Implication of Cardiac Shock Wave Therapy on Coronary Artery Disease Patients

Implication of Cardiac Shock Wave Therapy on Coronary Artery Disease Patients - An Observational Long-term Study

CAD is a challenging affliction which has a high annual morbidity rate in China and the world. Severe CAD may lead to compromised cardiac function, decreased exertional capacity and poor quality of life (QOL). The most common treatment for CAD is medication, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). However, some patients had long-term of history with complex severe artery lesions, they are not candidate for redo interventional therapy. Cardiac shock wave therapy (CSWT) is an exploring therapy used globally for CAD patients, which is known for its safety, non-invasiveness and effectiveness.The previous RCT from the investigators' team has already finished, and results are in submission processing.

This is a prospective, single arm, observational study design. CAD patients will be enrolled consecutively. The entire treatment period will last 3 months with 9 sessions. Outcomes are assessed as efficacy outcomes and safety outcomes. Efficacy outcomes include symptom (CCS score, NYHA classification, nitroglycerin dosage, SAQ questionnaire), exertional capacity (6MWT), quality of life (SF-36 questionnaire) and imaging evaluation (myocardial perfusion imaging and echocardiography). Safety outcome include the change of serum TNT, CKMB, BNP and adverse event (AE) occurrence. The participants will be followed up at 13th week, 6th months and 12th months.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: cardiac shock wave therapy

Detailed Description

CAD is a challenging affliction which has a high annual morbidity rate in China and the world. Severe CAD may lead to compromised cardiac function, decreased exertional capacity and poor quality of life (QOL). The most common treatment for CAD is medication, percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). However, some patients had long-term of history with complex severe artery lesions, they are not candidate for redo interventional therapy. Cardiac shock wave therapy (CSWT) is an exploring therapy used globally for CAD patients, which is known for its safety, non-invasiveness and effectiveness. In the previous clinical studies, CSWT can alleviated angina symptom, improved myocardial ischemia and increased exertional capacity. Many single arm studies proved its efficacy and safety. Our RCT has already finished, and results are in submission processing.

This is a prospective, single arm, observational study design. CAD patients will be enrolled consecutively. The entire treatment period will last 3 months with 9 sessions. CSWT will be administered in the first week, follow by a 3-week non-treatment interval. Outcomes are assessed as efficacy outcomes and safety outcomes. Efficacy outcomes include symptom (CCS score, NYHA classification, nitroglycerin dosage, SAQ questionnaire), exertional capacity (6MWT), quality of life (SF-36 questionnaire) and imaging evaluation (myocardial perfusion imaging and echocardiography). Safety outcome include the change of serum TNT, CKMB, BNP and adverse event (AE) occurrence. Symptom, 6MWT and questionnaires will be evaluated at baseline and 13th week, 6th months, 12th months of CSWT. Imaging outcomes will be evaluated at baseline and 13th week, 12th months of CSWT. The level of TNT, CKMB and BNP will be tested before and 1st week after initiation of CSWT.

• Study Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

• Study Contact: Name: Lingling Yu, MD; Phone Number: +8601085138105; Email: bjyyec@126.com
• Study Contact Backup: Name: Wei Liu; Phone Number: +8601085138105; Email: bjyyec@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Beijing Hospital
      • Contact: Lingling Yu; Phone Number: +8601085138105; Email: bjyyec@126.com
      • Contact: Liu; Phone Number: +8601085138105; Email: bjyyec@126.com
      • Principal Investigator: Qing He, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Severe CAD patients were enrolled and coronary angiography indicated complicated severe lesions. Although they were under OMT, stress myocardial perfusion imaging (MPI) showed obvious ischemia. They were not candidate for coronary revascularization.

Description

Inclusion Criteria:

• Multiple or diffused coronary artery stenosis via coronary angiography, and not the candidates for PCI or CABG;
• Myocardial ischemia documented by stressed MPI and echocardiography;
• Refractory angina that has not been alleviated after at least three months of optimal medication treatment (OMT);
• Left ventricular ejection fraction (LVEF) ≥ 30%.

Exclusion Criteria:

• Acute myocardial infarction within one month;
• PCI or CABG within one month;
• Heart transplant patient;
• Patients with prosthetic valves;
• Cases of atrial or ventricular thrombosis;
• Uncontrolled heart failure with LVEF <30%;
• Severe arrhythmia; (viii) patients with pacemakers;
• Cases of infective endocarditis;
• Chronic obstructive pulmonary disease patients;
• Pregnant or nursing women;
• Patients with silicone breast implants;
• Chest tumor patients;
• Patients already participating in other clinical trials.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Treatment group; The treatment group will receive cardiac shock wave therapy. The CSWT entire treatment will period last 3 months with 9 sessions. CSWT will administered in the first week, followed by a 3-week non-treatment interval.

Device: cardiac shock wave therapy; Two target segments of left ventricle will be chosen for all participants. In each target segment, 9 sties will be administered with 200 shots at each site. Low-intensity SW (200 impulses/spot; energy flux 0.09 mJ/mm2), will be administered under electrocardiographic R-wave gating. The entire treatment period will last 3 months with 9 sessions. CSWT will be administered in the first week, followed by a 3-week non-treatment interval.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summed Rest Score	Summed Rest Score of 17 segments of left ventricle under myocardial perfusion imaging. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 68. Higher score means worse ischemia.	Change from Baseline Summed Rest Score at 12 months.
Summed Stress Score	Summed Stress Score of 17 segments of left ventricle under myocardial perfusion imaging. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 51. Higher score means worse ischemia.	Change from Baseline Summed Stress Score at 12 months.
Summed Reverse Score	Summed Reverse Score of 17 segments of left ventricle under myocardial perfusion imaging. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 51. Higher score means worse ischemia.	Change from Baseline Summed Reverse Score at 12 months.
Regional Rest Score	Rest Score of target treatment segments of left ventricle under myocardial perfusion imaging. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 8. Higher score means worse ischemia.	Change from Baseline Regional Rest Score at 12 months.
Regional Stress Score	Stress Score of target treatment segments of left ventricle under myocardial perfusion imaging will be calculate. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 8. Higher score means worse ischemia.	Change from Baseline Regional Stress Score at 12 months.
Regional Reverse Score	Reverse Score of target treatment segments of left ventricle under myocardial perfusion imaging will be calculate. Each segment will be scored from 0 to 4. The minimum score is 0 while the maximum score is 8. Higher score means worse ischemia.	Change from Baseline Regional Reverse Score at 12 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CCS score	Canadian Cardiovascular Society score. The score is from 1 to 4 score. Higher score means worse ischemia.	Change from Baseline CCS score at 12 months.
NYHA classification	Now York Heart Association classification. The score is from 1 to 4. Higher score means worse heart function.	Change from Baseline NYHA classification at 12 months.
Seattle Angina Questionnaire	Seattle Angina Questionnaire has five domain: physical limitation, angina stability, angina frequency, treatment satisfaction and quality of life. Each domain are 0-100 scale.	Change from Baseline NYHA classification at 12 months.
QOL: SF-36 Questionnaire	SF-36 Questionnaire include vitality, physical functioning, body pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health. Each items are 0-100 scale.	Change from Baseline SF-36 score at 12 months.
Six minutes walk test	Six minutes walk test proceed according to ATS guideline. The total distance will be recored.	Change from Baseline 6MWT at 12 months.
Left ventricular ejection fraction	Left ventricular ejection fraction on echocardiography	Change from Baseline status at 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac enzyme	Serum Troponin T, CKMB	Change from Baseline status at 13th week after treatment.
Brain Natrium Peptide	Serum brain Natrium Peptide	Change from Baseline status at 13th week after treatment.

Collaborators and Investigators

• Sponsor: Beijing Hospital
• Investigators: Principal Investigator: Qing He, MD, Beijing Hospital

Publications and helpful links

General Publications

• Zhang Y, Shen T, Liu B, Dai D, Cai J, Zhao C, Du L, Jia N, He Q. Cardiac Shock Wave Therapy Attenuates Cardiomyocyte Apoptosis after Acute Myocardial Infarction in Rats. Cell Physiol Biochem. 2018;49(5):1734-1746. doi: 10.1159/000493616. Epub 2018 Sep 24.
• Qiu Q, Shen T, Wang Q, Yu X, Jia N, He Q. Cardiac shock wave therapy protects cardiomyocytes from hypoxia-induced injury by modulating miR-210. Mol Med Rep. 2020 Feb;21(2):631-640. doi: 10.3892/mmr.2019.10892. Epub 2019 Dec 18.
• Liu B, Zhang Y, Jia N, Lan M, Du L, Zhao D, He Q. Study of the Safety of Extracorporeal Cardiac Shock Wave Therapy: Observation of the Ultrastructures in Myocardial Cells by Transmission Electron Microscopy. J Cardiovasc Pharmacol Ther. 2018 Jan;23(1):79-88. doi: 10.1177/1074248417725877. Epub 2017 Sep 1.
• Du L, Shen T, Liu B, Zhang Y, Zhao C, Jia N, Wang Q, He Q. Shock Wave Therapy Promotes Cardiomyocyte Autophagy and Survival during Hypoxia. Cell Physiol Biochem. 2017;42(2):673-684. doi: 10.1159/000477885. Epub 2017 Jun 15.
• Yu W, Shen T, Liu B, Wang S, Li J, Dai D, Cai J, He Q. Cardiac shock wave therapy attenuates H9c2 myoblast apoptosis by activating the AKT signal pathway. Cell Physiol Biochem. 2014;33(5):1293-303. doi: 10.1159/000358697. Epub 2014 Apr 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 20, 2021
• Primary Completion (ANTICIPATED): January 1, 2023
• Study Completion (ANTICIPATED): June 20, 2023

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: January 1, 2021
• First Posted (ACTUAL): January 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 6, 2022
• Last Update Submitted That Met QC Criteria: January 5, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: coronary artery disease; myocardial perfusion imaging; myocardial ischemia; cardiac shock wave therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
• Other Study ID Numbers: 121-2016004-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Sorry for that because of policy constraint.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No