Klinik Veriler
- Hemodinamik Etkileri
Diastol sırasında ardışık olarak kafların şişmesi, retrograd aortik kan akımını dolayısı ile koroner kan akımını ve koroner perfüzyon basıncını artırır. Venöz dönüş ve kardiyak “output” (çıkış) artar. Sistol başlangıcında hızlı ve aynı anda kafların sönmesi sistemik vasküler direnci, afterload ve kardiyak iş yükünü azaltır. EECP Tedavisinin Hemodinamik etkileri aynı zamanda, basınç gradiyantını ve koroner kolleteral dolaşımı güçlendiren vasküler büyüme faktörlerinin salınımını artırır. Kan akışının artması Arter duvarlarındaki “Sheer Stressi” arttırır ve endotel fonksiyonunu iyileştirir.
Yapılan çalışmalar, EECP Tedavisinin hemodinamik etkilerinin, IntraAortik Balon Pompasına ( IABP ) benzediğini hatta birçok parametrede daha iyi sonuç verdiğini gostermistir.
UCSF ( University of California, San Francisco ) araştırmacılarının hemodinamik mekanizmayı kanıtlama konusunda dönüm noktası olarak bilinen araştırmaları EECP tedavisin hemodinamik etkilerini kateter laboratuarında girişimsel olarak göstermiştir. Bu araştırma sonuçları “Circulation” da yayınlanmıştır. “ EECP Tedavisi merkezi Aortik ve intrakoroner Diastolik basıncı ve Intrakroner kan akış hızını arttırır. EECP Tedavisi sırasında Aortik ve Intrakoroner basınç artar, Sol ventrikül sistolik boşalma sağlanır, kalbin is yuku azalir. ‘’
EECP Tedavisi, İskemik Kalp Hastalıkları ve Kalp Yetmezliği hastalıklarında egzersiz toleransı da dahil olmak üzere, klinik bulguları ve yaşam kalitesini artırır. Fonksiyonel kapasitede artma, Koroner arter hastalığı ve /veya kalp yetmezliği şikâyetlerinde belirgin iyileşme sağlar. Tedavi sonrası Nitrogliserin kullanımının da belirgin azalma yada hiç kullanmama gözlemlenir.EECP Tedavi Cihazında, taban hattında Kafların şişmesiyle artan basınç Intrakoroner phasic ve mean basınç izlemesi. Artan şişme basıncı ile Diastolik ( soluk oklar ) ve mean basınç artışı. Öteyanda Sistolik basınç ( koyu oklar ) azalması. Kâğıt hızı 25mm/ saniye. Eşzamanlı Merkezi Aortik ve Intrakoroner basınç, pik Diastolikde gittikçe artan basıncı ( soluk oklar ) ve Pik Sistolik basınçta azalmayla mean basıncı gösterir ( koyu oklar ).EECP Tedavisinde şişme basıncının 300mm yükselmesiyle Sistolik boşalma anlamına gelmektedir. Kâğıt hızı 25mm/ saniye. - Etki Mekanizması
EECP tedavisinin etkinliği 3 ayrı mekanizma ile açıklanmaktadır
- Nörohormonal değişiklikler: Yapılan çalışmalar EECP tedavisi sırasında ve sonrasında Nitrik oksit seviyesinde artma, Endotelin, BNP, ACE ve AgII seviyesinde azalma olduğunu göstermiştir. Ref: Masuda D, Nohara R, Kataoka K et al. Enhanced external counterpulsation promotes angiogenesis factors in patients with chronic stable angina . Circulation ( suppl ) 2001; 104:II445 (2109) Soran O, Crawford L, Schenieder VM, Feldman AM Enhanced external counterpulsation in the management of patients with cardiovascular disease. Clin cardiol 1999;22:173-8
- Endotel fonksiyonunda artma: son senelerde yapılan çalışmalar tedavi sonrasında endotel fonksiyonda belirgin iyilesme oldugunu kanıtlamıştır. Ref:Masoda D, Nohara R,Hirai T et al Enhanced external counterpulsation improved myocardial perfusyon and coronary flow reserve in patients with chronic stable angina . Eur Heart J 2001;22:141-58 ;Wu GF, Qiang SZ,Zheng ZS, et al . A Neorohormonal mechanism for the effectiveness on enhanced external counterpulsation. Circulation 1999; 100:I-832 (4390).Urano H,Ikeda H, Ueno T et al. Enhanced external counterpulsation improves exercise tolerance , reduces exercise-induced myocardial ishemia and improves left ventricular diastolic fiiling in patients with coronary artery disease. J Am Coll Cardiol 2001;37:93-9
- Kolleteral dolaşımda artma: Hayvan deneylerinde tedavi sonrası belirgin ölçüde kollateral dolaşım geliştiği gösterilmiştir. 2009 da yapılan plasebo kontrollü araştırmalar ise insanlarda EECP tedavi sonrası kollateral dolaşımda belirgin gelişme olduğunu kanıtlamıştır. Ref: Pagonas N,et al – Assesment of the effect of external counterpulsation myocardinal adoptive arteriogenesis by Invasive Functional Measurements – desingn of the arteriogenesis network trial2. Int J Catdiol (2009 ) doi:10.1016, Buschmann et al – Improvement of fractional flow reserve and collateral flow by treatment with external counterpulsation. Eur J Clin Investor 2009
- EECP Tedavisi, yarattığı Arteryal Diastolik ögmentasyon ile yararlı etkiler meydana getirmektedir. Retrograd Arteryal Basınç dalgası Koroner perfüzyon basıncını arttırarak, Miyokarddaki iskemik ve iskemik olmayan alanlar arasında orada olmayan Conduitleri bir araya getiren bir gradiyent oluşturmakta ve Miyokard perfüzyonu güçlendirmektedir. Artan Endothelyel Sheer Stres, Büyüme Hormonlarını serbest bırakmaktadır. Artan Nitrik Oksit ( NO ) ve Atrial Natriüretik Peptit ( ANP ) seviyeleri ve azalan Endothelin ( ET – 1 ) ve Beyin Natriüretik Peptiti ( BNP ) seviyeleri – aynı zamanda artan Sheer Stres’ e ve gelişen Endothelyal Fonksiyonla da bağıtlandırılan, periferal faydaların olasılığını ve aynı zamanda Koroner akım rezervinin korunmasını yükseltmektedir.
EECP Tedavisinin klinik yararlarına katkıda bulunduğu öne sürülen mekanizma, Endothelyal fonksiyonun gelişmesi, kolleteral oluşumuna yardımcı olması, ventriküler fonksiyonun güçlenmesi ve sürekli fiziksel egzersiz yapanlarda gözlenen olgulara benzer periferal etkileri de içermektedir.
EECP Tedavisinin klinik yararlarının sebep olduğu olası mekanizma.
Bonetti PO, Borsness GW, Keelan PC, et al. EECP Koroner Arter hastası hastaların endothhelial fonksiyonlarını geliştirir. Journal of the AmericanCollege of Cardiology. 2003 May 21:41(10);1761-8.
- Uzun Dönem Takip Verileri
Plasebo kontrollü klinik çalışma sonuçları da dahil olmak uzere ve Pittsburgh Üniversitesi Epidemoloji Veri Merkezi tarafından koordine edilen Uluslararası EECP Hasta Kayıt ( IEPR ) verileri, bir kür ( 35 seans ) EECP Tedavisini tamamlayan hastaların % 70 ila % 80 inde terapatik iyileşmenin sağlandığını ve yasam kalitesinde belirgin iyilesme oldugunu gostermistir.
Klinik çalışmalar tedavi etkinliğin hastaların %66’da 5 yıla kadar devam ettiği göstermiştir.Resmi Büyütmek için resme tıklayınız
Kaynak Loh PH,Cleland JG, Lois AA, Kennard ED, et al. Kronik Refarakter Angina’ da EECP Tedavisi: EECP Uluslararası Hasta Kayıt Çalışmasında Uzun Dönem Takip Sonuçları. Clinical Cardiology. 2008 Apr 10;31(4):159-164. I
IEPR ( Uluslar arası EECP hasta Kayıt ) hakkında bilgi ve IEPR bibliyografyasının tamamına www.edc.gsph.pitt.edu/iepr web sitesinden ulaşabilirsiniz. - Anahtar Çalışma Mekanizması
Hemodynamic Effects of EECP Therapy
Left Ventricular Systolic Unloading and Augmentation of Intracoronary Pressure and Doppler Flow During Enhanced External Counterpulsation
Michaels AD, Accad M, Ports TA, Grossman W.
Circulation. 2002 Sep 3;106(10):1237-1242.Summary: 10 patients underwent left heart catheterization significantly increasing their coronary diastolic pressure (93%), decreasing systolic pressure (15%) and their peak coronary flow velocity increased by 109% as measured by intracoronary Doppler ultrasound during EECP therapy when compared with baseline.
Endothelial Cell Function
Enhanced External Counterpulsation Improves Endothelial Function in Patients with Symptomatic Coronary Artery Disease
Bonetti PO, Barsness GW, Keelan PC, Schnell TI, Pumper GM, Kuvin JT, Schnall RP, Holmes DR, Higano ST, Lerman A.
Journal of the American College of Cardiology. 2003 May 21;41(10):1761-1768.Summary: 17 (74%) of the 23 patients with refractory angina improved at least 1 symptomatic Canadian Cardiovascular Society class with a significant increase in their endothelial function as measured by reactive hyperemia-peripheral arterial tonometry (RH-PAT) index which occurred after 1 hour of EECP treatment and remained high at 1-month follow-up.
Arterial Stiffness
Enhanced External Counterpulsation Treatment Improves Arterial Wall Properties and Wave Reflection Characteristics in Patients With Refractory Angina
Nichols WW, Estrada JC, Braith RW, Owens K,
Conti CR.
Journal of the American College of Cardiology. 2006 Sep 19;48(6):1209-1215. Epub 2006 Aug 25.Summary: 34, 1-hour EECP treatments in 20 stable angina patients caused a significant decline in the augmentation index and an increase in reflected wave travel time, demonstrating a reduction of arterial stiffness, resulting in a decrease in left ventricular afterload, myocardial oxygen demand and angina episodes and improved Canadian Cardiovascular Society functional class.
Inflammatory Markers
Effect of Enhanced External Counterpulsation on Inflammatory Cytokines and Adhesion Molecules in Patients with Angina Pectoris and Angiographic Coronary Artery Disease
Casey DP, Conti CR, Nichols WW, Choi CY, Khuddus MA, Braith RW.
American Journal of Cardiology. 2008 Feb 1;101(3):300-302. Epub 2007 Dec 11.Summary: 21 patients were randomly assigned to EECP or sham treatment, plasma tumor necrosis factor was reduced by 29% and monocyte chemoattractant protein-1 by 19% after active treatment compared with no significant changes in the sham group. Circulating level of proinflammatory cytokines are predictors of future coronary events.
Endothelial Progenitor Cell Release
The Effect of External Counter Pulsation Therapy on Circulating Endothelial Progenitor Cells in Patients with Angina Pectoris
Barsheshet A, Hod H, Shechter M, Sharabani-Yosef O, Rosenthal E, Barbash IM, Matetzky S, Tal R, Bentancur AG, Sela BA, Nagler A, Leor J.
Cardiology. 2008;110(3):160-6. Epub 2007 Dec 4.Summary: Circulating endothelial progenitor cells (EPCs) positive for CD34 measured by flow cytometry and kinase insert domain receptor (KDR) measured by the number of colony-forming units in 25 patients with angina pectoris randomized to 35 daily 1-hour EECP treatment sessions (n=15) and control (n=10) were significantly increased in the EECP treated group and not in the control group. Patients in the EECP therapy group also improved their anginal score from 3.0 pre-EECP therapy to 2.0 post EECP therapy (p<0.001). The improvement of angina post EECP treatment is associated with an increased number of colony-forming capacities of circulating EPCs.
Randomized Clinical Trials and Patient Registry Data in the Treatment of Angina Pectoris and Heart Failure
The Multicenter Study of Enhanced External Counterpulsation (MUST-EECP): Effect of EECP on Exercise-Induced Myocardial Ischemia and Anginal Episodes
Arora RR, Chou TM, Jain D, Fleishman B, Crawford L, McKiernan T, Nesto R.
The Journal of the American College of Cardiology. 1999 Jun;33(7):1833-1840.Summary: A multicenter (7 university hospitals), prospective, randomized, blinded, control trial of 139 angina patients with documented coronary artery disease and positive exercise treadmill tests were treated with either active counterpulsation (applied cuff pressure up to 350 mmHg), and inactive counterpulsation (<75 mmHg). Exercise duration increased in both groups, with time to ≥ 1-mm ST-segment depression increased significantly from baseline in the active group compared with the inactive group (p=0.11), as well as a significant reduction in the number of angina episodes (p<0.05). Nitroglycerin usage decreased in the active group but did not change in the inactive group; the between-group difference was not significant (p>0.7).
Enhanced External Counterpulsation Improves Exercise Tolerance in Patients With Chronic Heart Failure
Feldman AM, Silver MA, Francis GS, Abbottsmith CW, Fleishman BL, Soran O, de Lame PA, Varricchione T for the PEECH Investigators.
Journal of the American College of Cardiology. 2006 Sep 19;48(6):1199-1206. Epub 2006 Aug 25Summary: 187 subjects with mild-to-moderate symptoms of heart failure were randomized to either EECP treatment with protocol-defined pharmacologic therapy (PT) or PT alone. 35% in the EECP therapy group and 25% in control group increased their exercise time by at least 60 sec (p=0.016) at 6 months. However, there was no between group difference in the percentage of subjects with at least 1.25 ml/kg/min increase in peak volume of oxygen uptake. New York Heart Association (NYHA) functional class improved in the active treatment group at 1-week (p<0.01), 3 months (p<0.02), and 6 months (p<0.01 post treatment). The Minnesota Living with Heart Failure score also improved significantly in the treated group at 1 week (p<0.002) and 3 months (p=0.01) after treatment, versus no significant changes in the control group.
Enhanced External Counterpulsation Improves Exercise Duration and Peak Oxygen Consumption in Older Patients With Heart Failure: A Subgroup Analysis of the PEECH Trial
Abbottsmith CW, Chung ES, Varricchione T, de Lame PA, Silver MA, Francis GS, Feldman AM; Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) Investigators.
Congestive Heart Failure. 2006 Nov-Dec;12(6):307-311.Summary: This paper reports the results of a pre-specified subgroup analysis of 85 elderly patients (65 years or older) enrolled in the PEECH trial. At 6-months post treatment, the percentage of subjects with >60-second increase in exercise duration was significantly higher in EECP patients compared with the control group (p=0.08). Moreover, in contrast to the overall PEECH study (see above), the older patient group demonstrated a significantly higher percentage of responders with >1.25 ml/kg/min increase in peak volume of oxygen consumption (p=0.017). In addition, the mean changes in exercise duration and peak oxygen consumption from baseline were significantly increased compared with the control group at 1 week, 3 months and 6 months following completion of treatment.
Perfusion to Ischemic Region
Effects of Enhanced External Counterpulsation on Stress Radionuclide Coronary Perfusion and Exercise Capacity in Chronic Stable Angina Pectoris
Stys TP, Lawson WE, Hui JCK, Fleishman B, Manzo K, Strobeck JE, Tartaglia J, Ramasamy S, Suwita R, Zheng ZS, Liang H, Werner D.
The American Journal of Cardiology. 2002 Apr 1;89(7):822-824.7-centers, 175 patients divided into two groupsGroup 1 (4-centers, 97 pts)
Same Level Exercise Pre & Post EECPStress Nuclide Perfusion
• 83% had significant improvement
• 17% no change
• 0% worse RN
Double product no changeGroup 2 (3-centers, 78 pts)
Maximal Exercise Pre & Post EECPStress Nuclide Perfusion
• 54% improved RN perfusion
• 42% no change
• 8% worse
Double product no change
Enhanced External Counterpulsation in the Treatment of Chronic Refractory Angina: A Long-term Follow-up Outcome from the International Enhanced External Counterpulsation Patient Registry
Loh PH, Cleland JG, Louis AA, Kennard ED, Cook JF, Caplin JL, Barsness GW, Lawson WE, Soran OZ, Michaels AD.
Clinical Cardiology. 2008 Apr 10;31(4):159-164.
Experimental Studies
Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by Modifying Shear Stress Responsive Gene Expression in Hypercholesterolemic Pigs
Zhang Y, He X, Chen X, Ma H, Liu D, Luo J, Du Z, Jin Y, Xiong Y, He J, Fang D, Wang K, Lawson WE, Hui JC, Zheng Z, Wu G.
Circulation. 2007 Jul 31;116(5):526-534. Epub 2007 Jul 9.Summary: The coronary arteries and aortas of 35 male pigs randomly assigned to control, high-cholesterol diet and high-cholesterol diet +EECP (EECP started at week 9 to 15) were analyzed after 15 weeks. There was significant increase in peak diastolic arterial wall shear stress during EECP with reduction of intima-to-media area ratio by 42% compared with high-cholesterol group. EECP treated group also increased the protein expression of endothelial nitric oxide synthase suppressed the phosphorylation of extracellular signal-regulated kinases ½.
Cost-Effectiveness
Impact of External Counterpulsation Treatment on Emergency Department Visits and Hospitalizations in Refractory Angina Patients with Left Ventricular Dysfunction
Soran O, Kennard ED, Bart BA, Kelsey SF.
Congestive Heart Failure. 2007 Jan-Feb;13(1):36-40.Conservative Estimate of Annual Savings/Patient# HF PatientTotal # Hospital VisitsAverage Cost Per Hospital VisitTotal Cost to Healthcare System/1,000Before ECP 1,0003,000$5,456$16,368,000After ECP 1,000500$5,456$2,728,000Reduction in hospitalization costs after ECP $13,640,000Cost to treat with ECP $3,640,000Annual savings to healthcare $10,000,000Savings per patient $10,000
Review Paper
Enhanced External Counterpulsation and Future Directions: Step Beyond Medical Management for Patients with Angina and Heart Failure
Manchanda A, Soran O.
Journal of the American College of Cardiology. 2007 Oct 16;50(16):1523-1531. Epub 2007 Oct 1.Evidence
– Safe, non-invasive
– Increase blood flow
– Recruit collaterals
– Stimulate vascular growth
– Improve endothelial function
– Improve neurohormonal factors
– Reduce arterial stiffness
– Decrease angina pectoris
– Improve ischemic heart failure
– Long-term sustained effectsEECP therapy is effective in the treatment of ischemic heart disease (angina, heart failure)For a complete listing of publications about EECP therapy, please see the EECP Therapy Bibliography.
To view the IEPR bibliography visit www.edc.gsph.pitt.edu/iepr.