Global Metabolomic Profiling of Acute Myocarditis Caused by Trypanosoma cruzi Infection

© 2014 Gironès et al. Chagas disease is caused by Trypanosoma cruzi infection, being cardiomyopathy the more frequent manifestation. New chemotherapeutic drugs are needed but there are no good biomarkers for monitoring treatment efficacy. There is growing evidence linking immune response and metabolism in inflammatory processes and specifically in Chagas disease. Thus, some metabolites are able to enhance and/or inhibit the immune response. Metabolite levels found in the host during an ongoing infection could provide valuable information on the pathogenesis and/or identify deregulated metabolic pathway that can be potential candidates for treatment and being potential specific biomarkers of the disease. To gain more insight into those aspects in Chagas disease, we performed an unprecedented metabolomic analysis in heart and plasma of mice infected with T. cruzi. Many metabolic pathways were profoundly affected by T. cruzi infection, such as glucose uptake, sorbitol pathway, fatty acid and phospholipid synthesis that were increased in heart tissue but decreased in plasma. Tricarboxylic acid cycle was decreased in heart tissue and plasma whereas reactive oxygen species production and uric acid formation were also deeply increased in infected hearts suggesting a stressful condition in the heart. While specific metabolites allantoin, kynurenine and p-cresol sulfate, resulting from nucleotide, tryptophan and phenylalanine/tyrosine metabolism, respectively, were increased in heart tissue and also in plasma. These results provide new valuable information on the pathogenesis of acute Chagas disease, unravel several new metabolic pathways susceptible of clinical management and identify metabolites useful as potential specific biomarkers for monitoring treatment and clinical severity in patients.This work was supported by ‘‘Ministerio de Ciencia e Innovación’’ (SAF2010-17833); ‘‘Fondo de Investigaciones Sanitarias’’ (PS09/00538 and PI12/00289); ‘‘Red de Investigación de Centros de Enfermedades Tropicales’’ (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet);‘‘Universidad Autónoma de Madrid’’ and ‘‘Comunidad de Madrid’’ (CC08-UAM/SAL-4440/08); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD-2332) and ‘‘Fundación Ramón Areces’Peer Reviewe

Why Does Exercise “Triggerâ€? Adaptive Protective Responses in the Heart?

Numerous epidemiological studies suggest that individuals who exercise have decreased cardiac morbidity and mortality. Pre-clinical studies in animal models also find clear cardioprotective phenotypes in animals that exercise, specifically characterized by lower myocardial infarction and arrhythmia. Despite the clear benefits, the underlying cellular and molecular mechanisms that are responsible for exercise preconditioning are not fully understood. In particular, the adaptive signaling events that occur during exercise to “trigger� cardioprotection represent emerging paradigms. In this review, we discuss recent studies that have identified several different factors that appear to initiate exercise preconditioning. We summarize the evidence for and against specific cellular factors in triggering exercise adaptations and identify areas for future study

Abstract 267: Use of Real-time Feedback to Improve Outcomes for In-Hospital Cardiac Arrest: One Center’s Experience

Background: In a 2013 consensus statement, the American Heart Association encouraged the use of real-time feedback during cardiopulmonary resuscitation (CPR) as a recommended best practice for in-hospital cardiac arrest (IHCA). Recent evidence suggests that the use of real-time feedback may lead to improvements in CPR quality in this setting; however there is a paucity of data on its widespread use and effect on outcomes. Methods: In a single-center retrospective cohort study, we reviewed IHCA event and outcome data from an institutional registry between June 2011 and October 2015. Charts were reviewed to retrieve missing data. Data on CPR-sensing defibrillator (Philips MRx) usage was obtained by direct download from defibrillators. Chi square and fisher exact tests were used for analysis. Results: We captured 220 reported episodes of IHCA for analysis. CPR-sensing defibrillators were used in only 17 cases (or 7.7% of total events). Return of spontaneous circulation (ROSC) was achieved in 60% of cases. Pulseless electrical activity (PEA) and asystole were the most commonly reported initial rhythm (78.2%), followed by ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) (14.1%) and undocumented cases (7.7%). There was no difference in rates of ROSC or sustained ROSC &gt;20 minutes (p=0.38) based on initial rhythm. Survival to discharge and at 1 year was significantly higher in the VF/pulseless VT group than in the PEA/asystole group (46% vs. 14%, p&lt;0.0001, and 30.4% vs. 5.8%, p=0.0007, respectively). Use of real-time feedback during CPR was not associated with any improvement in the rates of ROSC (p=0.67), survival to discharge (p=0.58) or survival at 1 year (p=0.19). Conclusions: CPR-sensing defibrillators for real-time feedback were used only in a small minority of cases and were not associated with any improvement in outcomes. Sustained efforts are needed; larger and adequately powered studies may provide clinically relevant information regarding the utility of CPR-sensing defibrillators. </jats:p

Melatonin for blood pressure control in adults

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Critical objective To assess the effects of oral melatonin supplementation (immediate‑release (IR) and controlled‑/sustained‑release CR/SR; any dose; ≥ 1 week) versus placebo or no treatment on change in systolic and diastolic blood pressure (SBP, DBP) in adults. Important objectives To examine dose‑response relationships between melatonin dose and changes in SBP and DBP. To assess effects by key participant and intervention characteristics (prespecified subgroups): baseline blood pressure status; concomitant antihypertensive medication use; presence of diagnosed sleep disorder/insomnia; melatonin formulation (IR versus CR/SR); blood pressure measurement method (office versus ambulatory versus home; daytime versus nocturnal); age (\u3c 65 versus ≥ 65 years); sex. To evaluate adverse events (serious and non‑serious) and select patient‑important outcomes (quality of life, sleep quality). To describe any reported longer‑term cardiovascular outcomes (e.g. incident cardiovascular disease events, mortality) when sufficient data are available. These analyses are exploratory given anticipated sparse data

Abstract 16831: Effect of a Virtual Cardiac Rehabilitation Program on Functional Capacity and Risk Factor Modification in Veterans With Ischemic Heart Disease

Background: Cardiac rehabilitation (CR) is a comprehensive lifestyle change program proven to reduce cardiovascular disease (CVD) risk and improve quality of life in patients with ischemic heart disease but remains highly underutilized (&lt;20% of eligible patients) due to the inconvenience and cost of attending a facility-based program. We evaluated the efficacy of a home-based, virtual CR program using mobile health (mHealth) in veterans with coronary artery disease (CAD) on improving functional capacity, CVD risk factors, and depressive symptoms. Methods: We enrolled 196 Veterans with a qualifying CR diagnosis between May 2016 and April 2020. All participants underwent baseline functional evaluation with a 6-minute walk test (6MWT), followed by a 12-week home-based, virtual CR program delivered via the Movn smartphone app (Movn by Moving Analytics). The Movn app featured daily alerts to exercise, a digital diary to record activity and vital signs, and connectivity with a health coach who remotely monitored participants through an integrated dashboard and scheduled weekly phone visits. We compared the risk factor profile pre-intervention versus post-intervention with paired t-tests. Results: Among enrolled Veterans, the mean (SD) age was 61 (9) years, 95% were male, and 50% were black. A majority (63%) completed the full 12-week virtual CR program including an exit visit. Participants completed an average of 10.4 ± 1.9 (range 3–13) phone visits with the coach. There were concurrent improvements in 6MWT distance (443.9 vs. 481.9 meters; mean difference [MD], 38 meters; 95% CI, 26.6 – 50.8, P&lt;0.001), low-density lipoprotein cholesterol (80 vs. 69 mg/dL, MD, -10.9; 95% CI, -17.9 to -3.9, P=0.003), body mass index (31.1 vs 30.8; MD, -0.33; 95% CI, -0.60 to -0.06; P=0.001), and PHQ-9 depression scores (7.4 vs. 6; MD, -1.4, 95% CI, -2.4 to -0.44; P=0.005) among program completers. Conclusions: Among veterans with ischemic heart disease, a virtual CR program results in moderate improvements in functional capacity, CVD risk factors, and mood. The durability of these effects and whether virtual CR improves longer-term outcomes such as readmissions, survival, and cost remain to be determined. </jats:p