Electrophysiological effects and clinical utility of propafenone in children

Aim: This retrospective case series study sought to describe the safety and clinical effectiveness of propafenone for the control of arrhythmias in children with and without CHD or cardiomyopathy. Methods: We reviewed baseline characteristics and subsequent outcomes in a group of 63 children treated with propafenone at 2 sites over a 15-year period Therapy was considered effective if no clinically apparent breakthrough episodes of arrhythmias were noted on the medication. Results: Sixty-three patients (29 males) were initiated on propafenone at a median age of 2.3 years. CHD or cardiomyopathy was noted in 21/63 (33%). There were no significant differences between demographics, clinical backgrounds, antiarrhythmic details, side effect profiles, and outcomes between children with normal hearts and children with CHD or cardiomyopathy. Cardiac depression at the initiation of propafenone was more common amongst children with CHD or cardiomyopathy compared to children with normal hearts. Systemic ventricular function was diminished in 15/63 patients (24%) prior to starting propafenone and improved in 8/15 (53%) of patients once better rhythm control was achieved. Other than one child in whom medication was stopped due to gastroesophageal reflux, no other child experienced significant systemic or cardiac side effects during treatment with propafenone. Propafenone achieved nearly equal success in controlling arrhythmias in both children with normal hearts and children with congenital heart disease or cardiomyopathy (90% versus 86%, p = 0.88). Conclusion: Propafenone is a safe and effective antiarrhythmic medication in children.

Cardiac depression in severe acute pancreatitis: development mechanisms and possible treatment approaches. Review

Cardiac depression, also known as myocardial depression, is one of the typical complications of severe acute pancreatitis. The review describes modern views on the mechanism of development of this phenomenon; the place of the term myocardial depression factor at the current stage of study of the problem was discussed; pathogenetic factors of myocardial depression requiring further study have been identified. An attempt to consider cardiac depression as a phenomenon involving the whole cardiovascular system, rather than the heart along, was made. Each pathophysiological factor is examined in terms of the possibility of clinical use.

Abstract 13050: Acute Alcohol-Induced Enhanced Cardiac Depression in a Canine Model of Chronic Alcohol Consumption: Adverse Effects on Left Ventricle and Myocyte Contraction, [Ca 2+ ] i Transient and Ca 2+ Current

Background: Acute alcohol ingestion produces transient RAS activation. Alcoholics have an enhanced RAS activation after acute ethanol ingestion. Thus, chronic alcohol users may have enhanced cardiac functional responses to acute alcohol intake. However, it is unclear whether and how chronic alcohol intake alters cardiac response to acute alcohol exposure. We tested the hypothesis that acute alcohol may exacerbate cardiac depression and [Ca 2- ] i dysregulation, thus play important role in development of irreversible cardiomyopathy in alcoholics. Methods: We compared LV and cardiomyocyte response to acute alcohol in 6 chronically-instrumented conscious dogs before and 6 months after the once daily ingestion of alcohol (400 ml, 22% providing 33% of total daily caloric intake). Results: In conscious dogs, 6 months of alcohol significantly decreased LV contractility by 48% measured by the slopes of pressure-volume relations (E ES , 48%, 4.4 vs 8.4 mmHg/ml and M SW , 50.8 vs 98.6 mmHg) and increased the time constant of relaxation (τ, 78%, 47.8 vs 26.9 ms). In the alcoholic animals, when compared with the same animals prior to alcohol, acute alcohol (0.2 g/kg, iv, plasma level 62.3 ± 8 mg/dL) caused a greater decrease in LV contractility (47% vs 23%) and increase in τ (27% vs11%). In isolated myocytes, abrupt exposure to alcohol (250 mM) produced significant decreases in cell contraction, [Ca 2+ ] i transient ([Ca 2+ ] i ) and Ca 2+ current (I Ca,L ) in both normal and alcoholic myocytes. However, compared with the isolated cells obtained from LV biopsied tissues of the same animals prior to alcohol, the acute alcohol-induced decrease in I Ca,L (alcoholic: 50%, 1.3 vs 2.6; normal: 29%, 4.0 vs 5.6 pA/pF) was much greater in the alcoholic myocytes, the resulting reductions in the cell contractility, dL/dtmax (alcoholic: 46%, 36vs67; normal: 24%, 82vs108 μm/s), the percent shortening (49% vs 24%) and relengthening, dR/dtmax were doubled. Conclusion: In chronically alcohol-fed dogs, acute alcohol produces increased direct inhibition in LV and myocyte contractility, relaxation and exacerbates [Ca 2+ ] i hemostasis. The chronic alcohol-induced increased cardiac sensitivity to acute alcohol may play an important role in the functional impairment in alcoholic cardiomyopathy.

Abstract 16297: Persistent and Delayed Depression Predict All-cause Unplanned Rehospitalisations Following Acute Myocardial Infarction

Introduction: Depression following acute myocardial infarction (AMI) is a risk factor for future events and mortality. The aim of this study was to explore the post-AMI trajectory of depression as a risk factor for all-cause unplanned rehospitalisations. Methods: A total of 118 adults (101 men; mean±SD age = 64.76±11.16 years) completed the Cardiac Depression Scale (CDS) during and one month following AMI admission. On the basis of their CDS scores during index admission and 30 days post-AMI (≥ 95 = probable major depression) patients were categorized as having chronic; absent; recovered; or delayed depression. All-cause, unplanned rehospitalisations were sourced from electronic hospital databases (Cerner and TrakCare) from the time of the enrolment admission to census (11 th Dec 2019). Time in the study ranged from 61 days to 4.8 years. Results: A total of 41% of the sample (n = 48) had ≥ 1 all-cause unplanned rehospitalisation following their index AMI admission. Kaplan Meier Survival analyses revealed that worsening or persistent depression trajectories had earlier unplanned rehospitalisations (p < .05). Pairwise Log Rank tests showed that patients with delayed depression had significantly less time to their first all-cause unplanned rehospitalisation compared to those with absent or recovered depression (p < .05). Patients with chronic depression had significantly earlier unplanned rehospitalisations than those with recovered depression (p < .05). Cox Regression analyses revealed that chronic (HR = 9.62109 [95% CI 2.53, 36.62] and delayed depression (HR = 2.94 [95% CI 1.08, 7.97] significantly increased the risk of all-cause unplanned rehospitalisations, after adjusting for time in the study, demographic factors, illness severity, heart disease knowledge, state anxiety and psychological resilience. Conclusions: Persistent or delayed trajectories of depression from admission to 30 days following AMI independently increases the risk of all-cause unplanned hospital readmissions. Patients should be screened for depression during AMI admission and throughout the early adjustment period (2-3 months post-AMI). Further research to increase capacity to predict post-AMI depression trajectories is warranted.

Pharmacological Restoration of mOod in HEART Failure: outcomes of the PRO-HEART trial

Background Depression is common in chronic heart failure (CHF) patients and is associated with increased morbidity and mortality. Anti-depressant medication has shown benefits in coronary artery disease but efficacy has not been demonstrated in CHF patients. Purpose To assess whether escitalopram is more effective than placebo in treating major and/or minor depression in patients with CHF. Methods This was a randomized, placebo-controlled, double-blind, parallel group study. Adult patients with systolic CHF (NYHA Class ≥2, nadir LVEF &lt;40%) were screened for depression using the Cardiac Depression Scale (CDS) for a score ≥95 (sensitivity 97% at 85% specificity for major Depression (MDD)) followed by a clinical diagnosis of major or minor depression using the SCID interview. Patients were randomised to active escitalopram or matching placebo for 6 months, stratified for major or minor depression. Blinded therapy started with 5mg with automatic uptitration to 10mg after 2 weeks and further uptitration to 20mg at 2 months if CDS score remained ≥95. The primary end-point was change in CDS score over 6 months with secondary end-point change in Hamilton Depression Rating Scale (HAM-D). Results Of 28 CHF patients (males = 25; mean age = 63.61±10.32), mean CHF diagnosis 5.8 years, ischaemic aetiology (n=18), entry LVEF 42.2±9.6%; eGFR 61.8±15.4, 14 were diagnosed with major and 14 with minor depression. Two-way Mixed Model ANOVA showed a significant improvement from baseline to 6 months in both CDS (F(1,25)=18.76, p&lt;0.001) and HAM-D (F(1,25)=17.32, p&lt;0.001), but no significant interaction between condition and change over time. Three-way Mixed Model ANOVA showed no interaction between baseline depression diagnosis (Major or Minor) and response to treatment by condition. There were 7 SAEs for hospitalisation, unrelated to study medications and no differences between groups on AE/SAEs. Conclusions Patients showed a significant improvement in depression with both placebo and active drug but with no benefit of escitalopram over placebo. This suggests that there is no additional benefit from antidepressant therapy for CHF patients beyond that conferred by placebo. Further research is needed to explore whether greater benefits might be achieved by combination therapies or in particular subgroups of depressed CHF patients. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation of Australia, Beyond Blue

Mechanism and Development of Modern General Anesthetics

Background: Before October 1846, surgery and pain were synonymous but not thereafter. Conquering pain must be one of the very few strategies that has potentially affected every human being in the world of all milestones in medicine. Methods: This review article describes how various general anesthetics were discovered historically and how they work in the brain to induce sedative, hypnosis and immobility. Their advantages and disadvantages will also be discussed. Results: Anesthesia is a relatively young field but is rapidly evolving. Currently used general anesthetics are almost invariably effective, but nagging side effects, both short (e.g., cardiac depression) and long (e.g., neurotoxicity) term, have reawakened the call for new drugs. Conclusion: Based on the deepening understanding of historical development and molecular targets and actions of modern anesthetics, novel general anesthetics are being investigated as potentially improved sedative-hypnotics or a key to understand the mechanism of anesthesia.

2204Predicting the trajectory of depression following an acute coronary syndrome: the role of resilience

Background Depression is common in patients following an Acute Coronary Syndrome (ACS) substantially increases the risk of future events and mortality. Post-ACS depression typically resembles one of four longitudinal trajectories: chronic; absent; recovered, or delayed depression. Early identification of a patient's post-ACS depression trajectory will improve risk stratification, treatment implementation and risk management. Purpose To explore whether stable psychosocial traits, such as resilience, predict the trajectory of depression one month and 6 months following an ACS admission. Method Consecutive adult ACS patients (STEMI/NSTEMI) admitted to a large general hospital completed the Cardiac Depression Scale (CDS) and the Sense of Coherence scale during their admission, then one and six months following discharge. Results 132 ACS in-patients (males = 111; mean age = 63.13±13.47) satisfied enrolment criteria. Unconditional linear latent growth modelling identified a 3-class model for the trajectory of depression post-ACS (increasing depression; consistent non-depressed; decreasing non-depressed). For the increasing depression class, resilience at baseline was significant and negative compared to the consistent class, b=−0.06, Wald chi square (1) = 4.42, p=0.036 and the decreasing class, b=−0.09, Wald chi square (1) = 7.20, p=0.007. Conclusions Patients who reported lower levels of resilience during an ACS admission were significantly more likely to experience initially high levels of depressive symptoms (CDS ≥85) that exceeded the clinically relevant cut-off (CDS ≥95) at 6 months post-discharge. This study suggests that screening for resilience and depression will improve risk stratification for persistent and delayed depression post-ACS.