Sex-Specific Differences in Heart Failure:Pathophysiology, Risk Factors, Management, and Outcomes

Heart failure (HF) is a leading cause of hospitalisation, morbidity, and mortality in Canada. There are sex-specific differences in the etiology, epidemiology, comorbidities, treatment response, and treatment adverse effects that have implications on outcomes in HF. Sex-specific analyses of some HF trials indicate that optimal doses of drug therapies and benefit of device therapies may differ between male and female patients, but the trials were not designed to test sex differences. The under-representation of female participants in HF randomised controlled trials (RCTs) is a major limitation in assessing the sex-specific efficacy and safety of treatments. To ensure that female patients receive safe and effective HF therapies, RCTs should include participants proportionate to the sex-specific distribution of disease. This review outlines the sex-specific differences in HF phenotype and treatment response, and highlights disparities in services and gaps in knowledge that merit further investigation

Distinct pathophysiological pathways in women and men with heart failure

Aims Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and results In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p &lt; 0.0001). Conclusion In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.</p

Features of effective computerised clinical decision support systems : meta-regression of 162 randomised trials.

Objectives To identify factors that differentiate between effective and ineffective computerised clinical decision support systems in terms of improvements in the process of care or in patient outcomes. Design Meta-regression analysis of randomised controlled trials. Data sources A database of features and effects of these support systems derived from 162 randomised controlled trials identified in a recent systematic review. Trialists were contacted to confirm the accuracy of data and to help prioritise features for testing. Main outcome measures ?Effective? systems were defined as those systems that improved primary (or 50% of secondary) reported outcomes of process of care or patient health. Simple and multiple logistic regression models were used to test characteristics for association with system effectiveness with several sensitivity analyses. Results Systems that presented advice in electronic charting or order entry system interfaces were less likely to be effective (odds ratio 0.37, 95% confidence interval 0.17 to 0.80). Systems more likely to succeed provided advice for patients in addition to practitioners (2.77, 1.07 to 7.17), required practitioners to supply a reason for over-riding advice (11.23, 1.98 to 63.72), or were evaluated by their developers (4.35, 1.66 to 11.44). These findings were robust across different statistical methods, in internal validation, and after adjustment for other potentially important factors. Conclusions We identified several factors that could partially explain why some systems succeed and others fail. Presenting decision support within electronic charting or order entry systems are associated with failure compared with other ways of delivering advice. Odds of success were greater for systems that required practitioners to provide reasons when over-riding advice than for systems that did not. Odds of success were also better for systems that provided advice concurrently to patients and practitioners. Finally, most systems were evaluated by their own developers and such evaluations were more likely to show benefit than those conducted by a third party

Excess years of life lost to COVID-19 and other causes of death by sex, neighbourhood deprivation, and region in England and Wales during 2020: A registry-based study

BackgroundDeaths in the first year of the Coronavirus Disease 2019 (COVID-19) pandemic in England and Wales were unevenly distributed socioeconomically and geographically. However, the full scale of inequalities may have been underestimated to date, as most measures of excess mortality do not adequately account for varying age profiles of deaths between social groups. We measured years of life lost (YLL) attributable to the pandemic, directly or indirectly, comparing mortality across geographic and socioeconomic groups.Methods and findingsWe used national mortality registers in England and Wales, from 27 December 2014 until 25 December 2020, covering 3,265,937 deaths. YLLs (main outcome) were calculated using 2019 single year sex-specific life tables for England and Wales. Interrupted time-series analyses, with panel time-series models, were used to estimate expected YLL by sex, geographical region, and deprivation quintile between 7 March 2020 and 25 December 2020 by cause: direct deaths (COVID-19 and other respiratory diseases), cardiovascular disease and diabetes, cancer, and other indirect deaths (all other causes). Excess YLL during the pandemic period were calculated by subtracting observed from expected values. Additional analyses focused on excess deaths for region and deprivation strata, by age-group. Between 7 March 2020 and 25 December 2020, there were an estimated 763,550 (95% CI: 696,826 to 830,273) excess YLL in England and Wales, equivalent to a 15% (95% CI: 14 to 16) increase in YLL compared to the equivalent time period in 2019. There was a strong deprivation gradient in all-cause excess YLL, with rates per 100,000 population ranging from 916 (95% CI: 820 to 1,012) for the least deprived quintile to 1,645 (95% CI: 1,472 to 1,819) for the most deprived. The differences in excess YLL between deprivation quintiles were greatest in younger age groups; for all-cause deaths, a mean of 9.1 years per death (95% CI: 8.2 to 10.0) were lost in the least deprived quintile, compared to 10.8 (95% CI: 10.0 to 11.6) in the most deprived; for COVID-19 and other respiratory deaths, a mean of 8.9 years per death (95% CI: 8.7 to 9.1) were lost in the least deprived quintile, compared to 11.2 (95% CI: 11.0 to 11.5) in the most deprived. For all-cause mortality, estimated deaths in the most deprived compared to the most affluent areas were much higher in younger age groups, but similar for those aged 85 or over. There was marked variability in both all-cause and direct excess YLL by region, with the highest rates in the North West. Limitations include the quasi-experimental nature of the research design and the requirement for accurate and timely recording.ConclusionsIn this study, we observed strong socioeconomic and geographical health inequalities in YLL, during the first calendar year of the COVID-19 pandemic. These were in line with long-standing existing inequalities in England and Wales, with the most deprived areas reporting the largest numbers in potential YLL

Predicting Risk of Cardiotoxic Effects in Breast Cancer: Are We There Yet?

People with breast cancer are at increased risk of cardiovascular disease, myocardial injury, and heart failure (HF) due to underlying risk factors, a proinflammatory milieu, and cancer therapy–related cardiovascular toxic effects (CTR-CVT).1 Of the therapies for breast cancer, human epidermal growth factor receptor-2 (ERBB2)–targeted therapies, such as trastuzumab, and anthracyclines, such as doxorubicin, have the most well-described associations with both decline in left ventricular ejection fraction (LVEF), and clinical HF.2,3 Given that cardiotoxic effects are not always reversible and can result in significant morbidity and mortality, current European Society of Cardiology guidelines recommend risk stratification before starting potentially cardiotoxic anticancer therapy in all patients with cancer (Class 1B) to identify patients who are at high risk of developing CTR-CVT.4 Several risk prediction models have been developed to estimate adverse cardiac outcomes among patients with breast cancer. However, the design, performance, and methodological rigor of the risk prediction models have not been assessed systematically

Prevalence and outcomes of type 2 myocardial infarction in patients with cancer: A retrospective analysis from the National Inpatient Sample dataset.

This study aimed to investigate the prevalence, clinical characteristics and outcomes of type 2 myocardial infarction (T2AMI) in patients with versus without cancer. All hospitalizations with a primary discharge diagnosis of T2AMI were stratified according to cancer status (secondary diagnosis of any-cancer vs cancer-free) using data from the US National Inpatient Sample (2016-2019). The primary outcome was in-hospital all-cause mortality while secondary outcomes were in-hospital major adverse cardiovascular and cerebrovascular events (MACCE). Among 61,305 included hospitalizations with primary diagnosis of T2AMI, 3745 (6.1%) were associated with a diagnosis of cancer. Patients with T2AMI and cancer presented more frequently with acute respiratory failure (23.2% vs 18.1%), acute pulmonary embolism (3.7% v 1.3%), major bleeding (6.8% vs 4.1%) and renal failure (51.0% vs 46.8%), compared to patients without. On adjusted analysis, diagnosis of cancer was associated with lower odds of invasive coronary angiography (aOR 0.75, 95% CI 0.60 to 0.93, p = 0.009) but greater odds of mortality (aOR 1.95, 95% C.I. 1.26-2.99 p = 0.002). Among the different types of cancer, adjusted risk of all-cause mortality was higher in patients with colorectal (aOR 4.17 95% CI 1.68-10.32, p = 0.002), lung (aOR 3.63, 95% CI 1.83-7.18, p < 0.001) and haematologic (aOR 2.48, 95% CI 1.22-5.05, p = 0.001) cancer. Patients with cancer presenting with T2AMI have lower odds of management with invasive diagnostic coronary angiography and have higher rates of in-hospital all-cause death. Further studies are warranted to improve overall care and outcomes of cancer patients and cardiovascular diseases. [Abstract copyright: Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.