Sports-related sudden cardiac death due to myocardial diseases on a population from 1-35 years: a multicentre forensic study in Spain

This is a multicentre forensic study that identifies all sports-related sudden deaths (SRSDs) in young people,due to myocardial diseases (MDs) that occurred in a large area of Spain.The aim of the study is to assess the epidemiology,causes of death,and sport activities associated with these fatalities.This is a retrospective study based on forensic autopsies performed in the provinces of Biscay,Seville,Valencia and in the jurisdiction covered by the National Institute of Toxicology and Forensic Sciences in Madrid (Spain).The retrospective study encompasses from 2010 to 2017.All sudden cardiac deaths (SCDs) in persons 1-35years old were selected.The total number of SCDs were divided into death occurred during exercise (SRSD) and death during rest,sleep or normal activities (non-SRSD).Each of these two groups was subdivided according to the cause of death into MD (primary cardiomyopathies and myocarditis) and non-MD.Clinic-pathological,toxicological and genetic characteristics of SRSD due to MD were analysed.Over the 8-year study period,we identified 645 cases of SCD in the young: 75 SRSD (11.6%) and 570 non-SRSD (88.4%).MD was diagnosed in 33 (44.0%) of the SRSD and in 112 (19.6%) of the non-SRSD cases.All cases of SRSD due to MD were males (mean age (24.0±7.6) years) practicing recreational sports (85%).SRSDs were more frequent in arrhythmogenic cardiomyopathy (ACM) (37%) and hypertrophic cardiomyopathy (HCM) (24%),followed by myocarditis (15%) and idiopathic left ventricular hypertrophy (ILVH) (9%).Only in five cases of SRSD the MD responsible of death (HCM) had been diagnosed in life.Cardiovascular symptoms related to the disease were present in other seven patients (six of them with ACM).Postmortem genetic studies were performed in 15/28 (54%) primary cardiomyopathies with positive results in 12 (80%) cases.The most frequent sports disciplines were football (49%) followed by gymnastics (15%) and running (12%).In Spain,SRSD in young people due to MDs occurs in males who perform a recreational activity.Compared with control group we observed a strong association between MDs and exertion.One in three SRSDs are due to cardiomyopathy,especially ACM,which reinforces the need for preparticipation screening to detect these pathologies in recreational sport athletes.Further studies are warranted to understand the causes and circumstances of sudden death to facilitate the development of preventive strategies.

Effect of Fufang Danshen Pill on Bone Marrow Stem Mobilization when Myocardial Scathe

Objective：To investigate the effect of Fufang Danshen pill on bone marrow stem mobilization during myocardial scathe. Methods：Rat models with expansionary myocardial disease were established by Pituitrin and Furazolidone. Experimental rats were divided into the contrast group, the myocardial scathe group （MS group）, the myocardial scathe and Fufang Dansben pill group （ MS ＋ FD group） and the myocardial scathe and fluvastatin group （ MS ＋ FT group）. The ratio of CD34^＋ cells was examined at the 1^st, 3^nl and 6^th weekend. Index of heart structure and function including LVESD, LVEDD. LYEF, LVEDP and dp/dtmax were evaluated at the 6^th weekend. The HW/BW index was calculated. Results：In the MS group, the index of HW/BW, LVESD, LVEDD and LVEDP were obviously increased （P 〈 0.01 ） and index of dp/ dtmax and LVEF were obviously decreased （P 〈 0.05 ）. The ratio of CD34^＋ cells was significantly improved at the 1^at weekend and then reduced slowly with no difference from that of the contrast group at the 6th weekend. Compared the MS ＋ FD group and the MS ＋ FT group with the MS group, the index of HW/BW, LYESD, LYEDD and LYEDP of were signifi cantly decreased （ P 〈 0.05 ） and index of dp/dtmax and LVEF were increased （P 〈 0.01 ）. The ratio of CD34^＋ cells was significantly higher at the 1^st, 3^nl and 6^th weekend, but had no statistic meaning at 3^nl and 6^th weekend （P 〉 0.05 ）. Conclusion：Pituitrin and Furazolidone can be used to establish rat models with expansionary myocardial disease. There has bone marrow stem mobilization during the early period of myocardial scathe. Fufang Danshen pill has effect on improving bone marrow stem mobilization, lightening the expansionary degree of heart and protecting the heart function. The effect of Fufang Danshen pill is as same as that of fluvastatin.

Clinical Survey of 6 371 In-Paitent Cases of Acute Myocardial Infarction from 1984 to 1992 in Guangdong Province

6 371 cases of acute myocardialinfarction from 1984 to 1992 in Guangdong Province are reported in this article. The results show that the prevalence rate of acute myocardial infarction (AMI) has been increasing. The anterior walls are involved more often than the inferior ones are. The first symptom in 87. 4% of cases is pectoral pain. The most common complications are arrhythmia, heart failure and cardiac shock successively occurring in order. The mortality rate is 19.9%. The predominant causes of death is pump failure.

ASSOCIATION OF INSULIN RESISTANCE AND C-REACTIVE PROTEIN WITH CORONARY ARTERY DISEASE IN PATIENTS WITH NORMAL GLUCOSE TOLERANCE

Objective To examine insulin resistance and high sensitivity C-reactive protein （hsCRP） association with clinical and angiographic severity of coronary artery disease （CAD） in patients with normal glucose tolerance. Methods In 638 consecutive patients with normal glucose tolerance, 221 had atypical chest pain and normal coronary artery （control group）, 279 had stable angina and CAD （SAP group ）, and 138 suffered acute myocardial infarction （ MI group）. The degree of CAD was further divided into borderline lesion （ lumen diameter narrowing 50% - 69% ）, significant 1-, 2- or 3-vessel disease （ luminal diameter narrowing 〉I 70% ）. Fasting serum glucose, insulin and hsCRP levels and lipid profiles were measured, and homeostasis model assessment for insulin resistance （ HOMA-IR ） was calculated. Multivariate analysis was performed to assess risk factors for 3-vessel disease or acute MI. Results Serum hsCRP, lipoprotein （a） levels, and insulin resistance index （IRI） were higher in AMI group than those in SAP and control groups. Serum hsCRP level and IRI were also higher in 3-vessel disease than those in other groups. Multivariate regression analysis revealed that insulin resistance, cigarette smoking, serum hsCRP, and lipoprotein （a） levels were independent risk factors for acute MI. Lipoprotein （ a ） elevation was an independent risk factor for 3-vessel disease. Conclusion Insulin resistance and high serum hsCRP level were associated with occurrence of acute MI and angiographic severity of coronary disease in patients with normal glucose tolerance.

The Level of Serum Intact Terminal Peptide of Procollagen and Its Clinical Significance in Patients with Chronic Keshan Disease

Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N-terminal peptide of type procollagen (P NP) and intact N-terminal peptide of type procollagen were measured by radioimmunoassay in 35 patients with chronic KD and 31 normal control. Doppler ultrasounds was used to determine several parameters of left ventricular systole and diastole functions. Results The concentration of serum P NP (74.07±16.74)μg/L and the ratio of P NP/ P NP (18.02 ±4.60) in chronic KD were significantly increased as compared to the control (39.63±12.07 μg/L, 12.12±4.24; P< 0.001). Serum P NP (4.19±0.64)μg/L in chronic KD was higher than that in the control (3.36±0.65 μg/L,P < 0.001) too. The higher of serum concentration of P NP and the ratio of P NP/ P NP, the worse of cardiac function in patients with chronic KD. A negative correlation was found between serum P NP/ P NP, P NP and VE/VA, LVEF (γ=-0.4502, -0.4608, P< 0.01 and γ=-0.3936, -0.3904, respectively; P<0.05). Conclusions These findings suggested that tissue synthesis of collagen type and type was abnormally increased in chronic KD. On the other hand, our results indicated that P NP and P NP were related to several functional alterations of the left ventricle. Serum procollagen peptide measurements might therefore provide indirectly diagnostic information on myocardial fibrosis associated with chronic KD.

HDL signaling and protection against coronary artery atherosclerosis in mice

Atherosclerosis is a leading underlying factor in cardiovascular disease and stroke,important causes of morbidity and mortality across the globe.Abundant epidemiological studies demonstrate that high levels of high density lipoprotein（HDL） are associated with reduced risk of atherosclerosis and preclinical,animal model studies demonstrate that this association is causative.Understanding the molecular mechanisms underlying the protective effects of HDL will allow more strategic approaches to development of HDL based therapeutics.Recent evidence suggests that an important aspect of the ability of HDL to protect against atherosclerosis is its ability to trigger signaling responses in a variety of target cells including endothelial cells and macrophages in the vessel wall.These signaling responses require the HDL receptor,scavenger receptor class B type 1（SR-B1）,an adaptor protein（PDZK1） that binds to the cytosolic C terminus of SR-B1,Akt1 activation and（at least in endothelial cells） activation of endothelial NO synthase（eNOS）.Mouse models of atherosclerosis,exemplified by apolipoprotein E or low density lipoprotein receptor gene inactivated mice（apoE or LDLR KO） develop atherosclerosis in their aortas but appear generally resistant to coronary artery atherosclerosis.On the other hand,inactivation of each of the components of HDL signaling（above）in either apoE or LDLR KO mice renders them susceptible to extensive coronary artery atherosclerosis suggesting that HDL signaling may play an important role in protection against coronary artery disease.

Usefulness of dobutamine stress myocardial contrast echocardiography for assessing coronary artery disease

Background Quantitatively assessing myocardial perfusion and its reserve is of great importance for the diagnosis and stratification of patients with coronary artery disease （ CAD）, and represents an important goal of myocardial contrast echocardiography. In this study we sought to test the usefulness of low dose dobutamine stress real-time myocardial contrast echocardiography （RT-MCE） in the assessment of CAD, and to explore the relationship between perfusion reserve and contractile reserve. Methods Twenty-six patients with suspected or clinical diagnosed CAD were enrolled and underwent RT-MCE at baseline and under low dose dobutamine stress, and subsequent coronary angiography. RT-MCE images were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion and its reserve. Results At baseline, significant differences in beta （0.28± 0. 12, 0. 25± 0. 09, 0.22 ± 0. 06, 0. 20± 0.07 respectively, P 〈0. 01） and A x beta （1.37 ±0. 46, 1.28±0. 47, 1. 13 ±0. 37, 0.91±0. 32, respectively, P 〈0. 01 ） were observed among four segment groups with graded coronary artery stenosis severity （normal; 30% -69% stenosis; 70% -90% stenosis; and beyond 90% stenosis） , but not observed in parameter A. When under stress, significant differences in A （5.73 ± 1.28, 5.63 ± 1.01,4.96 ±0.81,4.57 _＋0.62, respectively, P〈0.01）, beta （0.67 ±0. 17, 0.55 ±0. 19, 0.32 ±0. 13, 0.25 ±0.08, respectively, P 〈0.01） and A x beta （3.81 ± 1.20, 3. 11±1.17, 1.59 ±0. 82, 1. 12 _＋0. 37, respectively, P 〈0. 01 ） were observed among the formerly mentioned groups. Graded decreases in A reserve （ 1.20 ±0. 53, 1.11 ±0. 16, 0.98 ±0. 12, 0. 99 ±0.13, respectively, P〈0.01）, beta reserve （2.65 ±1.07, 2. 32±0.82, 1.44±0.40, 1.29±0.34, respectively, P〈0.01） and A xbeta reserve （3.05 ± 1.63, 2.59 ±1.01, 1.42 ±0.44, 1.27±0.34, respectively, P 〈 0. 01 ） could also be observed with increasing coronary stenosis severity. In five segments groups scored by WMS （ 1 - 5 ） , concordance between contractile function and myocardial perfusion could be found both at rest （beta： 0.28±0. 11, 0. 22 ±0. 08, 0. 21 ±0.05, 0. 17 ±0.05,0. 19 ±0.06, respectively, P 〈0.01; A xbeta： 1.29 ±0.48, 0.98 ±0.45, 0.94±0.29, 0.76 ±0.30, 0.92 ±0.32, respectively, P〈 0.01） and under stress （beta： 0.59 ±0.20, 0.35 ±0.15, 0.27 ±0.08, 0. 17±0.05, 0.20±0.05, respectively, P〈0.01; A xbeta： 3.07 ±1.38, 1.62±0.82, 1.28 ±0.40, 0.78 ±0.24, 0.93 v0.22, respectively, P 〈0. 01 ）. This concordance is also valid in terms of the reserves, and the MCE parameters in segments with ameliorated contractile function are significantly higher than in those without. Conclusions Quantitative RT-MCE in conjunction with dobutamine stress shows promise in identifying and stratifying CAD and in exploring the perfusion-contractile correlation.

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease

Background Keshan disease （KD） is an endemic cardiomyopathy in China.The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease.Young women of child-bearing age are the most frequent victims in rural areas.The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.Methods We extracted RNA from the peripheral blood mononuclear cells of KD patients （12 women and 4 men） and controls （12 women and 4 men）.Then the isolated RNA was amplified,labeled and hybridized to Agilent human 4×44k whole genome microarrays.Gene expression was examined using oligonucleotide microarray analysis.A quantitative polymerase chain reaction assay was also performed to validate our microarray results.Results Among the genes differentially expressed in female KD patients we identified：HLA-DOA,HLA-DRA,and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7,involved in cardiomyocyte differentiation defect; and ADAMTS 8,CCL23,and TNFSF15,implicated in anti-angiogenic activities.These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.Conclusion Our results might help to explain the higher susceptibility of women to this disease.