Sarah J. Gutman

Heart failure with preserved ejection fraction is a complex and increasingly prevalent condition often associated with metabolic comorbidities such as obesity, diabetes, and hypertension. Although its burden is substantial, therapeutic progress has lagged compared with heart failure with reduced ejection fraction. GLP-1RAs (glucagon-like peptide-1 receptor agonists), initially developed for glycemic control in type 2 diabetes, have emerged as promising therapeutic agents for the obese/cardiometabolic heart failure with preserved ejection fraction phenotype. Recent trials, including STEP-HFpEF and SUMMIT, have demonstrated improvements in symptoms, quality of life, and reductions in heart failure events. Beyond inducing substantial weight loss, GLP-1RAs exert a range of metabolic, cardiovascular, and anti-inflammatory effects. In this review, we summarize weight-dependent and weight-independent actions of GLP-1RAs and outline how these mechanisms may influence cardiovascular physiology, myocardial remodeling, cardiac metabolism, renal sodium handling, and systemic inflammation in heart failure with preserved ejection fraction.

Background: The relationship between left ventricular wall stress (LVWS) and cardiac remodelling post structural intervention has not previously been examined. We examined the relationship between LVWS and cardiac remodelling 6 months post transcatheter aortic valve replacement (TAVR) and MitraClip (MC). Methods: LVWS was calculated in 40 patients with severe aortic stenosis (AS) and 11 patients with severe mitral regurgitation (MR) immediately preintervention and postintervention with TAVR or MC. LVWS was calculated by integrating invasive haemodynamic data with cardiac MR (CMR)-derived measures of left ventricular (LV) volume and mass. Patients underwent a 6 min walk test (6MWT), transthoracic echocardiogram and CMR preprocedure and 6 months postprocedure. Results: Both TAVR and MC resulted in significant improvements in functional capacity and cardiac remodelling with no significant difference in the degree of LV mass or volume reduction between the two groups. Linear regression analysis showed that baseline diastolic LVWS (D-LVWS) in the MC cohort and baseline systolic LVWS (S-LVWS) in the TAVR cohort were predictors of larger LV end-diastolic volumes (EDV) and lower ejection fractions (EF) at follow-up (in the MC cohort: B=7.86, p=0.015 for EDV, B=−1.4, p=0.02 for EF; in the TAVR cohort: B=1.53, p=0.04 for EDV and B=−0.702, p<0.001 for EF). Conclusions: Higher baseline D-LVWS in patients undergoing MC, and higher baseline S-LVWS in patients undergoing TAVR, were predictors of poorer EF and larger LV volumes at follow-up. These findings suggest that LVWS may be used to predict the degree of LV recovery postprocedure and suggest that intervening below a certain LVWS threshold may lead to better outcomes with regards to cardiac remodelling. Condensed LVWS was calculated in patients with AS and mitral regurgitation (MR) pre and immediately post valve intervention with TAVR or MC. The patients were followed up at 6 months with 6MWT, echocardiography and CMR imaging Both cohorts demonstrated significant functional improvements and cardiac remodelling postprocedure. Baseline D-LVWS in MC and baseline S-LVWS in TAVR were predictors of poorer EF and larger LV volumes at follow-up. This suggests that in patients with severe AS or MR, baseline LVWS may be useful to predict degree of recovery postintervention or determine need for early intervention.

Objective: Significant gender disparities exist in some medical specialties, particularly cardiology. We assessed work, personal life and work-life balance in women in cardiology in Australia and New Zealand (NZ), compared with other specialties, to determine factors that may contribute to the lack of women in the specialty. Methods: This study is a prospective survey-based cohort study comparing cardiology and non-cardiology specialties. An online survey was completed by female doctors in Australia and NZ, recruited via email lists and relevant social media groups. The survey included demographics, specialty, stage of training, work hours/setting, children and relationships, career satisfaction, income and perceptions of specialty. Results: 452 participants completed the survey (median age 36 years), of which 57 (13%) worked in cardiology. Of all respondents, 84% were partnered and 75% had children, with no difference between cardiology and non-cardiology specialties. Compared with non-cardiology specialties, women in cardiology worked more hours per week (median 50 hours vs 40 hours, p<0.001), were more likely to be on call more than once per week (33% vs 12%, p$3 00 000 (35% vs 10%, p<0.001). Women in cardiology were less likely to agree that they led a balanced life (33% vs 51%, p=0.03) or that their specialty was female friendly (19% vs 75%, p<0.001) or family friendly (20% vs 63%, p<0.001). Conclusions: Compared with other specialties, women in cardiology reported poorer work-life balance, greater hours worked and on-call commitments and were less likely to perceive their specialty as female friendly or family friendly. Addressing work-life balance may attract and retain more women in cardiology.

Objective This study was aimed to evaluate opioid use after cesarean delivery (CD) and to assess implementation of an enhanced recovery after CD (ERAS-CD) pathway and its association with inpatient and postdischarge pain control and opioid use. Study Design We conducted a baseline survey of women who underwent CD from January to March 2017 at a single, urban academic hospital. Patients were called 5 to 8 days after discharge and asked about their pain and postdischarge opioid use. An ERAS-CD pathway was implemented as a quality improvement initiative, including use of nonopioid analgesia and standardization of opioid discharge prescriptions to ≤25 tablets of oxycodone of 5 mg. From November to January 2019, a postimplementation survey was conducted to assess the association between this initiative and patients' pain control and postoperative opioid use, both inpatient and postdischarge. Results Data were obtained from 152 women preimplementation (PRE) and 137 women post-implementation (POST); complete survey data were obtained from 102 women PRE and 98 women POST. The median inpatient morphine milligram equivalents consumed per patient decreased significantly from 141 [range: 90–195] PRE to 114 [range: 45–168] POST (p = 0.002). On a 0- to 10-point scale, median patient-reported pain scores at discharge decreased significantly (PRE: 7 [range: 5–8] vs. POST 5 [range: 3–7], p < 0.001). The median number of pills consumed after discharge also decreased significantly (PRE: 25 [range: 16–30] vs. POST 17.5 [range: 4–25], p = 0.001). The number of pills consumed was significantly associated with number prescribed (p < 0.001). The median number of leftover pills and number of refills did not significantly differ between groups. Median patient-reported pain scores at the week after discharge were lower in the POST group (PRE: 4 [range: 2–6] vs. POST 3[range: 1–5], p = 0.03). Conclusion Implementing an ERAS-CD pathway was associated with a significant decrease in inpatient and postdischarge opioid consumption while improving pain control. Our data suggest that even fewer pills could be prescribed for some patients. Key Points

The World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD. In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2–8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0–4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65–7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not standardised. Latent RHD has a slow rate of progression but it is significantly higher compared to controls, with definite latent RHD having a higher rate of progression compared with borderline latent disease. There are a massive number of individuals at risk for RHD in the developing world as well as logistical challenges of screening and delivering penicillin prophylaxis. The low rate of progression from untargeted screening may be an important consideration in resource-constrained environments.

Aims This study aims to determine if traditional markers of disadvantage [female sex, low socio‐economic status (SES), and remoteness] are associated with lower prescription of evidence‐based therapy and higher mortality among patients with moderate–severe heart failure with reduced ejection fraction. Methods and results We recruited 452 consecutive class II–III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence‐based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow‐up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74–1.92, 0.48). There was no difference in prescription of beta‐blockers [χ²(1) = 0.91, 0.66], angiotensin‐converting enzyme inhibitors [χ²(1) = 0.001, 0.97], nor aldosterone antagonists [χ²(1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter‐defibrillator implantation in men compared with women [χ²(1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit. Conclusions In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents.

Background: The effects of empagliflozin on cardiac structure and function are not known.Aims: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with type 2 (T2D) diabetes using cardiac magnetic resonance (CMR) imaging.Methods: Twenty patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patients with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent CMR scans at baseline and 6 months. Inclusion criteria were established T2D, age < 75 years, estimated glomerular filtration rate ≥45 mL/min/1.73 m².Results: 17 of 20 in the empagliflozin group, and all of 8 in the control group completed the study. Empagliflozin therapy was associated with reduction in left ventricular end diastolic volume 155 mL (137 mL, 174 mL) at baseline to 145 mL (125 mL, 165 mL) at 6 months, P < 0.01, compared with the control group 153 mL (128 mL, 179 mL) at baseline and 158 mL (128 mL, 190 mL), not significant. There were no differences in measures of left ventricular mass, ejection fraction, heart rate or markers of cardiac fibrosis at baseline and 6 months in either group.Conclusions: This is the first CMR study to examine the effects of empagliflozin on cardiac function and structure, showing evidence of reduced end diastolic volume. This is likely to reflect change in plasma volume, and may explain the reduced cardiovascular death and heart failure seen in the EMPA‐REG OUTCOME trial.