| Background:Coronary artery disease (CAD) is the most common result of cardiovascular atherosclerotic disorder and the leading cause of ischemia, infarction and death in the developed countries. CAD is resulted due to the lipid filled plaque due to hyperlipidemia leading to the thickening of the artery wall therefore reducing the size of the inner lumen of the wall which ultimately partially blocks the supply of the oxygen in the heart muscle resulting in metabolic products accumulation i.e. ischemia which eventually result in coronary artery stenosis. CAD patients usually suffer from refractory angina and treated with medications, PCI and CABG. But the patients with end stage CAD, refractory angina and with failures of PCI are not usually eligible for multiple surgical interventions. Different treatment modality increases myocardial perfusion in end stage CAD and refractory Angina. Some therapy induces angiogenesis by injecting mitogens into the myocardium layer or by use of progenitor cells.Shock wave therapy has been used in the past in renal calculi and orthopedics which proved to be effective in most of the cases. Shock Wave is an acoustic wave, entering with the speed of water of ultrasound through body tissue. It is a single pressure pulse with a needle-like positive spike< 1 microsecond in duration and up to 100 MPa in amplitude, followed by a tensile part of several microseconds with lower amplitude. Myocardial ischemia or infarction are the results of coronary artery diameter reduction or occlusion by atheroma or plaque that affect all cardiac cells, which leads to the blockage of blood flow and results in necrosis which eventually can result in the CAD or the Heart failure. Recent research shows that shock waves provide new and non-invasive technique to neo vascularization and angiogenesis with just 10% of energy output of Lithotripsy. All of the CSWT research till date only gave the result of maximum 1 year follow up of the patients.Aim:Thus the purpose of this clinical experiment was to evaluate long term outcomes of CSWT in terms of cardiac functions and the quality of life in CAD patients.Materials and Methods:This clinical research was approved by the Institutional Review Board and Ethical Committee of the 1st affiliated hospital of the KMU (Kunming Medical University), and all study subjects signed written consent for participation in the clinical study and research undertaken by the 1st Hospital of KMU. Subjects were patients of the 1st affiliated hospital of the KMU with diagnosed CAD.Inclusion Criteria for the subject’s:Subjects were selected for the clinical study and for the 6 years follow up if they met any 1 of the following criteria.1) Computed Tomography Coronary angiography(CTCA) or CA referring coronary artery stenosis.2) Sonogram resulting more than 50% of infarction3) Angina or Refractory Angina not responding to the drug therapy.4) NYHA Classification 1 or higher than 15) CAD confirmed by the Sonogram and imaging examination and at least more than 2 weeks after surgical intervention or 1 month after AMIExclusion Criteria:Subjects were excluded from the clinical study if they had any of the following 1) Acute Myocardial Infarction (AMI) or surgical procedures of the heart before the 1 month of the clinical study 2) Heart transplantation surgery in the past 3) History of double valve replacement surgery or single valve replacement surgery 4) LVEF<30% 5) Ventricular Fibrillation (VF) or with HR< 40 bpm or> 120 bpm.6) Chronic skin diseases like infection, ulceration, eczema in the area to be given shock waves. The patients were grouped in 2 groups namely Control Group (CG Group) and Shock wave Group (SW Group). The management of all the patients was strictly in accordance with the related mainland China and European guidelines of CAD/CHD management initiated in 2007. The treatment strategy of SW Group followed the protocol established by Tohoku University of Japan and by the University of Essen, Germany 1. The Control group (n=11) was designed only for 11 patients as it was 72 months study who received all the treatment modalities except CSWT treatment 2. Another group was SW Group (n=41) which received additional Cardiac shock wave therapy and was monitored till 72 months.1 treatment session was 9 times,1 week 3 times given on 1,3, and 5th day of a week.Examination:Some of the examination was done under dobutamine. Dobutamine Stress Echocardiography (DSE) was done if patients result showed vascular lesion in the imaging analysis. M type echocardiography allows pre analysis of wall motion which can be unveiled as an M mode echocardiography. Myocardial layer were demarcated as the 2 neighboring abnormal layers with enhancement in contraction after dobutamine loading (reduction> 1 point). PSSR technique was elicited for resting and loading (dobutamine) conditions. Before Shock wave treatment, echocardiography under dobutamine loading condition and radionuclide imaging echocardiography were used to trace the ischemic and infarcted areas in each subject. Initial IV Dobutamine does at the rate of 5-12μg/kg/min was injected and the rate was improved to 30-40μg/kg/min if regional echo wall motion abnormalities could not be illustrated. Echo wall motion was calculated by wall motion score index (WMSI). Tissue Doppler was used to analyze peak PSSR under baseline and Dobutamine stressed situations. MPI was also calculated under resting and dobutamine stress conditions. MPI and the grading system was accordance to the American Society of Nuclear Cardiology (ASNC). An upsurge of 1 or increase in more than 1 point in Myocardial Perfusion Imaging (MPI) compared to baseline under both resting and dobutamine stress situations was taken as the criteria for tissue blood flow improvement in the myocardium. Six-minute walks test or 6MWT-Subjects were asked to walk for 6 minutes without any physical assistance and the distance covered was measured. The test was performed at the fastest speed possible.If subjects encountered any difficulty it was stopped and the maximum distance covered was recorded. Control group was not given any shock wave therapy but was under regular medications and other treatment modalities and regular follow up for 72 months. SW Group was additionally given CSWT therapy. If subject was comfortable with no chest pain or tightness SW energy was raised subsequently. In total, eighteen hundred Shock waves shots were given for each infarcted or ischemic segment (diagnosed by previous imaging or preoperative procedures).Follow-up:Patients were called for follow up at 3,6,12,24,36,48,60 and 72 months (6years). Cardiologists were not aware of the patients treatment modalities either control group or shock wave group. We evaluated NYHA functional classification, SAQ,6MWT. Echocardiography was done to illustrate LVDd, EDV, ESV, LVEF, echo wall motion analysis under baseline (resting) and Dobutamine stress conditions (M-mode), SR similarly under baseline (resting) and Dobutamine stress conditions, MPI (Myocardial Perfusion Imaging) under both baseline and stress conditions were calculated.Statistics:Data were calculated as (mean ± SD) for data with a normal distribution, for data of abnormal distribution represented as median with interquartile range and as number (%) for data with categorical distribution. Groups differences were calculated by one-way ANOVA Kruswal-Wallis (KW) test. Levene’s Test for Equality of Variances was done to illustrate p value, p< 0.05 represented statistically significant values. SPSS 19 software was used for the analysis of data.Results:A total of 52 subjects who met the inclusion criteria were enrolled in the clinical study. Subjects’physical characteristics are demonstrated below in Table 1. The 52 subjects were divided into control group CG Group (n= 11) and another Shock wave group SW group (n=41). The average age in the CG and SW Group was 71±6.52 and 63.4±10.8; respectively without substantial differences. In the CG Group (n=11), all subjects accomplished 72 months of follow up. In SW group (n=41),38 subjects completed the 72 months follow up because there were 3 mortality at 12,36, and 60 months respectively. All 3 deaths were due to end stage coronary heart disease resulting in heart failure. Thus 38 subjects finished the full CSWT therapy and 72 months follow up without major arrhythmia, heart failure, shortness of breath, hemorrhage, embolism, or cardiogenic shock. In our study no subjects had any major side effects during the 6 years follow up period. Only 10 subjects in SW group felt chest discomfort during the SW therapy of the lateral, apical and posterior segment, and it was comforted with the decrease of energy in the range of 0.08-0.06 mJ/mm2. Table Ⅱ represents the relationship of NYHA classification, SAQ score, and 6MWT at 3,6,12,24,36,48,60,72 months after treatment.6MWT in the control group was suggestively reduced at 60 and 72 months in comparison with 0 month. In SW group 6MWT was increased at 12 months later decreased at 24 and 36 months but finally increased at 72 months in comparison to 0 months. The NYHA grading was remarkably diminished in the SW group at 72 months compared to 0 months, but in the CG Group the NYHA Grading was increased eventually in compared to 0 months.SAQ in the control group was decreased significantly around 60 and 72 months but in the SW Group SAQ increased eventually around 60 and 72 months in compared with 0 months. In Figure I wall motion, PSSR, MPI is compared both under resting and Dobutamine loading conditions. Wall motion has been decreased subsequently in the CG Group than the SW Group at both resting and loading conditions.PSSR-PSSR shows significant differences between the baseline and Dobutamine loading conditions in between CG and SW Group comparing at 12 months and 72 months. MPI shows that perfusion in the myocardium segment has extensively decreased in the control group at 24 and 72 months but the perfusion in the myocardium has increased significantly in the SW Group both at resting and loading conditions. In Figure Ⅱ CCS Grading of Angina and Nitroglycerine dosage was compared. Data has been offered as a "mean ± SD". CCS grading has been increased at the maximum level for CG group than the SW group at 60 and 72 months in compared with 0 months. Thus increasing the dosage of nitrates for CG Group subsequently according to the CCS Grading of AnginaAccording to our study following 6 years of follow up, the CSWT provided better results that improved myocardial function and quality of life in comparing to the month 0 and the control group. These results recommend that, on long-term [72 months] CSWT indicates improved parameters in comparison to control group. Another technique used in this research called PSSR, has better resolution than M type echocardiography. The present study used PSSR to evaluate the cardiac function and its abnormality because it was a more precise study. PSSR was done by GE VV7 device. It has a complete Tissue Doppler imaging and SR imaging technology. SIMENS Sequoia 512 device (Berlin, Munich, Germany) was used to evaluate 2D-strain at the late study. Consistencies of the results were maintained by not altering the measurement variables. Past studies have successively shown the significant results of CSWT. For example Fukumoto et al 10-11 cured nine patients with CAD at the end stage not suitable for surgical interventions and at twelve months of follow-up testified that patients had reduced nitrate use (from 5.4±2.5 to 0.3±0.3 times/wk), upgraded CCS grading of Angina (2.7±0.2 to 1.8±0.2), and enhanced myocardial perfusion. Khattab et al 10 did clinical study for ten patients with angina (CCS class Ⅲ-Ⅴ) with shock wave therapy and found average CCS grading of angina reduced from 3.3±0.5 to 1.0 ±± 13 at reference point. Past studies with animal models of CAD showed that CSWT at approx. ten percent of the energy used for lithotripsy in renal stones could improve LV size, EF, EDV, and myocardial blood exchange. Belcaro et al proved the effect of SW therapy on microcirculation in patients who had critical limb ischemia. Most of the studies have shown that shock waves activates Ras, Stimulation, NO synthesis, by anti-inflammatory pathways of metalloproteases, chemokines and upregulation VEGF and VEFG receptors. It’s still unclear the mechanism of action of the shock waves. Some theories say that shock waves increases EPCs by up-regulation of SDF-1 in ischemic myocardium. In our clinical study,72 months have shown better follow up results in term of CCS Grading of Angina, Nitroglycerine use reduction, NYHA classification,PSSR,MPI,Echo wall motion and SAQ (mentioned in figures) in compare to control group. We hypothesize that the shock waves may be related with the molecular and cellular mechanisms of neovascularization. In the era of CSWT, this is the first study which has shown the follow up of the patients up to 6 years and the only limitation was that it had 11 patients in the control group because it was a long term study.Conclusions:Thus we can conclude that CSWT can improve clinical symptoms, morphology, functions of the heart in the diagnosed CAD patients with no option in a long term without any major side effects in compare to patients just on the drug therapy or repeated surgical interventions. PSSR, CCS grading of angina and SAQ scores were the newest factors (analyzing parameters) to analyse the complex CAD patients’disease situation. |
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