Moving the Paradigm Forward for Prediction and Risk-Based Primary Prevention of Heart Failure in Special Populations.

PURPOSE OF REVIEW: Heart failure (HF) treatment paradigms increasingly recognize the importance of primary prevention. This review explores factors that enhance HF risk, summarizes evidence supporting the pharmacologic primary prevention of HF, and notes barriers to the implementation of primary prevention of HF with a focus on female and sexual and gender minority patients. RECENT FINDINGS: HF has pathophysiologic sex-specific distinctions, suggesting that sex-specific preventive strategies may be beneficial. Pharmacologic agents that have shown benefit in reducing the risk of HF address the pathobiology underpinning these sex-specific risk factors. The implementation of pharmacologic therapies for primary prevention of HF needs to consider a risk-based model. Current pharmacotherapies hold mechanistic promise for the primary prevention of HF in females and gender and sexual minorities, although research is needed to understand the specific populations most likely to benefit. There are significant systemic barriers to the equitable provision of HF primary prevention.

Predicting 30-day readmission after congenital heart surgery across the lifespan.

INTRODUCTION: Hospital readmission is an important driver of costs among patients with CHD. We assessed predictors of 30-day rehospitalisation following cardiac surgery in CHD patients across the lifespan. METHODS: This was a retrospective analysis of 981 patients with CHD who had cardiac surgery between January 2011 and December 2012. A multivariate logistic regression model was used to identify demographic, clinical, and surgical predictors of 30-day readmission. Receiver operating curves derived from multivariate logistic modelling were utilised to discriminate between patients who were readmitted and not-readmitted at 30 days. Model goodness of fit was assessed using the Hosmer-Lemeshow test statistic. RESULTS: Readmission in the 30 days following congenital heart surgery is common (14.0%). Among 981 patients risk factors associated with increased odds of 30-day readmission after congenital heart surgery through multivariate analysis included a history of previous cardiac surgery (p < 0.001), longer post-operative length of stay (p < 0.001), as well as nutritional (p < 0.001), haematologic (p < 0.02), and endocrine (p = 0.04) co-morbidities. Patients who underwent septal defect repair had reduced odds of readmission (p < 0.001), as did children (p = 0.04) and adult (p = 0.005) patients relative to neonates. CONCLUSION: Risk factors for readmission include a history of cardiac surgery, longer length of stay, and co-morbid conditions. This information may serve to guide efforts to prevent readmission and inform resource allocation in the transition of care to the outpatient setting. This study also demonstrated the feasibility of linking a national subspecialty registry to a clinical and administrative data repository to follow longitudinal outcomes of interest.

Applying the ABCs of Cardiovascular Disease Prevention to the 2023 AHA/ACC Multisociety Chronic Coronary Disease Guidelines.

The 2023 American Heart Association/American College of Cardiology Multisociety Guideline for the Management of Patients with Chronic Coronary Disease provides updated recommendations for the management of chronic coronary disease. The term "chronic coronary disease" reflects the lifelong nature of the disease and diverse disease etiologies that come under the chronic coronary disease umbrella, beyond the presence of epicardial coronary stenosis, which require targeted lifestyle recommendations, serial optimization of medications, and involvement of multiple care team members. In this review, we highlight several areas where a collaborative approach between cardiologists, primary care clinicians, and internists is essential to optimize the care of patients with chronic coronary disease.

Chronic Hypertension in Pregnancy: A Lens Into Cardiovascular Disease Risk and Prevention.

Hypertension is a major, modifiable risk factor for cardiovascular disease (CVD) in the United States. Over the past decade, the prevalence of chronic hypertension (CHTN) during pregnancy has nearly doubled with persistent race- and place-based disparities. Blood pressure elevations are of particular concern during pregnancy given higher risk of maternal and fetal morbidity and mortality, as well as higher lifetime risk of CVD in birthing individuals with CHTN. When identified during pregnancy, CHTN can, therefore, serve as a lens into CVD risk, as well as a modifiable target to mitigate cardiovascular risk throughout the life course. Health services and public health interventions that equitably promote cardiovascular health during the peripartum period could have an important impact on preventing CHTN and reducing lifetime risk of CVD. This review will summarize the epidemiology and guidelines for the diagnosis and management of CHTN in pregnancy; describe the current evidence for associations between CHTN, adverse pregnancy outcomes, and CVD; and identify opportunities for peripartum care to equitably reduce hypertension and CVD risk throughout the life course.

New strategies and therapies for the prevention of heart failure in high-risk patients.

Despite declines in total cardiovascular mortality rates in the United States, heart failure (HF) mortality rates as well as hospitalizations and readmissions have increased in the past decade. Increases have been relatively higher among young and middle-aged adults (<65 years). Therefore, identification of individuals HF at-risk (Stage A) or with pre-HF (Stage B) before the onset of overt clinical signs and symptoms (Stage C) is urgently needed. Multivariate risk models (e.g., Pooled Cohort Equations to Prevent Heart Failure [PCP-HF]) have been externally validated in diverse populations and endorsed by the 2022 HF Guidelines to apply a risk-based framework for the prevention of HF. However, traditional risk factors included in the PCP-HF model only account for half of an individual's lifetime risk of HF; novel risk factors (e.g., adverse pregnancy outcomes, impaired lung health, COVID-19) are emerging as important risk-enhancing factors that need to be accounted for in personalized approaches to prevention. In addition to determining the role of novel risk-enhancing factors, integration of social determinants of health (SDoH) in identifying and addressing HF risk is needed to transform the current clinical paradigm for the prevention of HF. Comprehensive strategies to prevent the progression of HF must incorporate pharmacotherapies (e.g., sodium glucose co-transporter-2 inhibitors that have also been termed the "statins" of HF prevention), intensive blood pressure lowering, and heart-healthy behaviors. Future directions include investigation of novel prediction models leveraging machine learning, integration of risk-enhancing factors and SDoH, and equitable approaches to interventions for risk-based prevention of HF.

Association of State Medicaid Expansion Status With Hypertensive Disorders of Pregnancy in a Singleton First Live Birth.

BACKGROUND: Incidence of hypertensive disorders of pregnancy is increasing in the United States. Early detection is important to prevent adverse maternal and offspring outcomes. This ecological study evaluated changes in rates of hypertensive disorders of pregnancy among states that expanded Medicaid compared with states that did not expand Medicaid. METHODS: A quasi-experimental analysis using difference-in-differences models compared changes in rates of hypertensive disorders of pregnancy in Medicaid expansion states relative to non-Medicaid expansion states from 2012 to 2019. Maternal data from singleton first live births to individuals aged 20 to 39 years were obtained from the National Center for Health Statistics. Outcomes of interest included age-adjusted rates of de novo hypertension in pregnancy (gestational hypertension or preeclampsia) and prepregnancy hypertension. RESULTS: Data from 7 764 965 individuals with a singleton first live birth were analyzed from 17 states and Washington, DC that expanded Medicaid and 15 states that did not. Rates of de novo hypertension in pregnancy increased over the study period in both expansion (54.34 [95% CI, 48.25-60.43] to 74.87 [95% CI, 71.20-78.55] per 1000 births) and nonexpansion states (68.32 [95% CI, 61.02-75.62] to 84.79 [95% CI, 80.67-88.91] per 1000 births). In adjusted difference-in-differences analyses, expansion status was associated with a greater increase in rates of de novo hypertension in pregnancy (difference-in-differences coefficient, +8.18 [95% CI, 4.00-12.36] per 1000 live births) but a decline in rates of de novo hypertension in pregnancy complicated by low birth weight (-7.20 [95% CI, -13.71 to -0.70] per 1000 births with hypertensive disorders of pregnancy). In adjusted difference-in-differences analyses, there were no significant changes in rates of prepregnancy hypertension in expansion relative to nonexpansion states (+1.13 [95% CI, -0.09 to +2.35] per 1000 live births). CONCLUSIONS: Between 2012 and 2019, states that expanded Medicaid had a significantly greater increase in rates of de novo hypertension, with some evidence of better outcomes among those with de novo hypertension diagnosed in pregnancy.

Trends in the Incidence of New-Onset Hypertensive Disorders of Pregnancy Among Rural and Urban Areas in the United States, 2007 to 2019.

Background Hypertensive disorders of pregnancy are growing public health problems that contribute to maternal morbidity, mortality, and future risk of cardiovascular disease. Given established rural-urban differences in maternal cardiovascular health, we described contemporary trends in new-onset hypertensive disorders of pregnancy in the United States. Methods and Results We conducted a serial, cross-sectional analysis of 51 685 525 live births to individuals aged 15 to 44 years from 2007 to 2019 using the Centers for Disease Control and Prevention Natality Database. We included gestational hypertension and preeclampsia/eclampsia in individuals without chronic hypertension and calculated the age-adjusted incidence (95% CI) per 1000 live births overall and by urbanization status (rural or urban). We used Joinpoint software to identify inflection points and calculate rate of change. We quantified rate ratios to compare the relative incidence in rural compared with urban areas. Incidence (95% CI) of new-onset hypertensive disorders of pregnancy increased from 2007 to 2019 in both rural (48.6 [48.0-49.2] to 83.9 [83.1-84.7]) and urban (37.0 [36.8-37.2] to 77.2 [76.8-77.6]) areas. The rate of annual increase in new-onset hypertensive disorders of pregnancy was more rapid after 2014 with greater acceleration in urban compared with rural areas. Rate ratios (95% CI) comparing incidence of new-onset hypertensive disorders of pregnancy in rural and urban areas decreased from 1.31 (1.30-1.33) in 2007 to 1.09 (1.08-1.10) in 2019. Conclusions Incidence of new-onset hypertensive disorders of pregnancy doubled from 2007 to 2019 with persistent rural-urban differences highlighting the need for targeted interventions to improve the health of pregnant individuals and their offspring.

Biomarker profile in stable Fontan patients.

BACKGROUND: As the population of adults with congenital heart disease (CHD) grows, cardiologists continue to encounter patients with complex anatomies that challenge the standard treatment of care. Single ventricle Fontan palliated patients are the most complex within CHD, with a high morbidity and mortality burden. Factors driving this early demise are largely unknown. METHODS AND RESULTS: We analyzed biomarker expression in 44 stable Fontan outpatients (29.2 ± 10.7 years, 68.2% female) seen in the outpatient Emory Adult Congenital Heart Center and compared them to 32 age, gender and race matched controls. In comparison to controls, Fontan patients had elevated levels of multiple cytokines within the inflammatory pathway including Tumor Necrosis Factor-α (TNF-α) (p < 0.001), Interleukin-6 (IL-6) (p < 0.011), Growth Derived Factor-15 (GDF-15) (p < 0.0001), ß2-macroglobulin, (p = 0.0006), stem cell mobilization: Stromal Derived Factor-1∝ (SDF-1α) (p = 0.006), extracellular matrix turnover: Collagen IV (p < 0.0001), neurohormonal activation: Renin (p < 0.0001), renal dysfunction: Cystatin C (p < 0.0001) and Urokinase Receptor (uPAR) (p = 0.022), cardiac injury: Troponin-I (p < 0.0004) and metabolism: Adiponectin (p = 0.0037). Within 1 year of enrollment 50% of Fontan patients had hospitalizations, arrhythmias or worsening hepatic function. GDF-15 was significantly increased in Fontan patients with clinical events (p < 0.0001). In addition, GDF-15 moderately correlated with longer duration of Fontan (r = 0.55, p = 0.01) and was elevated in atriopulmonary (AP) Fontan circulation. Finally, in a multivariate model, VEGF-D and Collagen IV levels were found to be associated with a change in MELDXI, a marker of liver dysfunction. CONCLUSION: Multiple clinical and molecular biomarkers are upregulated in Fontan patients, suggesting a state of chronic systemic dysregulation.

Children's Nomenclatural Adventurism and Medical Evaluation study.

AIM: The aim of this study was to determine whether there is an association between a child's first name and the likelihood of inpatient admission following presentation to a paediatric emergency department (ED). METHODS: This was a retrospective review of electronic records held in the ED of an urban tertiary paediatric hospital. Data were obtained for all presentations up to the age of 16 years for a single month (n= 4260), each being allocated to 1 of the 10 predetermined first name categories. RESULTS: A statistically significant increased risk for hospital admission was found for the following first name categories: popular culture (relative risk (RR) = 1.91, P= 0.000, 95% confidence interval (CI) = 1.60-2.28), apparently unique (RR = 1.52, P= 0.000, 95% CI = 1.23-1.87), Old Testament (RR = 1.39, P= 0.001, 95% CI = 1.14-1.69) and surname as first name (RR = 1.36, P= 0.015, 95% CI = 1.07-1.72). CONCLUSIONS: Our data confirm the impression that children with certain categories of first names have an increased likelihood of admission to hospital after presenting to the ED. We speculate that our findings, which are in concordance with those from educational and psychological literature, may reflect socio-economic status and/or a 'self-fulfilling prophecy'. Further research may make it possible to assign names an RR rating (e.g. for hospital admission in the first 16 years of life), thus providing parents with another factor to consider when choosing names for their children. More studies are of course needed.

Improving the quality of transition and transfer of care in young adults with congenital heart disease.

The transition and transfer from pediatric to adult care is becoming increasingly important as improvements in the diagnosis and management of congenital heart disease allow patients to live longer. Transition is a complex and continuous process that requires careful planning. Inadequate transition has adverse effects on patients, their families and healthcare delivery systems. Currently, significant gaps exist in patient care as adolescents transfer to adult care and there are little data to drive the informed management of transition and transfer of care in adolescent congenital heart disease patients. Appropriate congenital heart disease care has been shown to decrease mortality in the adult population. This paper reviews the transition and transfer of care processes and outlines current congenital heart disease specific guidelines in the United States and compares these recommendations to Canadian and European guidelines. It then reviews perceived and real barriers to successful transition and identifies predictors of success during transfer to adult congenital heart disease care. Lastly, it explores how disease-specific markers of outcomes and quality indicators are being utilized to guide transition and transfer of care in other chronic childhood illnesses, and identifies existing knowledge gaps and structural impediments to improving the management of transition and transfer among congenital heart disease patients.

Assessing behavioral control across reinforcer solutions on a fixed-ratio schedule of reinforcement in rats.

Instrumental behavior can shift from flexible, goal-directed actions to automatic, stimulus-response actions. The satiety-specific devaluation test assesses behavioral flexibility by evaluating reward seeking after temporary devaluation of the reinforcer via satiety; a decrease in responding compared to control conditions indicates goal-directed behavior. We have observed variability in the outcome of this test that may be dependent on the reinforcer. Another test of habit, contingency degradation, involves changing the action-outcome association over the course of retraining and determines whether reward seeking is sensitive to changing contingencies. We hypothesized that the outcome of the contingency-degradation test would remain consistent across reinforcers, while the satiety-specific devaluation test may vary across reinforcers because it depends on the ability of the reinforcer to induce satiety. Therefore, we trained rats to self-administer 1.5% sucrose, 10% sucrose, 10% ethanol, or 10 mM monosodium glutamate (MSG) on a fixed-ratio (FR5) schedule that has been shown to promote long-term, goal-directed responding. Next, behavioral flexibility was evaluated in three satiety-specific devaluation tests over 6 weeks. Finally, we investigated reward seeking after contingency-degradation training. All groups displayed sensitivity to satiety-specific devaluation in the first test, indicating goal-directed behavior. While the 10% sucrose and ethanol groups remained goal-directed, the 1.5% sucrose and MSG groups exhibited habit-like behavior in later tests. Nevertheless, all groups displayed decreased responding in an extinction session after contingency-degradation training, indicating goal-directed behavior. These results demonstrate that tests of behavioral flexibility can yield dissimilar results in the same rats. Next, rats from the 1.5% sucrose group underwent the entire experiment again, now self-administering 10% sucrose. These rats showed pronounced goal-directed behavior in satiety-specific and contingency-degradation tests under 10% sucrose conditions, further suggesting that the reinforcer solution affected the outcome of the satiety-specific devaluation test. We conclude that reinforcer characteristics should be considered when investigating habit-like behavior in alcohol research.

Comparison of two benzodiazepines used for sedation of children undergoing suturing of a laceration in an emergency department.

OBJECTIVES: (1) To determine if oral diazepam (POD) is as effective in sedating children less than 6 years of age for laceration repair as oral midazolam (POM) or intranasal midazolam (INM); and (2) To determine if patients stayed longer in the department after sedation when given POD for sedation. DESIGN/METHODS: Block-randomized, single-blind trial. SETTING: Tertiary pediatric emergency department. PARTICIPANTS: Patients 1 to 5 years old with a laceration requiring sutures were enrolled. INTERVENTIONS: All patients had topical anesthetic applied to the wound and were randomly assigned to POD 0.5 mg/kg, POM 1.0 mg/kg, or INM 0.4 mg/kg for sedation. RESULTS: One hundred twenty-nine patients were enrolled, 42 POD, 45 POM, and 42 INM. Each group was similar at baseline for age, heart rate, respiratory rate, blood pressure, oxygen saturation, previous laceration or sedation, anxiety score, and site of laceration. POM and POD were better tolerated than INM (P = 0.05 and 0.034), respectively. Time to sedation was significantly longer in POD (31.0 +/- 9 min) than INM (26.1 +/- 9 min) (P = 0.011) but there was no significant difference when comparing the other groups. However, this difference was not clinically significant. POD was significantly worse at sedating children compared with POM and INM on all four scores (ie, doctor, nurse, parent, and investigator), but INM and POM were equivalent. Total time in the department was no different between POM and INM or POM and POD, but was significantly different for POD (53.9 +/- 16 min) and INM (48 +/- 12 min); however, this difference was minimal. More patients were said to be drowsy at home in the POM group (51%) than the POD group (32%). CONCLUSIONS: The oral route of delivery of POM and POD was better tolerated than INM. POM and INM were more effective at sedation than POD, but there was no clinical difference between any groups for time to sedation or time to discharge. More patients in the POM group had side effects after leaving the department. POD may be an alternative to POM, but a higher dose may be required, possibly with longer recovery times.

Paediatric sedation in emergency department: what is our practice?

OBJECTIVES: The aim of the present study was to document the use of sedation in paediatric patients in emergency departments within Australia and New Zealand. METHODS: A questionnaire was sent to 54 emergency departments throughout Australia and New Zealand. RESULTS: A total of 45 departments (83%) responded to the survey. Because the adult departments (n 5) reported few paediatric attendances, they were not included in the analysis. Thirty-nine of 40 departments (97.50%) reported using sedation in children. Midazolam was used most frequently (77%) for sedation. There was marked variation in the route of delivery and the dose of midazolam used. Ketamine was reported as the most efficacious agent used, but it was used only in 12% of cases. Formal guidelines existed in all paediatric departments but only in 58% of mixed departments, and formal discharge criteria were used in only 52% of all departments. The use of topical anaesthesia in wound closure was reported in only 3,000 of departments. CONCLUSIONS: There exists wide variation in practice regarding the use of sedation in children in emergency departments throughout Australia and New Zealand. Thus, the development of adequate guidelines, including discharge instructions and the use of topical agents, will improve sedation for children.