Clinical Characteristics Of Syncope And The Exploration Of Vasovagal Syncope Mechanism

Syncope refers to the transient loss of consciousness(TLOC)caused by transient hypoperfusion of the whole cerebral blood flow.Its core cause is transient decrease of the whole cerebral blood flow.Its main characteristics are rapid onset,transient and self recovery.During the attack,the whole cerebral blood flow decreased,resulting in muscle tension unable to maintain normal body position,resulting in falls.According to Soteriades and other reports,the incidence of syncope is 6.2 ‰ per year in American.There is no large-scale study on the incidence of syncope in China.Epidemiological data from the United States shows that about 9.5‰of the residents are hospitalized due to syncope every year,of which 10% are admitted to hospital,while most of the syncope patients do not pay attention to syncope and do not see a doctor.It is roughly estimated that about half of the general population have syncope at least once in their life.According to the syncope guidelines of the United States in2017 and the latest expert consensus on syncope of China in 2018,syncope is mainly divided into: 1.Neuroreflex syncope 2.Cardiogenic syncope 3.Orthostatic hypotension 4.Unexplained syncope.The prognosis of syncope is closely related to the cause of syncope.Although some syncope may have repeated attacks that affect the quality of life,the prognosis is good,such as neuroreflex syncope.Cardiogenic syncope may be life-threatening,such as evil Sexual arrhythmia can cause death of patients,the 1-year mortality rate is 5.7% ～ 15.5%;therefore,the screening of the causes of syncope is very important.Cardiogenic syncope,including the syncope caused by arrhythmia and organic cardiovascular disease,is the second common cause.Patients with acute myocardial infarction,especially those with arrhythmia,can often cause syncope.However,whether the severe coronary stenosis of non myocardial infarction is the cause of syncope,and whether the patients with syncope and coronary heart disease benefit from the treatment of coronary artery is still unclear.The mechanism of vasovagal syncope is not clear.At present,the most recogniz mechanism of vasovagal syncope is Bezold Jarisch reflex.Bezold Jarisch reflex(BJR)is a kind of neurocardiogenic reflex.That is to say,when venous congestion occurs in vasovagal syncope patients,the rapid decrease of left ventricular blood volume can excite Bezold Jarisch reflex ring,which can cause the increase of sympathetic nerve tension,resulting in the almost complete emptying of the ventricle The contraction state then stimulates the C fibers of the mechanoreceptors in the posterior inferior wall of the left ventricle to increase the afferent signals of the vagus nerve,thus causing the decrease of the resistance of the peripheral blood vessels and / or the slowing of the heart rate,thus causing syncope.Vasovagal syncope can be divided into cardiac inhibition,vascular inhibition and mixed type according to the degree of inhibition of the heart and blood vessels.Its core is the inappropriate response of sympathetic nerve and parasympathetic nerve.Catecholamine,as an important neurotransmitter regulating sympathetic nerve,can enhance the contraction of heart and blood vessels,but its role in vasovagal nerve is not clear.The dramatic changes of blood pressure and heart rate during vasovagal syncope are the causes of syncope,whileα1 receptor andβ1 receptor play an important role in regulating blood pressure and heart rate.There is no clear conclusion about the relationship between gene polymorphism and vasovagal syncope.Therefore,this study focuses on the analysis of the causes and the follow-up of patients with syncope in our single syncope center.To observe the hemodynamic changes of VVS patients during head up tilt table test and the effect of metoprolol succinate on hemodynamics.At the same time,we observed the changes of catecholamine during head up tilt table test to explore the role of catecholamine in vasovagal syncope,and to explore the correlation between common gene polymorphisms of α1 receptor and β1 receptor and vasovagal syncope.Meanwhile,it is found that patients with vasovagal syncope are often accompanied with anxiety during clinical diagnosis and treatment.Part 1 The etiology analysis of syncope patients in single centerObjective: To analyze the clinical characteristics and etiology of syncope patients in single syncope center.Methods: The clinical data of syncope patients admitted to our syncope center from January 2017 to December 2018 were collected and analyzed according to the syncope diagnosis and treatment guidelines or expert consensus.Results: From January 2017 to December 2018,there were 315 syncope inpatients.101(32.1%)were cardiogenic syncope,and 120(38.1%)were neuroreflex syncope,and 16(5.0%)were postural hypotension syncope.There were 78 patients with unexplained syncope,accounting for 24.8%.Sick sinus syndrome was the most common in cardiogenic syncope,accounting for 21.8%,followed by acute myocardial infarction(17.8%)and atrioventricular block(13.9%).Multivariate logistic regression analysis showed that older age(OR: 0.95,95%CI[0.93-0.97],P<0.01)and lower EF(OR: 0.95,95%CI[1.14-1.31],P<0.01)were important risk factors for cardiac syncope.While younger age(OR: 1.12,95%CI[1.09-1.15],P<0.01),lower BMI(OR: 1.26,95%CI[1.08-1.47],P<0.01)and recurrent syncope(OR: 3.14,95%CI[1.22-8.08],P=0.02)were risk factors for neurally mediated syncope.There were significant differences in all-cause mortality(P=0.03),rehospitalization(P=0.003)and recurrence of syncope(P=0.02)among the four types of syncope during the 3-year follow-up.Compared with non-cardiac syncope patients,cardiac syncope patients had a higher rehospitalization rate(HR: 2.86,95%CI[1.40-5.81],P<0.01)and a lower incidence of recurrent syncope(HR: 0.36,95%CI[0.19-0.69],P=0.02).Neurally mediated syncope patients had a higher re-syncope rate than non-neurally mediated syncope patients(HR: 2.34,95%CI[1.23-4.45],P<0.01),but a lower re-hospitalization rate than non-neurally mediated syncope patients(HR: 0.25,95%CI[0.13-0.48],P<0.01).The all-cause mortality(HR: 1.15,95%CI[0.29-4.53],P=0.84)and rehospitalization rates(HR: 1.17,95%CI[0.55-2.48],P=0.68)of patients with unexplained syncope were not lower than those of patients with unexplained syncope.Conclusions: Neurally mediated syncope and cardiac syncope are common causes of syncope in hospitalized patients with syncope.Older age and lower EF are risk factors for cardiac syncope.Younger age,lower BMI and recurrent syncope are risk factors for neurally mediated syncope.In terms of prognosis,the incidence of recurrent syncope is higher in patients with neurally mediated syncope.The rehospitalization rate and all-cause mortality are higher in patients with cardiac syncope,and the mortality and rehospitalization rate of unexplained syncope are not lower than those of patients with definite syncope,which deserves attention.Part 2 Prognosis of acute myocardial infarction patients with syncopeBackground and Objectives: Acute myocardial infarction(AMI)is the second leading cause of cardiac syncope after bradyarrhythmia.Syncope is the first symptom in some patients with acute myocardial infarction,but the clinical characteristics and prognosis of these patients are not clear.The aim of this study is to investigate the clinical characteristics and main clinical outcomes of patients with acute myocardial infarction complicated with syncope.Methods: From January 2015 to December 2020,the acute myocardial infarction patients with syncope were prospectively enrolled.The control group was AMI patients without syncope.All baseline data of these patients were recorded,and pre-specified follow-up was performed.Results: Of the 3494 patients with AMI from January 2015 to December 2020 in our hospital,121 patients had syncope as the main symptom(3.5%).The frequency distribution of culprit vessels in AMI patients with syncope were: the right coronary artery(RCA,48.8%),the left anterior descending artery(LAD,26.4%),the left circumflex artery(LCX,21.5%)and the left main artery(LM,3.3%).At one-month follow-up,AMI patients with syncope had significantly higher incidence of all-cause death(9.9% vs.5.2%,P=0.02),and the main contribution was cardiac mortality(9.1%vs.4.5%,P=0.02).At two-year follow-up,the survival curve suggested there was no significant difference in all-cause death and cardiac mortality between the two groups.(all-cause death:hazard ratio [HR]: 1.26;95% confidence interval [CI]:0.75-2.14,p=0.33;cardiac mortality:hazard ratio [HR]: 1.40;95% confidence interval[CI]: 0.78-2.53,p=0.18).Conclusion: The right coronary artery is the most common culprit vessels in acute myocardial infarction patients with syncope.Acute myocardial infarction patients with syncope had a higher risk of death within 1 month than those without syncope.At two-year follow up,the prognosis of these patients was similar.Part 3 Hemodynamic characteristics and mechanism of vasovagal syncopeObjective: To observe the hemodynamic changes of vasovagal syncope and explore its possible mechanism.Methods: Collect the patients with vasovagal syncope in syncope center of our hospital,and observe the characteristics of hemodynamic changes by head up tilt table test(HUTT);Observe the characteristics of hemodynamic changes of HUTT positive patients after using metoprolol succinate;Analyze the relationship between vasovagal syncope and adrenoceptor gene polymorphism.Results: A total of 76 patients with HUTT positive and 36 patients without syncope and HUTT negative(control group)were enrolled in this study.The heart rate increased significantly in 2 minutes duting basic tilt test.The heart rate increased significantly in 2 minutes of drug loading test in HUTT positive patients,which was significantly higher than that in the control group.The receiver operating characteristic(ROC)curve analysis showed that the change rate of heart rate in 2minutes(S2:2min)and 4 minutes(S2:4min)during drug loading phrase had a good predictive value for syncope during HUTT in VVS patients.The AUC of S2:2min was0.85,P<0.01,and the AUC S2:4min was 0.77,P<0.01.HUTT examination was performed again after metoprolol succinate,and the proportion of mixed type,vascular inhibition type and cardiac inhibition type of recurrent syncope were39.0%,71.4% and 0%.After treatment with metoprolol succinate,the increase of heart rate in HUTT positive patients was lower than that before treatment.The allele frequencies of arg347 and cys347 of ARDA1 in VVS group were 60.5% and 39.5%respectively.The allele frequencies of Arg347 and Cys347 in HUTT negative patients(control group)were 43.1% and 39.5% respectively.The allele frequencies of Ser49 and Gly49 of ADRB1 in the control group were 80.6% and 19.4% respectively,and the allele frequencies of Ser49 and Gly49 of ADRB1 in the VVS group were 80.6%and 19.4% respectively The allele frequencies of Arg389 and Gly389 were 72.2% and27.8% in the control group and 67.1% and 32.9% in the VVS group,respectively.Conclusion:(1)The rate of heart rate increase in HUTT positive patients was higher than that in control group at 2 minutes of drug challenge test;The rate of change in heart rate at 2minutes and 4 minutes during drug provocation is a good predictor of syncope during HUTT in VVS patients.(2)The application of metoprolol succinate can inhibit the heart rate change rate in VVS patients during HUTT test,improve the hemodynamic changes in HUTT positive patients during the second test,and has a certain preventive effect on patients with mixed syncope.(3)The norepinephrine in HUTT positive patients during syncope was lower than that in negative patients at the end of the trial,suggesting that syncope may be related to the inability to maintain a high level of norepinephrine.(4)The Arg347 Cys polymorphism of the adrenalα1 receptor gene is associated with VVS,while the Ser49 Gly and Arg389 Gly polymorphisms of the adrenal β 1receptor gene are not significantly associated with VVS.