Pathophysiological Sex Differences in Heart Failure Progression After Acute Coronary Syndrome: Insights From the EXAMINE Trial.

BACKGROUND: Therapies can reduce the risk of heart failure (HF) development and progression in type 2 diabetes; nevertheless, the risk of these outcomes is greater in females than in males. METHODS AND RESULTS: To investigate sex differences in HF development and progression, we compared baseline circulating proteins (Olink Cardiovascular II panel) in males and females with type 2 diabetes and recent acute coronary syndrome for the outcome of HF hospitalization. Data were from the placebo-controlled Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care (EXAMINE) trial. Pathophysiological sex-differences were interpreted with network and pathway over-representation analyses. The EXAMINE trial enrolled 5380 participants (32.1% females) with biomarker data available for 95.4% of individuals. Analyses revealed 43 biomarkers were differentially expressed in HF hospitalization, of which 18 were sex specific. Among these 43 biomarkers, interleukin-6 was identified as a central node for the pathogenesis of HF hospitalization in both females and in males. Additional pathway over-representation analyses demonstrated that biomarkers associated with inflammatory pathways related to endothelial dysfunction and cardiac fibrosis were more up-regulated in females than males with HF hospitalization. Differential expression of 3 biomarkers (pentraxin-related protein 3, hydroxyacid oxidase 1, and carbonic anhydrase 5A) was independently associated with an increased risk of HF hospitalization in females but not in males (interaction P < .05). CONCLUSIONS: In males and females with type 2 diabetes and acute coronary syndrome, interleukin-6 seems to be central in the pathogenesis of HF. Females exhibit higher levels of circulating proteins related to immunological pathways, reflecting sex-specific differences underlying HF development and progression.

The Cardiovascular Risks Associated with Aromatase Inhibitors, Tamoxifen, and GnRH Agonists in Women with Breast Cancer.

PURPOSE OF REVIEW: Cardiovascular disease accounts for up to 10% of all-cause mortality in women with a diagnosis of breast cancer, and the causes for this are multifaceted. Many women at risk of or with a diagnosis of breast cancer are on endocrine-modulating therapies. It is therefore important to understand the effect of hormone therapies on cardiovascular outcomes in breast cancer patients to mitigate against any adverse effects and to identify those most at risk so that they can be proactively managed. Here we discuss the pathophysiology of these agents, their effect on the cardiovascular system, and the latest evidence on their cardiovascular risks association. RECENT FINDINGS: Tamoxifen appears to be cardioprotective during treatment but not over the longer term, while the effect of AIs on cardiovascular outcomes remains controversial. Heart failure outcomes remain understudied, and the cardiovascular effects of gonadotrophin-releasing hormone agonists (GNRHa) in women need further research, especially since data from men with prostate cancer have indicated an increased risk of cardiac events in GNRHa users. There remains a need for a greater understanding of the effects of hormone therapies on cardiovascular outcomes in breast cancer patients. Further areas of research in this area include developing evidence to better define the optimal preventive and screening methods for cardiovascular effects and the risk factors for patients on hormonal therapies.

A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19.

BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

Bilateral Cardiac Sympathectomy and Extrapericardial Coil Implantation for the Management of Electrical Storm.

We present a novel multidisciplinary approach for the treatment of electrical storm combining bilateral cardiac sympathectomy, extrapericardial coil insertion, and implantable cardioverter defibrillator upgrade in a patient with nonischemic cardiomyopathy and ventricular arrhythmias refractory to conventional therapies. (Level of Difficulty: Advanced.).

Permission to prescribe: do cardiologists need permission to prescribe diabetes medications that afford cardiovascular benefit?

PURPOSE OF REVIEW: Antihyperglycemic therapies including sodium glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) have been demonstrated to confer significant cardiovascular benefit and reduce future events in patients with type 2 diabetes mellitus (T2DM). However, despite positive data from cardiovascular outcome trials, these therapies remain underutilized in a large proportion of patients who have clinical indications and meet coverage guidelines for their initiation. One of the causes of the observed gap between scientific evidence and clinical cardiology practice is therapeutic hesitancy (otherwise known as therapeutic inertia). The purpose of this review is to discuss the contributors to therapeutic hesitancy in the implementation of these evidence-based therapies and, more importantly, provide pragmatic solutions to address these barriers. RECENT FINDINGS: Recent studies have demonstrated that clinicians may not initiate cardiovascular protective therapies due to a reluctance to overstep perceived interdisciplinary boundaries, concerns about causing harm due to medication side effects, and a sense of unfamiliarity with the optimal choice of therapy amidst a rapidly evolving landscape of T2DM therapies. SUMMARY: Herein, we describe a multifaceted approach aimed at creating a 'permission to prescribe' culture, developing integrated multidisciplinary models of care, enhancing trainees' experiences in cardiovascular disease prevention, and utilizing technology to motivate change. Taken together, these interventions should increase the implementation of evidence-based therapies and improve the quality of life and cardiovascular outcomes of individuals with T2DM.

Therapeutic Drug Monitoring Guides the Management of Crohn's Patients with Secondary Loss of Response to Adalimumab.

Background: Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Methods: Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. Results: There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) ≥5µg/ml at index TDM with a median value of 12µg/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Conclusions: Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes. 10.1093/ibd/izy044_video1izy044.video15768828880001.

Outpatient management of pediatric acute mastoiditis.

OBJECTIVE: Evaluate the Montreal Children's Hospital experience with outpatient management of uncomplicated acute mastoiditis with parenteral antibiotic therapy alone and determine if it is a safe alternative to inpatient management. SUBJECTS AND METHOD: A retrospective review of pediatric patients diagnosed with acute mastoiditis at a tertiary care pediatric hospital between 2013 and 2015 was performed. Patients with syndromes, immunodeficiency, cholesteatoma, chronic otitis media, cochlear implant in the affected ear, or incidental mastoid opacity were excluded. RESULTS: 56 children age 6 months to 15 years old were treated for acute mastoiditis, including 29 hospitalizations and 27 outpatients. Patients managed as outpatient with daily intravenous ceftriaxone had a 93% cure rate. Eighteen hospitalized and one outpatient had complications of acute mastoiditis. Children with complications were more likely to be febrile (p = 0.045). Two patients failed outpatient therapy and were admitted; one for myringotomy and piperacillin-tazobactam treatment and one required a mastoidectomy. 4/27 children treated as outpatient underwent myringotomy and tube insertion, 2 underwent myringotomy and tube along with admission and 21 did not require tube insertion. The average total duration of intravenous antibiotic therapy was respectively 4.9 and 18.9 days in the outpatient and hospitalized group. The average duration of admission was 5.9 days. CONCLUSION: Outpatient medical therapy of uncomplicated pediatric mastoiditis is safe, successful, and efficient. Benefits include efficient use of surgical beds, cost savings and patient and family convenience. Careful patient selection and close monitoring are keys for successful outcome.