Single versus multiple arterial grafting in diabetic patients at 10 years: the Arterial Revascularization Trial.

AIMS: To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART). METHODS AND RESULTS: The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG). CONCLUSION: In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent.

Metagenomics in diagnosis and improved targeted treatment of UTI.

INTRODUCTION: The genomic revolution has transformed our understanding of urinary tract infection. There has been a paradigm shift from the dogmatic statement that urine is sterile in healthy people, as we are becoming forever more familiar with the knowledge that bacterial communities exist within the urinary tracts of healthy people. Metagenomics can investigate the broad populations of microbial communities, analysing all the DNA present within a sample, providing comprehensive data regarding the state of the microenvironment of a patient's urinary tract. This permits medical practitioners to more accurately target organisms that may be responsible for disease-a form of 'precision medicine'. METHODS AND RESULTS: This paper is derived from an extensive review and analysis of the available literature on the topic of metagenomic sequencing in urological science, using the PubMed search engine. The search yielded a total of 406 results, and manual selection of appropriate papers was subsequently performed. Only one randomised clinical trial comparing metagenomic sequencing to standard culture and sensitivity in the arena of urinary tract infection was found. CONCLUSION: Out of this process, this paper explores the limitations of traditional methods of culture and sensitivity and delves into the recent studies involving new high-throughput genomic technologies in urological basic and clinical research, demonstrating the advances made in the urinary microbiome in its entire spectrum of pathogens and the first attempts of clinical implementation in several areas of urology. Finally, this paper discusses the challenges that must be overcome for such technology to become widely used in clinical practice.

New horizons in management of heart failure in older patients.

Heart failure has a high prevalence in older populations, is a common and growing cause for hospital admission and carries a high risk of morbidity and mortality. Important co-morbidities in older patients with heart failure include atrial fibrillation, renal impairment, hypertension and anaemia. Diagnosing and managing heart failure in older patients are complicated due to atypical presentations, co-morbidities and a relative lack of evidence for commonly used treatments in younger patients. The growing epidemic of heart failure is also under-recognised and resourced in most health systems. Despite potential differences, we recommend that the basic approach to manage heart failure patients with an ejection fraction (EF) of <40% should be the same in older and younger. These treatments need to be started at low doses and titrated slowly along with the management of co-morbidities. Older patients with EF 40-49% can be treated in a similar manner to those with <40%, while the treatment of those with EF ≥50% is pragmatic in nature based on symptom control and management of co-morbidities although the evidence base for these recommendations is lacking. Overall management must be holistic and continuous based on the patient's social circumstances and ongoing needs. Finally, there is an urgent need for more research, evidence and resources directed towards older populations with heart failure to improve their care and the quality of life.

Safety of outpatient commencement of sotalol.

Background: Inpatient monitoring is recommended for sotalol initiation. Objective: The purpose of this study was to assess the safety of outpatient sotalol commencement. Methods: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated. Results: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation (P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy. Conclusion: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol.

Heightened risks of cardiovascular disease in South Asian populations: causes and consequences.

INTRODUCTION: South Asian individuals comprise almost a quarter of the world's population and have an excess risk of atherosclerotic cardiovascular disease (ASCVD) compared to other ethnicities. In part, this can be explained by higher prevalence, earlier onset, and suboptimal control of traditional cardiovascular risk factors, such as insulin resistance, metabolic syndrome, and dyslipidaemia. However, there remains a significant residual excess risk associated with South Asian ethnicity after controlling for traditional risk factors. AREAS COVERED: In this review, we describe the epidemiology of ASCVD in both native and diaspora South Asian populations. We explore how traditional cardiovascular risk factors, novel cardiovascular risk factors, and social determinants of health may contribute to the excess ASCVD risk seen in South Asian populations. EXPERT OPINION: There should be increased awareness of the relative importance of South Asian ethnicity and related social determinants of health, as risk factors for ASCVD. Systematic screening processes should be tailored to this population, and modifiable risk factors should be treated aggressively. Further research is required to quantify determinants of the excess ASCVD risk seen in South Asian populations and to develop targeted interventions to address these factors.

Cardiovascular considerations in management of patients with Turner syndrome.

Turner syndrome (TS) is a chromosomal disorder that affects 25-50 per 100,000 live born females. Patients with TS face a heavy burden of cardiovascular disease (congenital and acquired) with an increased risk of mortality and morbidity compared to the general population. Cardiovascular diseases are a major cause of death in females with TS. Approximately 50% of TS patients have a congenital heart abnormality, with a high incidence of bicuspid aortic valve, coarctation of the aorta and generalised arteriopathy. Frequently, females with TS have systemic hypertension, which is also a risk factor for progressive cardiac dysfunction and aortopathy. This paper aims to provide an overview of the cardiovascular assessment, management and follow up strategies in this high-risk population.

Influence of diabetes and obesity on ten-year outcomes after coronary artery bypass grafting in the arterial revascularisation trial.

AIMS: Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG. METHODS AND RESULTS: Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24% with diabetes, 30% with obesity). Patients in the "diabetes/no obesity" group had a higher risk of all-cause mortality following CABG (adjusted hazard ratio [aHR] 1.33, 95% confidence interval [CI] 1.08-1.64, p = 0.01) compared to the reference group of "no diabetes/no obesity". No excess risk was observed in the "no diabetes/obesity" or "diabetes/obesity" groups. Patients with insulin dependent diabetes had a significantly higher ten-year mortality risk compared to no diabetes (aHR 1.85, 95% CI 1.41-2.44, p = 0.00). Patients in the "diabetes/no obesity" and "diabetes/obesity groups" had a higher risk of sternal wound complications (HR 2.29, 95% CI 1.39-3.79, p < 0.001 and HR 3.21, 95% CI 1.89-5.45, p < 0.001 respectively). The composite outcome results were consistent with the mortality results. CONCLUSION: Diabetes, especially insulin dependent diabetes, is associated with a higher ten-year mortality risk after CABG, in contrast to obesity which does not appear to increase long term mortality compared to non-obese. The interaction between diabetes and obesity shows an apparent "protective" effect of obesity irrespective of diabetes on mortality. Both conditions are associated with a higher risk of post-operative sternal wound infections.

Coronary artery bypass grafting using bilateral internal thoracic arteries in patients with diabetes and obesity: A systematic review and meta-analysis.

Background: Patients with diabetes and obesity are at higher risk of adverse long-term outcomes following coronary artery bypass grafting. The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA), but BITA is not routinely used due to lack of clear evidence of efficacy and concerns over sternal wound complications. Methods: Medline, Embase and the Cochrane Library were searched for studies comparing the efficacy and safety of BITA and SITA grafting in patients with diabetes and obesity. Meta-analysis of mortality and sternal wound complications was performed. Results: We identified eight observational and ten propensity matched studies, and one RCT, comparing BITA and SITA which included patients with diabetes (n = 19,589); two propensity matched studies and one RCT which included patients with obesity (n = 6,972); mean follow up was 10.5 and 11.3 years respectively. Meta-analysis demonstrated a mortality reduction for BITA compared to SITA in patients with diabetes (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70-0.90; p = 0.0003). In patients with obesity there was a non-significant reduction in mortality in the BITA group (RR 0.73, 95% CI 0.47-1.12; p = 0.15). There was a significantly higher rate of sternal wound complications following BITA observed in patients with diabetes (RR 1.53, 95% CI 1.23-1.90; p = 0.0001) and obesity (RR 2.24, 95% CI 1.63-3.07; p < 0.00001). Conclusions: BITA is associated with better long-term survival in patients with diabetes. The effects of BITA grafting in patients with obesity are uncertain. BITA is associated with higher rates of sternal wound complications compared to SITA in both patients with diabetes and obesity.

Exercise and nutritional interventions on sarcopenia and frailty in heart failure: a narrative review of systematic reviews and meta-analyses.

The purpose of this review is to describe the present evidence for exercise and nutritional interventions as potential contributors in the treatment of sarcopenia and frailty (i.e. muscle mass and physical function decline) and the risk of cardiorenal metabolic comorbidity in people with heart failure (HF). Evidence primarily from cross-sectional studies suggests that the prevalence of sarcopenia in people with HF is 37% for men and 33% for women, which contributes to cardiac cachexia, frailty, lower quality of life, and increased mortality rate. We explored the impact of resistance and aerobic exercise, and nutrition on measures of sarcopenia and frailty, and quality of life following the assessment of 35 systematic reviews and meta-analyses. The majority of clinical trials have focused on resistance, aerobic, and concurrent exercise to counteract the progressive loss of muscle mass and strength in people with HF, while promising effects have also been shown via utilization of vitamin D and iron supplementation by reducing tumour necrosis factor-alpha (TNF-a), c-reactive protein (CRP), and interleukin-6 (IL-6) levels. Experimental studies combining the concomitant effect of exercise and nutrition on measures of sarcopenia and frailty in people with HF are scarce. There is a pressing need for further research and well-designed clinical trials incorporating the anabolic and anti-catabolic effects of concurrent exercise and nutrition strategies in people with HF.

Effects of the Atrial Fibrillation Better Care Pathway on Outcomes Among Clinically Complex Chinese Patients With Atrial Fibrillation With Multimorbidity and Polypharmacy: A Report From the ChiOTEAF Registry.

Background Patients with atrial fibrillation commonly have complex clinical backgrounds of multimorbidity and polypharmacy. The Atrial Fibrillation Better Care (ABC) pathway has been developed to help deliver integrated and holistic care for patients with atrial fibrillation. In this ancillary analysis, we assessed the adherence to and the effectiveness of the ABC pathway at reducing adverse outcomes in Chinese patients with atrial fibrillation with a complex clinical background of multimorbidity or polypharmacy. Methods and Results The ChiOTEAF (Optimal Thromboprophylaxis in Elderly Chinese Patients With Atrial Fibrillation) registry is a prospective, multicenter, nationwide study conducted from October 2014 to December 2018. The primary outcomes of interest were the composite end point of all-cause death and thromboembolic events, as well as individual end points of all-cause death, thromboembolic events, and major bleeding. Multimorbidity was defined as the presence of ≥2 comorbidities, and polypharmacy was defined as the concomitant use of ≥5 medications. The eligible cohort included 4644 patients with multimorbidity, of whom 2610 (56.2%) had available data to assess the ABC pathway usage (mean age, 74.4±10.2; 42.8% women). Among patients with polypharmacy (n=2262; mean age, 74.6±10.1; 43.3% women), 1328 (58.7%) had available data to assess the use of the ABC pathway. Adherence to the ABC pathway was associated with a lower risk of the primary composite outcome among patients with multimorbidity (odds ratio, 0.48; 95% CI, 0.29-0.79) and in the polypharmacy group (odds ratio, 0.39; 95% CI, 0.19-0.78). Health-related quality of life was lower in the non-ABC-adherent group compared with the ABC-treated patients. Conclusions This nationwide real-world registry shows that adherence to the ABC pathway is associated with improved clinical outcomes and health-related quality of life in clinically complex Chinese patients with atrial fibrillation with multimorbidity or polypharmacy.

Polypharmacy in Older People With Heart Failure: Roles of the Geriatrician and Pharmacist.

Heart failure (HF) is a common health condition that typically affects older adults. Many people with HF are cared for on an inpatient basis, by noncardiologists, such as acute medical physicians, geriatricians and other physicians. Treatment options for HF are ever increasing, and adherence to guidelines for prognostic therapy contributes to polypharmacy, which is very familiar to clinicians who care for older people. This article explores the recent trials in both HF with reduced ejection fraction and HF with preserved ejection fraction and the limitations of international guidance in their management with respect to older people. In addition, this article discusses the challenge of managing polypharmacy in those with advanced age, and the importance of involving a geriatrician and pharmacist in the HF multidisciplinary team to provide a holistic and person-centred approach to optimisation of HF therapies.

Arterial stiffness and atrial fibrillation: shared mechanisms, clinical implications and therapeutic options.

Arterial stiffness (AS) and atrial fibrillation (AF) share commonalities in molecular and pathophysiological mechanisms and numerous studies have analyzed their reciprocal influence. The gold standard for AS diagnosis is represented by aortic pulse wave velocity, whose measurement can be affected by arrhythmias characterized by irregularities in heart rhythm, such as AF. Growing evidence show that patients with AS are at high risk of AF development. Moreover, the subset of AF patients with AS seems to be more symptomatic and rhythm control strategies are less effective in this population. Reducing AS through de-stiffening interventions may be beneficial for patients with AF and can be a new appealing target for the holistic approach of AF management. In this review, we discuss the association between AS and AF, with particular interest in shared mechanisms, clinical implications and therapeutic options.

Therapeutic vs. prophylactic anticoagulation in COVID-19 patients: a systematic review and meta-analysis of real-world studies.

INTRODUCTION: Coagulopathy, in the form of either venous or arterial thromboembolism, is one of the most severe sequelae of coronavirus disease (COVID-19) and has been associated with poorer outcomes. However, the role of therapeutic anticoagulation (tAC) or prophylactic anticoagulation (pAC) in COVID-19 patients has not been definitely established. Therefore, the aim of this systematic review and meta-analysis was to gather all the available real-world data in the field and to provide a reliable effect size of the effect on mortality of tAC compared to pAC in COVID-19 patients. EVIDENCE ACQUISITION: Real-world studies (RWS) were identified by searching electronic databases from inception to 31st October, 2021. Randomized controlled trials were excluded. Mortality and bleedings were considered as primary and secondary outcomes, respectively. EVIDENCE SYNTHESIS: 10 RWS and 5541 patients were included in the analysis. Overall, tAC was associated with lower mortality (HR=0.62, 95% CI: 0.54-0.71). There was asymmetry at the funnel plot suggesting publication bias, that was not confirmed at the Egger test (P=0.07). For the secondary endpoint, there was a non-statistically significant tendency for more bleedings in patients treated with tAC compared to pAC (RR=1.75, 95% CI: 0.81-3.81). CONCLUSIONS: Our meta-analysis, based on RWS and adjusted estimates of risk, suggests a survival benefit of tAC over pAC in COVID-19 patients in the real world.

Renal Disease and Atrial Fibrillation.

Incidence and prevalence of atrial fibrillation (AF) and chronic kidney disease are increasing, and the two conditions commonly coexist. Renal impairment further increases the risk of ischemic stroke and systemic thromboembolism in patients with AF but also paradoxically predisposes to bleeding. Renal function should be monitored closely in patients with AF requiring oral anticoagulation therapy, particularly those receiving direct oral anticoagulants. Vitamin K antagonists can be used as part of a dose-adjusted anticoagulation regimen in patients with mild to moderate renal dysfunction. Dialysis-dependent patients taking vitamin K antagonists are at increased risk of sustaining major hemorrhage.

Is it Time to Say Goodbye to Culture and Sensitivity? The Case for Culture-independent Urology.

Next-generation sequencing has highlighted the limitations of conventional culture methods in the role of urology while discovering the intricate details of the role of microbiota in urologic health and disease. This review article explores: the utility and limitations of conventional culture methods; how culture-independent technologies are revolutionizing medicine; and how the implementation of these technologies may lead to improved patient outcomes. Finally, this article discusses the barriers to widespread adoption of culture-independent technologies, with suggestions for how these hurdles may be overcome.

The human gastrointestinal microbiota and prostate cancer development and treatment.

The human gastrointestinal microbiome contains commensal bacteria and other microbiota that have been gaining increasing attention in the context of cancer development and response to treatment. Microbiota play a role in the maintenance of host barrier surfaces that contribute to both local inflammation and other systemic metabolic functions. In the context of prostate cancer, the gastrointestinal microbiome may play a role through metabolism of estrogen, an increase of which has been linked to the induction of prostatic neoplasia. Specific microbiota such as Bacteroides, Streptococcus, Bacteroides massiliensis, Faecalibacterium prausnitzii, Eubacterium rectalie, and Mycoplasma genitalium have been associated with differing risks of prostate cancer development or extensiveness of prostate cancer disease. In this Review, we discuss gastrointestinal microbiota's effects on prostate cancer development, the ability of the microbiome to regulate chemotherapy for prostate cancer treatment, and the importance of using Next Generation Sequencing to further discern the microbiome's systemic influence on prostate cancer.