Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

Aims: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. Methods: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. Results: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). Conclusion: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times

Efficacy of intranasal administration of artesunate in experimental cerebral malaria

BACKGROUND: Improving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. Intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. Intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier. Therefore, it could be helpful and suitable to administer artesunate in the context of cerebral malaria, especially in young children. In this study, intranasal administration of artesunate to rescue from cerebral malaria using a murine model was tested. METHODS: CBA/J mice infected with Plasmodium berghei ANKA strain received artesunate (20 mg/kg) or a placebo solution intranasally, either on day 5, 6 or 7 post-infection, during a controlled, blinded, randomized trial. Primary endpoint was mortality on day 12 post-infection. Secondary endpoints were parasitaemia and clinical stage. Pharmacokinetics data following administration were collected in blood and brains of treated mice. Local toxicity was evaluated by histopathologic examination of brain and nasal sections in blinded manner. RESULTS: Intranasal administration of artesunate dramatically reduced the mortality rate (p < 0.001), preventing death in most cases. Parasitaemia loads decreased by 88.7% (61.8-100%) within 24 hours after administration. Symptoms of cerebral malaria were prevented or reversed. Dihydroartemisinin was detected in mice blood and brain within 15 minutes of intranasal administration. No direct nasal or brain toxicity was detected. CONCLUSION: Intranasal delivery is an efficient route to timely and efficiently administer artesunate and therefore may contribute to decreasing malaria-related mortality

Rivaroxabananddabigatraninpatientsundergoing catheter ablation of atrial fibrillation

Aims: The recent availability of the novel oral anticoagulants (NOACs) may have led to a change in the anticoagulation regimens of patients referred to catheter ablation of atrial fibrillation (AF). Preliminary data exist concerning dabigatran, but information regarding the safety and efficacy of rivaroxaban in this setting is currently scarce. Methods: and results Of the 556 consecutive eligible patients (age 61.0 ± 9.6; 74.6% men; 61.2% paroxysmal AF) undergoing AF catheter ablation in our centre (October 2012 to September 2013) and enroled in a systematic standardized 30-day follow-up period: 192 patients were under vitamin K antagonists (VKAs), 188 under rivaroxaban, and 176 under dabigatran. Peri-procedural mortality and significant systemic or pulmonary thromboembolism (efficacy outcome), as well as bleeding events (safety outcome) during the 30 days following the ablation were evaluated according to anticoagulation regimen. During a 12-month time interval, the use of the NOACs in this population rose from <10 to 70%. Overall, the rate of events was low with no significant differences regarding: thrombo-embolic events in 1.3% (VKA 2.1%; rivaroxaban 1.1%; dabigatran 0.6%; P = 0.410); major bleeding in 2.3% (VKA 4.2%; rivaroxaban 1.6%; dabigatran 1.1%; P = 0.112), and minor bleeding 1.4% (VKA 2.1%; rivaroxaban 1.6%; dabigatran 0.6%; P = 0.464). No fatal events were observed. Conclusion: The use of the NOAC in patients undergoing catheter ablation of AF has rapidly evolved (seven-fold) over 1 year. These preliminary data suggest that rivaroxaban and dabigatran in the setting of catheter ablation of AF are efficient and safe, compared with the traditional VKA

Fragmented QRS complex as a predictor of exercise-related sudden cardiac death

Introduction: Little is known about the association between electrocardiographic abnormalities and exercise-related sudden cardiac death.Therefore, our aim was to identify possible electrocardiographic findings related to exercise-induced sudden cardiac death. Methods and results: The FinGesture study includes 3,989 consecutive sudden cardiac deaths in northern Finland between 1998 and 2012, out of whom a total of 647 subjects had a previously recorded electrocardiography acquired from the archives of Oulu University Hospital. In 276 of these cases the death was witnessed, and the activity at the time of death was either rest or physical exercise (PEj; in 40 {14%} cases sudden cardiac death was exercise-related and in 236 (86%) cases death took place at rest. Fragmented QRS complex in at least two consecutive leads within anterior leads (V1-V3) was more common in the exercise-group compared to rest-group (17 of 40, 43% vs. 51 of 236,22%, P = 0.005). Pathologic Q wave in anterior leads was more common in the PE group (9 of 40,23% vs. 26 of 236,11%; P = 0.044). Median QRS duration was prolonged in the exercise-group compared to the rest-group (100 milliseconds vs. 94 milliseconds, P = 0.047), QTc interval, the prevalence of inverted T-waves, or other electrocardiographic abnormalities did not differ significantly between the two groups. Conclusions: As a conclusion, fragmented QRS complex in the anterior leads is associated with an increased risk of sudden cardiac death during PE.Peer reviewe

Auxetic cardiac patches with tunable mechanical and conductive properties toward treating myocardial infarction

An auxetic conductive cardiac patch (AuxCP) for the treatment of myocardial infarction (MI) is introduced. The auxetic design gives the patch a negative Poisson's ratio, providing it with the ability to conform to the demanding mechanics of the heart. The conductivity allows the patch to interface with electroresponsive tissues such as the heart. Excimer laser microablation is used to micropattern a re-entrant honeycomb (bow-tie) design into a chitosan-polyaniline composite. It is shown that the bow-tie design can produce patches with a wide range in mechanical strength and anisotropy, which can be tuned to match native heart tissue. Further, the auxetic patches are conductive and cytocompatible with murine neonatal cardiomyocytes in vitro. Ex vivo studies demonstrate that the auxetic patches have no detrimental effect on the electrophysiology of both healthy and MI rat hearts and conform better to native heart movements than unpatterned patches of the same material. Finally, the AuxCP applied in a rat MI model results in no detrimental effect on cardiac function and negligible fibrotic response after two weeks in vivo. This approach represents a versatile and robust platform for cardiac biomaterial design and could therefore lead to a promising treatment for MI

Vagus nerve stimulation: State of the art of stimulation and recording strategies to address autonomic function neuromodulation

International audienceObjective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans

Cardiac Screening of Young Athletes: a Practical Approach to Sudden Cardiac Death Prevention.

PURPOSE OF REVIEW: We aim to report on the current status of cardiovascular screening of athletes worldwide and review the up-to-date evidence for its efficacy in reducing sudden cardiac death in young athletes. RECENT FINDINGS: A large proportion of sudden cardiac death in young individuals and athletes occurs during rest with sudden arrhythmic death syndrome being recognised as the leading cause. The international recommendations for ECG interpretation have reduced the false-positive ECG rate to 3% and reduced the cost of screening by 25% without compromising the sensitivity to identify serious disease. There are some quality control issues that have been recently identified including the necessity for further training to guide physicians involved in screening young athletes. Improvements in our understanding of young sudden cardiac death and ECG interpretation guideline modification to further differentiate physiological ECG patterns from those that may represent underlying disease have significantly improved the efficacy of screening to levels that may make screening more attractive and feasible to sporting organisations as a complementary strategy to increased availability of automated external defibrillators to reduce the overall burden of young sudden cardiac death

Cardiac troponin T is necessary for normal development in the embryonic chick heart

The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula