770 Small heart and single coronary artery in a young patient with chronic fatigue syndrome: a case report

Aims Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a clinically defined condition reported mostly in adults, characterized by fatigue and unexplained aspecifical symptoms. Patients with CFS/ME frequently have reduced stroke volume with an inverse relation between cardiac output and post-exertional malaise severity. We describe a rare case of a young man affected by CFS/ME, small heart, and anomalous anatomy of left main coronary artery (LMCA). Methods and results A 19-year-old Caucasian male referred to our clinic complaining weakness, lack of concentration, and sleepiness. He suffered by CFS/ME, D hypovitaminosis, inflammatory bowel disease, and exocrine pancreas insufficiency. Blood tests revealed no pathological findings. Faecal exams documented intestinal dysbiosis and low pancreatic elastase. He was treated with oxygen-ozone rectal insufflations and probiotics. Physical examination was unremarkable. Electrocardiogram showed normal sinus rhythm. Echocardiogram revealed reduced diameters of the left ventricle (LV), normal aortic root dimensions and, in a five-chamber apical view, a binary structure that seemed to cross the aorta perpendicularly. Cardiac magnetic resonance (CMR) found reduced LV stroke volume (34 ml/m2) and end-diastolic volume (57 ml/m2) together with reduced end-diastolic wall mass (51 g/m2). Right ventricle volumes were reduced too. In addition, the exam confirmed the anomalous origin of LMCA stemming from the proximal segment of right coronary artery and following a retro-aortic course. Mechanism of CFS/ME remains unknown, although various factors have been implicated, including immune activation, chronic viral infection, and emotional disorders. A considerable number of patients affected by CFS has an anatomically small heart. Small heart syndrome, in fact, may contribute to the onset of CFS/ME. Previous studies hypothesized that clinical manifestations of CMS/ME were caused by reduced venous return, cardiac output, and heart mass, together with decreased arterial oxygen saturation. Single coronary artery is an uncommon congenital anatomic abnormality identified by a single coronary ostium giving rise to all arteries supplying the heart. Thus, we reported a rare case of a very young man affected by chronic fatigue syndrome and small heart, investigated not only with echocardiogram but also with CMR, not often used in this clinical setting. More, we found an anomalous origin of LMCA. From literature, it’s not reported any cases of a patient including these three rare conditions (CFS/ME, small heart, and single coronary artery). Conclusions This case highlights that CFS/ME together with small heart is a condition possible also in young people. More studies and reports could be necessary to better define the association between cardiac congenital anomalies and CFS/ME. 770 Figure

Analysis of corrected QT dispersion, tp-e values in small heart syndrome patients

Funding Acknowledgements Type of funding sources: None. Background and objectives We aimed to evaluate the marker of ventricular arrhythmias such as Tp-e/QT, Tp-e/QTc, Tp-e/JT and Tp-e/JTc ratios in ‘Small Heart Syndrome’ female patients and also aimed to evaluate the association between ‘small heart syndrome’ and fibromyalgia in female patients. Methods A total of 94 female, including 47 small-heart and 47 normal-heart patients, who applied from March 2018 to February 2020 and who were examined by a physical therapy and rehabilitation specialist, were included in the study by calculating their cardiothoracic ratios (CTR) from the chest x-ray. QTmax, QTmin,QRS, JT and Tp-e intervals were measured. In addition, Tp-e/QTmax, Tp-e/QTc max, Tp-e/JT and Tp-e/JTc rates and QTc max, QTc min, cQTd and JTc intervals were calculated. Results cQTd (24,246 ± 9,046 ms vs. 35,495 ± 14,358 ms, p < 0.001), Tp-e (67,32 ± 11,661 ms vs. 72,67 ± 11,028 ms, p = 0.04), Tp-e/QTc max (0,166 ± 0.028 vs. 0.181 ± 0.027, p = 0,012), Tp-e/JTc (0,214 ± 0.038 vs. 0.232 ± 0.034, p = 0,022) values were significantly higher in small heart patient group. QT min (330,68 ± 26,611 ms vs. 323,04 ± 30,829 ms, p = 0,202) values were significantly lower in patient group. Conclusion Compared to control group potential ECG repolarization predictors were significantly increased in ‘Small Heart Syndrome’ patients. TableElectrocardiographic findings o Control group(n = 47) Patient group(n = 47) P value Heart rate, bpm 87,81 + 15,532 83,81 + 14,372 0,223 QRS; ms 83,23 + 6,948 81,91 + 10,052 0,206 QT max; ms 354,93 + 26,796 358,54 + 28,434 0,528 QT min; ms 330,68 + 26,611 323,04 + 30,829 0,202 JT; ms 265,7 + 25,16 271,88 + 23,104 0,218 QTc max; ms 403,59 + 18,208 400,20 + 18,336 0,371 QTc min; ms 379,34 + 20,064 364,71 + 23,149 0,004* JTc; ms 314,37 + 21,325 313,55 + 22,526 0,856 cQTd; ms 24,246 + 9,046 35,495 + 14,358 <0,001* Tp-e; ms 67,32 + 11,661 72,67 + 11,028 0,040* Tp-e/QT max 0,190 + 0,034 0,203 + 0,031 0,063 Tp-e/QTc max 0,166 + 0,028 0,181 + 0,027 0,012* Tp-e/JT 0,255 + 0,047 0,267 + 0,036 0,295 Tp-e/JTc 0,214 + 0,038 0,232 + 0,034 0,022*

Small heart anomalies as cardiac manifestations of hereditary connective tissue disorders

Introduction. Small heart anomalies (SHA) are the morphological basis for functional changes in cardiac activity and can exacerbate the course of organic heart lesions. The most studied SHA include false chords of the left ventricle (FCLV) and mitral valve prolapse. Prevalence, association with external signs of dysembryogenesis, as well as the predictive value of SHA are not sufficiently studied. Materials and methods. We examined 611 people between the ages of 18 and 23 (average age 20.3 1.6 years), including 257 boys and 354 girls. All of the surveyed performed phenotypic, anthropometric and echocardiographic examinations. To identify the SHA links to heart rhythm disorders, the 205 surveyed performed Holters ECG monitoring. Results. SHA identified in 90% of the individuals surveyed: atrial septum aneurysm (24%), tricuspid valve prolapse (23.4%), asymmetry of the aortic valve (20.6%), additional papillary muscles (39.4%) and FCLV (75,1%). Correlation analysis showed the presence of links between these SHA and bone signs of dysembryogenesis (chest deformities, arachnodactyllia, dolistennomely and high palate), as well as heart rhythm disorders (supraventricular and ventricular extrasystoles, rhythm driver migration and episodes of AV-blockade 1 degree). Patients with marfanoid habitus have a higher average number of SHA (2.1 1.4 vs 0.9 0.7, p 0.005). Conclusions. SHA are identified in the vast majority of healthy people. Bone signs of dysembryogenesis are associated with significant SHA and can serve as a marker for the involvement of the heart in the dysplastic process. Patients with SHA have significant cardiac arrhythmias.

Structure-function indices of echocardiography in civil aviation pilots of senior age groups

Echocardiography is an important method for non-invasive evaluation of the structural and functional indicators of the cardiovascular system, which is valuable in early detection of the cardiovascular pathology, especially in older people, because, the prevalence of the most cardiovascular diseases significantly increases with age. Material and methods. 1189 civil aviation pilots aged 54–68 years who underwent routine in-patient examination at the Central Clinical Hospital of Civil Aviation on a regular basis were examined with further medical assessment at the Central Medical Flight Expert Commission of Civil Aviation of the Russian Federation in 2009–2010. The average age was 56.75 ± 0.07. Transthoracic echocardiography was performed in 1170 flight personnel (98.4%) for evaluation of the structural and functional indicators of the cardiovascular system. Results. Echocardiography abnormalities were detected in 95.7% of pilots of the senior age group, 14.1% of these changes were in mixt form. Signs of atherosclerosis of the thoracic aorta were most common — 94% of cases. Left ventricle diastolic dysfunction of type I was noted in 60.3% of pilots. Structural and/or functional changes of the heart valves were noted in 18.2% of the subjects, most of them were localized in the aortic valves: 16% of cases. Dilation of the heart chambers were detected in 4.8% of the examined. LVH was found in 1% of pilots of the senior age group, and signs of LV concentric remodeling — in 60.7% of individuals. The decrease in LV myocardial contractility was detected only in one pilot with EF 53%. Small heart abnormalities were identified only in 0.6% of cases. Conclusions. Echocardiography abnormalities are quite common in pilots of the senior age group, however, «gross» echocardiographic changes are much less common than in the population, which is natural, because these individuals undergo initial medical screening and subsequent follow-up. The use of this method for screening in civil aviation pilots of senior age groups is reasonable, because the prevalence of cardiovascular disease in this group is increasing.

Roles of Physiological Responses and Anthropometric Factors on the Gravitational Force Tolerance for Occupational Hypergravity Exposure

Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1–5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio: 9.91; 95% confidence interval: 4.11–23.88). The chances of failure were inversely related to the HR increase percentage (p for trend <0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.

Cardiomyocyte-Restricted High-mobility group box 1 (HMGB1) deletion leads to small heart and inflammation through GR/PGC-1a signaling

Cardiomyocyte-Restricted High-mobility group box 1 (HMGB1) Deletion Leads to small heart and inflammation Through GR/PGC-1a signaling Background Cardiac growth and remodeling are key biological process influencing the physiological performance of the heart. Previous study showed critical role of intracellular HMGB1 in vitro. However, the in vivo study using conditional Hmgb1 ablation did not significantly affect the cellular and organic function. Purpose Previously we have demonstrated the extracellular effect of HMGB1 as a proinflammatory molecule on cardiac remodeling. Here, to elucidate the intracellular effect of HMGB1 on cardiac function in vivo, we perform the study. Methods Conditional genetic deletion of HMGB1 mouse was constructed using cTnT-Cre Hmgb1fl/fl. And then we detected body weight, and analyzed cardiac function of 12-week old mice using echocardiography. The subcelluar morphology was detected using the transmission electron microscopy (TEM) examination, and the changes of glycolipid metabolism was detected by the positron emission tomography (PET)/computed tomography (CT) imaging and GC-FID/MS analysis in heart tissue. And Then we used RNA-seq to find transcriptomic changes. And co-immunoprecipitation experiments, chromatin immunoprecipiptation (ChIP) were used to validate the binding of HMGB1 and glucocorticoid receptor (GR). The downstream signal changes were detected using western blot analysis. To validate the result, we further constructed the cardiac HMGB1 deficient mouse using Ckmm-Cre Hmgb1fl/fl, and measured body weight and cardiac function. Results We found HMGB1 deletion by cTnT-Cre in mouse hearts altered GR function, glycolipid metabolism, and eventually led to growth retardation, small heart, and heart failure. The subcelluar morphology didn't show significant change caused by HMGB1 knockout. The heart showed significantly elevation of glycolysis and free fatty acid deposition, and related enzyme changes. Transcriptomic analysis revealed a list of differential expressed genes, which coincide with the glucocorticoid receptor function in neonatal mice, and significant increase inflammatory genes of the adult ones. The cardiac HMGB1 knockout lead to a series changes of PGC-1a, UCP3, and glycerol kinase, which were the cause of metabolic change and further impact the cardiac function. And the Ckmm-Cre Hmgb1fl/fl mouse didn't show significant phenotype, which was consistent with the reported negative result of Cardiomyocyte-specific Hmgb1 deletion via MHC-Cre. Conclusions Therefore, our results demonstrated that HMGB1 plays an essential role in maintaining normal cardiac growth and function by regulating GR function and glycolipid metabolism. And the strikingly different phenotype from the cardiac-specific HMGB1-deficient mice may be caused by the cross with different Cre mouse. Main results and graphic summary Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China

Cardiomyocyte-restricted high-mobility group box 1 (HMGB1) deletion leads to small heart and glycolipid metabolic disorder through GR/PGC-1α signalling

Cardiac growth and remodelling are key biological processes influencing the physiological performance of the heart, and a previous study showed a critical role for intracellular HMGB1 in vitro. However, the in vivo study, which used conditional Hmgb1 ablation, did not show a significant effect on cellular or organic function. We have demonstrated the extracellular effect of HMGB1 as a pro-inflammatory molecule on cardiac remodelling. In this study, we found that HMGB1 deletion by cTnT-Cre in mouse hearts altered glucocorticoid receptor (GR) function and glycolipid metabolism, eventually leading to growth retardation, small heart and heart failure. The subcellular morphology did not show a significant change caused by HMGB1 knockout. The heart showed significant elevation of glycolysis, free fatty acid deposition and related enzyme changes. Transcriptomic analysis revealed a list of differentially expressed genes that coincide with glucocorticoid receptor function in neonatal mice and a significant increase in inflammatory genes in adult mice. Cardiac HMGB1 knockout led to a series of changes in PGC-1α, UCP3 and GyK, which were the cause of metabolic changes and further impacted cardiac function. Ckmm-Cre Hmgb1fl/fl mice did not show a specific phenotype, which was consistent with the reported negative result of cardiomyocyte-specific Hmgb1 deletion via MHC-Cre. We concluded that HMGB1 plays essential roles in maintaining normal cardiac growth, and different phenotype from cardiac-specific HMGB1-deficient mice may be caused by the cross with mice of different Cre strains.