Minimally Invasive Transapical Septal Myectomy in the Beating Hearts for the Treatment of Hypertrophic Obstructive Cardiomyopathy: Safety and Efficacy Results of a Phase I First-in-man Clinical Trial
Phase: NA
Conditions: Hypertrophic Obstructive Cardiomyopathy
Sponsor: Xiang Wei

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Minimally Invasive Transapical Septal 
Myectomy in the Beating Hearts for the 
Treatment of Hypertrophic Obstructive 
Cardiomyopathy: Safety and Efficacy Results 
of a Phase I First-in-man Clinical Trial 
 
 
 
 
 
 
 
Sponsor: Tongji Hospital, Tongji Medical College, Huazhong 
University of Science and Technology 
 
 
April 24, 2022 
 
 
 
 

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Contents 
1 
BACKGROUND ................................................................................................................................... 5 
2 
OBJECTIVES ....................................................................................................................................... 6 
3 
BEATING-HEART MYECTOMY DEVICE ........................................................................................ 6 
3.1 
BEATING-HEART MYECTOMY DEVICE ......................................................................................................... 6 
3.2 
SURGICAL PROCEDURES ......................................................................................................................... 7 
4 
ENDPOINTS ......................................................................................................................................... 8 
4.1 
PRIMARY ENDPOINT ............................................................................................................................. 8 
4.2 
SECONDARY ENDPOINTS ........................................................................................................................ 8 
4.3 
SECONDARY SAFETY ENDPOINTS .............................................................................................................. 9 
5 
STATISTICAL ANALYSIS ................................................................................................................. 10 
5.1 
ANALYSIS SETS ................................................................................................................................... 10 
5.2 
ANALYSIS METHODS ............................................................................................................................ 10 
6 
OVERALL DESIGN ........................................................................................................................... 11 
6.1 
TRIAL DESIGN .................................................................................................................................... 11 
6.2 
TRIAL PROCESS .................................................................................................................................. 19 
7 
RISK ANALYSIS AND COUNTERMEASURES .............................................................................. 25 
7.1 
ANALYSIS OF EACH SUBJECT BEFORE ENROLLMENT..................................................................................... 25 
7.2 
COMMON RISK TYPES AND MANIFESTIONS OF STUDY DEVICES ...................................................................... 26 
7.3 
METHODS TO MINIMIZE RISK ................................................................................................................ 26 
7.4 
PARAMETERS OF SAFETY EVALUATION ..................................................................................................... 28 
7.5 
CALCULATION OF SAMPLE SIZE .............................................................................................................. 28 
7.6 
SIGNIFICANCE LEVEL AND POWER OF CLINICAL TRIAL .................................................................................. 28 
7.7 
EXPECTED DROP-OUT RATE ................................................................................................................... 28 
7.8 
QUALIFIED/UNQUALIFIED CRITERIA OF CLINICAL TRIAL RESULTS .................................................................... 28 
7.9 
CRITERIA AND REASONS FOR TERMINATING THE TEST BASED ON STATISTICAL REASONS ...................................... 28 
7.10 
STATISTICAL METHOD OF ALL DATA, INCLUDING TREATMENT OF UNREASONABLE DATA, SUCH AS MISSING, UNUSED 
OR WRONG DATA (INCLUDING DROP OUT AND WITHDRAWAL) ......................................................................................... 28 
7.11 
PROCEDURES OF REPORTING DEVIATION FROM STATISTICAL PLAN ............................................................ 29 
7.12 
CRITERIA AND REASONS OF SUBJECTS INCLUDED IN THE ANALYSIS ............................................................ 29 
7.13 
EXCLUSION OF SPECIAL INFORMATION AND REASONS (IF APPLICABLE) IN HYPOTHESIS TESTING ....................... 29 

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8 
DATA MANAGEMENT ...................................................................................................................... 29 
8.1 
MANAGEMENT OF DATABASE ............................................................................................................... 29 
8.2 
PERMISSION ASSIGNMENT ................................................................................................................... 29 
8.3 
DATA ENTRY ...................................................................................................................................... 30 
8.4 
DESIGN AND ESTABLISHMENT OF DATABASE ............................................................................................. 30 
8.5 
SENDING AND SOLVING OF QUERY ......................................................................................................... 30 
8.6 
MODIFICATION AND REVIEW OF DATA ..................................................................................................... 30 
8.7 
EDIT CHECK ....................................................................................................................................... 30 
8.8 
CRF SIGNATURE ................................................................................................................................. 30 
8.9 
LOCKING AND EXPORT OF DATABASE ....................................................................................................... 31 
8.10 
ARCHIVE ...................................................................................................................................... 31 
9 
FEASIBILITY ANALYSIS ................................................................................................................. 31 
9.1 
FEASIBILITY ANALYSIS OF SUCCESS .......................................................................................................... 31 
9.2 
FEASIBILITY ANALYSIS OF FAILURE ........................................................................................................... 32 
9.3 
POTENTIAL RISKS AND BENEFITS ............................................................................................................ 32 
10 
QUALITY CONTROL OF CLINICAL TRIAL ................................................................................. 35 
10.1 
SELECTION OF CLINICAL SITES AND INVESTIGATORS ............................................................................... 35 
10.2 
TRAINING .................................................................................................................................... 35 
10.3 
MONITORING OF CLINICAL TRIAL ...................................................................................................... 35 
11 
ETHICAL ISSUES OF CLINICAL TRIAL AND INFORMED CONSENT ..................................... 36 
11.1 
ETHICAL CONSIDERATIONS ............................................................................................................... 36 
11.2 
INFORMED CONSENT PROCESS AND TEXT OF INFORMED CONSENT ........................................................... 36 
12 
REQUIREMENTS OF REPORTING AES AND DEVICE DEFECTS ............................................. 37 
12.1 
AES ............................................................................................................................................ 37 
12.2 
SAES .......................................................................................................................................... 38 
12.3 
DEVICE DEFECTS ............................................................................................................................ 39 
12.4 
RELATIONSHIP BETWEEN AES AND DEVICE .......................................................................................... 39 
12.5 
REPORTING PROCEDURE AND CONTACT INFORMATION .......................................................................... 39 
13 
CLINICAL STUDY PROTOCOL DEVIATION AND REVISION OF CLINICAL STUDY 
PROTOCOL ................................................................................................................................................. 40 
13.1 
CLINICAL STUDY PROTOCOL DEVIATION ............................................................................................... 40 
13.2 
REQUIREMENTS OF REVISION OF CLINICAL STUDY PROTOCOL .................................................................. 40 
14 
DIRECT ACCESS TO SOURCE DATA AND FILES ........................................................................ 40 
15 
FINANCE AND INSURANCE ........................................................................................................... 41 

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16 
COVERAGE OF THE CLINICAL TRIAL REPORT ....................................................................... 41 
17 
CONFIDENTIALITY ......................................................................................................................... 41 
17.1 
CONFIDENTIALITY STATEMENT OF THE PROTOCOL ................................................................................. 41 
17.2 
CONFIDENTIALITY STATEMENT OF STUDY MATERIALS AND INFORMATION ................................................... 41 
18 
PUBLICATION AGREEMENT OF TRIAL RESULTS ..................................................................... 42 
18.1 
PUBLICATION OF TRIAL RESULTS ........................................................................................................ 42 
18.2 
CONDITIONS FOR PUBLICATION ........................................................................................................ 42 
19 
RESPONSIBILITIES .......................................................................................................................... 42 
19.1 
RESPONSIBILITIES OF ETHICS COMMITTEE .......................................................................................... 42 
19.2 
RESPONSIBILITIES OF THE SITE .......................................................................................................... 45 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
Background 
Hypertrophic cardiomyopathy (HCM) is the most common Autosome inherited heart 
disease that is characterized by obvious left ventricular hypertrophy, usually without 
enlargement (normal or narrowing) of the left ventricular cavity, and excludes other factors 
that can cause ventricular wall thickening. According to hemodynamics, HCM can be divided 
into 
hypertrophic 
obstructive 
cardiomyopathy 
and 
hypertrophic 
non-obstructive 
cardiomyopathy. Hypertrophic obstructive cardiomyopathy can be divided into left 
ventricular outflow tract obstruction (LVOTO), middle obstruction and apical obstruction 
according to the site of obstruction. According to epidemiological surveys, the crude 
prevalence of HCM in the overall population in China is 0.16%, the prevalence in men is 
0.22% higher than that in women 0.10%, and the prevalence adjusted for age and sex is 
0.08%, according to which it is estimated that there are more than 1 million HCM patients in 
China. The clinical manifestations of hypertrophic obstructive cardiomyopathy mainly 
include exertional dyspnea, chest pain, palpitations, and syncope. For patients with symptoms 
and the presence of LVOTO, the first-line treatment is medication. Patients who cannot 
effectively control symptoms despite sufficient medication can undergo invasive treatment, 
with surgical septectomy being the preferred treatment option for ventricular septal reduction. 
Foreign studies have shown that there is no statistically significant difference in 1-year, 
5-year, and 10-year survival rates between patients with hypertrophic obstructive 
cardiomyopathy after surgery and the general population, and they are significantly better 
than patients who have not undergone surgery. Due to the limitations of conventional scalpel 
operation of traditional open-heart surgery to remove hypertrophic myocardial tissue, the 
difficulty of operation, angle and thickness of hypertrophic myocardial tissue resection are 
high, according to the "Guidelines for the Management of Hypertrophic Cardiomyopathy 
2017", common complications in the early stage after surgical ventricular septectomy include 
ventricular septal perforation, aortic regurgitation and residual obstruction, so it is still 
necessary to explore safer and more effective treatment methods clinically.  
In recent years, a number of minimally invasive treatments for HOCM have emerged, 
aiming to shorten the operation time, reduce trauma, reduce the incidence of surgery-related 
complications and their incidence, and improve the quality of life of patients. These include 
percutaneous ventricular septal alcohol ablation, percutaneous femoral ventricular septal 
radiofrequency ablation, percutaneous intramyocardial intraventricular septal radiofrequency 
ablation, etc. The main complications of percutaneous ventricular septal alcohol ablation 

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were perioperative death (perioperative mortality is 1.0%-1.4%), myocardial infarction at 
coronary artery injury and non-target ablation sites, intraoperative and postoperative 
ventricular arrhythmias. The main complication of percutaneous femoral ventricular septal 
radiofrequency ablation was complete atrioventricular block, and the proportion of complete 
atrioventricular block with percutaneous femoral septal radiofrequency ablation requiring 
dual-chamber pacemaker implantation was about 21.1%. Experience and long-term safety 
follow-up data on percutaneous intraventricular septal radiofrequency ablation are limited. 
Combining the limitations of traditional open-heart surgery and minimally invasive surgery, 
upgrading existing open-heart surgical instruments or upgrading existing surgical approaches 
is an effective way to explore safer and more effective treatment methods in the clinic. 
2 
Objectives 
The primary purpose of this study is to evaluate the feasibility, the safety and the 
efficacy of the transapical beating-heart septal myectomy for the treatment of hypertrophic 
obstructive cardiomyopathy. 
3 
Beating-heart myectomy device 
3.1 
Beating-heart myectomy device 
The BMD (Wei-Xin-Tan Cooperation, Wuhan, China) was constructed with a 
bullet-headed resection tube, a multi-functional handle, and a catheter connecting the 
chambers of the device. The resection tube was made of stainless steel and coated with 
polyurethane foam to eliminate acoustic artifacts under echocardiography. The resection tube 
was composed of an outer-layer sleeve tube, a tubular blade mounted inside the sleeve tube in 
a sliding fit, a paraxial puncture needle inside the tubular blade, and a multiporous tunnel 
outside the sleeve tube with a porous surface facing the tubular cavity. A resection window 
was formed on the sidewall in the head portion of the sleeve tube. The resection window was 
sealed by the tubular blade when the device was in the OFF state. Based on the length of the 
resection window and the diameter of the sleeve tube, a series of models of the BMD were 
fabricated with the following sizes (length–diameter in millimetres): 11–30, 11–40, 13–30, 
and 13–40.  
Before entering the ventricular chamber, air in the device was evacuated by carefully 
flushing with normal saline through the catheter in the OFF state. Before resection, the 
puncture needle and the tubular blade were pulled back to switch the device to the ON state. 
The target myocardium and the resection window were brought together with the aid of 
negative pressure generated through the multiporous tunnel connecting the vacuum aspirator. 

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On aspiration, the puncture needle was pushed forward to puncture and capture the target 
myocardium. The tubular blade was then advanced to excise the captured myocardium and 
the device was returned to the OFF state. The resected myocardium, together with the BMD, 
were retrieved from the ventricular chamber, thereby completing one resection. 
 
Figure 1. Structure diagram of the the beating-heart myectomy device 
3.2 
Surgical procedures 
Surgery was performed under general anaesthesia in supine position. Mini-thoracotomy 
was mostly performed in the fifth and (less commonly) in the sixth intercostal space at the 
left midclavicular line, as determined by the transthoracic echocardiography-identified 
location of the LV apex (Central Illustration). Following incision and suspension of the 
pericardium, double-circumferential purse-string sutures with Teflon felt pledgets were 
placed in the avascular zone of the apex and secured with snares to provide haemostasis and 
LV entrance for the BMD (Central Illustration). Upon heparinisation, LV apical pressure, 
which represents the highest pressure generated by LVOT obstruction, was measured using a 
manometric catheter inserted through the purse-string. The systolic pressure gradient between 
the apical pressure and the peripheral arterial pressure, reflecting the LVOT gradient, was 
calculated. An isoproterenol provocation test (infused at 0.01-0.1 μg/kg/min) was performed 
if the resting LVOT gradient was less than 50 mmHg.  
An apical puncture was produced inside the purse-string and was dilated using a dilator 
along a guidewire. After deairing, the BMD in the OFF state was introduced into the LVOT 
through the apical puncture under the navigation of transoesophageal echocardiography 
(Central Illustration). The location of the resection window was three-dimensionally 
identified by transoesophageal echocardiography. Specifically, the depth of the BMD tip was 
identified in the mid-esophageal long-axis view. The orientation of the resection window was 

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identified in the transgastric short-axis views at the basal and mid-ventricular levels. The first 
resection was performed in the basal anterior septum, which was located 5–10 mm beneath 
the aortic valve in the long-axis view, and to the midpoint of the septum in the short-axis view. 
Based on the first resection, the second resection was performed in the basal anterior septum 
parallel but slightly anterior to the first resection. The orientation of the second resection was 
identified on the short-axis view and was achieved by rotating the device 60–120° clockwise 
from the first resection. The morphology of the septal bulge, the LVOT gradient, the MR 
grade, and the remaining thickness of the target septum were evaluated after each resection. 
Subsequent resections were performed at the discretion of pre-procedural planning and 
real-time echocardiographic evaluations. In particular, excisions of the anterior and posterior 
septum were performed by rotating the BMD clockwise or anticlockwise from the location of 
the first resection in the short-axis view. Resections of the mid-ventricular septum were 
achieved by apically pulling the BMD from the basal segment in the mid-esophageal 
long-axis view. Additional resections were performed to tailor satisfactory improvements in 
the LVOT gradient, MR, and LV morphology. After completing the SM, the provocation test 
was repeated. Additional resections were performed if the provocation test was not 
satisfactory. The apical puncture was closed using the purse strings. A cell saver was used for 
blood reservation. 
4 
Endpoints 
4.1 
Primary endpoint 
1. All-cause mortality at 3-month follow-up; 
2. Procedural success: Resting left ventricle outflow tract gradients < 30 mmHg, provoked 
left ventricle outflow tract adients < 50 mmHg, and mitral regurgitation (MR) ≤ grade 1+ 
at 3-month follow-up. 
4.2 
Secondary endpoints 
3. Device success 
Definition：uccessful accession, delivery, and retrieval of the resection device, successful 
resection of the septal myocardium, resting left ventricle outflow tract gradient less than 
50 mmHg and mitral regurgitation (MR) ≤ grade 2+ during operation after resection, and 
free from conversion to midline thoracotomy during operation. 
4. Septal thickness (at 7-day and 3-month follow-up) 
Basal and mid septal thickness as measured by echocardiography. 

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5. Left ventricle mass (at 3-month follow-up) 
Left ventricle mass index (the ratio of left ventricle mass to body weight) as measured by 
cardiac magnetic resonance. 
6. Left ventricle volume (at 3-month follow-up) 
Left ventricle end-diastolic volume as measured by echocardiography. 
7. Cardiac diastolic function (at 7-day and 3-month follow-up) 
The ratio between early mitral inflow velocity and mitral annular early diastolic velocity 
(E/e') as measured by echocardiography. 
8. Left atria volume (at 3-month follow-up) 
The left atria volume as measured by echocardiography. 
9. New York Heart Association class (NYHA) (at 7-day and 3-month follow-up) 
New York Heart Association class, including grade I, grade II, grade III, grade IV. A 
higher grade means worse heart function. 
10. 6-minute walking test (at 3-month follow-up) 
6-minute walking test. A longer distance means better heart function. 
11. Heart function-associated quality of life (at 3-month follow-up) 
Score of the Kansas City Cardiomyopathy Questionnaire. A higher score means better 
heart function. 
12. Left ventricular outflow tract gradient (at 7-day and 3-month follow-up) 
Left ventricular outflow tract gradient as measured by echocardiography. 
13. Evaluation of the mitral valve (at 7-day and 3-month follow-up) 
Grade of mitral regurgitation and systolic anterior motion as measured by 
echocardiography. 
14. Left ventricular outflow tract diameter (at 7-day and 3-month follow-up) 
Left ventricular outflow tract diameter as measured by echocardiography. 
4.3 
Secondary safety endpoints 
4.3.1 Adverse events 
1. All-cause mortality and sudden cardiac death within 30 days after operation; 
2. Adverse event rate during operation and within 30 days after operation (complete heart 
block requiring permanent pacemaker implantation, sternotomy conversion, iatrogenic 
ventricular septal perforation, iatrogenic valvular injury, and imaging examination-validated 
cerebral complications, etc.) and the total number of incidents that occurred; 
3. Incidence rate (%) and number of (serious) adverse events related to surgery and 

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equipment during operation and within 30 days after operation. 
4.3.2 Abnormal vital signs and laboratory tests 
1. General indicators: body temperature, heart rate, respiration, blood pressure; 
2. Abnormal results of laboratory tests: blood routine, urine routine, liver and kidney function 
(ALT, AST, Cr, BUN); 
5 
Statistical Analysis 
5.1 
Analysis sets 
(1) Full analysis set (FAS) 
According to the intention-to-treat (ITT) principle, all cases that have been treated and 
have at least one follow-up record constitute the FAS of this study. 
(2) Per-protocol set (PPS) 
The criteria for the PPS set and its population will be finalized during data blind 
verification, including at least the following criteria: compliance with the inclusion criteria 
specified in the trial protocol; completion of the treatment protocol without serious protocol 
deviation, and evaluable efficacy indicators. 
(3) Safety set (SS) 
All enrolled patients who have undergone treatment and have recorded safety indicators 
constitute the safety population of this study. 
The curative effect evaluation of this study was analyzed by FAS and PPS. SS is the 
main population for the safety evaluation of this study. 
5.2 
Analysis methods 
(1) General principles: A two-sided p-value of less than 0.05 was considered statistically 
significant.  
(2) Statistical description: Normal distribution of continuous variables was assessed by 
Kolmogorov–Smirnov test. Continuous normal distributed variables were presented as means 
(standard deviation). Continuous non-normal distributed data were expressed as medians 
(interquartile ranges, IQR). Categorical variables were presented as counts and percentages. 
(3) Statistical analysis method: Continuous normal distributed variables of repeated 
measurements were compared using matched t-test for two groups and the repeated measures 
ANOVA for multiple groups. Continuous non-normal distributed variables were compared 
using Wilcoxon signed ranks test for two group and Friedman test for multiple groups. 
Repeated measurements of one-way ordered ranking data were compared using Friedman 

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test. 
(4) Dropout analysis: Count the dropout/rejection rate and the reasons. 
(5) Effectiveness analysis: Count the number and percentage of deaths at 3-month follow-up. 
Count the number and percentage of procedural success cases. 
(6) Safety analysis: Calculate the incidence of adverse events, and list and describe the 
adverse events that occurred in this trial and their associations with the devices. 
Statistical analyses are done using the SPSS software (version 23.0). 
6 Overall design 
6.1 
Trial design 
This is a prospective, single-arm, single-center, first-in-man study. 
6.1.1 Sample size determination 
This study plans to recruit 50 subjects. 
6.1.2 Primary Purpose 
The primary purpose of this study is to evaluate the feasibility, the safety and the 
efficacy of the transapical beating-heart septal myectomy for the treatment of hypertrophic 
obstructive cardiomyopathy. 
6.1.3 Follow-up visit point 
The total follow-up period of the trial is 3 months, with 5 visits conducted during the 
screening/baseline period (-7~0 days), surgery day (day 0), visit 3 (postoperative day 1), visit 
4 (postoperative day 7 ± 2 days), and visit 5 (postoperative month 3 ± 7 days). The efficacy 
evaluation at the main time point is on the day of surgery (day 0). 
6.1.4 Medical devices 
Devices Name: Transapical beating-heart septal myectomy 
Product Model：TASM-1130、TASM-1140、TASM-1330、TASM-1340 
Model 
Outer pipe 
diameter D
（mm） 
Cut slot length L0
（mm） 
Effective length 
of outer tube 
L(mm) 
Expander head 
width D2(mm) 
TASM-1130 
11 
30 
170 
11.5±1  
TASM-1140 
11 
40 
170 
11.5±1  
TASM-1330 
13 
30 
170 
13.5±1  

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TASM-1340 
13 
40 
170 
13.5±1  
 
6.1.5 Subject selection 
6.1.5.1 Study population 
Patients with hypertrophic obstructive cardiomyopathy accompanied by symptoms of 
left ventricular outflow tract stenosis. 
6.1.5.2 Inclusion Criteria 
1) Patients whose resting or provoked left ventricular outflow tract gradient>50 mmHg, 
and maximal ventricular septal wall thickness ≥ 15 mm. 
2) Patients with heart function of New York Heart Association ≥ class II. 
3) Patients with drug-refractory symptoms or intolerable to pharmaceutical therapies. 
4) Patients who was informed the nature of the clinical trial, consented to participate in 
all of the activities of the clinical trial, and signed the informed consent form. 
6.1.5.3 Exclusion Criteria 
1) Patients who were pregnant. 
2) Patients who had concomitant diseases such as intrinsic valvular disease or coronary 
artery disease that needed open-heart surgery. 
3) Patients who had severe heart failure with left ventricle ejection fraction < 40%. 
4) Patients whose estimated life expectancy < 12 m. 
5) Patient who were non-compliant. 
6) Patients under circumstances which were considered not suitable or prohibitive for 
participating the clinical trial at the discretion of the attending medical team and the 
researchers. 
6.1.5.4 Delete Criteria 
Principal Investigator, the Sponsor and the Statistical Organ determine whether a subject 
is excluded before statistical analysis of data. In case of any of the following circumstances, 
Principal Investigator shall determine whether to exclude the subject according to the 
completion degree of the trial and withdrawal reason, and make appropriate explanations. 
  1) The subject shall be excluded in case of violating inclusion/exclusion criteria;  
  2) During the trial, the investigator stops the subject from continuing to participate in 
the trial, thinking the subject is subject to other factors that preclude him/her from continuing 
the trial; 
  3) The subject changes the treatment protocol during the trial;  

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  4) During the trial, the subject doesn’t comply with trial schedule and has poor 
compliance, such as never use of the investigational product, or failure to collect samples for 
efficacy and safety evaluation according to the trial protocol, or unavailability of any data.  
6.1.5.5 Criteria and procedures of withdrawal/termination of the trial 
Criteria of withdrawal/termination of the trial:  
It refers to that the subject discontinues the trial instead of completing the trial as 
required by the protocol. The objective of discontinuation is to safeguard the subject’s 
benefit, ensure trial quality and avoid unnecessary economic loss. The investigator 
determines that the subject can not continue the clinical trial, in case of the following 
circumstances:  
  1) The subject is lost to follow-up or requests for withdrawal; 
  2) In case of clinical adverse events (AEs), abnormal laboratory test or comorbidity, 
the investigator doesn’t think that continuation meets the subject’s best benefit;  
  3) Other circumstances that the investigator thinks withdrawal is necessary, such as 
the subjects losses ability to express willing due to imprisonment or quarantine;  
  4) Circumstances that the Sponsor thinks discontinuation is necessary, such as not 
meeting inclusion criteria, failure to implant devices as required or receiving other 
interventions that influence the subject’s safety or evaluation of the trial results;  
  5) Circumstances that discontinuation is necessary due to other reasons; and 
  6) The subject dies.  
The subject has the right to withdraw from the trial at any time without any reason. If the 
subject decides to withdraw from the trial, the investigator shall try to find out the reason for 
withdrawal and record the reason as original text data. 
The investigator has the right to discontinue the subject’s participation in the trial when 
the following circumstances occur: The investigator must carefully evaluate the subject who 
discontinues the trial, take positive treatment measures, and record in detail in original 
records. If the subject withdraws from the trial due to AEs, abnormal laboratory test or test 
failure, it must also be evaluated and treated accordingly, and be recorded in detail in original 
records. The investigator can also determine whether the subject should continue the clinical 
trial based on medical judgment at any time during the trial. 
Criteria of termination of the trial： 
Termination of the trial means that the trial is stopped before completing evaluation of 
all subjects as planned. After the trial is terminated, new subjects will not be included. The 
subjects who have been included but not yet dropped out will be checked and interviewed 

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according to the results of the discussion between the Sponsor and the investigator. 
  1) If no clinical value of the product is found during the trial, the trial shall be 
terminated; 
  2) If any major error in the clinical trial protocol is found during the trial and it’s 
difficult to evaluate product effect, the trial shall be terminated; 
  3) If severe deviation occurs during the trial, and it’s difficult to evaluate product 
effect if the trial continues, the trial shall be terminated; 
  4) The Sponsor requests termination (due to the reason of funding or management); 
  5) NMPA orders to terminate the trial due to some reasons;  
  6) Ethics Committee terminates the trial to safeguard the rights and interests of the 
subjects.  
If any subject terminates the trial prematurely, the investigator should try to find out the 
reasons for withdrawal, such as AEs, ineffective correction measures, withdrawal based on 
the investigator’s decision or other reasons. The reasons of withdrawal shall be recorded in 
CRF. 
It is necessary to complete efficacy and safety evaluation when withdrawal or 
termination of the trial occurs as specified in the protocol, complete safety follow-up, and 
record AEs and outcomes completely. The investigator can advise or provide new or 
alternative therapies to the subject according to actual situation of the subject.  
If the subject refuses to go to the study site for further visit, study-related information 
shall be collected continuously, unless the subject withdraws the consent of disclosing further 
information or being contacted. In this case, no more evaluation shall be conducted and no 
more data shall be collected. 
Premature termination or suspension： 
The present study can be terminated or suspended prematurely. This may be due to the 
decision of regulatory authority, change of opinions of Ethics Committee, efficacy or safety 
of the investigational drug, or decision of the Sponsor. In addition, the Sponsor who decides 
to suspend/terminate the study will send a written notice and reasons for termination or 
suspension of the study to the investigator, the Sponsor and regulatory authority. The 
investigator should notify Ethics Committee and the Sponsor, and clarify relevant reasons 
immediately.  
Reasons for premature termination or suspension of the study may include:  
• Definite unexpected, major or unacceptable risks facing the subject.  

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• Existing efficacy results support premature termination of the study.  
• Low compliance as required by the protocol.  
Once the problems mentioned above are resolved, the study can be continued upon 
approval by the Sponsor, Ethics Committee or regulatory authority. . 
6.1.5.6 Expected duration of the clinical trial and rationale 
Personnel training will begin after the Sponsor and medical institute of the clinical trial 
sign the clinical trial protocol through amicable negotiations. Case observation record will be 
printed according to defined evaluation criteria of the investigational product. The Sponsor 
will provide sufficient investigational products, and take into account relevant factors such as 
the patient referral rate and the number of patients who agree to participate in the trial. As 
planned, the clinical trial will start upon approval by the Ethics Committee and the signing of 
clinical trial agreement Fifteen patients are expected to be enrolled from January 2022 to 
December 2023. Summary of clinical study will be completed in February 2024. Duration of 
the trial will be modified according to actual progress of the trial. If all cases are not 
completed, the trial will be postponed until all cases have been completed. 
6.1.5.7 Expected duration of participation of each subject 
The duration of participation of each subject is defined as the period of time from the 
subject’s signing the informed consent to the end of final follow-up. In this trial, the expected 
duration of participation of each subject is 3.3 months, including 1 week of screening, 1 day 
of surgery and 3 months of following up.  
6.1.6 Evaluation Index 
6.1.6.1 Explanation of Outcome Measures 
Primary Outcome Measure: 
1) All-cause mortality 
Death from any cause during the observation period. 
[Time Frame: 3 months] 
2) Procedural success 
Resting left ventricle outflow tract gradients < 30 mmHg, provoked left ventricle 
outflow tract gradients < 50 mmHg, and 
mitral regurgitation (MR) ≤ grade 1+. 
[Time Frame: 3 months] 
Secondary Outcome Measure: 
3) Device success 

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Successful accession, delivery, and retrieval of the resection device, successful resection 
of the septal myocardium, resting left ventricle outflow tract gradient less than 50 mmHg and 
mitral regurgitation (MR) ≤ grade 2+ during operation after resection, and free from 
conversion to midline thoracotomy during operation. 
[Time Frame: 1 day] 
4) Septal thickness 
Basal and mid septal thickness as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
5) Left ventricle mass 
Left ventricle mass index (the ratio of left ventricle mass to body weight) as measured 
by cardiac magnetic resonance. 
[Time Frame: 3 months] 
6) Left ventricle volume 
Left ventricle end-diastolic volume as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
7) Cardiac diastolic function 
The ratio between early mitral inflow velocity and mitral annular early diastolic velocity 
( E/e') as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
8) Left atria volume 
The left atria volume as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
9) Major adverse cardiovascular and cerebral events 
In-hospital mortality, atrioventricular block that need permanent pacemaker implantation, 
sternotomy conversion, iatrogenic ventricular septal perforation, iatrogenic valvular injury, 
imaging examination-validated cerebral complications. 
[Time Frame: 3 months] 
10) New York Heart Association class 
New York Heart Association class, including grade I, grade II, grade III, grade IV. A 
higher grade means worse heart function. 
[Time Frame: 7 days and 3 months] 
11) 6-minute walking test 
6-minute walking test. A longer distance means better heart function. 
[Time Frame: 3 months] 

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12) Heart function-associated quality of life 
Score of the Kansas City Cardiomyopathy Questionnaire. A higher score means better 
heart function. 
[Time Frame: 7 days and 3 months] 
13) Left ventricular outflow tract gradient 
Left ventricular outflow tract gradient as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
14) Evaluation of the mitral valve 
Grade of mitral regurgitation and systolic anterior motion as measured by 
echocardiography. 
[Time Frame: 7 days and 3 months] 
15) Left ventricular outflow tract diameter 
Left ventricular outflow tract diameter as measured by echocardiography. 
[Time Frame: 7 days and 3 months] 
6.1.6.2 Evaluation of Device Performance 
➢ The investigator evaluates the operation performance of study device 
intraoperatively, according to the following evaluation criteria:  
⚫ Excellent: The device is easy to operate without error touch. It can quickly and 
precisely puncture and fix the tissue to be resected and remove it. Negative pressure 
aspiration is successful. There is no tissue detachment or debris generation during 
removal. The cutting edge of the removed tissue is regular and free of burrs. The device 
does not interfere with ultrasound. The intraoperative positioning is precise.  
⚫ Good: The device is easy to operate without error touch. It can precisely 
puncture and fix the tissue to be resected. Negative pressure aspiration is successful. 
There is no tissue detachment or debris during removal. The cutting edge of the removed 
tissue is regular and free of burrs. The device does not interfere with ultrasound. 
Intraoperative positioning is precise.  
⚫ Medium: The device enables smooth operation with ≤3 intraoperative error 
touches. It can puncture and fix the tissue to be resected. Negative pressure aspiration is 
successful. There is basically no tissue detachment or debris generation during removal. 
The cutting edge of the removed tissue is relatively regular without obvious burr. The 
device interferes with ultrasound, but there is no impediment in intraoperative 
positioning. 
⚫ Poor: Use of the device in left ventricle is difficult with multiple (>3) error 

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touches. Puncturing and fixation of the tissue to be resected are difficult. Negative 
pressure aspiration is not satisfactory. There is tissue detachment or debris generation 
during removal. The cutting edge of the removed tissue is not regular with obvious burr. 
The device interferes with ultrasound significantly. Intraoperative positioning is difficult.  
6.1.6.3  Description of Safety Parameters 
1) All-cause mortality rate and sudden cardiac death rate within 30 days after surgery; 
2) Incidence of severe AEs (severe pericardial effusion, arrhythmia, aortic valve injury, 
mitral valve injury, ventricular septal defect, ischemic cerebral infarction, apical tear, 
hemorrhagic shock) within 30 days after surgery and number of events;  
3) Incidence (%) of surgery and device-related (serious) AEs within 30 days after 
surgery, and number of events. 
6.1.6.4  Method and time for evaluation, recording and analysis of parameters 
➢ AEs: all-cause mortality rate and sudden cardiac death rate within 30 days after 
surgery 
AEs refer to adverse medical events during the clinical trial, which are related or 
unrelated to the medical device used. All-cause mortality and sudden cardiac death within 30 
days after surgery are key events of monitoring. The incidence of AEs is calculated with the 
sum of AEs in all subjects as the numerator and number of included cases with all evaluable 
AEs as the denominator.  
➢ Incidence of severe adverse events within 30 days after surgery 
Serious AEs (SAEs) refer to the events that occur during the clinical trial and lead to 
death or severe worsening of health, including fatal diseases or injury, permanent defect of 
physical structure or functions, hospitalization or extension of hospitalization, medical or 
surgical intervention to avoid permanent defect of physical structure or functions; or the 
events leading to fetal distress, fetal death, congenital abnormality, congenital defect, etc.  
SAEs that may occur during this study include severe pericardial effusion, arrhythmia, 
aortic valve injury, mitral valve injury, ventricular septal defect, ischemic cerebral infarction, 
apical tear, hemorrhagic shock, etc. The incidence of SAEs is calculated with the sum of 
SAEs in all subjects as the numerator and the number of included cases with all evaluable 
SAEs as the denominator. 
❖ Time points of visits: Screening/baseline (Day -7 to Day 0), the day of surgery (Day 0), 
Visit 3 (1 day after surgery), Visit 4 (1 week ± 2 days after surgery), Visit 5 (1 month ± 3 days 
after surgery). 

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➢ Incidence (%) of surgery and device-related (serious) AEs within 30 days after 
surgery and number of events 
Device defects refer to unreasonable risks that may endanger human health and life 
safety in normal use of medical devices in clinical trials, such as label errors, quality 
problems, failures and other events. The incidence (%) of surgery and device-related (serious) 
AEs refers to the incidence of surgery and device-related adverse medical events or AEs. The 
incidence of device-related (serious) AEs is calculated with the sum of surgery and 
device-related (serious) AEs as the numerator and the number of included cases with all 
evaluable AEs as the denominator. 
6.2 
Trial Process 
6.2.1 Trial Process 
Visit 1: Screening/Baseline Period (-7-0 days) 
1) Sign an informed consent form; 
2) Record past or current medical history, accompanied by disease and treatment history, 
family history, surgical history, trauma history, allergic history 
3) Verify inclusion/exclusion criteria; 
4) Demographic data: including gender, age (date of birth), ethnicity, and weight; 
5) Vital signs include body temperature, respiration, heart rate, and blood pressure; 
6) Physical examination: including general conditions, skin and mucous membranes, 
lymph nodes, head, neck, chest, abdomen, spine and limbs, nervous system, and other routine 
examinations; 
7) Blood routine: Red blood cell, white blood cell, platelet count, hemoglobin, 
percentage of neutrophils, percentage of lymphocytes; 
8) Urinary routine: urine sugar, urine pH, bilirubin, urine protein, urine ketone body, 
urine specific gravity, red blood cell count, white blood cell count; 
9) Blood biochemistry: liver function, kidney function, electrolytes, including enzymes 
such as glutathione aminotransferase, alanine aminotransferase, total protein, albumin, 
globulin, total bilirubin, indirect bilirubin, direct bilirubin, alkaline phosphatase γ- 
Glutamyltranspeptidase, total cholesterol, lactate dehydrogenase, urea, creatinine, uric acid, 
hydrocarbon, eGFR, potassium, sodium, chloride, calcium, corrected calcium; 
10) Coagulation function: prothrombin time, prothrombin activity, international 
standardized ratio, fibrinogen, activated partial thromboplastin time, thrombin time; 
11) Echocardiography: Left ventricular outflow tract pressure difference (LVOTG), left 

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ventricular outflow tract diameter, end diastolic interventricular septal thickness, end diastolic 
left ventricular diameter, end systolic left ventricular diameter, end diastolic left ventricular 
volume, end systolic left ventricular volume, left ventricular ejection fraction, diastolic mitral 
valve E-peak and A-peak velocities; 
12) Cardiac MRI or chest enhanced CT 
13) Myocardial enzymology: High sensitivity cardiac troponin I, myoglobin, creatine 
kinase MB type isoenzymes; 
14) B-type natriuretic peptide; 
15) Electrocardiogram; 
16) NYHA assessment; 
17) 6-minute walking test; 
18) Quality of life score; 
19) Evaluation of combined medication use; 
20) Adverse event evaluation: Record the adverse events/serious adverse events that 
occurred/existed during the screening period of the subjects; 
21) Make an appointment for the next visit. 
Note: The laboratory examination results and imaging results (echocardiography) within 
7 days and 30 days prior to signing the informed consent are both valid 
Visit 2: On the day of surgery (Day 0) 
1) Verify inclusion/exclusion criteria; 
2) Surgical records; 
3) Echocardiography: Left ventricular outflow tract pressure difference (LVOTG), left 
ventricular outflow tract diameter, end diastolic interventricular septal thickness, end diastolic 
left ventricular diameter, end systolic left ventricular diameter, end diastolic left ventricular 
volume, end systolic left ventricular volume, left ventricular ejection fraction, diastolic mitral 
valve E-peak and A-peak velocities; 
4) Electrocardiogram; 
5) Immediate success evaluation after surgery; 
6) Product device performance evaluation; 
7) Record the situation of combined medication use; 
8) Record the occurrence of adverse events; 
10) Make an appointment for the next visit. 
Visit 3: 1 day after surgery 
1) Vital signs: body temperature, respiration, heart rate, blood pressure 

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2) Electrocardiogram; 
3) Record the situation of combined medication use; 
4) Record the occurrence of adverse events; 
6) Make an appointment for the next visit. 
Visit 4: 1 week ± 1 day after surgery  
1) Vital signs: body temperature, respiration, heart rate, blood pressure; 
2) Blood routine: Red blood cell, white blood cell, platelet count, hemoglobin, 
percentage of neutrophils, percentage of lymphocytes; 
3) Urinary routine: urine sugar, urine pH, bilirubin, urine protein, urine ketone body, 
urine specific gravity, red blood cell count, white blood cell count; 
4) Blood biochemistry: liver function, kidney function, electrolytes, including enzymes 
such as glutathione aminotransferase, alanine aminotransferase, total protein, albumin, 
globulin, total bilirubin, indirect bilirubin, direct bilirubin, alkaline phosphatase γ- 
Glutamyltranspeptidase, total cholesterol, lactate dehydrogenase, urea, creatinine, uric acid, 
hydrocarbon, eGFR, potassium, sodium, chloride, calcium, corrected calcium; 
5) Echocardiography: Left ventricular outflow tract pressure difference (LVOTG), left 
ventricular outflow tract diameter, end diastolic interventricular septal thickness, end diastolic 
left ventricular diameter, end systolic left ventricular diameter, end diastolic left ventricular 
volume, end systolic left ventricular volume, left ventricular ejection fraction, diastolic mitral 
valve E-peak and A-peak velocities; 
6) Cardiac MRI or chest enhanced CT; 
7) B-type natriuretic peptide; 
8) Electrocardiogram; 
9) NYHA assessment; 
10) Quality of life score; 
11) Record the situation of combined medication use; 
12) Record the occurrence of adverse events; 
14) Make an appointment for the next visit. 
Visit 5: 3 months ± 7 days after surgery  
1) Vital signs: body temperature, respiration, heart rate, blood pressure; 
2) Blood routine: red blood cells, white blood cells, platelet count, hemoglobin, 
percentage of neutrophils, percentage of lymphocytes 
3) Blood biochemistry: liver function, kidney function, electrolytes, including enzymes 
such as glutathione aminotransferase, alanine aminotransferase, total protein, albumin, 

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globulin, total bilirubin, indirect bilirubin, direct bilirubin, alkaline phosphatase γ- 
Glutamyltranspeptidase, total cholesterol, lactate dehydrogenase, urea, creatinine, uric acid, 
hydrocarbon, eGFR, potassium, sodium, chloride, calcium, corrected calcium; 
4) Echocardiography: Left ventricular outflow tract pressure difference (LVOTG), left 
ventricular outflow tract diameter, end diastolic interventricular septal thickness, end diastolic 
left ventricular diameter, end systolic left ventricular diameter, end diastolic left ventricular 
volume, end systolic left ventricular volume, left ventricular ejection fraction, diastolic mitral 
valve E-peak and A-peak velocities; 
5) Cardiac MRI or chest enhanced CT; 
6) Myocardial enzymology: High sensitivity cardiac troponin I, myoglobin, creatine 
kinase MB type isoenzymes; 
7) B-type natriuretic peptide; 
8) Electrocardiogram; 
9) NYHA assessment; 
10) Quality of life score; 
11) 6-minute walking test; 
12) Record the situation of combined medication use; 
13) Record the occurrence of adverse events. 
6.2.2 Standard use of device 
6.2.2.1  Auxiliary devices 
1) 18G vascular puncture needle, 0.035 inch short wire 
2) Echocardiogram 
3) Negative pressure flushing and aspiration system 
All these auxiliary devices are (possibly) medical devices used during the surgery. 
Validation of compatibility with the product dilator is necessary before use of puncture and 
wire. In addition, this device is a myocardial resection device, and compatibility with other 
devices shall be validated before use. Surgical operation is performed as per the instructions.  
6.2.2.2  Operation methods 
⚫ Preparation of patients 
1) The patient is in supine position. After disinfection of surgical field, make a small 
incision of 3-5 cm in left 5th rib under general anaesthesia;  

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2) Open the pericardium and expose left ventricular apex. Place two purse-string sutures 
in advance 2 cm lateral end of left anterior descending branch.  
⚫ Preparation of device 
1) Read and understand the instructions. 
2) Ensure intact packing and sterilization within expiry.  
Warning: Do not use if the packing is broken or opened. 
3) Take out the device from the sterile package, perform sterile operation, check the 
integrity of the product, and confirm that the resection slot is fully closed. If it is not 
completely closed, push the rear part of the handle to completely close the resection slot. 
Note: Do not use the device if it is broken, puncture needle is exposed or the safety 
device is in unlocked position. Failure of keeping the device and auxiliary device sterile may 
lead to infection.  
⚫ Operation of device 
  1) Use the 18G vascular puncture needle to perform apical puncture in the 
purse-string suture. Insert a 0.035-inch short wire into the heart for guidance. After removal 
of the puncture needle, hold the handle of the dilator, and insert the dilator into the apex pole 
along the wire for dilation. When the stopper of the dilator contacts the heart, dilation is 
completed;  
  2) Fill 50 ml normal saline to expel internal air through a flexible pipe;  
  3) Remove the dilator and tighten up the purse-string suture to stop bleeding. Insert 
the minimally-invasive myocardial resection system through the apical pole slowly into left 
ventricular outflow tract along the interventricular septum under ultrasound monitoring;  
4) Under real-time ultrasound monitoring, align the resection slot with the site to be 
resected, reverse the handle, push the button, open the resection slot, and ensure that there is 
no other cardiac structure in the resection slot except hypertrophic myocardial tissue; 
5) Apply a certain pressure to the resection slot, turn on the negative pressure system to 
a negative pressure -0.07 Mpa, and place the tissue to be resected completely into the 
resection slot. At this time, press the button downward and push the button forward to the 
front end to fix the tissue to be resected. Note that during the pushing process, keep the 
device still and close to the resected site; 

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6) After the puncture needle is in place, the handle is rotated left and right to resect 
under real-time ultrasound monitoring. When the handle is rotated and pushed to the front 
end, the resction is completed. Take out the minimally-invasive cardiac resection system 
under ultrasound monitoring, tighten the apical purse-string suture to stop bleeding, turn off 
the negative pressure system, step back the handle and push button in turn, open the resection 
slot and take out the rescted tissue.  
7) Left ventricular outflow tract gradient (LVOTG) is measured by ultrasound. If the 
hypertrophic ventricular septal myocardial tissue needs to be resected again, the resection slot 
should be thoroughly cleaned to ensure that there are no residual myocardium, tissue 
fragments, blood clots in the resection slot. Restore the device to the original state, and then 
repeat above steps 2, 3, 4, 5, and 6 for resection. 
6.2.3 Monitoring Plan 
According to the complexity of the trial and number of sites, the Sponsor shall assign 
qualified monitors and formulate corresponding monitoring plans to ensure that the rights and 
interests of subjects in the clinical trial are protected, data of trial records and reports are 
accurate and complete, and the trial complies with approved protocol and relevant 
regulations. 
Pre-trial monitoring items include devices, study documents, study staff and study 
training. Items of monitoring during trial include screening of subjects, informed consent, 
routine visits, documents to be submitted to the Ethics Committee during the trial, and 
adverse events. Items of monitoring at (Premature end) the end of trial include recovery of 
investigational products, recovery of CRF and data query, confirmation of the integrity of 
study documents, notification of Ethics Committee, review of AE and SAE, closure of sites, 
statistical analysis reports of clinical trials, and clinical trial reports. 
The monitor shall have relevant professional background in clinical medicine, pharmacy, 
biomedical engineering and statistics, be familiar with management specifications and 
relevant regulations for clinical trials of medical devices after necessary training, as well as 
non-clinical information of study medical device, clinical information of similar products, 
and also clinical trial protocol and relevant documents. 
The monitoring frequency in the approved Monitoring Plan shall prevail.  
The monitor shall comply with Good Clinical Practice (GCP) principles, and ensure that 
the clinical trial is strictly conducted as per the protocol through effective supervision. Trial 
data are authentic, integral and accurate. Specific responsibilities include:  

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    (1) Confirm that the clinical study site has appropriate conditions before the trial, 
including staffing and training, complete laboratory equipment, good working conditions, 
sufficient number  of subjects, and participants familiar with the trial requirements; 
(2) Monitor whether the clinical study site and investigator comply with approved 
clinical trial protocol, Good Clinical Practice of medical device or relevant regulations before, 
during and after the trial; 
  (3) Confirm that each subject signs the informed consent before participating in the trial; 
understand the enrollment rate and progress of the trial; record the trial and test that the 
investigator doesn’t conduct and correction of errors and omissions clearly and actually; and 
confirm that subjects whose visits aren’t completed to re-sign the revised informed consent;  
  (4) Confirm that all CRFs are filled correctly and consistent with original data. All errors 
or omissions have been corrected or noted, signed and dated by the researcher. The type of 
disease, total number of cases, age and effectiveness in each trial shall be confirmed and 
recorded; 
  (5) Confirm that withdrawal or non-compliance with the informed consent is recorded, 
and discuss the case with the investigator; 
  (6) Confirm that all adverse events and device defects should be recorded, and SAEs and 
major device defects that may lead to SAEs should be reported and recorded within specified 
time; 
  (7) Monitor the supply, use and maintenance of the study medical devices and treatment 
process of medical devices after trial; 
(8) Ensure that the equipment related to clinical trial evaluation is regularly maintained, 
calibrated and recorded; 
(9) Ensure that the investigator receives the latest copies of all documents related to the 
clinical trial; 
(10) A written report shall be submitted to the Sponsor and clinical study site after each 
monitoring. The report shall indicate the date and time of monitoring, name of the monitor, 
location of monitoring, name of the investigator, monitoring content, completion of the trial, 
monitoring findings, facts, deviations, conclusions and correction of errors and omissions. 
7 
Risk analysis and countermeasures 
7.1 
Analysis of each subject before enrollment 
Before enrollment of each subject, it is necessary to perform a thorough risk analysis, 
describe in detail the type of risk, estimate the severity, and demonstrate the possibility to 

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minimize the risk and the rationality between risk and expected benefit. Risk analysis scope 
covers expected benefits and potential clinical effects of failure identified in equipment 
evaluation strategy, as well as the risks or inherent processes that may be related to potential 
disease, are not related to the equipment, and benefit from the unique equipment design. 
7.2 
Common risk types and manifestions of study devices 
7.2.1 Types of device defect  
Types of device defects include but are not limited to defects of device design, defects of 
manufacturing and packaging process, operation defects, and clinical application accidents 
caused by patients’ special anatomical characteristics. 
7.2.2 Possible defects of study device 
Include: 
➢ Cutting knife fails to work normally, resulting in device failure and surgery 
failure 
➢ The puncture force of the puncture component is too small, resulting in failure 
of the device to puncture and fix the tissue and also difficulty of subsequent surgery 
➢ Air-tight seal is not up to standard, the negative pressure aspiration fails, and 
fixation of tissue and subsequent surgery are difficult 
➢ The cutting knife does not move smoothly, the cutting edge is not regular with 
many burrs, and the detached tissue forms plug during cutting process 
➢ Surface coating interferes with ultrasound imaging and forms ultrasound 
artifacts, resulting in difficulty of ultrasound-guided surgery in Surgery II 
➢ The product material is corroded in blood environment, this causes the release of 
harmful substances and detachment of particles, and substances produced by reaction 
between the product and tissue fluid cause adverse reactions of patients 
➢ The handle control is slow or the button fails, resulting in device failure and 
surgery failure 
7.3 
Methods to minimize risk 
Standard methods and additional mitigation strategies may be adopted to protect 
individual subjects and future participants. Examples of standard and additional risk 
mitigation strategies include: 
7.3.1 Study site that provides appropriate therapy  
A study site that provides appropriate alternative therapy when necessary and manages 

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AEs with sufficient expertise and resources.  
7.3.2 Fully trained and qualified investigators  
Confirm that fully trained and qualified investigators can conduct early feasibility study; 
7.3.3 Obtain more human factor information plans  
During the study, obtain more information about human factors, screen more suitable 
population for device treatment, exclude special conditions that may affect the effect of 
surgery, analyze the obstruction site of enrolled subjects in detail, and select appropriate 
surgical methods based on overall health; 
7.3.4 Organize peer experts to conduct scientific and reasonable discussion and 
analysis  
Ensure correct interpretation of inclusion and exclusion criteria, and organize peer 
experts to conduct scientific and reasonable discussion and analysis on the conditions that 
may affect diseases and successful surgery that are not clearly listed in inclusion and 
exclusion criteria; 
7.3.5 Retrospective analysis of data of each follow-up point  
Regular follow-up that is more frequent than traditional feasibility or key study. 
Retrospective analysis of data of each follow-up to monitor subject safety and equipment 
effectiveness in real time; 
7.3.6 Retrospective systemic summary analysis of AEs  
Regular reporting of AEs rather than each occurrence and retrospective systemic 
summary analysis of each AE; 
7.3.7 Detailed field records of every use of device  
Detailed field records of every use of device. Report performance parameters of the 
equipment after use, which can help to determine whether the equipment runs as expected;  
7.3.8 Detailed analysis of every enrolled subject whose surgery is successful  
Whether every enrolled subject whose surgery is successful has anatomical 
characteristics that are beneficial for operation of device? If it only meets the qualification 
requirements but does not have such special anatomical characteristics, may it increase the 
difficulty of using the equipment? Screen more suitable population for device treatment and 
exclude special conditions that may affect the surgery effect. 

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7.4 
Parameters of safety evaluation 
Safety analysis: Safety analysis is based on safety analysis set (SS).  
For both safety evaluation and device defect evaluation, statistical description method is 
adopted to describe AEs (or SAEs), device-related AEs (or SAEs), type, number of cases and 
incidence of device defects, and list the type, frequency, severity and relationship with study 
device of AEs that occurred in this trial. 
7.5 
Calculation of sample size 
This study is an exploratory study aiming to investigate the effectiveness and safety of 
the product, so sample size is not calculated. It’s expected that 10 subjects are included to 
resect ventricular septal myocardial tissue through apex of the heart by myocardial resection 
system under the guidance of ultrasound. 
7.6 
Significance level and power of clinical trial 
This study is an exploratory pre-trial without significance level or power. 
7.7 
Expected drop-out rate 
This study is an exploratory pre-trial without expected drop-out rate. 
7.8 
Qualified/unqualified criteria of clinical trial results 
This study is an exploratory study aming to investigate the effectiveness and safety of 
the product, so qualified/unqualified criteria are not set.  
7.9 
Criteria and reasons for terminating the test based on statistical reasons 
This study has no interim analysis and doesn’t terminate based on statistical reasons.  
7.10 Statistical method of all data, including treatment of unreasonable data, such as 
missing, unused or wrong data (including drop out and withdrawal) 
After the database is locked, perform statistical analysis and logic testing according to 
statistical analysis plan, and provide a statistical analysis report according to the results. 
➢ Treatment of missing values: Missing value will not be imputed in principle. 
Specific treatment method will be clarified in detail in the statistical analysis plan. 
➢ Treatment of unreasonable data: In the process of data management, the data 
will be checked logically. If unreasonable data are found, the investigator or data entry 
staff will be queried, and the database can be locked until all unreasonable data are 
resolved. 
➢ Treatment of wrong data: In the process of data management, quality 
management of data will be performed. If wrong data are found, the investigator or data 

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entry staff will be queried until all wrong data are corrected, then data management will 
be performed.  
7.11 Procedures of reporting deviation from statistical plan 
In case of “incomplete implementation of statistical analysis plan”, the change procedure 
shall be applied in advance, and changes of the statistical plan shall be recorded in the 
statistical analysis plan, including changes in location, reason and time. Protocol deviations 
shall be reported by the investigator to the hospital organization office and Ethics Committee. 
7.12 Criteria and reasons of subjects included in the analysis  
This clinical trial has three statistical data sets, ie. full analysis set (FAS) and per 
protocol set (PPS) for safety analysis, and safety set (SS) for safety analysis.  
➢ FAS: According to intention-to-treat (ITT) principle, all subjects who are 
enrolled and use the device and receive at least one effect evaluation.  
➢ PPS: A sub set of FAS, includes subjects who don’t violate main 
inclusion/exclusion criteria, have good compliance, don’t have any protocol violation 
that affects main efficacy parameters.  
➢ SS: All subjects who participate in the trial, use the study device and receive at 
least one safety evaluation.  
7.13 Exclusion of special information and reasons (if applicable) in hypothesis testing 
None. 
8 
Data Management 
8.1 
Management of database 
Paper CRF is used to collect data in this trial. Data management will be performed in 
accordance with the principles of Technical Guidelines for Clinical Trial Data Management to 
ensure integrity, accuracy, authenticity and reliability of clinical trial data.  
8.2 
Permission assignment 
The system administrator grants different permissions according to different roles of 
data-entry staff, data administrator, (principal) investigator and clinical monitor. Data-entry 
staff has the authority to enter, modify, browse and answer queries. Investigator has the 
authority to enter, modify, browse and answer queries. Besides the authority of the 
investigator, Principal Investigator has the authority of signature. The monitor has the 
authority to browse, send/close queries and check original data. Data administrator has the 
authority to browse, send/close queries, review, lock data and lock authority. 

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8.3 
Data entry 
Clinical investigator or the data-entry staff (clinical coordinator) designated by the 
investigator shall enter source data into CRF timely and accurately.  
During the study, the study site shall store original record of each subject, including 
study medical records, laboratory data and any other examination and evaluation results as 
well as visit records, basic information and medical information of the subject and also 
original copy of the informed consent signed by the subject, so as to obtain relevant original 
data necessary for CRF. Field monitor can inspect to validate at any time.  
8.4 
Design and establishment of database 
The database is established by the data management department and shall comply with 
FDA 21 CFR Part 11. The database shall be used to manage system login, data entry, 
modification, deletion and other data traces. For establishment of the database, it is necessary 
to adopt or refer to CDISC standard.  
8.5 
Sending and solving of query 
After entry into the Electronic Data Capture (EDC) database, the system will check the 
data as per the data check plan (edited logic check), and issue the request of system query for 
questioned data. Clinical monitor and data administrator check the data manually, and send 
manual queries of questioned data to the EDC database. Data-entry staff or the investigator 
confirms and answers manual query and system query, and modifies wrong data if necessary 
until the query is resolved. If the answer fails to resolve the query, the data administrator and 
clinical monitor can query the data again, and all records are saved in the EDC database. 
8.6 
Modification and review of data 
Data-entry staff or the investigator can modify the data after check, and fill the reasons 
for modification in the CRF. Principal Investigator has the authority to sign all final data. 
8.7 
Edit check 
Edit of data includes computerized edit check, manual check (medical check, statistical 
check) and data check meeting. The investigator or designated staff shall correct or clarify 
inconsistent data (Data Query) found in the check process timely.  
8.8 
CRF signature 
The monitor and data administrator check the data in the database, after that, Principal 
Investigator will confirm the authenticity and integrity of data and sign.  

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8.9 
Locking and export of database 
After all data are reviewed, the data administrator will lock the database according to the 
database locking protocol. After all data are accurately entered into the database, Principal 
Investigator, the Sponsor, clinical monitor, data administrator and statistical analysts will hold 
a data review meeting to report the project and discuss existing problems. After all the 
problems are resolved, the data administrator can start database locking after confirming that 
all parties have no questions. After all data are entered into the EDC accurately, the monitor 
checks all original data, the data administrator reviews all data, Principal Investigator signs 
all data electronically, and the database can be locked upon approval. 
In case of any modification after the database is locked, an application shall be 
submitted, and database unlocking and modification can be performed only after the Sponsor, 
investigator, data-entry staff, monitor and data administrator discuss and sign for 
confirmation. 
8.10 Archive 
CRF will be archived as required at the end of study. Clinical study site will store 
clinical trial materials for 10 years after end of study.  
Safety and environmental issues shall be considered for archiving. No study documents 
shall be destroyed without written permission of the investigator. 
9 
Feasibility Analysis 
9.1 
Feasibility analysis of success 
1) The ultrasound-guided transapical approach is widely applied, such as repair or 
replacement of aortic valve and mitral valve. The technique is mature, and its safety and 
reliability have been verified in clinical practice. For this trial, a new cardiac resection device 
is used for tissue resection through a new surgical approach at the apex of the heart. This 
approach doesn’t need chest or extracorporeal circulation, can evaluate obstruction level and 
modify surgical field in real time, and dredge LVOTO through multiple resections. Feasibility 
and safety of this approach have been verified in porcine trial. Therefore, it is expected that 
the investigational product can meet the requirements of clinical trials with reliable safety 
performance and sufficient countermeasures of surgical risk in the apical approach. 
  2) This clinical trial is conducted by professional hospitals and investigators with 
qualification of clinical trial. The investigators have rich experiences of clinical practice, 
receive CGP training, provide treatment as per the clinical trial protocol and advise the 
subject to comply with medical advice.  

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9.2 
Feasibility analysis of failure 
Conduct of this trial does not comply with trial protocol, the use instructions or 
precautions, all observation results in the clinical trial are not complete, and lack of original 
data and other factors may cause the trial to fail. 
There may also be other unpredictable risks in this study, such as poor physical 
constitution, severe allergies, disease worsening, accidents and unpredictable events during 
the trial, which may lead to study failure. However, the risk can be minimized by complying 
with this protocol, participating in clinical study at the specified study site, complying with 
inclusion criteria, and closely monitoring the physical condition of subjects during the study 
and/or follow-up. 
The investigator shall record all AEs and device defects found during the clinical trial, 
and analyze the reasons of AEs together with the Sponsor. 
9.3 
Potential risks and benefits 
9.3.1 Prediction of AEs and measures 
Possible intraoperative or postoperative AEs of surgery guided by minimally-invasive 
myocardial revascularization system ultrasound navigation mainly include arrhythmia, mitral 
valve injury, aortic valve injury, pericardial effusion, stroke, ventricular septal defect and 
hemorrhagic shock as follows:  
⚫ Arrhythmia 
When the hypertrophic tissue of ventricular septum is resected, the atrioventricular 
conduction system of the heart running in ventricular septum may be damaged due to tissue 
resection. Arrhythmia includes atrioventricular block, left bundle branch block, atrial 
fibrillation.  
It is necessary to enhance the investigator’s training, improve the proficiency of 
investigator, define non-injurable myocardial resection range, enhance monitoring of 
intraoperative rhythm, observe ECG change when myocardial tissue is resected and provide 
appropriate and timely treatment if persistent severe arrhythmia occurs. Asymptomatic 
patient who has first-degree or mild second-degree atrioventricular block doesn’t need 
treatment, and implantation of a pacemaker is necessary for complete atrioventricular block. 
Asymptomatic patient who has left bundle branch block doesn’t need treatment, and cardiac 
resynchronization therapy can be performed for complete left bundle branch block. 
Anticoagulant therapy can begin for patient whose atrial fibrillation is graded as high-risk 
embolism, and drug or electric cardioversion and catheter ablation are prepared.  

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⚫ Mitral valve injury 
When the myocardial resection system enters the left ventricle through the apex under 
the guidance of ultrasound, location of resected tissue may cause mitral valve injury. It is 
necessary to enhance the investigator’s training, improve the proficiency of the investigator, 
and understand cardiac anatomical marker under ultrasound. This can reduce mitral valve 
injury effectively. In case of intraoperative mitral regurgitation or worsening of mitral 
regurgitation, the investigator shall determine no treatment, mitral valve repair or mitral valve 
replacement according to mitral valve injury and regurgitation.  
⚫ Aortic valve injury 
When the myocardial resection system enters the left ventricle through the apex under 
the guidance of ultrasound, location of resected tissue may cause aortic valve injury. 
It is necessary to enhance the investigator’s training, improve the proficiency of the 
investigator, understand cardiac anatomy, and modify according to the patient’s actual 
condition. This can reduce aortic valve injury effectively. For mild aortic valve injury (reflux 
per stroke showed by apical ultrasound), special treatment is unnecessary; aortic valve repair 
can be performed for severe injury; and aortic valve replacement can be performed for 
irreparable injury.  
⚫ Pericardial effusion 
Pericardial effusion may be caused by postoperative incision effusion and apical tear. 
Dyspnea is the most common symptom of pericardial effusion. A large amount of pericardial 
effusion can cause pericardial tamponade, and the syndrome of hypotension, low heart 
murmur and jugular vein distension will occur. 
It is necessary to enhance the investigator’s training. Careful operation and tight suture 
for apical closure ensure suture. Accurate determination of the cause of pericardial effusion is 
critical.In case of pericardial effusion, emergent pericardiocentesis is necessary to relieve 
symptoms of pericardial tamponade. It is necessary to define the primary cause of pericardial 
effusion and treat the primary disease.  
⚫ Stroke 
Postoperative atrial fibrillation causes thrombosis. When the thrombus flows through the 
aorta and carotid artery through the internal cerebral artery, cerebral artery embolism may 
occur, even leading to ischemic stroke. 
Monitor the patient’s ECG after surgery. Patients with atrial fibrillation who have a high 
risk of thrombus shall take anticoagulant drugs as soon as possible and take medicine or 
electric cardioversion. Patients whose conditions permit can receive radiofrequency catheter 

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ablation. 
⚫ Ventricular septal defect 
Myocardial resection system aspirates myocardial tissue in the negative-pressure tube by 
negative pressure, ultrasound imaging is unclear, and aspiration of over tissues may cause 
ventricular septal defect. Small area of ventricular septal defect and less left-to-right shunt 
have few effect on the patient’s daily activities; large area of ventricular septal defect and 
more left-to-right shunt can cause systemic ischemia and symptoms of pulmonary congestion.  
Evaluate ventricular septal hypertrophic tissue before surgery, and perform careful 
operation and rotary resection of target hypertrophic tissue. The ventricular septal defect 
found during surgery can be repaired at the same time. 
⚫ Hemorrhagic shock 
There is a risk of blood loss at the purse-suture during and after the apical approach. 
Hemorrhagic shock will occur when rapid blood loss accounts for 30-35% of total blood.  
Enhance the investigator’s training, and perform careful operation. Identify abnormal 
bleeding and bleeding site, and perform emergent hemostasis.  
For above risks, effective measures can be taken to minimize risks. Specific measures 
are as follows:  
1. The investigator with rich experience of cardiac surgery via apical approach is 
selected. After training, the investigator resects ventricular septal myocardial tissue with the 
myocardial resection system via apical approach under the guidance of ultrasound according 
to SOP;  
2. The investigator controls the subject’s inclusion/exclusion criteria strictly;  
3. Follow the subject after surgery via apical approach under the guidance of ultrasound, 
and provide the subject with the follow-up card, including contact of the investigator and 
postoperative precautions. The subject can contact and consult with the investigator in case of 
any discomfort at any time, or return to the hospital for examination and treatment according 
to the investigator’s determination. The subject will be monitored closely during following up. 
In case of any unpredictable risk, the investigator will provide proper and reasonable medical 
treatment timely according to the subject’s condition.  
9.3.2 Benefits 
The subject does not need to pay relevant tests during this clinical study, including vital 
signs, physical examination and laboratory examination. During the trial, the subject can 
receive good medical services and the disease will be diagnosed;  

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Important information obtained from this study may provide information to patients and 
healthcare providers who will use such devices in future, and help to increase their own or 
other patients’ treatment options. 
10 Quality control of clinical trial 
10.1 Selection of clinical sites and investigators 
The Sponsor will select qualified investigators who have received unified training for 
this study, have experience and have legal right to conduct clinical study to participate in this 
clinical trial. Selection of study site will be based on recent review results of study sites and 
comprehensive ability of the principal investigator in the study site.  
10.2 Training 
10.2.1 Training in study site 
All investigators/study staff must participate in the training provided by the Sponsor. 
The training can be conducted in the form of investigator meetings, initiation visits of the 
study site or other appropriate forms. Telephone training can also be conducted if necessary. 
The contents of training for investigators/study staff include, but are not limited to, study 
protocol, CRF filling, responsibilities of study staff and training of SOP for surgery. All 
trained investigators/study staff must sign a training log (or similar form) after receiving the 
training. Before signing the training log, investigators/study staff shall not engage in any 
work related to the trial that is beyond the scope of the treatment standard of the study site. 
10.2.2 Training of the Sponsor/monitor 
The Sponsor and/or the designated monitor will receive training on the use of relevant 
protocol, CRF and medical devices (if applicable), and the training process will be recorded 
according to written procedures. 
10.3 Monitoring of clinical trial 
10.3.1 Designate monitor 
The trial monitor is the person specially responsible for monitoring the trial progress. 
The monitor shall be appropriately trained and qualified to monitor the progress of clinical 
study. The Sponsor can designate the additional monitor at any time during the trial. For other 
information about the staff in charge of monitoring, please contact the Sponsor. 
10.3.2 Visit 
Before the trial starts, the Sponsor’s monitor (or representative) will visit the 

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investigator to ensure that the following standards are met:  
The investigator understands and accepts the obligation to conduct clinical trials in 
accordance with the study protocol and applicable laws and regulations, and signs clinical 
trial agreement; 
The investigator and staff have sufficient time and facilities to conduct the study, and 
can contact a sufficient number of appropriate subjects to conduct the study;  
There must be original data to prove the appropriateness of informed consent procedure, 
compliance with study protocol, adequate reporting and follow-up of AEs, accuracy of data 
collected by CRF and device information. The investigator/study site will allow access to 
these records. The study site shall keep the signature log of monitor visit. The investigator 
agrees to take sufficient time to cooperate with the monitoring process, and the investigator 
and/or study coordinator shall be present during monitoring visit. The investigator shall 
provide an appropriate working environment for the monitor to review relevant documents. 
11 Ethical issues of clinical trial and informed consent 
11.1 Ethical considerations 
11.1.1 Ethics and regulations 
This trial complies with Helsinki Declaration, Good Clinical Practice of Medical Device 
and relevant national regulations.  
11.1.2 Medical Ethics Committee 
Before the clinical trial, the investigator submits the study protocol, informed consent 
form (ICF) and other relevant documents to the Ethics Committee (EC) of the hospital where 
the study site is located. The clinical trial can only be started after approval by EC. Any 
modification of the study protocol must be approved by EC before conduct. SAEs during the 
clinical trial shall be submitted to EC in written format timely. 
11.2 Informed consent process and text of informed consent 
Before enrolling for this study, the investigator must explain the details of the clinical 
trial to the subject or his/her guardian, including the nature, purpose and expected efficacy of 
the trial as well as possible AEs and countermeasures, and answer relevant questions raised 
by the patient. Subjects can be included only after they fully understand the trial and sign the 
informed consent. The informed consent shall be signed by the investigator, the subject or 
his/her guardian in duplicate, with each party keeping one copy. 

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12 Requirements of reporting AEs and device defects 
12.1 AEs 
12.1.1 Definition of AEs 
AEs refer to adverse medical events that occur during the clinical trial, regardless of 
whether they are related to the medical device used in the trial. The following events are 
included:  
All events related to the study device or control device; 
All events related to the study process (all procedures in the clinical study plan); 
Other AEs. 
12.1.2 Determination of severity of AEs 
Observe the process, severity, treatment and outcome of AEs and fill in the AE report 
form. 
According to the following criteria, the severity of AEs can be classified into mild, 
moderate and severe. 
Mild: It does not affect the treatment and the time of admission and discharge, requires 
no special treatment, and has no significant impact on the health and daily life of the subject. 
Moderate: It needs special treatment and has adverse impact on the health and daily life 
of the subject. 
Severe: It causes death or serious worsening of health, including fatal disease or injury, 
permanent defect of physical structure or function, need for hospitalization or extension of 
hospitalization, need for medical or surgical intervention to avoid permanent defect of 
physical structure or function. 
12.1.3 Relationship between AEs and the device 
According to 6 documents including Application and Approval Form for Ethical Review 
of Clinical Trials of Medical Devices issued by NMPA (No. 58, 2016), the relationship 
between AEs and medical devices is considered based on:  
① Definitely related: belonging to the AEs caused by the used product, the AE has 
reasonable time sequence, occurs during intraoperative use, is not a common AE of the 
surgery, can not be explained by other reasons or the subject’s current disease;  
② Probably related: The AE, a known type of reactions of the used product, has 
reasonable time sequence, can not be explained by other reasons, is a intraoperative AE, is 
not a common AE of the surgery, and can not be explained by the subject’s current disease; 

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③ Possibly related: The AE, a known type of reactions of the used product, has 
reasonable time sequence after treatment, is a perioperative AE, is not a common 
intraoperative AE of the surgery, and can not be explained by other reasons or the subject’s 
current disease;  
④ Possibly unrelated: The AE, a known type of reactions of the used product, has 
reasonable time sequence after treatment, can be explained by other reasons, is not a 
perioperative AE, can be explained by the subject’s current disease; 
⑤ Definitely unrelated: The AE, not a known type of reactions of the used product, 
doesn’t have reasonable time sequence after treatment, can be explained by other reasons, 
is not a perioperative AE, and can be explained by the subject’s current disease; 
➢ Evaluation criteria of the relationship between AEs and the device 
 
Definitely 
related 
Probably 
related 
Possibly 
related 
Possibly 
unrelated 
Definitely 
unrelated 
Has reasonable 
time sequence 
Y 
Y 
Y 
Y 
N 
Type of device 
defect and AE 
Y 
Y 
Y 
Y/.N 
N 
Common AE of 
the surgery 
N 
N 
Y/N 
Y/.N 
Y 
Time of the AE 
Intraoperative 
use 
Intraoperative Perioperative 
？ 
Not 
perioperative 
Explained by 
other reasons 
N 
N 
Y/N 
Y 
Y 
Explained by 
the subject’s 
current disease 
N 
N 
Y/N 
Y/.N 
Y 
Note: Y, yes; N, no; Y/N, difficult to be yes or no; ?, unclear 
12.1.4 Record of AEs 
All AEs that occur during the study must be truthfully recorded in the AE table. The 
investigator shall provide treatment and follow-up services for the AE until the symptoms 
disappear or stabilize, and analyze the cause of the event together with the Sponsor. The 
investigator shall make a preliminary judgment on AEs, which can be basically classified into 
intraoperative AEs, extra-treatment AEs and post-treatment AEs. AE is the adverse medical 
event that occurs during the clinical trial, regardless of the relationship with the study medical 
device.  
12.2 SAEs 
SAE is the event that occurs during the clinical trial and causes death or serious 

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worsening of health, including fatal diseases or injury, permanent defect of physical structure 
or functions, need for hospitalization or extension of hospitalization, medical or surgical 
intervention to avoid permanent defect of physical structure or functions; events that lead to 
fetal distress, fetal death or congenital abnormality or defect.  
12.3 Device defects 
Device defects refer to unreasonable risks that may endanger human health and safety 
during normal use of the medical device during the clinical trial, such as label error, quality 
problem and malfunction. 
12.4 Relationship between AEs and device 
The investigator shall determine whether the medical device can cause AEs or be a 
factor of AE. The conclusion must be recorded in appropriate CRF. The investigator shall 
evaluate the temporal relationship, correlation with underlying disease and whether there is a 
more reasonable reason before making a judgment. 
12.5 Reporting procedure and contact information 
12.5.1 Reporting procedure of SAE 
When SAEs occur during the clinical trial, the investigator shall immediately take 
appropriate treatment measures for the subject, report in writing to the authority about the 
clinical trial of medical device at the clinical site, and notify the Sponsor in writing. The 
authority of clinical trial of medical device shall report in writing to appropriate Ethics 
Committee and the drug administration departments and health authorities at the levels of 
provinces, autonomous regions and municipalities directly under the Central Government. 
Clinical site and the investigator shall provide all necessary information of death case to 
Ethics Committee and the Sponsor.  
12.5.2 Reporting procedure of device defect 
The investigator shall record device defects found during the clinical trial, analyze the 
cause together with the Sponsor, write a written analysis report, put forward suggestions on 
continuing, suspending or terminating the trial, and submit it to the Ethics Committee for 
review by the management of clinical trial of medical device at the clinical site.  
For SAEs and device defects that may lead to SAEs, the Sponsor shall report to the drug 
administration and the same level of health authorities within 5 work days after being 
informed, and shall also report to other clinical sites and investigators participating in the trial, 
and notify the Ethics Committee of the clinical site in time through the authority of clinical 

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trial of medical device. 
13 Clinical study protocol deviation and revision of clinical study protocol 
13.1 Clinical study protocol deviation 
The investigator shall not change or deviate from the study protocol, except in an 
emergency to protect the subject’s life and safety. If the investigator deviates from the test 
protocol in order to protect the subject’s life and safety in an emergency, he/she shall notify 
the Sponsor and the Ethics Committee (if applicable) of the deviation and those deviations 
that affect the scientific nature of the clinical study. 
All protocol deviations, causes and date must be recorded and reported to the Sponsor. 
The Sponsor will review and evaluate these protocol deviations and take necessary corrective 
and preventive measures timely, including but not limited to informing the site to retrain or 
close the site. Specific protocol deviations can include, but are not limited to, the following 
types: 
Included subject doesn’t meet the inclusion/exclusion criteria;  
The subject doesn’t (or accurately) receive trial and/or test required in the clinical study 
protocol; 
The investigator doesn’t report AEs or device defect within a period required by the 
clinical study protocol;  
The subject is included when the Ethics Committee’s approval is invalid.  
13.2 Requirements of revision of clinical study protocol 
Generally speaking, the clinical study protocol shall be strictly implemented after being 
approved by the Ethics Committee. If it is necessary to supplement or revise the study 
protocol after the study starts, the investigator and the Sponsor should revise it after 
agreement and submit it again to the Ethics Committee for approval before implementation. 
Modification of the study protocol shall be recorded in detail, including specific contents and 
reasons of the modification, communication letter submitted to the Ethics Committee for 
re-approval and approval document of the Ethics Committee. 
14 Direct access to source data and files 
The investigator/site will allow relevant personnel to directly access original 
data/information related to the trial to cooperate with the monitor, check, evaluation of the 
Ethics Committee and inspection of the regulatory authority 啥，又是动词 又是名词的.  
When the subject signs the informed consent, it means that the Sponsor or its designated 

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staff is allowed to review the information in the medical record that is related to the trial. As a 
part of the informed consent, the investigator will obtain the permission of the subject to 
allow the monitor or regulatory authority to review any record with the subject’s identity in 
the clinical trial at the study site, but it must be kept confidential. These information can be 
shared with regulatory authority. However, the Sponsor shall not disclose personal and 
private information of the subject in other ways according to the local laws of data protection. 
15 Finance and insurance 
All parties in this clinical study will sign a written agreement with the clinical site, 
which will specify the finance and payment of this clinical trial in detail. For details, see the 
agreement signed by the parties.  
All parties promise to bear the treatment cost and corresponding economic 
compensation for the subject who suffers from injury or death related to the clinical trial, 
except for damage caused by the fault of the clinical site and healthcare staff in diagnosis and 
treatment activities.  
16 Coverage of the clinical trial report  
The investigator shall verify the safety and effectiveness of the medical device used in 
the trial according to the design requirements of the clinical study protocol, and complete the 
clinical trial report. The clinical trial report shall be consistent with the clinical study protocol. 
The clinical trial report shall be signed and dated by the investigator, reviewed, dated and 
sealed by the administration of clinical trial of medical device at the clinical site, and then 
submitted to the Sponsor. 
17 Confidentiality 
17.1 Confidentiality statement of the protocol 
This protocol is used to guide the clinical trial in which drugs via apex approach 
delivered by minimally-invasive myocardial rescetion system under guidance of ultrasound 
can not control hypertrophic obstructive cardiomyopathy with symptoms of left ventricular 
outflow tract obstruction. The included information is confidential and shall not be disclosed 
to any third party.  
17.2 Confidentiality statement of study materials and information 
The study site shall keep all materials and information that are obtained, but not limited 
to performance structure, trial data, reports and results related to the subjects confidential. 
The records obtained from this trial will be submitted to the Sponsor and relevant drug 

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administration for review. These data may also be submitted to the health authorities of other 
countries that may approve this product for reference. The results of the trial may be 
published in academic meetings or journals, but the privacy of the subjects will never appear 
in the information published above. 
18 Publication agreement of trial results 
18.1 Publication of trial results 
A separate publication plan that is periodically updated will be issued based on the study 
progress.  
18.2 Conditions for publication 
1) The sponsor agreement must be signed before publication;  
2) If co-investigators participating in this study belong to the same site, only the 
principal investigator of the site can designate the name of the person who is in the authorship 
(principal investigator and co-investigator); 
    3) The number of co-authors in the authorship shall meet specific requirements of 
each journal; 
4) The name of the Sponsor shall be quoted in all publications, and at least one 
project team member in the main author list is from the Sponsor. 
Any designated author shall meet all the criteria that the following authorship should 
meet: 
  Has made great contributions to the idea or design of this work or to data acquisition, 
analysis or summary; 
  Compile or strictly revise this work for important knowledge content; 
  Final approval of the version to be published;  
  Sign an agreement, be responsible for all aspects of the work, and ensure that 
problems related to the accuracy and completeness of the work can be appropriately handled 
and explained. 
19 Responsibilities 
19.1 Responsibilities of Ethics Committee 
The Ethics Committee of the clinical study site of medical device shall consist of at least 
five members, including medical professionals and non-medical professionals, male or 
female. Non-medical professional members consist of at least one legal worker and one 
person outside the clinical study site. Members in the Ethics Committee shall have the 

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qualification or experience of evaluating scientific, medical and ethical aspects of this clinical 
trial. All members shall be familiar with the ethical principles and relevant regulations of 
clinical trials of medical devices, and comply by the regulations of the Ethics Committee. 
The Medical Device Ethics Committee shall comply with the ethical principles of 
Helsinki Declaration of the World Medical Congress and the provisions of drug regulatory 
authority, establish corresponding work procedures, formulate documents, and perform its 
duties in accordance with the work procedures. 
Members of the Ethics Committee who are independent of the investigator and the 
Sponsor have the right to express their opinions and participate in the voting of the relevant 
trials. 
The Ethics Committee shall issue a notice before the meeting. The number of 
participants in review and voting shall be no less than 5. Any decision shall be passed by 
more than half of the members of the Ethics Committee. 
The investigator can provide information about any aspect of the trial, but shall not 
participate in the review, vote or express opinions. 
When reviewing some special trial, the Ethics Committee may invite experts in relevant 
fields to participate. 
The Ethics Committee shall strictly review the study protocol and relevant documents to 
safeguard the subject’s rights and interests, and shall focus on the following contents:  
  1) The investigator’s qualification, experience and whether he/she has sufficient time 
to participate in the clinical trial;  
  2) Whether the staffing and equipment conditions of the clinical study site meet the 
requirements;  
  3) Whether the risks of the subject are proportional to the expected benefits;  
  4) Whether the study protocol considers ethical principles and conforms to scientific 
nature, including whether the study purpose is appropriate, whether the subject’s rights and 
interests are protected, whether other people may be protected from risks, and whether the 
selection method of the subjects is scientific. 
Method of selecting subjects: 
  1) Whether the information about the trial provided to the subject or his/her guardian 
is complete, whether the subject can understand it, and whether the method of obtaining the 
informed consent is appropriate; 
  2) If necessary, the Ethics Committee shall organize the representatives of the subject 
population to test the comprehensibility of data, evaluate whether the informed consent is 

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appropriate, and evaluation results shall be recorded in writing and kept for 10 years after the 
end of the clinical trial; 
  3) Whether the treatment and insurance measures are adequate if the subject suffers 
injury or death related to the clinical trial; 
  4) Whether the modification on the study protocol is acceptable;  
  5) Whether the possible harm to the subject can be analyzed and evaluated regularly 
during the clinical trial; 
  6) Protocol deviations may affect the subject’s rights, interests, safety and health, or 
affect the scientificity and integrity of the trial, and whether it is acceptable. 
In order to ensure consistent and timely review, the Ethics Committee of the leading 
institution shall establish the work procedure of collaborative review for ethical review of 
multi-center clinical trial. The Ethics Committee of the leading clinical study site shall review 
the ethical rationality and scientificity of the study protocol before the trial. On the premise of 
accepting the review opinions of the leading clinical study site’ Ethics Committee, the Ethics 
Committees of other clinical study sites can review the feasibility of this trial in the clinical 
study site in the form of meeting review and document review, including qualification and 
experience of the investigator, equipment and conditions. Generally, the study protocol will 
not be modified, yet the trial in the clinical study site can be refused.  
After receiving the application for clinical trial of medical devices, the Ethics 
Committee shall convene a meeting to review and discuss, issue written comments, seal, and 
attach a list of persons attending the meeting, specialty and personal signature. 
The opinions of the Ethics Committee include:  
  1) Agree; 
  2) Agree after necessary modification; 
  3) Not agree; 
  4) Suspend or terminate approved trial.  
The Ethics Committee shall follow and supervise the clinical trial in the clinical study 
site, and may request in writing to suspend or terminate the clinical trial at any time in case of 
any situation where the subject’s rights and interests cannot be guaranteed. 
The suspended clinical trial shall not be resumed without the consent of the Ethics 
Committee. 
The Ethics Committee shall keep all relevant records for at least 10 years after 
completion of the clinical trial. 

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19.2 Responsibilities of the Site 
The clinical site shall evaluate relevant resources according to the characteristics of the 
medical device used in the trial to determine whether to accept the clinical trial before 
accepting the clinical trial by the clinical study site. The clinical trial site shall keep clinical 
trial records and basic documents appropriately according to the agreement with the Sponsor. 
The investigator responsible for the clinical trial shall meet the following conditions:  
  1) Associate chief physician, associate professor, associate investigator and other 
relevant professional and technical titles and qualifications of working in the clinical study 
site;  
  2) Expertise and experience required for the medical device, and relevant training if 
necessary;  
  3) Be familiar with information and reference related to the clinical trial required and 
provided by the Sponsor; Have the ability to coordinate, control and use persons and 
equipment in the clinical trial, and handle AEs caused by the study medical device and other 
relevant events;  
  4) Be familiar with relevant laws, regulations and the present protocol.  
  5) Clinical study site and the investigator shall ensure the authenticity, accuracy, 
clarity and safety of the data, documents and records formed in the clinical trial. 
  6) Clinical study site and the investigator shall accept the monitoring and inspection 
of the Sponsor and the supervision of the Ethics Committee, and provide all necessary 
records related to the trial. If the drug administration and health authority send inspectors to 
carry out the inspection, the clinical trial site and the investigator shall cooperate. 
  7) When the clinical trial site and the investigator find that risks overweigh the 
possible benefits, or have obtained the results sufficient to judge the safety and efficacy of the 
study medical device, and need to suspend or terminate the clinical trial, they should notify 
the subject, and ensure that the subject receives appropriate treatment and follow-up services, 
and provide detailed written explanations as required. If necessary, report to local drug 
administration of the province, autonomous region, or municipality directly under the Central 
Government. When receiving the notice from the Sponsor or the Ethics Committee that the 
clinical trial needs to be suspended or terminated, the investigator shall promptly notify the 
subject and ensure that the subject receives appropriate treatment and follow-up services.