Congestive Heart Failure

Enhanced External counter pulsation (EECP�): Congestive Heart Failure update

Prepared by Dr. Ramasamy

The value of EECP� in Chronic ischemia is well established. We know from the Anginal studies With EECP�, coronary blood flow is increased during diastolic phase (1,2), cardiac output is increased (3), cardiac after load is decreased, collateral vessels are recruited and enlarged, nitric oxide, antioxidant (4), VEGF, ANP (5) levels rise. Renin (6) endothelia (7) and BNP levels fall (8), PET (9), Thallium (10,11), Exercise tolerance, Exercise induced myocardial ischemia improves (12) and frequency of angina decreases, use of nitro decreases and patient sense of well-being and quality of life improves (13). Also the beneficial effects of EECP� attained during the treatment have been shown to last for three to five years (14, 15).

FDA granted 510(k) clearance to Heal your heart EECP�-MC2 treatment for CHF on July 2002.

The prevalence of congestive heart Failure is growing rapidly as a result of the aging of the population and the improved survival rate of people after heart attacks. Also, because the condition frequently entails visits to the emergency room and in-patient treatment, two-thirds of all hospitalizations for people over age 65 are due to CHF. It is now certain the prevalence of heart failure will continue to grow both in developed and developing nations.

EECP� is the only medical device can be used with all classes of CHF patients.

I. Objective findings of EECP� in Heart failure symptoms

Efficacy and safety of EECP� in Mild to moderate heart failure. Preliminary report. (Journal of cardiac failure 2000 6(3): 48(180)

Total 6 patients ---- 5 Ischemic Cardiomyopathy and 1 dilated Cardiomyopathy.
All patients clinically stable with LVEF < 35%. NYHA class II AND class III.
V02 Max (ml/kg/min) --------------------Increase 18.7 %
Exercise duration ------------------------- Increase 33.9%
Quality of life------------------------------ Improved 35.3%

Conclusion :
EECP� is Efficacious and well tolerated by Heart failure patients in short term.

Enhance External counter pulsation in Heart Failure patients. A Multicentre feasibility study (CHF. 2002; 204-208,227) Total 32 patients. 1 week and 6 month follow up. All patients are clinically stable with LVEF< 23.2%�7.4 Adverse event leading to discontinuation of treatment 1 patient due to severe back pain EECP� related 3 patients due to Arrhythmia and worsening of CHF not related to EECP�.

At 6 months when compare to the baseline mean Exercise time increased by 15.5% and peak oxygen uptake increased by 27.09%.

Conclusion :

The benefit consists of significant increase in exercise capacity (peak oxygen uptake and exercise duration) and the benefits were persisting when followed up to 6 months. The benefits were similar in both Ischemic and idiopathic Cardiomyopathy.

Improvement in Left Ventricular performance by Enhance External counter pulsation in patients with Heart Failure.

No of patients 8 with NYHA Class II OR III with LVEF < 35% Significant improvement in preload-adjusted maximal power (PAMP) Decrease in heart rate.

Conclusion :

EECP� may be beneficial to LV function in Heart failure patients improvement in preload-adjusted maximal power (PAMP) indicate improvement in myocardial contractility independent of pre-load and has the potential as an adjunctive to medical therapy in these patients.

Does EECP� improve Cardiac Function in Ischemic Cardiomyopathy?

Presented at the American Federation for Medical Research, Baltimore Maryland April 12 2002.
Total patients 24.

Parameter	19 patients (LVEF>35%)	5 Patients (LVEF< 35%) Ischemic
Stroke Volume (cc)	0%	12%
Systemic Vascular Resistance	+ 4%	- 11%
Cardiac output (L/min)	- 4%	18%
Cardiac index (L/min/m2)	- 4%	15%

Conclusion :

EECP� improves cardiovascular indices in patients with severe left ventricular dysfunction. The improvement in cardiovascular indices in more pronounced in patients with severe left Ventricular dysfunction with EF < 35%.

II. Mechanism of EECP� in Heart Failure.

Enhance External counter pulsation Improves Exercise Tolerance, Reduces Exercise Induced Myocardial Ischemia and Improves Left Ventricular Diastolic Filling in patients with coronary artery disease

J Am Coll Cardiol 2001: 37: 93-9

This paper indicates the mechanism of EECP�. It looks at the effect of EECP� on Diastolic dysfunction. EECP� shown to decrease left ventricular end diastolic pressure (LVEDP), increase peak filling rate and decrease time to peak filling rate. Also decrease the plasma level of Brain Natriuretic peptide.

In ventricular diastolic dysfunction, ventricular end diastolic pressure increases reflecting its stiffness against filling during the diastole phase of the heart. This impaired filling due to problem in relaxing of ventricle leads to accumulation of fluid in the feet, ankles and legs. EECP� has been clearly shown to improve left Ventricular diastolic filling, which may result in improvement of edema and clinical symptoms.

Plasma brain Natriuretic peptide rises in symptomatic heart failure and Abnormal LVEF. BNP is mainly secreted from left ventricular wall when subjected to stress or stretch. BNP level greater than >100pg/mL indicates heart failure. Plasma level BNP significantly reduced after EECP�. BNP negatively correlate with ventricular filling pressure. Improved diastolic filling associated with decrease BNP.

Enhance External counter pulsation improved myocardial perfusion and coronary flow reserve in patients with chronic stable angina.

European Heart Journal (2001) 22, 1451-1458

This paper gives another insight in to the mechanism of EECP� in congestive heart failure by measuring Nitric oxide, Brain Natriuretic peptide and atrial Natriuretic peptide.

From previous study we know EECP� decreases the plasma level of BNP but we have no clue about how long the effect will last. This study measures the decrease level of BNP and ANP was maintained for I month after completion of EECP� treatment. The raised level of nitric oxide also was maintained for 1 month. This increase nitric oxide suggests a profound improvement in endothelial function. The increase nitric oxide would not only be confined to coronary arteries but also to systemic arteries. This result suggests the decrease in after load during EECP�. This gives the insight the benefit of EECP� is not only due to improvement in myocardial perfusion but also due to decrease in cardiac workload and improvement in endothelial dysfunction.

A Neurohormonal Mechanism for the effectiveness of Enhance External counter pulsation.

(Circulation 1999; 100(8))

EECP� cause a sheer stress in Vascular Endothelium, which stimulates the release of Neurohormonal factor. The endothelial dependent Vasoreactivity is a balance between endothelial derived relaxing factors and endothelial derived contracting factors. Any deviation from this balance mostly impairment of vasorelaxation is defined as Endothelial Dysfunction. One of the non-pharmacological stimuli that cause vasorelaxation is Shear stress.

To study the effect o sheer stress in vascular endothelium causes by EECP� the investigator Gu-fu Wu measures the two Neurohormonal factors nitric oxide and endothelia.

Effects of EECP� Treatment Changes in Plasma

Effects of EECP� Treatment Changes in Plasma Nitric Oxide

Endothelia and nitric oxide were measures pre-EECP� 1 hr, 12th hr, 26th hr, 36th hr and 1st and 3rd month of EECP� treatment. The nitric oxide significantly increased and endothelia level significantly decreased proposition to the duration of treatment. The change in ratio was significant even after 1 month after the treatment. By 3rd month the ration tends to move towards the baseline.

Intermittent shear stimuli by Enhance External counter pulsation (EECP�) restores Endothelial Function in patients with coronary artery diseases

(Circulation 102:18 Suppl. II Oct 00')

Endothelial health is a key indicator of cardiovascular health and long time outcome of the patients. Endothelial dysfunction is the imbalance between the vasodilatation and vasoconstriction factors secreted by Endothelium. We already know EECP� improves the vasodilatation by increasing the nitric oxide level and decreases the vasoconstriction by decreasing the endothelia level. This study shows EECP� improves the Ischemic symptoms and long-time outcome by restoring endothelial function. Endothelial function can be accurately assessed by brachial flow arm mediated vasodilatation technique.

Flow mediated Brachial Vasodilatation was significantly impaired at the baseline at 4% and increases up to 3 fold after 35 hrs of EECP� restoring almost towards the normal value.

Improvement of renal perfusion and function by pneumatic external counter pulsation.

D. Werner et al 20th Congress of the European Society of Cardiology Abstract P3660 September �98 Vienna, Austria.

The increase in retrograde blood flow during diastolic period not only increases coronary circulation but also improves blood flow in other organs including kidney. Parameters of kidney functions where measured in 12 healthy individuals. External counter pulsation increases renal perfusion, urinary production, sodium and chloride excretion and decreases plasma endothelia and renin production. These findings were summarized in the tabular column below.

Parameter	Pre-EECP�	5 Patients (LVEF< 35%)	% Change
Stroke Volume (cc)	522 ml/min	676 ml/min	+ by 21%
Systemic Vascular Resistance	0.18 mmol/min	0.35 mmol/min	+ by 94%
Cardiac output (L/min)	0.1 mmol/min0%	0.22 mmol/min	+ by 120%
Cardiac index (L/min/m2)	3.3 ml/min	3.2 pg/ml	- by 37%
Cardiac index (L/min/m2)	4.4 pg/ml0%	14.3%	- by 37%
Cardiac index (L/min/m2)	9.5 pg/ml	7.5 pg/ml	- by 27%

The Neurohormonal change in heart failure occurs due to decrease in cardiac out put and increase in wall stress. The notable changes take place in adrenergic system, renin angiotensin-aldosterone system (RAAS), hypothalamic-neurohypophyseal system and endothelia. All this system activation helps to increase blood volume, enhance contraction of ventricles, and maintain mean arterial pressure to preserve the vital perfusion pressure in coronary, cerebral and other organs. This system activation provides short time Hemodynamic support but in long time it is deleterious associated with Myocardial fibrosis, adverse ventricular remoulding and endothelial dysfunction.

 -One of the important vasoconstrictor endothelia level decreases by 27%. This again confirms the previous study finding.
 -Increase urine production and sodium and chloride excretion. This diuretic effect of EECP� may reduce the diuretic dosage and improve heart failure symptoms.
 -The 37% decrease in renin, which is the main activator of RAAS system, will have favourable effect on Neurohormonal like Angiotensin converting enzyme (ACE) Angiotensin II and Aldosterone plasma level.

Beneficial effect of EECP� on the Renin-Angiotensin in patients with coronary artery disease

(European society of cardiology sep-1-5 2001) Stockholm Sweden.

We now know from our previous study, EECP� increases renal perfusion and causes sheer stress in vascular endothelium, which in turns mediate, the release of nitric oxide and decrease the endothelia concentration in the plasma.

This study shows the beneficial effect of the increase renal perfusion in Renin-Angiotensin-Aldosterone system (RAAS). There is decrease in Angiotensin converting enzymes and Angiotensin II. This inhibition of RAAS system has favourable effect on decreasing the stiffness of the ventricle and improving ventricular filling, improving the homodynamic burden placed on the failing ventricles, and decreasing myocyte apoptosis. All this factors together responsible for the potential benefit of EECP� treatment.

Effects of EECP� on Plasma ANG II Activity

III. CLINICAL EFFICACY OF EECP� IN HEART FAILURE PATIENTS.

Enhance External counter pulsation Pulsation is a safe and Effective treatment for Angina in patients with severe left ventricular dysfunction. (IEPR) (Journal of cardiac failure 1999; 5(3): 72(#268)).

Total 466 patients.

127 (27.3%), LVEF < 35%, 83% completed the treatment (LVD)
339 (72.8%), LVEF > 35%, 82% completed the treatment.(PLVF)

	LVD	PLVD
Total (466)	127	339
Aggravation of CHF	3.9%	1.9%
Anginal Improvement	3.1 to 1.7	2.8 to 1.4
Treatment Completed	83%	7.5 pg/ml

Conclusion:

EECP� is safe and effective and the Anginal class improvement is independent of the degree of left ventricular dysfunction.

Data presented in August of 2000 at the European Society of Cardiology meeting in Amsterdam. Journal of Cardiac Failure 2000; 6 (3): 75 (282).

Because of the higher mortality associated with CHF this study perform 6 month follow up on patient with LVD and chronic angina for Major averse cardiac event and mortality.

Total Patients 554 Six month follow up.

	LVD	PLVD
Total (554)	129	425
LVEF	< 35%	> 35%
Death	7.0	1.6
MACE (Death/MI/CABG/PCI)	10.6	6.6
Anginal Improvement	70%	79%

90% of patients with severe LVD did not suffer any major cardiac events.

Conclusion:

Patients with LVD achieved considerable reduction with EECP� and the majority of these patients this reduction was maintained at six month.

Benefit and safety of Enhance External counter pulsation in treating Coronary artery Disease patients with a history of Congestive Heart Failure. (IEPR)

Cardiology 2001; 96; 78-84

otal 1,957 patients, 548 with history of heart failure and 1,409 without history of heart failure. Events occurring during the 6 months following EECP� therapy by CHF status. Major adverse cardiac events (Death/MI/CABG/PCI)

	Without H/O CHF (N= 1,157)	With H/O CHF (N= 444)
MI	2.5	3.6
Unstable Angina	7.4	9.0
CHF	2.4	7.2
CABG	2.0	1.1
PTCA	2.9	2.5
Death	2.2	7.9
Cardiac hospitalization	13.6	19.1

Given the severity of the disease suffered by this group MACE is within expectation.

In subgroup analysis patients with a history of CHF and severe left ventricular dysfunction (EF<35%) revealed that this patients benefited similarly to those patients with less severe ventricular dysfunction after EECP� treatment.

Conclusion :

EECP� is effective in improving angina in coronary patients with a history of CHF. Acute treatment did not cause major adverse cardiac events in this high-risk group of patients, although 7.3% experienced worsening of their CHF. At 6 months majority of the patients maintained their improvement.

REFERENCES

1. Pneumatic external counter pulsation a new treatment for selected patients with Symptomatic coronary artery disease. Werner et al Supplement to circulation; American heart association scientific section 11/98,Abstract 1839.

2. Pneumatic external counter pulsation; A new non-invasive method to improve organ perfusion. Werner, D, American journal of cardiology 1999 84,950-52

3. Maximizing the Hemodynamic benefit of Enhance External Counterpulsation. Clin. Cardiology, 21, 649-653(1998)

4. Effects of enhance external counter pulsation on nitric oxide production in coronary artery disease. Xiao-xian Quan et al. 1st international congress on heart disease-new trends in research, diagnosis and treatment. The Journal of heart disease 1; 1 may 91

5. Masuda et,al. Euro Heart Journal 2001

6. Improvement of renal perfusion and function by Pneumatic external counter pulsation. D, Werner et al 20th congress of the European society of cardiology abstract P3660 September 98 Vienna, Austria.

7. A Neurohormonal mechanism for the effectiveness of Enhance External counter pulsation. Wu,Giu-Fu et al circulation 100;18; supplement 1Abstact 4388 1999

8. Enhance External counter pulsation Improves Exercise tolerance, Reduces Exercise-Induced Myocardial Ischemia and Improves Left Ventricular Diastolic filling in Patients with coronary artery disease. American college of cardiology Jan 2001

9. Improvement of Regional Myocardial and Coronary Blood Flow Reserve in a patient treated with Enhanced External counter pulsation. Evaluation by Nitrogen-13 Ammonia PET. Japanese Circulation Journal Vol 63 No.5 May 1999.

10. Efficacy of Enhance External counter pulsation in the treatment of angina pectoris. Lawson WE Hui JCK et al: American Journal of Cardiology 1992 70:859-862.

11. Can Angiographic findings predict which coronary patients will Benefit from Enhance External counter pulsation? American Journal Of Cardiology 1996; 77:1107-09

12. The Multicentre study of Enhanced External counter pulsation (MUST-EECP�): effect of EECP� on Exercise-Induced Myocardial Ischemia and Anginal Episodes. Journal of American College of Cardiology. 1999

13. Psychosocial effect of Enhance External counter pulsation in the angina patients: Fricchione GL et al: Psychosomatics 1995,36: 494-97.

14. Three year sustained Benefit from Enhance External counter pulsation in chronic angina pectoris. American Journal of Cardiology 1995:75-840-841.

15. Long-times prognosis of patients with Angina Treated with Enhanced External counter pulsation: Five year follows up study. Clinical Cardiology 2000 23:254-58.