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BRIEF COMMUNICATION Enhanced external counterpulsation improves peripheral resistance artery blood flow in patients with coronary artery disease Joseph C. Avery, Darren T. Beck, Darren P. Casey, Paloma D. Sardina, and Randy W. Braith
Abstract: Enhanced external counterpulsation (EECP) increases coronary artery perfusion and improves endothelium-dependent vasodilation in peripheral muscular conduit arteries. It is unknown whether vasodilatory capacity is improved in the peripheral resistance vasculature. Here we provide novel evidence from the first randomized, sham-controlled study that EECP increases peak limb blood flow and improves endothelium-dependent vasodilation in both calf and forearm resistance arteries in patients with coronary artery disease. Key words: enhanced external counterpulsation, resistance arteries, venous occlusion plethysmography, coronary artery disease. Résumé : La contrepulsation externe a` haut rendement (« EECP ») accroît la perfusion de l’artère coronaire et améliore la vasodilatation induite par le flux dans les conduits artériels musculaires en périphérie. On ne sait pas si la capacité vasodilatatoire est améliorée dans les vaisseaux résistifs en périphérie. Nous présentons ici des données probantes originales issues de la première étude aléatoire avec groupe de simulation : l’EECP accroît le débit sanguin de pointe dans les membres et améliore la vasodilatation induite par le flux dans les artères résistives du mollet et de l’avant-bras de patients aux prises avec une coronaropathie. [Traduit par la Rédaction] Mots-clés : contrepulsation externe a` haut rendement, artères résistives, occlusion veineuse, pléthysmographie, coronaropathie.
Introduction Enhanced external counterpulsation (EECP) is a noninvasive outpatient therapy, approved by the United States Food and Drug Administration in 1995, for the treatment of patients with coronary artery disease (CAD) and refractory angina pectoris. Data from the International Patient Registry demonstrate that EECP decreased angina episodes and nitrate usage and increased exercise tolerance (Arora et al. 1999). The anti-ischemic benefits occur early and are sustained up to 3 years in more than 75% of patients with a favorable initial response to EECP (Soran et al. 2006). Historically, the popular hypothesis has been that EECP promotes coronary collateral growth and improves myocardial perfusion via augmentation of intracoronary diastolic pressure, suggesting that external compression may serve as a mechanical assist device (Braith et al. 2010; Stys et al. 2002). However, recent studies by us (Braith et al. 2010; Casey et al. 2011; Gurovich and Braith 2013) and others (Akhtar et al. 2006; Hashemi et al. 2008) have identified peripheral vascular mechanisms by which EECP confers anti-ischemic benefits in patients with symptomatic CAD. Specifically, endothelium-dependent flow mediated dilation (FMD) in muscular conduit vessels, such as the brachial and femoral artery, is improved 51% and 30%, respectively, after EECP (Braith et al. 2010). Bioavailability of nitric oxide and 6-keto-prostaglandin F1␣ (6-keto-PGF1␣) is improved by 36% and 71%, respectively, by EECP (Braith et al. 2010). Stiffness of central elastic conduit arteries (aorta) and peripheral muscular conduit arteries (brachial, femoral) is decreased significantly after EECP (Casey et al. 2011). Importantly, these improvements in arterial function were paral-
leled by reductions in wasted left ventricular energy and decreases in myocardial demand (Casey et al. 2011). In aggregate, these recent data suggest that improvements in elastic and muscular conduit arteries may explain improvements in angina class and exercise tolerance observed in patients with CAD after EECP. Impaired endothelial function in CAD patients, however, is not limited to conduit arteries. Rather, endothelial dysfunction is a systemic phenomenon that persists in resistance arteries, ultimately resulting in the loss of atheroprotective effects of the normal endothelium (Casey et al. 2010). To date, the effects of EECP on endothelial-dependent vasodilatory capacity of the resistance arteries in the arms and legs are unknown. Therefore, in the present randomized sham-controlled study we tested the hypothesis that chronic blood shear stimulus associated with EECP would improve endothelium-dependent vasodilation of forearm and calf resistance arteries in patients with CAD.
Materials and methods Baseline status of subjects Forty-two patients with chronic stable angina referred for EECP were randomized in a 2:1 manner into either an EECP group or a sham EECP control group. The patients experienced chronic angina for >3 months caused by myocardial ischemia in the presence of angiographic multi-vessel CAD that could not be controlled by a combination of medical therapy, angioplasty/stent, and/or coronary artery bypass graft (CABG) surgery. The study was approved by the institutional review board of the University of Florida, and written
Received 5 July 2013. Accepted 19 August 2013. J.C. Avery, P.D. Sardina, and R.W. Braith. Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL 32611, USA. D.T. Beck. Malcom Randall VA Medical Center, Gainesville, FL 32611, USA. D.P. Casey. Department of Physical Therapy and Rehabilitation, College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Corresponding author: Randy W. Braith (e-mail: [email protected]fl.edu). Appl. Physiol. Nutr. Metab. 39: 405–408 (2014) dx.doi.org/10.1139/apnm-2013-0309
Published at www.nrcresearchpress.com/apnm on 11 October 2013.
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Appl. Physiol. Nutr. Metab. Vol. 39, 2014
Table 1. Resting patient descriptive characteristics and metabolic profile before and after enhanced external counterpulsation (EECP) or Sham. EECP (N = 28: 22 male, 6 female)
Age, y Height, cm Weight, kg HR, bpm SBP, mm Hg DBP, mm Hg BMI, kg/m Glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL LDL, mg/dL HDL, mg/dL
SHAM (N = 14: 12 male, 2 female)
Before
After
Before
After
P
64.4±9.6 172.7±21.6 92.6±17.2 59±7.8 135±20 76±8.2 30.88±11.15 121.5±46.8 148.4±70.9 142.6±3.4 69.8±33.4 39.3±16.4
— — 92.4±17.3 61±9.2 127±17** 73±8.3* 30.80±11.02 144.6±92.2 176.1±101.6 142.1±23.8 67.8±28.9 37.1±16.2
64.2±10.4 173.9±8.34 100.8±12.4 60±7.4 137±10 78±12.2 33.37±4.24 138.4±57.9 162.3±79.8 144.3±36.8 74.2±30.1 37.6±5.8
— — 100.2±12.8 61±8.7 135±13 78±8.8 33.19±4.34 145.86±50.85 154.89±92.72 141.6±31.7 72.6±25.7 38.11±5.8
0.906 0.360 0.518 0.454 0.004 0.024 0.460 0.973 0.263 0.829 0.962 0.379
Note: Data are expressed as means ± SD. There were no significant differences (p > 0.05) in patient descriptive characteristics or metabolic profile between EECP and Sham groups at baseline. Significant values are reported from repeated measures ANOVA and Tukey's post hoc analysis. HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein. *, P < 0.05, **, P < 0.01.
informed consent was obtained from all patients. The descriptive characteristics of the patients are presented in Table 1. Exclusion criteria Exclusion criteria were absence of ST-segment depression (1 mm minimum) during exercise testing, >75 years of age, CABG within the past 3 months or percutaneous coronary intervention in the past 6 months, cardiac catheterization for any reason within the past 2 weeks, arrhythmia that would interfere with the EECP device, left ventricular ejection fraction
BRIEF COMMUNICATION Enhanced external counterpulsation improves peripheral resistance artery blood flow in patients with coronary artery disease Joseph C. Avery, Darren T. Beck, Darren P. Casey, Paloma D. Sardina, and Randy W. Braith
Abstract: Enhanced external counterpulsation (EECP) increases coronary artery perfusion and improves endothelium-dependent vasodilation in peripheral muscular conduit arteries. It is unknown whether vasodilatory capacity is improved in the peripheral resistance vasculature. Here we provide novel evidence from the first randomized, sham-controlled study that EECP increases peak limb blood flow and improves endothelium-dependent vasodilation in both calf and forearm resistance arteries in patients with coronary artery disease. Key words: enhanced external counterpulsation, resistance arteries, venous occlusion plethysmography, coronary artery disease. Résumé : La contrepulsation externe a` haut rendement (« EECP ») accroît la perfusion de l’artère coronaire et améliore la vasodilatation induite par le flux dans les conduits artériels musculaires en périphérie. On ne sait pas si la capacité vasodilatatoire est améliorée dans les vaisseaux résistifs en périphérie. Nous présentons ici des données probantes originales issues de la première étude aléatoire avec groupe de simulation : l’EECP accroît le débit sanguin de pointe dans les membres et améliore la vasodilatation induite par le flux dans les artères résistives du mollet et de l’avant-bras de patients aux prises avec une coronaropathie. [Traduit par la Rédaction] Mots-clés : contrepulsation externe a` haut rendement, artères résistives, occlusion veineuse, pléthysmographie, coronaropathie.
Introduction Enhanced external counterpulsation (EECP) is a noninvasive outpatient therapy, approved by the United States Food and Drug Administration in 1995, for the treatment of patients with coronary artery disease (CAD) and refractory angina pectoris. Data from the International Patient Registry demonstrate that EECP decreased angina episodes and nitrate usage and increased exercise tolerance (Arora et al. 1999). The anti-ischemic benefits occur early and are sustained up to 3 years in more than 75% of patients with a favorable initial response to EECP (Soran et al. 2006). Historically, the popular hypothesis has been that EECP promotes coronary collateral growth and improves myocardial perfusion via augmentation of intracoronary diastolic pressure, suggesting that external compression may serve as a mechanical assist device (Braith et al. 2010; Stys et al. 2002). However, recent studies by us (Braith et al. 2010; Casey et al. 2011; Gurovich and Braith 2013) and others (Akhtar et al. 2006; Hashemi et al. 2008) have identified peripheral vascular mechanisms by which EECP confers anti-ischemic benefits in patients with symptomatic CAD. Specifically, endothelium-dependent flow mediated dilation (FMD) in muscular conduit vessels, such as the brachial and femoral artery, is improved 51% and 30%, respectively, after EECP (Braith et al. 2010). Bioavailability of nitric oxide and 6-keto-prostaglandin F1␣ (6-keto-PGF1␣) is improved by 36% and 71%, respectively, by EECP (Braith et al. 2010). Stiffness of central elastic conduit arteries (aorta) and peripheral muscular conduit arteries (brachial, femoral) is decreased significantly after EECP (Casey et al. 2011). Importantly, these improvements in arterial function were paral-
leled by reductions in wasted left ventricular energy and decreases in myocardial demand (Casey et al. 2011). In aggregate, these recent data suggest that improvements in elastic and muscular conduit arteries may explain improvements in angina class and exercise tolerance observed in patients with CAD after EECP. Impaired endothelial function in CAD patients, however, is not limited to conduit arteries. Rather, endothelial dysfunction is a systemic phenomenon that persists in resistance arteries, ultimately resulting in the loss of atheroprotective effects of the normal endothelium (Casey et al. 2010). To date, the effects of EECP on endothelial-dependent vasodilatory capacity of the resistance arteries in the arms and legs are unknown. Therefore, in the present randomized sham-controlled study we tested the hypothesis that chronic blood shear stimulus associated with EECP would improve endothelium-dependent vasodilation of forearm and calf resistance arteries in patients with CAD.
Materials and methods Baseline status of subjects Forty-two patients with chronic stable angina referred for EECP were randomized in a 2:1 manner into either an EECP group or a sham EECP control group. The patients experienced chronic angina for >3 months caused by myocardial ischemia in the presence of angiographic multi-vessel CAD that could not be controlled by a combination of medical therapy, angioplasty/stent, and/or coronary artery bypass graft (CABG) surgery. The study was approved by the institutional review board of the University of Florida, and written
Received 5 July 2013. Accepted 19 August 2013. J.C. Avery, P.D. Sardina, and R.W. Braith. Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, Gainesville, FL 32611, USA. D.T. Beck. Malcom Randall VA Medical Center, Gainesville, FL 32611, USA. D.P. Casey. Department of Physical Therapy and Rehabilitation, College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Corresponding author: Randy W. Braith (e-mail: [email protected]fl.edu). Appl. Physiol. Nutr. Metab. 39: 405–408 (2014) dx.doi.org/10.1139/apnm-2013-0309
Published at www.nrcresearchpress.com/apnm on 11 October 2013.
406
Appl. Physiol. Nutr. Metab. Vol. 39, 2014
Table 1. Resting patient descriptive characteristics and metabolic profile before and after enhanced external counterpulsation (EECP) or Sham. EECP (N = 28: 22 male, 6 female)
Age, y Height, cm Weight, kg HR, bpm SBP, mm Hg DBP, mm Hg BMI, kg/m Glucose, mg/dL Triglycerides, mg/dL Total cholesterol, mg/dL LDL, mg/dL HDL, mg/dL
SHAM (N = 14: 12 male, 2 female)
Before
After
Before
After
P
64.4±9.6 172.7±21.6 92.6±17.2 59±7.8 135±20 76±8.2 30.88±11.15 121.5±46.8 148.4±70.9 142.6±3.4 69.8±33.4 39.3±16.4
— — 92.4±17.3 61±9.2 127±17** 73±8.3* 30.80±11.02 144.6±92.2 176.1±101.6 142.1±23.8 67.8±28.9 37.1±16.2
64.2±10.4 173.9±8.34 100.8±12.4 60±7.4 137±10 78±12.2 33.37±4.24 138.4±57.9 162.3±79.8 144.3±36.8 74.2±30.1 37.6±5.8
— — 100.2±12.8 61±8.7 135±13 78±8.8 33.19±4.34 145.86±50.85 154.89±92.72 141.6±31.7 72.6±25.7 38.11±5.8
0.906 0.360 0.518 0.454 0.004 0.024 0.460 0.973 0.263 0.829 0.962 0.379
Note: Data are expressed as means ± SD. There were no significant differences (p > 0.05) in patient descriptive characteristics or metabolic profile between EECP and Sham groups at baseline. Significant values are reported from repeated measures ANOVA and Tukey's post hoc analysis. HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein. *, P < 0.05, **, P < 0.01.
informed consent was obtained from all patients. The descriptive characteristics of the patients are presented in Table 1. Exclusion criteria Exclusion criteria were absence of ST-segment depression (1 mm minimum) during exercise testing, >75 years of age, CABG within the past 3 months or percutaneous coronary intervention in the past 6 months, cardiac catheterization for any reason within the past 2 weeks, arrhythmia that would interfere with the EECP device, left ventricular ejection fraction
