Matheen A. Khuddus

Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic Angina A Randomized Sham-Controlled Study

Background— Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. Methods and Results— Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F1&agr;, endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-&agr;, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F1&agr; (+71% versus +1%), whereas it decreased endothelin-1 (−25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (−28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-&agr; (−16% versus +12%), monocyte chemoattractant protein-1 (−13% versus +0.2%), soluble vascular cell adhesion molecule-1 (−6% versus +1%), high-sensitivity C-reactive protein (−32% versus +5%), and the lipid peroxidation marker 8-isoprostane (−21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (−62% versus 0%; P<0.001) in treatment versus sham groups, respectively. Conclusions— Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.

Effects of enhanced external counterpulsation on arterial stiffness and myocardial oxygen demand in patients with chronic angina pectoris.

Enhanced external counterpulsation (EECP) is a noninvasive technique for treatment of symptomatic coronary artery disease in patients not amenable to revascularization procedures. However, the mechanisms underlying the benefits of EECP remain unknown. We hypothesized that decreases in arterial stiffness and aortic wave reflection are a therapeutic target for EECP. Patients with coronary artery disease and chronic angina pectoris were randomized (2:1 ratio) to 35 1-hour sessions of EECP (n = 28) or sham EECP (n = 14). Central and peripheral arterial pulse-wave velocity and aortic wave reflection (augmentation index) were measured using applanation tonometry before, and after 17 and 35 1-hour treatment sessions. Wasted left ventricular pressure energy and aortic systolic tension-time index, markers of left-ventricular myocardial oxygen demand, were derived from the synthesized aortic pressure wave. Exercise duration, anginal threshold, and peak oxygen consumption were measured using a graded treadmill test. Central arterial stiffness and augmentation index were decreased after 17 and 35 sessions in the treatment group. Measurements of peripheral arterial stiffness were decreased after 35 sessions in the treatment group. Changes in aortic pressure wave reflection resulted in decreased measurements of myocardial oxygen demand and wasted left ventricular energy. No changes in central or peripheral arterial stiffness were observed in the sham group. Furthermore, measurements of exercise capacity were improved in the EECP group but unchanged in the sham group. In conclusion, EECP therapy decreases central and peripheral arterial stiffness, which may explain improvements in myocardial oxygen demand in patients with chronic angina pectoris after treatment.

Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease.

Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.

Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic AnginaClinical Perspective

Background— Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. Methods and Results— Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F1&agr;, endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-&agr;, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F1&agr; (+71% versus +1%), whereas it decreased endothelin-1 (−25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (−28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-&agr; (−16% versus +12%), monocyte chemoattractant protein-1 (−13% versus +0.2%), soluble vascular cell adhesion molecule-1 (−6% versus +1%), high-sensitivity C-reactive protein (−32% versus +5%), and the lipid peroxidation marker 8-isoprostane (−21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (−62% versus 0%; P<0.001) in treatment versus sham groups, respectively. Conclusions— Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.

Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic AnginaClinical Perspective: A Randomized Sham-Controlled Study

Background— Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. Methods and Results— Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F1&agr;, endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-&agr;, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F1&agr; (+71% versus +1%), whereas it decreased endothelin-1 (−25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (−28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-&agr; (−16% versus +12%), monocyte chemoattractant protein-1 (−13% versus +0.2%), soluble vascular cell adhesion molecule-1 (−6% versus +1%), high-sensitivity C-reactive protein (−32% versus +5%), and the lipid peroxidation marker 8-isoprostane (−21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (−62% versus 0%; P<0.001) in treatment versus sham groups, respectively. Conclusions— Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.