohorts. The greatest excess mortalities were seen in men, rural populations and in Asian/Pacific Islander and Native Americans. Interestingly the greatest overall mortality was seen in the Black American population. Our study highlights important, both pre and during the pandemic, in obesity related cardiovascular disease mortality which has important implications for ongoing public health measures.

Effects of probiotics, prebiotics and synbiotics on anthropometric, cardiometabolic and inflammatory markers: An umbrella review of meta-analyses.

BACKGROUND & AIMS: Though probiotics, prebiotics and synbiotics have been shown to confer health benefits, their effects on cardiometabolic risk factors remain unclear. Therefore, we conducted an umbrella review to examine their effectiveness on anthropometric, cardiometabolic and inflammatory markers. METHODS: We conducted an umbrella review on eligible systematic reviews with meta-analysis (SRMA) published from journals' inception till 13 January 2023 retrieved from seven electronic databases (CINAHL, EMBASE, ProQuest, PubMed, Scopus, The Cochrane Library, and Web of Science). Methodological quality was appraised using the Assessment of Multiple Systematic Reviews 2 (AMSTAR2) tool and certainty of evidence was graded into five classes. Random-effects meta-analyses were performed on outcome effect sizes at the SRMA and primary study levels. Extent of overlapping articles were evaluated using corrected cover area. RESULTS: 24 systematic reviews representing 265 unique studies, 1076 unique effect sizes and 25,973 subjects were included. Synbiotics were evidently more effective in improving weight (-1.91 kg, 95%CI -3.45 kg to -0.37 kg, p = 0.02), total cholesterol (-12.17 mg/dl, 95%CI -17.89 mg/dl to -6.46 mg/dl, p < 0.001), low-density lipoprotein (-12.26 mg/dl, 95%CI -18.27 mg/dl to -6.25 mg/dl, p < 0.01), waist circumference (-1.85 cm, 95%CI -2.77 cm to -0.94 cm, p < 0.01), and fasting plasma glucose (-9.68 mg/dl, 95%CI -16.18 mg/dl to -3.18 mg/dl, p < 0.01). Prebiotics were more effective in improving body mass index (-0.34 kg/m2, 95%CI -0.48 kg/m2 to -0.20 kg/m2, p < 0.01), and HOMA-IR (-0.92, 95%CI -1.91 to 0.07, p = 0.06). Probiotics were shown to be more effective in reducing diastolic blood pressure (-1.34 mmHg, 95%CI -2.14 mmHg to -0.55 mmHg, P < 0.01) improving insulin level change (-0.84 mIU/mL, 95%CI -1.27 mIU/mL to -0.41 mIU/mL, p < 0.01), and the percentage of body fat (-0.66%, 95%CI -0.70% to -0.61%, p < 0.01). For all outcomes, the credibility of evidence was classified as class IV. CONCLUSION: Pre-, pro-, and synbiotics can significantly enhance anthropometric indices, glucose and lipid profiles, blood pressure, and inflammatory markers in individuals confronting obesity. While suggesting their supplementation holds promise for this population, the true clinical impact hinges on tailoring these interventions to specific indications and customizing treatment strategies to align with individual patient needs.

Continued demographic shifts in hospitalised patients with COVID-19 from migrant workers to a vulnerable and more elderly local population at risk of severe disease.

OBJECTIVES: In the early months of the COVID-19 pandemic in Singapore, the vast majority of infected persons were migrant workers living in dormitories who had few medical comorbidities. In 2021, with the Delta and Omicron waves, this shifted to the more vulnerable, elderly population within the local community. We examined evolving trends among the hospitalised cases of COVID-19. METHODS: All patients with polymerase chain reaction-positive SARS-CoV-2 admitted from February 2020 to October 2021 were included and subsequently stratified by their year of admission (2020 or 2021). We compared the baseline clinical characteristics, clinical course, and outcomes. RESULTS: A majority of cases were seen in 2020 (n = 1359), compared with 2021 (n = 422), due to the large outbreaks in migrant worker dormitories. Nevertheless, the greater proportion of locally transmitted cases outside of dormitories in 2021 (78.7% vs 12.3%) meant a significantly older population with more medical comorbidities had COVID-19. This led to an observably higher proportion of patients with severe disease presenting with raised inflammatory markers, need for therapeutics, supplemental oxygenation, and higher mortality. CONCLUSION: Changing demographics and the characteristics of the exposed populations are associated with distinct differences in clinical presentation and outcomes. Older age remained consistently associated with adverse outcomes.

Social disparities in cardiovascular mortality of patients with cancer in the USA between 1999 and 2019.

Background: Temporal trends of the impact of social determinants on cardiovascular outcomes of cancer patients has not been previously studied. Objectives: This study examined social disparities in cardiovascular mortality of people with and without cancer in the US population between 1999 and 2019. Methods: Primary cardiovascular deaths were identified from the Multiple Cause of Death database and grouped by cancer status. The cancer cohort was subcategorized into breast, lung, prostate, colorectal, and haematological. The number of cardiovascular deaths, crude cardiovascular mortality rate, cardiovascular age-adjusted mortality rate (AAMR), and percentage change in cardiovascular AAMR were calculated by cancer status and cancer type, and stratified by sex, race, ethnicity, and urban-rural setting. Results: 17.9 million cardiovascular deaths were analysed. Of these, 572,222 occurred in patients with a record of cancer. The cancer cohort were older and included more men and White racial groups. Regardless of cancer status, cardiovascular AAMR was higher in men, rural settings, and Black or African American races. Cardiovascular AAMR declined over time, with greater reduction in those with cancer (-51.6% vs -38.3%); the greatest reductions were in colorectal (-68.4%), prostate (-60.0%), and breast (-58.8%) cancers. Sex, race, and ethnic disparities reduced over time, with greater narrowing in the cancer cohort. There was increase in urban-rural disparities, which appeared greater in those with cancer. Conclusions: While most social disparities narrowed over time, urban-rural disparities widened, with greater increase in those with cancer. Healthcare plans should incorporate strategies for reduction of health inequality equitable access to cardio-oncology services.

Inflammatory phenotypes may be more important than age and comorbidities in predicting clinical outcomes in hospitalised patients with COVID-19.

Objectives: In critically ill patients with COVID-19, distinct hyperinflammatory and hypoinflammatory phenotypes have been described, with different outcomes and responses to therapy. We investigated if similar phenotypes exist in non-severe illness. Methods: Consecutive patients with polymerase chain reaction (PCR) confirmed SARS-CoV-2 were examined. Baseline demographics and laboratory investigations were tabulated, including serum C-reactive protein. Patients were divided into those who were hyperinflammatory (defined as C-reactive protein >17 mg/l) or hypoinflammatory. Adverse outcomes, defined as requiring oxygenation, intensive care, or death, were recorded during the hospital stay. Clinical characteristics and outcomes were compared. Results: Of the 1781 patients examined, 276 (15.5%) had a hyperinflammatory phenotype. They were older (51.8 ± 17.2 vs 40.3 ± 13.8 years, P <0.001), had a lower PCR cycle threshold (PCR cycle threshold value 19.3 ± 6.3 vs 22.7 ± 15.4, P = 0.025) at presentation, and more medical comorbidities. The hyperinflammatory phenotype was independently associated with adverse clinical outcomes, even after adjusting for age, medical history and viral load on multivariable analyses (adjusted odds ratio 5.78, 95% confidence interval 2.86-11.63). Conclusion: Even in non-severe COVID-19, there are distinct hyper- and hypoinflammatory phenotypes, with the hyperinflammatory phenotype strongly associated with adverse clinical outcomes, that could be distinguished with a simple biomarker.

The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications.

Despite the elucidation of the pathways behind the development of aortic stenosis (AS), there remains no effective medical treatment to slow or reverse its progress. Instead, the gold standard of care in severe or symptomatic AS is replacement of the aortic valve. Oxidative stress is implicated, both directly as well as indirectly, in lipid infiltration, inflammation and fibro-calcification, all of which are key processes underlying the pathophysiology of degenerative AS. This culminates in the breakdown of the extracellular matrix, differentiation of the valvular interstitial cells into an osteogenic phenotype, and finally, calcium deposition as well as thickening of the aortic valve. Oxidative stress is thus a promising and potential therapeutic target for the treatment of AS. Several studies focusing on the mitigation of oxidative stress in the context of AS have shown some success in animal and in vitro models, however similar benefits have yet to be seen in clinical trials. Statin therapy, once thought to be the key to the treatment of AS, has yielded disappointing results, however newer lipid lowering therapies may hold some promise. Other potential therapies, such as manipulation of microRNAs, blockade of the renin-angiotensin-aldosterone system and the use of dipeptidylpeptidase-4 inhibitors will also be reviewed.

The obesity paradox: association of obesity with improved survival in medically managed severe aortic stenosis.

INTRODUCTION: The obesity paradox, where obesity is associated with improved survival, has been described in patients undergoing haemodialysis and in those with heart failure. It was also demonstrated in patients undergoing valve replacement for aortic stenosis (AS). We explored this phenomenon in medically managed severe AS. METHODS: 154 patients with medically managed severe AS (aortic valve area index [AVAi] < 0.6 cm2/m2; mean pressure gradient > 40 mmHg and peak velocity > 400 cm/s) and preserved left ventricular ejection fraction (> 50%) were categorised into the obese (body mass index [BMI] Asian cut-off ≥ 27.5 kg/m2) and non-obese groups. Their clinical and echocardiographic profiles were compared. RESULTS: 24 (15.6%) patients were obese. Obese patients were similar to non-obese patients in age (68.5 ± 11.6 years vs. 68.9 ± 13.1 years) but had higher prevalence of cardiovascular risk factors. Left atrial diameter (43.7 ± 6.7 mm vs. 38.5 ± 10.2 mm) was larger in obese patients, while left ventricular outflow tract diameter (19.5 ± 1.7 mm vs. 20.4 ± 2.1 mm) was smaller. Despite lower AVAi in obese patients (0.36 ± 0.10 cm2/m2 vs. 0.43 ± 0.11 cm2/m2), there was lower mortality (37.5% vs. 41.0%, log-rank 4.06, p = 0.045) on follow-up (8.0 ± 5.7 years). After adjusting for age and AVAi, higher BMI ≥ 27.5 kg/m2 remained protective for mortality (hazard ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.046). CONCLUSION: We demonstrated that obesity was associated with improved survival in severe AS despite lower AVAi and increased prevalence of cardiovascular risk factors.

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease.

Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial-based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule-targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS-scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.

Meta-Analysis Comparing Risk Factors, Incidence, and Outcomes of Patients With Versus Without Prosthesis-Patient Mismatch Following Transcatheter Aortic Valve Implantation.

Current guidelines on the management of patients with aortic valvular disease have widened the use of transcatheter aortic valve implantation (TAVI) with an emphasis on avoidance of prosthesis-patient mismatch (PPM). This study sought to examine the incidence, risk factors, and all-cause mortality of PPM after TAVI. Medline and Embase databases were searched from inception to August 10, 2021. Patients were compared along 2 arms: (1) any degree of PPM and those without PPM, (2) severe PPM, and nonsevere PPM. A total of 22 articles involving 115,442 patients after TAVI were included. Pooled incidence for any degree of PPM was 30.1% and 10.7% in severe PPM. Incidence was significantly higher (p <0.001) for any degree of PPM in Europe (33.1%) and North America (34.4%) compared with Asia (10.4%). Incidence of severe PPM was higher (p = 0.015) in older generation (13.6%) compared with current-generation valves (6.3%). Severe PPM increased the risk of all-cause mortality relative to nonsevere PPM (hazard ratio: 1.86, 95% confidence interval: 1.05 to 3.29, p = 0.034). Patients of younger age, increased body surface area, lower left ventricular ejection fraction, and classified New York Heart Association Class III/IV were at greater risk of both any degree and severe PPM. Smaller prosthesis size increased the risk of any degree of PPM, whereas postdilation and larger prostheses were protective factors. In conclusion, all-cause mortality was significantly affected in severe PPM compared with nonsevere cases, whereas this excess mortality was not observed between those with any degree of PPM and those without. Closer attention to patient and bioprosthetic valve factors is required to minimize the occurrence of severe PPM.

Prevalence and outcomes of concomitant cardiac amyloidosis and aortic stenosis: A systematic review and meta-analysis.

OBJECTIVE: Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a large variation in the reported prevalence figures, due to differences in populations and diagnostic methods. We aimed to investigate the prevalence, risk factors and outcomes of concomitant CA and AS. METHODS: We performed a systematic review and meta-analysis of the literature searched on MEDLINE, Embase, Scopus and CENTRAL. We analysed the prevalence of CA in patients with AS grouped according to the diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS were analysed in AS patients referred for surgical or transcatheter aortic valve replacement (AVR). RESULTS: A total of 21 studies were included, involving 4,243 patients. The pooled prevalence of CA in patients with AS was 14.4%, with substantial heterogeneity. The pooled prevalence of AS in patients CA was 8.7%, with substantial heterogeneity. Patients with both AS and CA had higher all-cause mortality than those with AS or CA alone. In AS patients requiring AVR, CA was associated with increasing age, male sex, higher NT-proBNP levels, increased interventricular septal end diastole (IVSd) thickness and lower left ventricular ejection fraction. Concomitant AS and CA was associated with increased all-cause mortality and pacemaker implantation post-procedure. Study limitations included heterogeneity of the results and the fair to good quality of the studies published. CONCLUSION: Overall, a substantial proportion of patients with AS may have CA, and they have poorer prognosis. A high degree of clinical suspicion is needed to identify the "red flags" and perform appropriate diagnostic imaging.

The placebo response rate and nocebo events in obesity pharmacological trials. A systematic review and meta-analysis.

Background: There is a growing number of trials examining the effectiveness of pharmacotherapies for obesity, however, little is known about placebo and nocebo effect in these trials. Hence, we sought to examine the effect of placebo in obesity trials, to better understand the potential factors affecting clinical endpoints in them. Methods: Medline, Embase, and Cochrane CENTRAL were searched for articles examining weight-loss RCTs examining patients with overweight or obesity in placebo-controlled arms from inception till 25 June 2022. This paper was registered online with PROSPERO (CRD42022302482). A single arm meta-analysis of proportions was used to estimate the primary outcomes, ≥5%, ≥10%, and ≥15% total weight loss - and the adverse effects that patients experienced during the trial. A meta-analysis of means was used to estimate the pooled mean differences of the secondary outcomes including, body weight measurements, lipid levels, glycemic indices, and blood pressure over time. Findings: A total of 63 papers involving 20,454 patients and 69 trials were included. The proportion of patients that had ≥5%, ≥10%, and ≥15% weight loss was 20·4% (CI:16·1% to 25·0%), 8·3% (CI:6·1% to 10·9%), and 6·2% (CI:3·8% to 9·7%), respectively. Analysis by duration of trials showed stepwise increase in proportion of patients with ≥5% and ≥10% weight loss with increasing duration of study. Analysis of secondary outcomes found modest improvement in all analyses. The pooled average rate of overall AEs, serious AEs, and discontinuation was 73·7% (CI:68·0% to 79·0%), 3·4% (CI:2·4% to 4·5%), and 5·2% (CI:4·0% to 6·5%), respectively. In psychiatric complications, the pooled rates of anxiety and depression were 2·7% (CI:1·8% to 3·7%) and 2·5 (CI:1·7% to 3·3%). Interpretation: Our meta-analysis of placebo-treated participants in weight-loss RCTs indicate a significant placebo and nocebo effect. These findings are important to quantify their effect and may inform the design of future RCTs. Funding: This research did not receive additional support from organizations beyond the authors' academic institutions.