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Original Research
Received: August 11, 2005 Accepted after revision: March 15, 2006 Enhanced External Counterpulsation
Reduces Lung/Heart Ratio at Stress in
Patients with Coronary Artery Disease

Chii-Ming Lee a Yen-Wen Wu a Hsiang-Yiang Jui a Ming-Fong Chen a a National Taiwan University Hospital, Taipei , Taiwan; b University of Pittsburgh, Pittsburgh, Pa. , USA Key Words
statistically signifi cant. We concluded that EECP im- Enhanced external counterpulsation ؒ Thallium-201 proved LV function, shown as the reduction of lung/heart single-photon emission computed tomography ؒ Lung/ ratio at stress, in patients with coronary artery disease, Abstract
Enhanced external counterpulsation (EECP) is a recently
Introduction
approved treatment modality for patients with angina and heart failure. However, the effi cacy of EECP on left New therapeutic treatments are emerging for the in- ventricular (LV) function has not been well established. creasing number of patients with chronic angina and con- The study was aimed to determine whether EECP leads gestive heart failure that have been refractory to conven- to an improvement in objective parameters of LV func- tional pharmacological and interventional approaches. tion. Patients with coronary artery disease (n = 10) who Enhanced external counterpulsation (EECP) is a recently showed evidence of stress-induced myocardial ischemia approved treatment modality for patients with angina despite conventional medical or surgical therapies were and heart failure [1–8] . In patients with chronic stable enrolled and received EECP therapy for a total of 35 h. angina, objective evidences for the effi cacy of EECP in- The therapeutic effects of EECP were examined by thal- clude improvement in time to ST-segment depression [2] lium-201 single-photon emission computed tomogra- in stress-induced myocardial ischemia using radionuclide phy ( 201 Tl-SPECT). Compared with baseline, the lung/ heart ratio at stress decreased signifi cantly from 0.40 8 EECP is also a safe treatment in patients with coronary 0.08 to 0.35 8 0.08 (p = 0.001) at 1 month and 0.33 8 0.10 artery disease (CAD) and severe left ventricular (LV) dys- (p = 0.03) at 6 months following EECP treatment. LV ejec- function. EECP effectively improves angina symptoms tion fraction marginally improved from 56.7 8 7.7% to and quality of life. These benefi ts are maintained at 6 57.6 8 5.9% (p = 0.382) at 1 month and to 60.1 8 8.6% months after EECP treatment [6] . The effi cacy results in (p = 0.062) at 6 months after EECP therapy, although not a recent study for patients with symptomatic heart failure Tel. +886 2 2312 3456, Fax +886 2 2393 4176 suggested that EECP can improve exercise capacity, qual- 201 Tl-SPECT Imaging Protocol and Analysis ity of life and functional status both in short term and also 201 Tl-SPECT was performed at baseline, 1 and 6 months after EECP therapy. Exercise stress testing with use of a modifi ed Bruce for 6 months after completion of the EECP therapy [7] . protocol as previously described was applied to eight patients [12] . Recently, a multicenter, prospective, randomized, In two subjects who could not exercise adequately, dipyridamole controlled clinical trial to verify the effi cacy of EECP as was intravenously infused to induce coronary hyperemia [13] . an adjunctive therapy in the management of patients with In the stress and delay unprocessed anterior projection image chronic stable heart failure has been fi nalized [8] . The (number 9 of 32), the LHR of 201 Tl activity was measured using a region of interest method as previously described [9] . preliminary data indicates that EECP improves exercise For analysis, the LV myocardium was divided into 17 segments tolerance (Feldman et al., ACC Scientifi c Meeting as American Heart Association recommended [14] . The myocar- dial 201 Tl activity in each segment was graded on a 0- to 4-point Stress thallium-201 single-photon emission computed scale. Summed scores were calculated by adding the 17 individual tomography ( 201 Tl-SPECT) is a well-established method segment scores [15] . A summed stress score (SSS) was obtained by adding the scores of stress images. A summed rest score (SRS) was for the detection of CAD. In addition to the reversible and obtained similarly by adding the scores of the re-injection or redis- fi xed perfusion defects of myocardium, the incremental tribution images. The sum of the differences between each segment value of lung/heart ratio (LHR) has been reported to re- under stress and delay images was defi ned as the summed differ- fl ect LV decompensation, which could be due to an in- ence score (SDS). Two experienced observers independently inter- crease in end-diastolic volume and pressure [9, 10] . Even preted the SPECT images without knowledge of patients’ identity and time point. In cases of disagreement, a consensus was reached in patients with normal LV systolic function and myocar- after images reviewed. Our inter-observer agreement for 201 Tl- dial perfusion, elevated 201 Tl lung uptake, especially in SPECT interpretation was 96% ( ␬ = 0.90, SEM = 0.079) [13] . response to stress, is a marker of elevated fi lling pressure which probably refl ects LV diastolic dysfunction [11] . To establish an objective marker for evaluating the All enrolled patients were included for statistical analysis. Data are shown as mean 8 SD. Comparisons between baseline and fol- therapeutic effects of EECP on LV dysfunction, we did a low-up tests were made by use of the paired t-test for continuous prospective study of CAD patients treated with EECP variables. and analyzed their response to therapy by 201 Tl-SPECT prior to and at 1 and 6 months after completion of EECP treatment. We studied ten CAD patients who were positive on stress myocardial perfusion imaging for ischemia despite conventional medical or surgical therapies ( table 1 ). None of them had EECP treatment prior to this study. All sub- A total of ten patients with documented CAD despite conven- tional medical or surgical therapies were consecutively enrolled in jects maintained their medication throughout the study this study. Evidence of CAD required at least one of the following: course without change of regimen. Among them, 9 (90%) (1) signifi cant stenosis ( 1 70% of luminal diameter) in at least one had undergone prior percutaneous coronary intervention major coronary artery proved by angiography and had undertaken or CABG, and 8 (80%) had a history of previous myocar- either percutaneous coronary intervention or coronary artery by-pass graft (CABG); (2) positive stress myocardial perfusion imaging dial infarction. All patients showed myocardial perfusion studies for ischemia. Patients were not included if any of the fol- defects on Tl-SPECT images at stress (SSS: 20.7 8 7.5). lowing were present: myocardial infarction or CABG in the preced- Most of these defects persisted at rest (SRS: 13.9 8 7.5), ing 3 months, unstable angina, signifi cant valvular heart disease, and only a small portion of the defects was reversible blood pressure 1 180/100 mm Hg, unprotected left main stenosis (SDS: 6.8 8 6.0). The mean LV ejection fraction (LVEF) greater than 50%, severe symptomatic peripheral vascular disease, deep vein thrombosis, atrial fi brillation or frequent ventricular pre- measured by using two-dimensional echocardiography mature beats that would interfere with EECP triggering. All pa- was 56.7 8 7.7%. All patients completed EECP therapy tients provided written informed consent before the procedure. The and received 1- and 6-month follow-up tests. No cardio- protocol and consent were approved by the Institutional Review vascular adverse events occurred during the study pe- Boards at National Taiwan University Hospital. The EECP therapy was given as a 1-hour session, once daily, for a total of 35 sessions. The pressure applied to the cuffs was ap-proximately 250 mm Hg. Patients were instructed to continue their optimal medical treatment for the duration of the study. cally signifi cant. LVEF slightly increased from 56.7 8 In eight patients who underwent exercise stress testing, 7.7% to 57.6 8 5.9% (p = 0.382) at 1 month and to 60.1 the exercise duration before (8.2 8 1.0 min) and after (1- 8 8.6% (p = 0.062) at 6 months after EECP therapy, al- month: 8.0 8 0.6 min, p = 0.558; 6 months: 8.3 8 1.2 though the improvement was not statistically signifi - min, p = 0.399) EECP treatment were not signifi cantly different. The changes of SSS, SRS, and SDS from base-line were not statistically signifi cant in 1- and 6-month follow-up tests ( table 2 ). Interestingly, LHR at stress, de- Discussion
creased signifi cantly from 0.40 8 0.08 to 0.35 8 0.08(p = 0.001) at 1 month and the effect sustained at 6 months In this report, the stress LHR declined signifi cantly at (0.33 8 0.10, p = 0.03) following EECP treatment. The 1 and 6 months after EECP treatment. These fi ndings effect of EECP treatment on LHR at rest was not statisti- suggest that the improvement of LV function after EECP may stem from the improvement of myocardial perfusion at stress [3, 4] . However, the indicator of myocardial isch-emia, shown as SDS on 201 Tl-SPECT, did not improve Table 1. Baseline characteristics (n = 10)
signifi cantly in this study as reported elsewhere [3, 4] . The discrepancy may originate from the high prevalence (up to 80%) of previous myocardial infarction in our study subjects, which results in large burden of scar tissue and low volume of reversible ischemic myocardium. This is supported by the relatively high SRS and low SDS at base- The effects of EECP on the improvements of angina symptoms, exercise capacity, functional status, and qual- ity of life can be maintained for at least 6 months after EECP treatment [6, 8, 16, 17] . In this reports, we docu- mented that the reduction of stress LHR, an objective marker for the therapeutic effects of EECP, can also be maintained up to 6 months after EECP treatment [18] . It has been reported that EECP did not alter LV sys- CABG = coronary artery bypass graft; MI = tolic function but improved diastolic fi lling [5] . Since myocardial infarction; PCI = percutaneous LHR at stress correlates with LV diastolic volume and pressure [10] , it is not surprising that the improvement Table 2. 201Tl SPECT analyses
a Only eight patients who can perform stress exercise test are included. LHR = Lung/ heart ratio; LVEF = left ventricular ejection fraction; SDS = summed difference score;SRS = summed rest score; SSS = summed stress score; * p < 0.05 when compared with baseline.
of LHR at stress after EECP treatment did not accom- is no control group. Although it is technically diffi cult to pany with a signifi cant improvement of LVEF in this conduct a double-blind, placebo-controlled study for study. EECP, a larger, randomized study with parallel control The majority (90%) of patients included in this clinical group will be helpful to confi rm the effi cacy of EECP study have prior percutaneous coronary intervention or CABG, or both. Thus, although the study is relatively small in sample size, it does represent one of the applica-tions of EECP in the real world, i.e., for the treatment of Conclusion
patients with CAD that have been refractory to conven-tional interventional approaches. EECP improved LV function, shown as the reduction There are several limitations in this study. First of all, of LHR at stress, in patients with CAD. For long-term the statistic power is limited by the small sample size, benefi cial effects on LV systolic function, a large-scale which may cause the improvement of LV systolic func- study with repeat augmentation may be indicated. tion at 6 months after EECP be marginal. Second, there References
1 Lawson WE, Hui JC, Cohn PF: Long-term 7 Soran O, Fleishman B, Demarco T, Grossman 13 Ho FM, Huang PJ, Liau CS, Lee FK, Chieng prognosis of patients with angina treated with PU, Su CT, Lee YT: Dobutamine stress echo- enhanced external counterpulsation: fi ve-year Feldman AM: Enhanced external counterpul- follow-up study. Clin Cardiol 2000;23:254– sation in patients with heart failure: a multi- thallium-201 single-photon emission comput- center feasibility study. Congest Heart Fail ed tomography in detecting coronary artery 2 Arora RR, Chou TM, Jain D, Fleishman B, 8 Soran O: A new treatment modality in heart 14 Cerqueira MD, Weissman NJ, Dilsizian V, Ja- multicenter study of enhanced external coun- failure enhanced external counterpulsation terpulsation (MUST-EECP): effect of EECP on Rumberger JA, Ryan T, Verani MS: Standard- exercise-induced myocardial ischemia and an- 9 Kurata C, Tawarahara K, Taguchi T, Sakata ized myocardial segmentation and nomencla- ginal episodes. J Am Coll Cardiol 1999;33: K, Yamazaki N, Naitoh Y: Lung thallium-201 ture for tomographic imaging of the heart: a uptake during exercise emission computed to- statement for healthcare professionals from the 3 Stys TP, Lawson WE, Hui JC, Fleishman B, Cardiac Imaging Committee of the Council on Manzo K, Strobeck JE, Tartaglia J, Ramasamy 10 Martinez EE, Horowitz SF, Castello HJ, Cas- Clinical Cardiology of the American Heart As- S, Suwita R, Zheng ZS, Liang H, Werner D: sociation. Circulation 2002;105:539–542. Effects of enhanced external counterpulsation Roberti RR, Saragoca MA, Barbieri A: Lung 15 Wu YW, Yen RF, Chieng PU, Huang PJ: Tl- on stress radionuclide coronary perfusion and and myocardial thallium-201 kinetics in rest- 201 myocardial SPECT in differentiation of exercise capacity in chronic stable angina pec- ing patients with congestive heart failure: cor- ischemic from nonischemic dilated cardiomy- relation with pulmonary capillary wedge pres- opathy in patients with left ventricular dys- 4 Tartaglia J, Stenerson J Jr, Charney R, Rama- function. J Nucl Cardiol 2003;10:369–374. samy S, Fleishman BL, Gerardi P, Hui JC: Ex- 11 Goland S, Shimoni S, Livschitz S, Loutaty G, 16 Soran O, Fleishman B, Demarco T, Grossman ercise capability and myocardial perfusion in Azulay O, Levy R, Caspi A, Arditi A: Dipyri- chronic angina patients treated with enhanced damole-induced abnormal Tl-201 lung uptake Feldman AM: Enhanced external counterpul- external counterpulsation. Clin Cardiol 2003; in patients with normal myocardial perfusion: sation in patients with heart failure: a multi- a marker of increased left ventricular fi lling center feasibility study. Congest Heart Fail 5 Urano H, Ikeda H, Ueno T, Matsumoto T, pressures. J Nucl Cardiol 2004;11:305–311. Murohara T, Imaizumi T: Enhanced external 12 Huang PJ, Chieng PU, Lee YT, Chiang FT, 17 Lawson WE, Hui JC, Kennard ED, Barsness counterpulsation improves exercise tolerance, Tseng YZ, Liau CS, Tseng CD, Su CT, Lien G, Kelsey SF: Predictors of benefi t in angina reduces exercise-induced myocardial ischemia WP: Exercise thallium-201 tomographic scin- patients one year after completing enhanced and improves left ventricular diastolic fi lling in tigraphy in the diagnosis of coronary artery dis- external counterpulsation: initial responders to patients with coronary artery disease. J Am ease: emphasis on the effect of exercise level. J treatment versus nonresponders. Cardiology 18 Michaels AD, Barsness GW, Soran O, Kelsey Kelsey SF, Strobeck JE, Soran O, Feldman AM: Benefi t and safety of enhanced external quency and effi cacy of repeat enhanced exter- counterpulsation in treating coronary artery nal counterpulsation for stable angina pectoris disease patients with a history of congestive (from the International EECP Patient Regis- heart failure. Cardiology 2001;96:78–84.

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