A Real World Study of Valvular Heart Disease in Jiangxi Province
Conditions: Valvular Heart Disease, Treatment Adherence and Compliance
Sponsor: Xiao Huang

 
Clinical Research Project Program                                                            Version No.: V1.0 Version Date: December 10,2021 
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Clinical Research Protocol 
Project letter 
 
 
Program name: A Real World Study of Valvular Heart 
Disease in Jiangxi Province                
Program No.:  
Type of study: A real world registration research     
Funding Source: Jiangxi Province Science and Technology 
Department  
Version No.:  
    
Applicant: Wu Yanqing              Tel: 13870885171            
Institution: The Second Affiliated Hospital of Nanchang University 
Address: No.1 Minde Road, Donghu District, Nanchang City           
Email:  wuyanqing01@sina.com                    
Filing date: December 1, 2021     
 
 
 
 
 
 
 
 
 
 
Clinical Research Center of The Second Affiliated Hospital of Nanchang University 

 
 
 
Clinical Study Protocol                                                   Version No.: V1.0 Version Date: December 1, 2021 
 

 
 
 
Clinical Study Protocol Version                                                        No.: V1.0 Version Date: December 1, 2021 
 
Program version revision history
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1     The table is not enough, you can expand the additional pages, but do not attach other irrelevant materials 

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1. Major participants in the project 
2
 
  
Numb
e r 
Name 
Title 
Unit (Section) 
Division of 
labor 
Whether to obtain 
GCP certificate 
Signature 
1 
Yanqing Wu  
Director 
Cardiovascular 
Medicine 
Project Leader 
Yes 
2 
Jinsong Xu 
Director 
Cardiovascular 
Medicine 
Surgery 
execution 
Yes 
3 
Ren Gong 
Main 
Treatmen 
t 
Cardiovascular 
Medicine 
Surgery 
execution 
Yes 
4 
Shiyuan, 
Zhang 
Deputy 
Director 
Cardiovascular 
Medicine 
Ultrasound of 
the heart 
Yes 
5 
Xiao Huang 
Deputy 
Director 
Cardiovascular 
Medicine 
Program 
guidance and 
adjustment 
Yes 
6 
Jiandi Liu 
7 
Ziheng Tan 
8 
Siyi Chen 
9 
10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2    Major project members are required to receive GCP training and certification 

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2. Summary of the study protocol (should include study title, study purpose, 
design type, study populations, sample size, inclusion criteria,  observation  
indicators,  statistical analysis methods, etc.) 

 
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Clinical Study Protocol                                                            Version No.: V1.0 Version Date: December 1, 2021 
 
Research Title: A Real World Study of Valvular Heart Disease in Jiangxi Province
 
Purpose of the study. 
① Main objectives: To examine the current incidence of valvular heart disease in Jiangxi 
Province, to establish a “Formal treatment model” for patients with valvular heart disease, 
and to manage the collection of diagnostic,  therapeutic and prognostic data on patients. 
② Secondary objective: To investigate the composite of all-cause mortality, disabling stroke,  
permanent pacemaker implantation,  and moderate or  greater valve regurgitation in the 
"Formal treatment model" group and the "Conventional treatment model" group. The 
Conventional group was matched to patients who were not in the " Formal treatment model 
" during the same period. 
Design type: a prospective, observational, real-world study (at least 1.5 years). No pre-established fixed 
treatment protocols, only a Formal treatment model,with all treatment choices made entirely by clinicians following 
relevant textbooks, expert consensus on clinical guidelines, and based on the patient's condition. 
Subjects:  All patients with moderate to severe heart valve disease were  collected from the 
Second Affiliated Hospital of Nanchang University and hospitals at all levels in Jiangxi Province 
from September 2022 to September 2023. 
Inclusion criteria: ① All moderate-to-severe heart valve disease, including aortic, mitral, and 
tricuspid valves; ② Comply with the ESC/EACTS Guidelines for the Management of Valvular Heart 
Disease (2021) indications for surgery for valvular heart disease; ③ Understand and voluntarily sign the 
informed consent form 
Exclusion criteria:  ( i)  those with severe mental disorders and unable to express their will; 
(ii) those with obvious other abnormal signs, laboratory tests and clinical diseases that,  in the 
judgment of the investigator,  make them unsuitable for participation in the study; (iii) those who, 
in the judgment of the investigator, are unable to complete long-term follow-up. 
Main indicators of observation: (a) all-cause death; (b) disabling stroke, cardiogenic death; 
(c) permanent pacemaker implantation; (d) regurgitation at the diseased valve 
 
 

 
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Technical approach.  
① Outpatient screening of patients with cardiac valve disease, assessed by cardiac 
ultrasound, arterial CTA and coronary angiography, with definite moderate to severe 
heart valve disease. 
② Eligible patients were divided into "Formal treatment model" and "Conventional treatment 
model " groups according to whether they received surgical treatment (including medical 
and surgical treatment), and were enrolled in the study. 
③  Postoperative (if any), 30-day, and 1-year follow-up reviews were conducted to inquire 
about current physical status,  medication use,  record the occurrence of endpoint 
events ( e. g. ,  cardiac death,  all- cause death,  myocardial infarction, stroke,   pacemaker 
implantation) ,   cardiac ultrasound to assess valve and cardiac function, and blood was 
drawn for biochemical indicators such as routine blood and liver and kidney function. 
 
Formal treatment model group: Patients who agree and accept the surgical treatment recommendation 
(including medical and surgical treatment) enter the formal treatment model group. 
Those who have received any of the following treatments (including but not limited to) as 
recommended by the standardized treatment process are considered to have received the standardized 
treatment, otherwise, they have not. 
1) Surgical procedures: valve repair or replacement, left auricular ligation, left auricular clip. 
2) Internal surgery: transcatheter valve replacement, radiofrequency ablation of atrial fibrillation, 
and left heart ear occlusion. 
Conventional treatment model group: Patients who do not agree to enter the Formal treatment model 
group will automatically enter the Conventional treatment model group. 
Study endpoints 
(1) Primary endpoints and definitions: all-cause mortality, disabling stroke, and incidence of 
cardiogenic stroke,  permanent pacemaker implantation rate, and moderate or greater 
valve regurgitation at 1 year after surgery or discharge from treatment. 
(2) Secondary endpoints and definitions. 
(a) All-cause mortality 30 days after surgery or discharge from hospital after treatment 
(all-cause mortality includes: cardiac death, non-cardiac death). 
( b) Incidence of stroke at 30 days after surgery or discharge from hospital after 
treatment.  
 

 
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(c) The rate of permanent pacemaker implantation 30 days after surgery or hospital 
discharge after treatment.  
( d)  Postoperative or treated discharges with moderate or greater valvular 
regurgitation.  
( e)  Readmission rates for complications related to aortic stenosis and/or valve 
implantation at 30 days and 1 year after discharge from the hospital after surgery or 
treatment. 
( f)  The incidence of temporary intraoperative valve size changes (including 
increasing or decreasing valve size). 
( g)  The incidence of abnormal intraoperative valve position ( abnormal valve position 
includes: valve displacement, valve embolism, and valve ectopic release). 
(h) Incidence of implantation of two or more valves during aortic valve replacement.  
( i)  The incidence and number of intraoperative valve recoveries (recoveries 
include partial and complete recoveries). 
( j)  Incidence of intraoperative conversion to surgical open- heart surgery. 
(k) The incidence of extracorporeal circulatory support beyond what is expected 
intraoperatively.  
( l)  The incidence of intraoperative coronary occlusion.  
(m) Incidence of major vascular complications associated with surgery. 
(n) Health status of subjects 30 days after surgery or discharge from hospital after 
treatment and at 1 year: evaluation using the Barthel index. 
(o) 30 days postoperative or post-treatment discharge and 1-year NYHA 
classification.  
 

 
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3. Study Background 
 
Project basis 
Valvular heart disease is a common clinical cardiac disease with high morbidity and 
mortality. Mitral regurgitation (MR) is the most common valvular defect, followed by aortic 
stenosis (AS) and aortic regurgitation (AR)
[1-4]  . These diseases  are  currently  receiving 
increasing  attention  in  the  field  of cardiovascular medicine,  mainly because of the 
changes in the etiology and treatment of these diseases over the past 60 years. Although valvular
heart disease can be caused by congenital valve defects,  systemic inflammatory diseases,  
endocarditis, and many other conditions, degenerative valve disease has gradually become the 
predominant lesion type, resulting in important changes in the clinical characteristics of patients and 
the distribution of valvular lesion types
[5]  . The management of patients with valvular disease has 
also undergone important changes in the last few decades with the development of minimally 
invasive interventional techniques, such as transcatheter aortic valve placement (TAVR) with 
transcatheter mitral valve repair and other new technologies. Progressive changes in the etiology of 
cardiac valvular disease, significant differences in clinical presentation, and the diversity of 
treatment modalities emphasize the importance of documenting signs,  symptoms,  and treatment 
outcomes in patients with different heart valve diseases, not only to describe changes in the 
condition but also to effectively adjust treatment regimens
[ 6 ]   . 
The Second Affiliated Hospital of Nanchang University has completed many heart valve 
disease surgeries since the establishment of the valvular heart disease treatment team in 2015. Under 
the leadership of our center, the current cause of heart valve disease related treatment in Jiangxi 
province is developing well,  however, so far, we have not yet established the key technology 
research and full information big data platform construction and cohort construction for the 
assessment of valvular heart disease in our province. 
We intend to establish different cohorts of people with valvular heart disease, to 
clarify the etiology and pathogenesis, and to control valvular heart disease from the source. We will 
rely on the all-information big data platform and cohort construction, and take the population 
characteristics and key technologies of disease assessment as the important foothold of the 
platform and cohort construction. Through large real-world cohort studies, we will examine the 
current incidence of valvular heart disease and the influence of related risk factors on its 
occurrence,  development,  treatment,  prognosis  and  control;  establish 
 

 
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, 
appropriate technologies for effective prevention and treatment of valvular heart disease and its risk 
factors, focus on building a diagnosis and treatment center for aging valvular disease, improve the 
diagnosis and treatment rate of patients, reduce the prevalence and mortality rate, and strive to 
move forward the window of disease prevention and treatment. Through the establishment of a life-
cycle data collection and management system,  we will develop the most suitable treatment 
methods for patients to save their lives and improve their quality of life to the greatest extent.  
References 
[1] Cary T, Pearce J. Aortic stenosis: pathophysiology, diagnosis, and medical management of nonsurgical 
patients [J]. Crit Care Nurse,2013,33(2):58-72. 
[2] Carita P, Coppola G, Novo G, et al. Aortic stenosis: insights on pathogenesis and clinical implications [J]. J 
Geriatr Cardiol,2016, 13(6):489-498. 
[3] Dweck M R, Boon N A, Newby D E. Calcific aortic stenosis: a disease of the valve and the myocardium 
[J]. J Am Coll Cardiol,2012,60( 19):1854- 1863. 
[4] Sathyamurthy I, Alex S. Calcific aortic valve disease: is it another face of atherosclerosis?[J]. Indian Heart 
J,2015,67(5):503-506. 21/44101205167077. 
[5] Soler-Soler J, Galve E. Worldwide perspective of valve disease. Heart[J], 2000, 83:721-725. 
[6] Mrsic Z, Hopkins SP, Antevil JL, Mullenix PS. Valvular Heart Disease. Prim Care 2018;45:81-94. 
 
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4. Study purpose 
 
1. Study purpose. 
To establish different cohort populations of valvular heart disease,  to clarify the etiology and 
pathogenesis, and to control valvular heart disease from the source, we will rely on the all-
information big data platform and cohort  construction, and take the population characteristics and
key technology of disease assessment as the important foothold of the platform and cohort 
construction. Through large real-world cohort studies, we will examine the current incidence of 
valvular heart disease and the influence of related risk factors on its occurrence, development, 
treatment, prognosis and control; establish appropriate technologies for effective prevention and 
treatment of valvular heart disease and its risk factors, focus on building a diagnosis and 
treatment center for aging valvular disease, improve the diagnosis and treatment rate of patients, 
reduce the     prevalence and mortality rate, and strive to move forward the window of disease 
prevention and treatment. Through the establishment of a life-cycle data collection and management 
system, we will develop the most suitable treatment methods for patients to save their lives and 
improve their quality of life to the greatest extent.  
2. Study endpoints 
(1) Primary endpoints and definitions: all-cause mortality, disabling stroke, and incidence of 
cardiogenic stroke,  permanent pacemaker implantation rate, and moderate or greater 
valve regurgitation at 1 year after surgery or discharge from treatment. 
(2) Secondary endpoints and definitions. 
( a) All-cause mortality at 30days postoperative or post-treatment  discharge (all-
cause mortality includes: cardiac death, non-cardiac death). 
( b) Incidence of stroke at 30 days after surgery or discharge from hospital after 
treatment.  
(c) The rate of permanent pacemaker implantation 30 days after surgery or hospital 
discharge after treatment.  
( d)  Postoperative or treated discharges with moderate or greater valvular 
regurgitation.  
( e)  Readmission rates for complications related to aortic stenosis and/or valve 
implantation at 30 days and 1 year after discharge from the hospital after surgery or 
treatment. 
( f)  The incidence of temporary intraoperative valve size changes (including 
increasing or decreasing valve size). 
 

 
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( g)  The incidence of abnormal intraoperative valve position ( abnormal valve position 
includes: valve displacement, valve embolism, and valve ectopic release). 
(h) Incidence of implantation of two or more valves during aortic valve replacement.  
( i)  The incidence and number of intraoperative valve recoveries (recoveries 
include partial and complete recoveries). 
( j)  Incidence of intraoperative conversion to surgical open- heart surgery. 
(k) The incidence of extracorporeal circulatory support beyond what is expected 
intraoperatively.  
( l)  The incidence of intraoperative coronary occlusion.              
(m) Incidence of major vascular complications associated with surgery. 
(n) Health status of subjects 30 days after surgery or discharge from hospital after 
treatment and at 1 year: evaluation using the Barthel index. 
(o) 30 days postoperative or post-treatment discharge and 1-year NYHA 
classification.  
 

 
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5. Study Design 
 
1. Study site and study population 
All patients with moderate to severe heart valve disease in the Second  Affiliated Hospital 
of Nanchang University and hospitals at all levels in Jiangxi Province from September 2022 to 
September 2023 were collected 
Inclusion criteria: ① All moderate-to-severe heart valve disease, including aortic, mitral, 
and tricuspid valves; ② Comply with the ESC/EACTS  uidelines for the Management of Valvular 
Heart Disease (2021) indications for surgery for valvular heart disease; ③ Understand and voluntarily sign the 
informed consent form 
Exclusion criteria: (i) those with severe mental disorders and unable to express their will; 
(ii) those with obvious other abnormal signs, laboratory tests and clinical diseases that,  in the 
judgment of the investigator,  make them unsuitable for participation in the study; (iii) those who, 
in the judgment of the investigator, are unable to complete long-term follow-up. 
2. Research Design Flow Chart 
 
3. Methodology for determining the sample size required for the study 
Through a real-world cohort study, this study relies on an all-information big data platform to 
examine the incidence of valvular heart disease and the influence of related risk factors on its 
occurrence, development, treatment, prognosis and control;  to establish appropriate 
technologies for effective 
 

 
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prevention and treatment of valvular heart disease and its risk factors, and to focus on 
building a treatment center for geriatric valvular disease; and to develop the most suitable 
treatment modalities by establishing a whole-life data collection and management system. By 
establishing a life-cycle data   collection and management system, we will develop the most 
suitable treatment method for patients. The expected incidence of the primary study endpoint 
is 30%, β=0.1, certainty (test efficacy) 1- β=90%, requiring a two-sided test with α of 0.05 and 
certainty (1- β) of 90%, requiring a total sample size of 947 cases, and assuming a 10% loss of 
follow-up rate, a total of 1052 cases. 
 

 
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6. Safety evaluation (including definition and assessment of adverse events, serious 
adverse events, etc.) 
 
1. Definition of adverse event: An adverse medical event, whether device related or not, that occurs 
in a subject during the use of an experimental medical device. 
2. Abnormal laboratory and instrumental findings. 
3. Serious Adverse Events: The main adverse events after the relevant procedures may be related 
to the operation, anesthesia and other procedures, including but not limited to the following: 
( a)  Abnormal laboratory indicators ( including electrolyte disturbances)  ( b)  Allergic 
reactions to anesthesia,  contrast media or device materials 
(c) Cardiovascular injury, including perforation of a blood vessel, ventricle or vascular 
entrapment,  myocardial or valvular structures that may require intervention 
(d) Impaired conduction system, such as new postoperative left bundle branch, high 
atrioventricular block,  permanent pacemaker may be required 
( e)  Cardiac arrest 
(f) Embolism, including air, calcified/thrombotic valve material, or thrombus ( g)  Decreased 
exercise tolerance or weakness 
( h)  Arteriovenous fistula or pseudoaneurysm of the femoral artery ( i)  
Infections,  including sepsis and endocarditis 
( j)  Pericardial effusion 
( k)  Peripheral ischemia or nerve injury 
( l)  Stroke/ transient ischemic attack or neurological deficit 
( m)  Coronary artery flow obstruction/ valvular flow disorder 
( n)  Valve Failure 
( o)  Emergency heart surgery 
( p)  Mitral valve injury 
( q)  Perivalvular or mid- valve leaks 
( r)  Release the valve in an unexpected position 
( s)  Valvular Stenosis 
4. Severity assessment 
 

 
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, 
Light: does not interfere with daily activities. 
Medium:  affects daily activities. 
Severe: loss of ability to perform daily activities. 
 
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7. Data Collection and Management 
 
1. Survey Content (CRF Form) 
Variables.  
( a) Basic patient information: name, gender, age, education level, co-morbidities, 
past medical history, etc. 
( b)  Patient admission: chief complaint symptoms,  general condition,  vital signs, cardiac 
function classification, STS score, etc. 
( c)  Preoperative laboratory and instrumentation tests:  biochemical indexes,  cardiac 
ultrasound, CTA examination, etc. 
(d) Information related to the surgical procedure (if any): surgical access, valve selection, etc. 
( e) Intraoperative complications, if any: death, ring rupture, permanent pacemaker 
implantation,  etc. 
(f) Postoperative laboratory and instrumentation tests (if any): biochemical indicators, cardiac 
ultrasound, etc. 
( g) Postoperative medication (if any). 
( h)  The occurrence of adverse events during hospitalization.  
( i) Status at follow-up: chief complaint symptoms, general condition, vital signs, cardiac 
function classification, etc. 
( j)  Laboratory and instrumental tests at follow- up:  biochemical indicators, cardiac 
ultrasound, etc. 
( k) Occurrence of adverse events at follow-up visits. 
2 .  Data Management and Statistical Analysis 
For all subjects who have signed the informed consent form and qualified for enrollment, 
all items in the electronic medical record report form must be recorded carefully and in detail, 
with no empty items or omissions. 
The investigator followed the original medical record and the inpatient major medical 
record to enter the data into the electronic medical record report form, and the investigator ensured 
that the completed data were true and accurate. 
Data that are significantly high or outside the clinically acceptable range must be verified 
and the investigator must provide the necessary explanation.  
When the investigator makes changes to the data for filling reasons, a dialog box will 
would appear on the electronic medical record report form and the investigator will need to 
 

 
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indicate the reason for the changes. Any modification made by the investigator will all leave a trace to 
ensure the authenticity of the data. 
After the investigator has completed the data, the monitor has performed the monitoring, 
and the investigator has resolved all data queries to ensure the data are accurate, the data manager 
locks the database. The data is reviewed by the data manager, principal investigator, statistical 
analyst,  implementer and monitor manager, and the final definition and judgment of the analyzed 
population is completed, after which the database is finally locked by the data manager. 
Locked databases or files may not normally be changed again. 
 

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8.  Quality management program  ( please introduce the relevant 
measures to ensure the qual ity and progress of the project) 

 
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Monitoring of observational cohort studies 
Supervisors will visit the study center periodically during the study to ensure that all elements of 
the study protocol are strictly adhered to and that the original data are checked to ensure that the data 
are true, complete and correct. 
1. Measurement method 
(1) CTA. 
(2) Electrocardiogram: 12-lead conventional electrocardiogram. 
(3) Blood routine, urine routine, liver and kidney function, blood biochemical index:  determined 
by automatic biochemical instrument. 
(4) Ultrasound of the heart. 
(5) Adverse event records. 
2. Completion of electronic case report form 
An electronic case report form (CRF) was used for this trial. For all subjects who have signed 
the informed consent form and qualified for enrollment, all items in the electronic medical record 
report form shall be carefully and thoroughly recorded, and no empty items or omissions shall be 
allowed. All data in the   electronic medical record report form should be checked against the 
subject's original medical record data to ensure that they are error-free. The investigator ensures that 
these data are true and accurate. 
3. Preservation of original information 
The original data of this trial, including the signed informed consent form, records of the test 
product distribution, relevant laboratory test reports, case records and other relevant records, should 
be kept in the national drug clinical trial institution of the hospital where the research center is 
located. Medical institutions should keep clinical trial information until five years after the 
termination of the trial. Implementers should save clinical trial information until ten years after the 
final production of the product into use. 
 

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9. Pre-assessment of project risks and benefits and risk control plan (Please 
describe the risks and benefits that may be assumed by the investigator, the 
subject and the medical institution during the implementation of the 
project; if there are risks, please describe the measures and feasibility of risk control.) 

 
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1. Benefit/risk evaluation 
(1) Benefit: Through real-world cohort studies and relying on the 
all-information big data platform, we examine the incidence of valvular heart disease and the 
influence of related risk factors on its occurrence, development,  treatment,  prognosis and 
control;  establish appropriate technologies for effective prevention and treatment of valvular 
heart disease and its risk factors, and focus on building a treatment center for geriatric valve 
disease; through the establishment of a whole-life data collection and management system, we 
develop the most suitable The treatment method that is most suitable for the patients will be 
developed through the establishment of the whole life cycle data collection and management 
system. 
(2) Surgical risks (if surgery is performed). 
1) Cardiac conduction block 
This is by far the most common complication of TAVR. This complication can be reduced 
by avoiding placing the valve stent too deep (>6 mm), choosing a valve with too large a diameter, 
selecting a balloon-expandable valve for patients with right bundle-branch block, and choosing a 
dilating balloon with a small internal diameter. For patients with no postoperative ECG changes and 
no preoperative right bundle branch block, the temporary pacing electrodes can be removed 
immediately after surgery, and postoperative ECG monitoring should be continued for 24 h. For 
patients with preoperative right bundle branch block or postoperative ECG changes, the temporary 
pacing electrodes should be left in place for 24 h and further  evaluated. In patients with high or 
complete intra- or postoperative AV block that does not recover within 48 h after surgery, a 
permanent pacemaker should be   implanted.  
2) Perivalvular leakage 
Most patients have a mild to mild perivalvular leak, and self-expanding valves may be 
reduced over time. Studies have shown a correlation between moderate or greater perivalvular 
leakage and long-term mortality in patients. Small valve selection, excessive calcification or large 
calcified masses, and shallow or deep valve placement are risk factors for the development of 
perivalvular leaks.   Evaluation of perivalvular leak and its extent should be performed after 
valve placement, using means including aortic root angiography, hemodynamic measurements (aortic 
regurgitation index may be used), and Doppler ultrasound to provide a comprehensive assessment 
of the extent, location, and hemodynamic impact of   perivalvular leak;  for moderate or greater 
perivalvular leak, aggressive intervention should be attempted. Techniques such as post-balloon 
dilation (when valve expansion is incomplete or the apposition is poor), repositioning of valve 
stents (when the valve is too high or too low), and blockers to seal perivalvular leaks can be used. 
Severe patients require surgical intervention. Avoidance of selection of patients with excessive 
valve calcification,  selection of the 
 

 
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appropriate type of valve, and accurate positioning of valve depth can reduce the incidence of 
perivalvular leaks. 
3) Coronary artery occlusion 
Coronary artery obstruction is a rare (0.66%) but fatal complication of TAVR and is one of 
the main reasons for preoperative imaging screening and exclusion of patients from TAVR. The 
main mechanism of coronary artery obstruction in TAVR is autologous valve upstaging blocking 
the coronary artery opening. In addition, coronary artery obstruction can be caused by a valve 
stent placed too high with the skirt blocking the coronary artery opening. The preoperative CT 
evaluation should be a combination of three aspects: valve leaflet condition, aortic sinus anatomy, 
and characteristics of the valve to be placed. TAVR should be avoided in patients with 
inappropriate anatomy,  and intraoperative selection of an       appropriate balloon and aortic root 
imaging with balloon dilation to observe  coronary artery visualization can help to further assess the 
risk of coronary artery occlusion. Prevention and treatment strategies for patients at high risk of   
coronary artery occlusion: (1) selection of a smaller valve and moderately deeper placement, if 
allowed, may reduce the risk of coronary artery occlusion, but the occurrence of perivalvular 
leakage may increase; (2) feasible coronary artery protection strategies, including prepositioning of 
guidewires, balloons, or stents in the coronary arteries; (3) if acute or delayed coronary artery occlusion 
occurs, emergency coronary intervention or surgery is feasible (3) In case of acute or delayed 
coronary occlusion, emergency coronary intervention or open-heart surgery with coronary artery 
bypass grafting is indicated.  
4) Stroke 
Stroke may be associated with the detachment of calcified material from the valve. The 
incidence of clinically symptomatic stroke is 2% to 3%, and cranial magnetic resonance imaging 
shows that ischemic brain injury is common after TAVR (80% to 90%). risk factors for stroke 
associated with TAVR include surgical factors such as balloon pre-expansion, time in the body of 
the delivery system, rapid pacing, and valve recovery reset, in addition to the patient's own 
characteristics. Repeated operations should be avoided intraoperatively and the number of operations 
should be reduced, which may reduce the incidence of stroke. Cerebral protection devices may be 
considered in high-risk patients. Clinical studies have shown that brain protection devices may 
reduce brain injury on MRI monitoring, but whether they reduce clinical events requires further 
study. If a stroke occurs, a     neurologist should be consulted for collaborative management.  
5) Local vascular complications 
Mainly the inlet vessels, femoral, iliac, and abdominal aorta, develop  entrapment, 
occlusion, and rupture bleeding, with a previous incidence of up to 16.7%. With the use of 
delivery systems of 18 F and below, the incidence of this complication has decreased to 4.2%. 
Elderly patients, especially those with many 
 

 
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comorbidities such as hypertension,  chronic renal insufficiency,  diabetes     mellitus, and 
hereditary hypercholesterolemia, are prone to stenosis, atheromatous plaque, calcification, and 
excessive tortuosity, which can lead to vascular   complications.  Preoperatively, MSCT should 
be used to comprehensively and     carefully evaluate the vascular access diameter, select the 
access diameter with good vascular conditions, avoid selecting access vessels with too small 
internal diameter and too much distortion, and avoid rough operation. In case of vascular 
complications,  peripheral vascular balloons, peripheral overlapping stents, and vascular surgery if 
necessary, can be used to deal with them. 
6) Cardiac tamponade 
The incidence is 1% to 2%. To reduce the occurrence of this complication, the head end 
of the stiffened guidewire should be shaped into a circle, and the stiffened guidewire should be 
secured during balloon dilation and into the delivery sheath. When entering the left ventricle with a 
straight tip guidewire, excessive force should be avoided, causing perforation of the aortic sinus 
or the left  ventricle.  
7) Aortic dissection and laceration 
A fatal complication of TAVR. Accurate measurement of the aortic annulus size and not using 
oversized dilating balloons may reduce this complication. 
2. Moral Ethics 
(1) Ethics committee (should describe how the plan was approved by the research ethics 
committee/ institutional review board)  
1) In conclusion, the Second Affiliated Hospital of Nanchang University has completed 
many heart valve disease surgeries since the establishment of the   valvular heart disease 
treatment team in 2015. Under the leadership of our center, the current cause of heart valve 
disease related treatment in Jiangxi province is developing well, however, so far, we have 
not yet established the key technology research of valvular heart disease assessment in our 
province and the construction of all-information big data platform and cohort construction. 
Therefore, we intend to establish a cohort population of valvular heart disease, clarify the 
etiology and pathogenesis, and control valvular heart disease from the source, which will 
rely on the construction of the all-information big data platform and cohort, with the 
population characteristics and key technologies of disease assessment as the important 
foothold of the platform and cohort construction.  Through large     real-world cohort 
studies, we will examine the current incidence of valvular heart disease and the influence of 
related risk factors on its occurrence, development, treatment, prognosis and control; 
establish appropriate technologies for effective prevention and treatment of valvular heart 
disease and its risk factors, focus on building a diagnosis and treatment center for aging 
valvular disease, improve the diagnosis and treatment rate of patients, reduce the prevalence
and mortality rate, and strive to move forward the window of disease prevention and 
treatment. Through 
 

 
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the establishment of a life-cycle data collection and management system, we will develop the most 
suitable treatment methods for patients to save their lives and improve their quality of life to the 
greatest extent. 
2) Overview of the undertaking unit (personnel, assets, business and management 
status). 
The Department of Cardiology of the Second Affiliated Hospital of Nanchang University is 
the excellent innovation team of the Ministry of Education, the national clinical key specialty, 
the leading medical discipline of Jiangxi    Province, the key discipline of the 11th Five-Year Plan 
of Jiangxi Province, the leading discipline of Nanchang University in granting the doctoral 
degree of  internal medicine, the affiliated unit of the Cardiovascular Special Committee of Jiangxi 
Medical Association, the Pacemaker and Electrophysiology Special Committee of Jiangxi Biological 
Engineering Society and Jiangxi Cardiac Association,  the Institute of Cardiovascular Tuberculosis 
of Nanchang University, and the Institute of Genetic Diseases and Genes of Jiangxi Province. The 
Department of Cardiovascular Diseases of Nanchang University,  the Institute of Cardiovascular 
Diseases of  Nanchang University, and the Institute of Genetic Diseases and Genetics of Jiangxi 
Province. The Department has a GCP platform of the major new drug innovation project of the Ministry 
of Science and Technology of China, a platform of the Cardiovascular Interventional Therapy and 
Devices Research Engineering Center of the Ministry of Education,  a research platform for genetic 
gene screening for cardiovascular  diseases of the Provincial Education Department, an innovation 
team of Changjiang scholars of the Ministry of Education, a superior science and technology 
innovation team of Jiangxi Province, a "311 project" of the Provincial Education Department, a 
cardiovascular engineering research center, and a cardiovascular research center of Jiangxi Province.  
Cardiovascular Engineering Research Center,  Jiangxi      Provincial Molecular Medicine Key 
Laboratory Sharing Platform, Nanchang University Institute of Cardiovascular Diseases,  Jiangxi 
Provincial Institute of Medical Genetics, Jiangxi Provincial Key Laboratory of Cardiovascular
Diseases and a series of experimental platforms. The department has a strong echelon of talents. 
There are 238 medical and nursing staff, 65 physicians (including 39 doctors, accounting for 60.0% 
of physician positions); 36 people have overseas study experience,  accounting for 55.38%. 
There are 7 second-level professors, 11 doctoral       supervisors, 24 master's supervisors, 32 senior 
titles, 7 special allowances from the State Council, 2 national outstanding science and technology 
workers, 1   national outstanding educator, 1 national "May Day" Labor Medal, 1 expert directly 
under the control of the Central Organization Department, 1 national hundred  million talents, 2 
young experts with outstanding contributions from the Ministry of Health. In addition, there are 
also Jiangxi provincial government allowances, 
 

 
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Jiangxi talents with outstanding contribution and "Gan Pao Talent 555" leading talents, and one
advanced individual of national health and family planning system. In addition, there are more than 20 
people including Jiangxi provincial government allowance, Jiangxi outstanding talents and 
"GANPOW Talent 555" leading talents and 100 million talents. 
3) Advantages of participating units. 
1. The Second Affiliated Hospital of Nanchang University is one of the few units in Jiangxi 
province that can independently perform TAVR surgery, and has completed most of the TAVR 
surgeries in the province and accumulated rich surgical experience; at the same time, it has 
participated in many provincial and national clinical studies on TAVR surgery, and has the 
technical and staff management  advantages to complete the surgery. 
2. Ltd. has been dedicated to the research, development, production and sales of high-
end medical devices since its establishment, and now has a complete and sound R&D and 
manufacturing capability, as well as a perfect research laboratory and a 10,000-class purification 
workshop. The company has 35 R&D personnel,   specializing in structural design, electronics, 
materials and other fields. The company has undertaken the projects of National Innovation Fund, 
Shanghai Torch Plan, Shanghai High-tech Achievement Transformation Project, Shanghai 
Innovation Fund, Shanghai Talent Development Fund, Shanghai Science and Technology Small Giant 
Cultivation, etc., and won the awards of National Innovation and Entrepreneurship Competition 
Outstanding Enterprise, Shanghai Patent Pilot Enterprise and Jiading District Science and 
Technology Progress Award. At present, the company has 26 patents, among which 7 are 
authorized invention patents, establishing the brand image of "leading technology and independent
innovation". As a high-tech enterprise and Shanghai Small Giant Cultivation Enterprise,  the 
company has successfully developed and transformed three series of products: 1) Intra-cardiac 
interventional products for angiography and stent placement; 2) Minimally invasive vertebral 
interventional products for vertebral compression fractures and bone tumors caused by 
osteoporosis; 3) Intestinal balloon catheters for intestinal imaging, CT and MRI examination and 
treatment. 
(2) Patient Information and Informed Consent 
This cohort study was conducted in compliance with the current version of the Declaration 
of Helsinki, medical device clinical trial regulations, GCP and relevant national regulations.  
Prior to the start of the study, the investigator must submit the study protocol, informed 
consent form and other relevant documents to the medical ethics 
 

 
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committee of the hospital where the clinical trial is conducted. The clinical trial can only be started 
after the approval of the ethics committee is obtained. Any modification of the study protocol must 
be approved by the ethics committee before implementation.  Serious adverse events during the 
clinical trial should be    submitted to the Ethics Committee in writing in a timely manner. 
Prior to enrollment in this study, the investigator must provide subjects and their relatives 
with details of the clinical trial, including the content of the trial, its purpose, expected efficacy, 
possible adverse events, and countermeasures.  Subjects will not be enrolled until they fully 
understand the trial, accept the informed process, and sign the informed consent form. 
The informed consent form is signed in duplicate by the study physician and the subject or his
or her legal representative, and one copy is kept by each party.