153 Fragmented QRS in athletes

Aims Fragmented QRS (fQRS), defined as the presence of additional peaks within the QRS complex (<120 ms) in at least two contiguous leads, was considered as a pattern of fibrosis. However, fQRS can also be detected during pre-participation cardiovascular screening. To assess determinants of fQRS in athletes of different sports. Methods and results Retrospective study conducted on 605 non-sedentary subjects undergoing pre-participation cardiovascular screening for competitive activity in six disciplines (athletics, football, cycling, swimming, basketball, and volleyball). All subjects underwent ECG for the search of fQRS and transthoracic echocardiography. Predictors of fQRS were investigated using multivariate logistic analysis adjusted for. fQRS was found in 47 of 605 subjects. On multivariate logistic analysis, fQRS was positively associated with age (OR: 1.03; 95% CI: 1.01–1.05), male sex (OR: 0.35; 95% CI: 0.13–0.94), whereas no association with sport discipline was observed (0.91; 0.73–1.12). When echocardiographic parameters were considered, fQRS was associated with cardiac mass index (OR: 1.02; 95% CI: 1.00–1.03) and E wave (OR: 0.98; 95% CI: 0.96–0.99). Conclusions At pre-participation cardiovascular screening, the fQRS finding increases with age, is more frequent in males, and seems to be independent from practiced sport. Furthermore, fQRS in athletes appears to be associated with parameters of physiological hypertrophy (LV cardiac mass index and diastolic function).

Cardioprotective responses to aerobic exercise-induced physiological hypertrophy in zebrafish heart

Herein, we aimed to establish an aerobic exercise-induced physiological myocardial hypertrophy zebrafish (Danio rerio) model and to explore the underlying molecular mechanism. After 4 weeks of aerobic exercise, the AMR and Ucrit of the zebrafish increased and the hearts were enlarged, with thickened myocardium, an increased number of myofilament attachment points in the Z-line, and increased compaction of mitochondrial cristae. We also found that the mTOR signaling pathway, angiogenesis, mitochondrial fusion, and fission event, and mitochondrial autophagy were associated with the adaptive changes in the heart during training. In addition, the increased mRNA expression of genes related to fatty acid oxidation and antioxidation suggested that the switch of energy metabolism and the maintenance of mitochondrial homeostasis induced cardiac physiological changes. Therefore, the zebrafish heart physiological hypertrophy model constructed in this study can be helpful in investigating the cardioprotective mechanisms in response to aerobic exercise.

LncRNA CPhar Induces Cardiac Physiological Hypertrophy and Promotes Functional Recovery After Myocardial Ischemia-Reperfusion Injury

Background: Exercise training's benefits in cardiovascular system have been well accepted, however, the underlying mechanism remains to be explored. Here, we report the initial functional characterization of an exercise-induced cardiac physiological hypertrophy associated novel lncRNA. Methods: Using lncRNA microarray profiling, we identified lncRNAs in contributing the modulation of exercise-induced cardiac growth that we termed Cardiac Physiological hypertrophy associated regulator (CPhar). Mice with Adeno-associated virus serotype 9 (AAV9) driving CPhar overexpression and knockdown were used in in-vivo experiments. Swim training was used to induce physiological cardiac hypertrophy in mice and ischemia reperfusion injury (IR/I) surgery was conducted to investigate the protective effects of CPhar in mice. To investigate the mechanisms of CPhar's function, we performed various analysis including RTqPCR, western blot, histology, cardiac function (by echocardiography), functional rescue experiments, mass spectrometry, in vitro RNA transcription, RNA pull down, RNA immunoprecipitation, chromatin immunoprecipitation assay, luciferase reporter assay, and coimmunoprecipitation assays. Results: We screened the lncRNAs in contributing the modulation of exercise-induced cardiac growth via lncRNA microarray profiling and found that CPhar was increased with exercise and was necessary for exercise-induced physiological cardiac growth. Gain- and loss- of function of CPhar regulated the expression of proliferation markers, hypertrophy, and apoptosis in cultured neonatal mouse cardiomyocytes (NMCMs). Overexpression of CPhar prevented myocardial ischemia reperfusion injury and cardiac dysfunction in vivo . We identified DDX17 as a binding partner of CPhar in regulating CPhar downstream factor ATF7 by sequestering C/EBPβ. Conclusions: Our study of this lncRNA CPhar provides new insights into the regulation of exercise-induced cardiac physiological growth, demonstrating the cardioprotective role of CPhar in the heart, as well as expanding our mechanistic understanding of lncRNA function.

Cardiac Remodeling During Pregnancy With Metabolic Syndrome

Background: The heart undergoes physiological hypertrophy during pregnancy in healthy individuals. Metabolic syndrome (MetS) is now prevalent in women of child-bearing age and might add risks of adverse cardiovascular events during pregnancy. The present study asks if cardiac remodeling during pregnancy in obese individuals with MetS is abnormal and whether this predisposes them to a higher risk for cardiovascular disorders. Methods: The idea that MetS induces pathological cardiac remodeling during pregnancy was studied in a long-term (15 weeks) Western diet–feeding animal model that recapitulated features of human MetS. Pregnant female mice with Western diet (45% kcal fat)–induced MetS were compared with pregnant and nonpregnant females fed a control diet (10% kcal fat). Results: Pregnant mice fed a Western diet had increased heart mass and exhibited key features of pathological hypertrophy, including fibrosis and upregulation of fetal genes associated with pathological hypertrophy. Hearts from pregnant animals with WD-induced MetS had a distinct gene expression profile that could underlie their pathological remodeling. Concurrently, pregnant female mice with MetS showed more severe cardiac hypertrophy and exacerbated cardiac dysfunction when challenged with angiotensin II/phenylephrine infusion after delivery. Conclusions: These results suggest that preexisting MetS could disrupt physiological hypertrophy during pregnancy to produce pathological cardiac remodeling that could predispose the heart to chronic disorders.

FoxO1 is required for physiological cardiac hypertrophy induced by exercise but not by constitutively active PI3K

The insulin-like growth factor 1 receptor (IGF1R) and phosphoinositide 3-kinase p110a (PI3K) are critical regulators of exercise-induced physiological cardiac hypertrophy, and provide protection in experimental models of pathological remodeling and heart failure. Forkhead box class O1 (FoxO1) is a transcription factor which regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K activation in vitro, but its role in physiological hypertrophy in vivo was unknown. We generated cardiomyocyte-specific FoxO1 knockout (cKO) mice and assessed the phenotype under basal conditions and settings of physiological hypertrophy induced by 1) swim training, or 2) cardiac-specific transgenic expression of constitutively active PI3K (caPI3KTg+). Under basal conditions, male and female cKO mice displayed mild interstitial fibrosis compared with control (CON) littermates, but no other signs of cardiac pathology were present. In response to exercise training, female CON mice displayed an increase (~21%) in heart weight normalized to tibia length vs untrained mice. Exercise-induced hypertrophy was blunted in cKO mice. Exercise increased cardiac Akt phosphorylation and IGF1R expression, but was comparable between genotypes. However, differences in Foxo3a, Hsp70 and autophagy markers were identified in hearts of exercised cKO mice. Deletion of FoxO1 did not reduce cardiac hypertrophy in male or female caPI3KTg+ mice. Cardiac Akt and FoxO1 protein expression were significantly reduced in hearts of caPI3KTg+ mice, which may represent a negative feedback mechanism from chronic caPI3K, and negate any further effect of reducing FoxO1 in the cKO. In summary, FoxO1 contributes to exercise-induced hypertrophy. This has important implications when considering FoxO1 as a target for treating the diseased heart.

Abstract 14620: LncExACT1 Acts as a Pivotal Switch Between Physiological and Pathological Cardiac Growth

Rationale: Pathological hypertrophy commonly leads to heart failure (HF) and loss of cardiomyocytes, while physiological hypertrophy protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain unclear. While long noncoding RNAs (lncRNAs) are important in cardiac development and disease, their role in physiological hypertrophy is unknown. Objective: To investigate the role of lncRNAs in physiological hypertrophy. Methods and Results: Mice underwent voluntary wheel running for eight weeks or transverse aortic constriction (TAC) for two or ten weeks. RNAseq identified a novel set of lncRNAs altered in exercised hearts, which we termed l ong n on c oding Ex ercise- A ssociated C ardiac T ranscripts (lncExACTs). lncExACT1 was highly conserved and uniquely downregulated in exercised hearts but upregulated in pathological animal models and hearts from HF patients vs controls (1.8-fold; p <0.001, N=24) as well as plasma from HF patients with reduced (2.9-fold; p =0.032, N=16) and preserved ejection fraction (3.4-fold; p =0.006, N=18). In mice, AAV9 lncExACT1 overexpression increased cardiac lncExACT1 7-fold at 16 weeks and increased heart (HW) and lung (LW) weight relative to tibial length (TL), reduced fractional shortening (FS) and increased relative wall thickness (RWT) ( p <0.05 for all). These changes were associated with a pathological gene expression pattern. In contrast, antisense lncExACT1 inhibition reduced cardiac expression 2-fold at 2 weeks and increased HW/TL without an increase in LW/TL, improved cardiac function, and increased RWT ( p <0.05 for all). LncExACT1 inhibition induced a physiological gene expression pattern and increased markers of cardiomyogenesis. LncExACT1 inhibition reduced TAC-induced HW/TL and fibrosis, while increasing FS ( p <0.05 for all). Mechanistic studies revealed that lncExACT1 works by binding miR-222 and as a novel regulator of Hippo/Yap1 signaling through modulation of dachsous cadherin-related 2. Conclusions: lncExACT1 acts as a master switch toggling the heart between physiological and pathological growth and provides a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.

Bilateral Breast Abscess in a Newborn Baby

Background: In this study we wish to attract attention to mistaken interventions to the breast tissue of neonates and to increase awareness about this topic among personnel providing health services to neonates. Case presentation: A fourteen-day male infant was brought to the pediatric emergency clinic with swelling, redness, hardness and discharge complaints in the region of both breasts. Ultrasonography of the breast tissue of the patient identified appearance compatible with a dense-content abscess in the form of hyperechoic or hypoechoic avascular mass. Bilateral breast abscess responded to surgical and medical treatment. Conclusions: It is important to recognize physiological breast hypertrophy in newborns. In physiological hypertrophy, the breast bud is neither red nor soft and heals spontaneously. No intervention is required.

P4429Cardiac magnetic resonance characteristics of professional athletes and hypertrophic cardiomyopathy patients in the grey zone of hypertrophy

Differentiation between athlete's heart and hypertrophic cardiomyopathy (HCM) may cause difficulties especially in patients in the grey zone of hypertrophy. We aimed to determine conventional cardiac magnetic resonance (CMR) parameters such as left ventricular (LV) ejection fraction (EF), BSA-corrected end-diastolic (EDVi), end-systolic and stroke volume (SVi), mass (Mi), derived CMR parameters such as maximal end-diastolic wall thickness to LVEDVi ratio (EDWT/LVEDVi), LVM to LVEDV ratio (LVM/LVEDV), and CMR based strain values (global longitudinal (GLS), radial (GRS) and circumferential strain (GCS)) in male HCM patients and athletes. We consecutively enrolled male HCM patients with only slightly elevated EDWT (13–18 mm) and highly trained healthy athletes (n=30, 18.7±1.2 training hrs/week) with marked LV hypertrophy. HCM patient group was divided into sedentary (n=30, <7 training hrs/week) and athletic HCM group (n=10; >7 h/week, 12.7±7.3 h training hrs/week). Both sedentary and athletic HCM patients showed higher LVEF, lower LVEDVi and LVESVi and higher EDWT compared to the healthy athletes. LVMi of both healthy athletes and athletic HCM patients was significantly higher than in sedentary HCM patients, respectively (98.9±11.4; 94.5±7.8 vs 78.1±14.4 /m2). EDWT/LVEDVi ratio was higher in both sedentary and athletic HCM patients compared to healthy athletes, respectively (0.19±0.04; 0.17±0.04 vs 0.11±0.02). LVM/LVEDV also showed significant difference between HCM patients and healthy athletes. GLS and GRS showed no significant difference between the three groups, GCS was higher in athletic HCM compared to healthy athletes (−20.7±2.2 vs −17.8±2.3%). Figure 1. Feature tracking analysis of a healthy athlete and a patient with HCM. CMR characteristics of athletic and sedentary HCM may fundamentally alter. Our preliminary data suggest that besides conventional CMR parameters, derived parameters such as EDWT/LVEDVi and LVM/LVEDV ratios and deformation imaging may also help the differentiation between pathological and physiological hypertrophy. Acknowledgement/Funding National Research, Development and Innovation Office (NKFIH) of Hungary (K 120277). Project no. NVKP_16-1-2016-0017