enhanced external counterpulsation

1. Enhanced External Counterpulsation Enhanced External Counterpulsation -- EECP�, employs a time proven, technically advanced treatment system using fundamental hemodynamic principles to treat CAD by promoting the development of collateral circulation to ischemic areas of the heart. This presentation introduces EECP� treatment as a non-invasive option for patients with angina pectoris.Enhanced External Counterpulsation -- EECP�, employs a time proven, technically advanced treatment system using fundamental hemodynamic principles to treat CAD by promoting the development of collateral circulation to ischemic areas of the heart. This presentation introduces EECP� treatment as a non-invasive option for patients with angina pectoris.

3. The Weight of Clinical Evidence In most patients, EECP treatment... Reduces anginal pain Increases functional ability Improves quality of life � both short-term and long-term

4. Target Population for EECP Therapy Coronary artery disease patients with angina pectoris refractory to medical therapy.

5. EECP Therapy Covered by Medicare For patients with a diagnosis of disabling angina pectoris who, in the opinion of their cardiologists or cardiac surgeons, are not readily amenable to invasive procedures because� They are inoperable or at high risk of operative complications or failure Their coronary anatomy is not readily accessible to such procedures Co-morbid states create excessive risk

6. The EECP Procedure

7. Enhanced External Counterpulsation The heart, unlike other organs, does not get most of its oxygenated blood supply during systole. During systole, coronary arterial pressure is high; but so is coronary vascular resistance, caused by the heart�s contraction compressing the coronary arteries and restricting coronary flow. Approximately 80% of coronary flow occurs, therefore, during diastole, at relatively low diastolic pressure. For normal hearts, this is more than enough to meet myocardial demand, even under the most extreme conditions. However, in hearts with occluding coronary artery disease, regional coronary blood flow upon exertion may be insufficient. The result is myocardial ischemia, often accompanied by the pain of angina pectoris. Many patients with angina pectoris can benefit from the hemodynamic effects of Enhanced External Counterpulsation -- EECP� : Increased diastolic augmentation increases coronary perfusion pressure and, consequently, coronary blood flow to ischemic regions. Increased systolic unloading to decrease cardiac workload and myocardial oxygen demand. Increased venous return to raise cardiac output. .The heart, unlike other organs, does not get most of its oxygenated blood supply during systole. During systole, coronary arterial pressure is high; but so is coronary vascular resistance, caused by the heart�s contraction compressing the coronary arteries and restricting coronary flow. Approximately 80% of coronary flow occurs, therefore, during diastole, at relatively low diastolic pressure. For normal hearts, this is more than enough to meet myocardial demand, even under the most extreme conditions. However, in hearts with occluding coronary artery disease, regional coronary blood flow upon exertion may be insufficient. The result is myocardial ischemia, often accompanied by the pain of angina pectoris. Many patients with angina pectoris can benefit from the hemodynamic effects of Enhanced External Counterpulsation -- EECP� : Increased diastolic augmentation increases coronary perfusion pressure and, consequently, coronary blood flow to ischemic regions. Increased systolic unloading to decrease cardiac workload and myocardial oxygen demand. Increased venous return to raise cardiac output. .

8. Cuffs Inflation/Compression Sequence The cuffs inflate sequentially, from the calves, to the lower thighs, to the upper thighs. This inflation sequence creates a retrograde arterial wave that raises coronary perfusion pressure during diastole. The compression sequence also increases venous return, raising cardiac output significantly.The cuffs inflate sequentially, from the calves, to the lower thighs, to the upper thighs. This inflation sequence creates a retrograde arterial wave that raises coronary perfusion pressure during diastole. The compression sequence also increases venous return, raising cardiac output significantly.

9. Required Treatment Regimens A total of 35 hours is required Regimen:1 or 2 hours daily At least 5 days per week for 4 to 7 weeks Results of stress test data indicate that most angina patients respond satisfactorily to 1 or 2 hours of daily EECP� treatment to a total of 35 treatment hours. For patients on a 2-hour daily regimen, an interval of at least 30 minutes between treatment periods is recommended. Not all patient tolerate 2 hours daily well, however. One hour daily, and two hours daily treatment regimens can be mixed in line with increased comfort over time or for convenience as long as 35 hours total is achieved in 7 weeks or less.Results of stress test data indicate that most angina patients respond satisfactorily to 1 or 2 hours of daily EECP� treatment to a total of 35 treatment hours. For patients on a 2-hour daily regimen, an interval of at least 30 minutes between treatment periods is recommended. Not all patient tolerate 2 hours daily well, however. One hour daily, and two hours daily treatment regimens can be mixed in line with increased comfort over time or for convenience as long as 35 hours total is achieved in 7 weeks or less.

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11. History of External Counterpulsation 1950�s: - Kantrowitz Brothers - diastolic augmentation - Sarnoff - LV unloading - Birtwell - combined concepts - Gorlin - defined counterpulsation 1960�s: - Birtwell & Soroff - Dennis- Osborne - hydraulic external counterpulsation 1970�s: - Soroff - cardiogenic shock - Banas - stable angina - Amsterdam - acute MI 1980�s: - Failure to gain acceptance - China; redeveloped technology- pneumatic system - Soroff, Hui, Zheng collaboration at Stony Brook

12. SUNY Stony Brook: The first publication - 1992 Background: Of 18 patients with chronic angina refractory to medical therapy: - 8 had 19 prior revascularization attempts - 7 had 14 prior mycardial infarcts Methods: 36 one-hour treatment sessions Pre- and post-treatment thallium treadmill stress tests to identical exercise times Separate post-treatment maximal routine treadmill stress test Results: All patients reported improvement in anginal symptoms: - 16 patients (89%) reported no angina during usual activities: - 12 patients (67%) with resolution of reversible perfusion defects - 2 patients (11%) with improvement of reversible perfusion defects - 4 patients (22%) with no change Lawson WE, Hui JCK, Soroff HS, et al. Efficacy of enhanced external counterpulsation in the treatment of angina pectoris. Am J Cardiol. 1992;70:859-862.

13. SUNY Stony Brook: 3-year follow-up of the first 18 patients Background: Clinical follow-up of 18 initially treated patients was conducted after 3 years Methods: Repeat stress thallium test performed to same exercise duration as initial study Results: Of 14 patients who showed resolution/improvement in initial study: - 11 patients remained free of limiting angina - 1 patient was lost to follow-up and 1 refused another stress test - 1 patient had surgical revascularization, 1 patient had an MI Of the remaining 10 patients, 8 retained benefits and 2 reverted to pre- treatment baseline perfusion defects despite symptomatic benefit Lawson WE, Hui JCK, Zheng ZS, et al. Three year sustained benefit from enhanced external counterpulsation in chronic angina pectoris. Am J Cardiol. 1995;75:840-841.

14. SUNY Stony Brook: Patient Response Studies Results: In sixty patients with CAD, after EECP treatment, improvement or resolution of reversible radionuclide perfusion defects were seen in: 86% (18/21) of patients with residual 1-vessel disease 85% (17/20) of patients with residual 2-vessel disease 53% (10/19) of patients with residual 3-vessel disease 75% (45/60) of patients overall Conclusion: A proximally patent conduit may be necessary to allow transmission of augmented diastolic pressure and flow to distal coronary circulation. Lawson WE, Hui JCK, Tong G et al. Prior Revascularization Increases the Effectiveness of enhanced external counterpulsation? Clin. Cardiol. 1998; 21:841-844.

15. SUNY Stony Brook: 5-year Follow-up Background: A five-year follow-up was conducted on 33 angina patients treated between 1989 and 1992 with EECP, to assess morbidity and mortality. Methods: Review of patient records at 5 years post-EECP (range 4-7 years). Results: 29 of 33 patients remained alive. Of these, 9 patients were hospitalized (4 acute MI, 6 CABG/PTCA, 1 unstable angina and 1 other cardiac surgery). Conclusions: Five-year survival without an interim event of 60% of patients treated with EECP appears similar to that seen with comparable populations treated with CABG/PTCA. Lawson WE, Hui JCK, Burger L, et al. Five-year follow-up of morbidity and mortality in 33 angina patient treated with enhanced external counterpulsation. J Invest Med. 1997;45:212A.

16. Effect of EECP Treatment on Exercise-Induced Radionuclide Defects in Fifty Consecutive Patients at SUNY Stony Brook

17. Results of The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP): EECP Reduces Time to ST-Segment Depression and Episodes of Angina with Improved Long-term Quality of Life Rohit R. Arora, MD; Tony Chou, MD; Diwakar Jain, MD; Richard Nesto, MD; Bruce Fleishman, MD; Lawrence Crawford, MD and Thomas McKiernan, MD for the MUST-EECP Investigators

18. MUST-EECP: Study Sites

19. MUST-EECP: Study Goals To confirm efficacy and safety of EECP using rigorous scientific method, i.e. a randomized, sham-controlled, double-blinded protocol generally reserved for drug trials To broaden study experience beyond initial trial site To determine effect vs. placebo

20. MUST-EECP: Method Design: Multicenter, randomized, sham- controlled, double-blinded trial Randomization: Even assignment to EECP group or sham group in blocks of 10 allocated to each center Subjects: 139 patients with chronic stable  angina pectoris (137 evaluable ) Duration: May 1995 - July 1997

21. MUST-EECP: Pre-specified Parameters Evaluate effect of EECP on... Measured by� Exercise ability Exercise duration Time to ST-segment depression Clinical status Frequency of anginal episodes Intake of nitroglycerin Adverse experiences Physical exams Lab tests Daily questions Statistical analysis P-values calculated for between-group differences using Cochran-Mantel-Haenszel Chi-Squared tests for ordered categories stratified by investigator

22. MUST-EECP: Inclusion Criteria Written informed consent 21-81 years of age Canadian Cardiovascular Society Class I, II, or III Evidence of CAD by one of following criteria: Angiographic (1 or more major arteries with >70% stenosis) or Documented evidence of MI or Positive nuclear stress test, plus... A positive exercise stress test within 4-week baseline period

23. MUST-EECP: Exclusion Criteria Pregnant or childbearing potential without contraception Unstable angina MI and/or CABG in prior 3 months Cardiac catheterization in prior 2 weeks Arrhythmias (AF or VPBs) interfering with triggering of EECP Marked baseline ECG abnormalities limiting interpretation (digoxin use, LVH with strain, LBBB) Permanent pacemaker or defibrillator CHF (LVEF <30%) Significant valvular heart disease

24. MUST-EECP: Demographic Characteristics

25. MUST-EECP: CV Morbidity Profiles

26. MUST-EECP: Exercise Results

27. MUST-EECP:Exercise Results

28. MUST-EECP: Angina Change Results

29. MUST-EECP: Percentage Change in Angina Counts 

30. MUST-EECP: On-demand Nitro. Results

31. MUST-EECP: Percentage Change in On-demand Nitroglycerin 

32. MUST-EECP: Adverse ExperiencesConsidered by investigators not to be device related

33. MUST-EECP: Adverse ExperiencesConsidered by investigators to be probably, possibly or definitely device related:

34. Summary of Clinical Results Compared to sham, EECP: Increased time to exercise-induced ST segment depression (p= 0.01) Decreased the frequency of angina episodes (p< 0.04) Compared to baseline: Exercise duration increased significantly in both groups(Sham- p<0.03, Active- p< 0.001) Time to ST segment depression increased significantly in Active Group only (p< 0.002) EECP was generally well tolerated but with significantly fewer adverse experiences reported in the sham group.

35. International EECP Patient Registry (Department of Epidemiology, University of Pittsburgh School of Public Health) Before treatment, the first 445 consecutive patients� 75% had Functional Class III or IV disease (With a mean of 9 angina episodes per week before treatment) 78% have multi-vessel disease 81% had prior CABG or PTCA 66% were not eligible for CABG or PTCA 66% had a prior MI 38% have diabetes

36. International EECP Patient Registry CCS Classes Pre- & Post- Treatment (N=268)

37. International EECP Patient Registry CCS Classes Pre- & Post- Treatment (N=268)

38. Discussion and Conclusions Despite study size limitations, overall, patients who received EECP reported that they experienced less activity-limiting physical pain were in better general health one year post-treatment were more satisfied with their energy level, and the degree of stress, chest pain and shortness of breath that they were experiencing. SHAM-treated patients reported no statistically significant improvement. Results of the outcomes study are consistent with previous clinical study results and demonstrate that the short-term benefits reported in MUST-EECP may extend over the longer term.

39. The Weight of Clinical Evidence: Summary EECP is a safe and effective treatment for angina pectoris refractory to medical therapy Benefits of EECP include an improvement of functional status in more than 70% of patients Benefits accrue both short-term and long-term

40. EECPEnhanced External Counterpulsation