Treadmill Exercise Time Research Articles

Multifactorial Determinants of Functional Capacity in Peripheral Arterial Disease: Uncoupling of Calf Muscle Perfusion and Metabolism

We aimed to investigate the pathophysiology of peripheral arterial disease (PAD) by examining magnetic resonance imaging (MRI) and spectroscopic (MRS) correlates of functional capacity. Despite the high prevalence, morbidity, and cost of PAD, its pathophysiology is incompletely understood. Eighty-five patients (age 68 ± 10 years) with mild-to-moderate PAD (ankle-brachial index 0.69 ± 0.14) had their most symptomatic leg studied by MRI/MRS. Percent wall volume in the superficial femoral artery was measured with black blood MRI. First-pass contrast-enhanced MRI calf muscle perfusion and 31P MRS phosphocreatine recovery time constant (PCr) were measured at peak exercise in calf muscle. All patients underwent magnetic resonance angiography (MRA), treadmill testing with maximal oxygen consumption measurement, and a 6-min walk test. Mean MRA index of number and severity of stenoses was 0.84 ± 0.68 (normal 0), % wall volume 74 ± 11% (normal 46 ± 7%), tissue perfusion 0.039 ± 0.015 s−1(normal 0.065 ± 0.013 s−1), and PCr 87 ± 54 s (normal 34 ± 16 s). MRA index, % wall volume, and ankle-brachial index correlated with most functional measures. PCr was the best correlate of treadmill exercise time, whereas calf muscle perfusion was the best correlate of 6-min walk distance. No correlation was noted between PCr and tissue perfusion. Functional limitations in PAD are multifactorial. As measured by MRI and spectroscopy, atherosclerotic plaque burden, stenosis severity, tissue perfusion, and energetics all play a role. However, cellular metabolism is uncoupled from tissue perfusion. These findings suggest a potential role for therapies that regress plaque, increase tissue perfusion, and/or improve cellular metabolism. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678)

Evaluation of Cooper 12-Minute Walk/Run Test as a Marker of Cardiorespiratory Fitness in Young Urban Children with Persistent Asthma

To evaluate Cooper 12-minute run/walk test (CT12) as a one-time estimate of cardiorespiratory fitness and marker of fitness change compared with treadmill fitness testing in young children with persistent asthma. A cohort of urban children with asthma participated in the asthma and exercise program and a subset completed pre- and postintervention fitness testing. Treadmill fitness testing was conducted by an exercise physiologist in the fitness laboratory at an academic children's hospital. CT12 was conducted in a college recreation center gymnasium. Forty-five urban children with persistent asthma aged 7 to 14 years participated in exercise interventions. A subset of 19 children completed pre- and postintervention exercise testing. Participants completed a 9-week exercise program where they participated in either swimming or golf 3 days a week for 1 hour. A subset of participants completed fitness testing by 2 methods before and after program completion. CT12 results (meters), maximal oxygen consumption ((.)Vo2max) (mL x kg(-1) x min(-1)), and treadmill exercise time (minutes). CT12 and maximal oxygen consumption were moderately correlated (preintervention: 0.55, P = 0.003; postintervention: 0.48, P = 0.04) as one-time measures of fitness. Correlations of the tests as markers of change over time were poor and nonsignificant. In children with asthma, CT12 is a reasonable one-time estimate of fitness but a poor marker of fitness change over time.

VEGF Gene Therapy Fails to Improve Perfusion of Ischemic Myocardium in Patients With Advanced Coronary Disease: Results of the NORTHERN Trial

Despite the promise of proangiogenic gene therapy most clinical trials have failed to show benefit for the primary end point analysis. The NOGA angiogenesis Revascularization Therapy: assessment by RadioNuclide imaging (NORTHERN) trial was a double-blind, placebo-controlled study of intramyocardial vascular endothelial growth factor (VEGF165) gene therapy versus placebo, involving seven sites across Canada, designed to overcome major limitations of previous proangiogenic gene therapy trials. A total of 93 patients with refractory Canadian Cardiovascular Society (CCS) class 3 or 4 anginal symptoms were randomized to receive 2,000 microg of VEGF plasmid DNA or placebo (buffered saline) delivered via the endocardial route using an electroanatomical NOGA guidance catheter. There was no difference between the VEGF-treated and the placebo groups in the primary end point of change in myocardial perfusion from baseline to 3 or 6 months, assessed by single photon emission tomography (SPECT) imaging, although a significant reduction in the ischemic area was seen in both groups. Also, similar improvements in exercise treadmill time and anginal symptoms were seen in the VEGF and the placebo groups at 3 and 6 months, although again there were no differences between these groups. Despite the intramyocardial administration of a high "dose" of plasmid DNA using a percutaneous guidance catheter system, there was no benefit of VEGF gene therapy at 3 or 6 months for any of the end points studied.

Randomized Double-Blind Trial of Darbepoetin Alfa in Patients With Symptomatic Heart Failure and Anemia

Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [-0.2, 1.0] g/dL; P<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > or = 1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; P=0.10). Occurrences of adverse events were similar in both treatment groups. In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed.

Effect of losartan on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation

The aim of this study was to assess the effects of losartan treatment on exercise tolerance and echocardiographic parameters in patients with mitral regurgitation (MR) secondary to mitral valve prolapse or rheumatic heart disease. Twenty-seven patients (14 males, 13 females, mean age 51+/-11, range 21-76) with moderate MR due to mitral valve prolapse or rheumatic heart disease were examined by means of Doppler echocardiography. The subjects were submitted to treadmill exercise tests using the modified Bruce protocol at baseline, after six hours and after the six-week treatment period to be evaluated based on their exercise tolerance. Mitral Regurgitant Volume (MRV), effective regurgitant orifice diameter, left atrial volume, left ventricle (LV) end-diastolic volume index, LV end-systolic volume index, LV ejection fraction (LVEF), left ventricle mass index were calculated at baseline and after six weeks of treatment with single dose of losartan (50 mg/day). Total treadmill exercise time increased from 477.7+/-147.9 to 535.7+/-149.0 seconds after six hours (p<0.01) and to 559.6+/-142.8 seconds after six weeks of treatment. Also, metabolic equivalent values increased following six hours of first dose and six weeks of losartan treatment (from 10.9+/-2.9 to 11.8+/-3.1, p=0.006 and 12.4+/-3.1, p=0.002; respectively). However, peak exercise systolic blood pressure (BP) was reduced after six hours and six weeks of treatment, and resting diastolic BP did not change after six hours but reduced at the end of the treatment period. MR volume decreased significantly from 29.3+/-14.1 ml to 25.1+/-14.8 ml, (p=0.025) without significant change in regurgitant orifice diameter (0.72+/-0.37 cm vs. 0.66+/-0.37 cm, p=NS), left atrium diameter and area while LVEF increased from 51.70+/-13.37 to 54.11-11.75 (p=0.015) with losartan. We conclude that the angiotensin II receptor antagonist losartan improves exercise tolerance and echocardiographic parameters in patients with moderate MR.

Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial)

Experimental studies have demonstrated that bone marrow (BM) cells can induce angiogenesis in ischaemic myocardium. Recently, several non-randomized pilot studies have also suggested that direct BM cells implantation appears to be feasible and safe in patients with severe coronary artery diseases (CAD). We performed a randomized, blinded, and placebo-controlled trial in 28 CAD patients. After BM harvesting, we assigned patients to receive low dose (1 x 10(6) cells/0.1 mL, n = 9), high dose (2 x 10(6) cells/0.1 mL, n = 10) autologous BM cells or control (0.1 mL autologous plasma/injection, n = 9) catheter-based direct endomyocardial injection as guided by electromechanical mapping. Our primary endpoint was the increase in exercise treadmill time and our secondary endpoints were changes in Canadian Cardiovascular Society (CCS) and New York Heart Association (NYHA) class, and myocardial perfusion and left ventricular ejection fraction (LVEF) assessed by single-photon emission computed tomography and magnetic resonance imaging, respectively. A total 422 injections (mean 14.6 +/- 0.7 per patient) were successfully performed at 41 targeted ischaemic regions without any acute complication. Baseline exercise treadmill time was 439 +/- 182 s in controls and 393 +/- 136 s in BM-treated patients, and changed after 6 months to 383 +/- 223s and 464 +/- 196 s [BM treatment effect +0.43 log seconds (+53%), 95% CI 0.11-0.74, P = 0.014]. Compared with placebo injection, BM implantation was associated with a significant increase in LVEF (BM treatment effect +5.4%, 95% CI 0.4-10.3, P = 0.044) and a lower NYHA class (odds ratio for treatment effect 0.12, 95% CI 0.02-0.73, P = 0.021) after 6 months, but CCS reduced similarly in both groups. We observed no acute or long-term complications, including ventricular arrhythmia, myocardial damage, or development of intramyocardial tumour or calcification associated with BM implantation. Direct endomyocardial implantation of autologous BM cells significantly improved exercise time, LVEF, and NYHA functional class in patients with severe CAD who failed conventional therapy.

The Coronary Collateral Circulation in Man

Well developed coronary collateral arteries in patients with coronary artery disease (CAD) mitigate myocardial infarcts with less ventricular aneurysm formation and improved ventricular function, they reduce future cardiovascular events, and improve survival. Myocardial infarct size is a product of coronary artery occlusion time, area at risk for infarction and the inverse of collateral supply. Collateral arteries preventing myocardial ischemia during brief vascular occlusion are present in 1/3 of patients with CAD. Collateral flow sufficient to prevent myocardial ischemia during coronary occlusion amounts to ≥25% of the normal flow through the open vessel. Among individuals without relevant coronary stenoses, there are preformed collateral arteries preventing myocardial ischemia in 20-25%. Coronary collateral flow can be assessed only during vascular occlusion of the collateral-receiving artery. Presently, the gold standard for clinical coronary collateral assessment is the measurement of intracoronary occlusive pressure- or velocity- derived collateral flow index which expresses collateral as a fraction of flow during vessel patency. Clinical variables predicting the development of collateral arteries are the hemodynamic severity of coronary stenoses and the duration of myocardial ischemic symptoms. One fifth to one third of patients with CAD cannot be revascularized by percutaneous coronary intervention or coronary artery bypass grafting; therapeutic promotion of collateral growth appears to be a valuable treatment strategy in those patients. Promotion of collateral growth should aim at inducing the development of large conductive collateral arteries (i.e. arteriogenesis) and not so much the sprouting of capillary like vessels (i.e. angiogenesis). So far, the largest, controlled clinical angiogenesis trials on the efficacy of VEGF and basic FGF have been negative with regard to treadmill exercise time and myocardial scintigraphic data. Large conductive collateral arteries (i.e. arteriogenesis) appear to be effectively promoted via the activation of monocytes / macrophages, which release VEGF, FGF, tumor necrosis factor alpha, granulocyte colony stimulating factors and other growth and remodelling-associated factors. Keywords: Coronary circulation, collateral circulation, arteriogenesis, angiogenesis

Plantar Flexion as an Alternative to Treadmill Exercise for Evaluating Patients with Intermittent Claudication

The aim of this study was to examine whether the plantar flexion test could adequately replace treadmill testing in patients who were unable to exercise. Prospective observational study. Twenty-seven patients with intermittent claudication secondary to peripheral arterial disease (PAD). Patients performed two treadmill tests and two plantar flexion tests. Ankle pressure, near infrared spectroscopy (NIRS) data, heart rate and blood pressures were monitored along with pain-free and maximum walking distances for treadmill, pain-free and maximum exercise time for plantar flexion. Maximum exercise time and walking distance were well correlated (R=0.74). Eleven patients (41%) developed non-claudicating symptoms during the treadmill test but not during the flexion test. Rate pressure product was significantly higher after the treadmill but not after the plantar flexion. Plantar flexion test showed good reliability and correlation. Plantar flexion may serve as an alternative to treadmill testing in evaluating muscle pain in patients with intermittent claudication.

Randomized trials are also essential for device therapy: reply

Randomized trials are also essential for device therapy: reply

Effect of Losartan and Hydrochlorothiazide on Exercise Tolerance in Exertional Hypertension and Left Ventricular Diastolic Dysfunction

A randomized, double-blind study of 6 months of losartan 50 mg or hydrochlorothiazide (HCTZ) 12.5 mg was performed in 40 subjects with left ventricular diastolic dysfunction (mitral flow velocity E/A ratio < 1), exercise systolic blood pressure (BP) > 200 mm Hg, systolic BP at rest < 150 mm Hg, ejection fraction > 50%, and no ischemia. Before treatment, exercise systolic BP was 213 +/- 13 mm Hg (mean +/- SD) in the 19 patients randomized to losartan and 209 +/- 11 mm Hg in the 21 patients who received HCTZ. After 6 months, exercise systolic BP was similarly reduced in patients who received losartan (197 +/- 23 mm Hg, p < 0.01) and HCTZ (191 +/- 11 mm Hg, p < 0.01). With losartan, treadmill exercise time increased from 894 +/- 216 to 951 +/- 225 seconds (p = 0.011), and quality of life improved from 15 +/- 12 to 7 +/- 10 (p = 0.015) without a change in oxygen consumption (1,895 +/- 470 to 1,954 +/- 539 ml/min, p = 0.30). With HCTZ, exercise time (842 +/- 225 to 872 +/- 239 seconds, p = 0.32) and quality of life (19 +/- 21 vs 19 +/- 24, p = 0.43) did not change, whereas oxygen consumption decreased from 2,144 +/- 788 to 1,960 +/- 706 ml/min (p = 0.022). In conclusion, in patients with diastolic dysfunction and hypertensive responses to exercise, 6 months of losartan and HCTZ blunted systolic BP during exercise. Only losartan increased exercise tolerance and improved quality of life.

Maximum oxygen uptake corrected for skeletal muscle mass accurately predicts functional improvements following exercise training in chronic heart failure

Skeletal muscle mass and peak oxygen uptake are important predictors of functional status and outcome in patients with stable chronic heart failure. To assess changes in skeletal muscle mass and peak oxygen uptake following an exercise training program. Thirty-six patients with moderate stable chronic heart failure were randomly allocated to either a bicycle ergometer (bike) or functional electrical muscle stimulators (FES) applied to quadriceps and gastrocnemius muscles to be used daily for six weeks. Dual-energy X-ray absorptionometry (DEXA) scanning was performed before and after training along with symptom limited cardiopulmonary exercise test, quadriceps strength and fatigue resistance, and 6-min walk test. Both exercise modalities resulted in improvements in treadmill exercise time, leg strength, 6-min walk test and peak oxygen uptake per kilogram of skeletal muscle. Despite significant improvements in functional capacity, there were no significant changes in body composition for total skeletal muscle mass, leg muscle mass or total body fat content. Skeletal muscle mass was strongly predictive of maximum oxygen uptake at baseline (r=0.61, p<0.001) and after exercise training (r=0.68, p<0.001). In moderate stable chronic heart failure, exercise training using bicycle ergometer or FES results in favourable qualitative rather than quantitative changes in skeletal muscle. Correction of maximum oxygen uptake for skeletal muscle mass rather than total body mass is a more sensitive measure of changes associated with exercise training.

An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial

Refractory angina pectoris leads to significant morbidity. Treatment options include percutaneous myocardial laser revascularization (PMR) and spinal cord stimulation (SCS). This study was designed to compare these two treatments. Subjects with Canadian Cardiovascular Society (CCS) class 3/4 angina and reversible perfusion defects were randomized to SCS (34) or PMR (34). The primary outcome was to compare exercise treadmill time on a modified Bruce protocol over 12 months. Thirty subjects in both groups completed 12-month follow-up. The mean total exercise time was 6.38 +/- 3.45 min in the SCS group and 7.41+/-3.68 min in the PMR group at baseline and 7.08 +/- 0.67 min in the SCS group and 7.12 +/-0.71 min in the PMR group at 12 months (95% confidence limits for the difference between the groups -1.02 to + 2.2 min, P = 0.466). There were no differences in angina-free exercise capacity, CCS class, and quality of life between treatments. SCS patients had more adverse events in the first 12 months, mainly angina or SCS system related (P = 0.001). There was little evidence of a difference in effectiveness between SCS and PMR in patients with refractory angina.

ICL670 Removes Cardiac Iron in a Gerbil Model of Iron Overload.

Introduction: Deferasirox (ICL670) is a novel tridentate oral iron chelator currently being evaluated for the treatment of transfusional iron overload. Phase III clinical trials have demonstrated that once-daily ICL670 (20 mg/kg) is equally effective at controlling liver iron concentration as standard deferoxamine therapy (40 mg/kg/day, 5 days per week). While ICL670's long serum half-life should offer good protection against cardiac iron accumulation, little is known regarding its ability to remove stored cardiac iron. Therefore, we compared the relative efficacy of ICL670, deferiprone (L1), and deferoxamine (DFO) in removing cardiac iron from iron-loaded gerbils.Methods: 37 8–10 week old female gerbils underwent ten weekly iron dextran injections of 200 mg/kg/D, followed by a 13 day equilibration period. Five animals were then sacrificed to determine pre-chelation iron burdens. Chelation was initiated in 3 groups of 8 animals (ICL670 100 mg/kg/D po QD, L1 375 mg/kg/D po divided TID, DFO 200 mg/kg/D sub Q divided BID) five days per week and maintained for 12 weeks. The remaining 8 animals received sham chelation. All animals underwent ECG and treadmill assessment at baseline, following iron loading, and after completing chelation therapy. Animals were sacrificed for liver and heart iron measurement (Mayo Medical Laboratory) and semiquantitative histology. Hearts were evaluated for iron loading/distribution, tissue fibrosis, and myocyte hypertrophy, while livers were scored for iron loading/distribution and fibrosis.Results: Chelator-independent iron excretion and redistribution was evident, unlike in humans. Cardiac and liver iron contents fell 30.4% and 23.2%, respectively, with sham chelation; all subsequent chelator comparisons are reported with respect to the sham-chelated animals. ICL670 reduced cardiac iron content 20.5%. There were no changes in cardiac weight, myocyte hypertrophy, fibrosis, or wet-to-dry weight ratio.ICL670 treatment reduced liver iron content 51%. Iron elimination was greatest in hepatocytes with no detectable Kupfer-cell iron clearance.L1 produced comparable reductions in cardiac iron content (18.6%). Wet weight cardiac iron concentration fell nearly 30% but this was offset by greater cardiac mass (16.5% increase). Histologic analysis demonstrated decreased iron staining but increased myocyte hypertrophy. L1 decreased liver iron content 24.9%. Wet weight liver iron concentration fell 43.8% but was offset by a 30% increase in liver weight and water content. Iron elimination was balanced between Kupfer cells and hepatocytes. DFO did not reduce biochemically-assayed cardiac or liver iron content, although it improved histologic iron scores in both organs. Hearts from DFO treated animals were enlarged and had greater fibrosis.Cardiac and liver iron contents were closely correlated (r = 0.66), but ICL670 animals had lower hepatic iron contents for any given cardiac iron content. Iron loading broadened QRS duration by 10.6%; this effect was antagonized by both L1 and ICL670 therapy. PR, QRS, and QTc interval were weakly correlated with cardiac and liver iron contents. Treadmill exercise time was independent of chelation therapy.Conclusion: ICL670 and L1 were equally effective in removing stored cardiac iron in a gerbil animal model but ICL670 removed more hepatic iron for a given cardiac iron burden.

Autologous Bone Marrow Stem Cells (ABMC) for Cardiormyoplasty in 15 Patients with Acute and Chronic Myocardial Disease (ACMD) in Colombia.

Introduction: ACMD disease accounts for 50% of all cardiovascular deaths and is the leading cause of congestive heart failure as well as premature permanent disability in workers. Unfortunately no medication or procedure has shown efficacy in replacing myocardial tissue or neovascularization. Some clinical human trials indicate that ABMC transplantation improves cardiac function and is feasible, safe and beneficial. We report the first experience in Colombia with this type of therapyMethodology: This is the six months follow-up of 15 patients 23 - 60 years-old, 10M/5F with: A. an extensive, viability absence, acute myocardial infarction of anterior myocardial wall, 10 patients, with ejection fraction ≤ 40% that received standard postinfarction medical treatment, successful coronary percutaneous intervention and after intracoronary transfer of G-CSF mobilized ABMC, CD34 range 15–20 in millions. B. Five patients with chronic coronary heart disease and/or severe ischemic heart failure without option for standard revascularization therapies recibed epicardic implantation of G-SCF mobilized ABMC, CD34 range 14.5–19 in millions.Results: It was demonstrated in both groups:improvement in the mean ejection fraction from 29.44±3.36% before to 45±14,97% (p<0.001) after six monthsthe exercise capacity increased in meaningful form evidenced by mean increase in the six minutes test from 295.07±66.04ms before to 648.4±93.15 ms after six months (p<0.001), the treadmill exercise time and the functional capacity in Mets from a mean of 4,8±1.02 before to 12.8±2.59 (p<0.001).there were significant changes in the myocardial perfusion at six months follow-up by nuclear images at diagnosis [Display omitted] and 6 months later [Display omitted] There were no presented complications related to the Cellular Transplant or the utilization of the G-CSF.Conclusions: This is the first experience in Colombia with stem cells for intracoronary and epicardic cardiomyoplasty in acute and chronic coronary heart disease. It was observed functional recovery of the left ventricle, improvement in the exercise capacity without adverse effects or complications related to this therapy. In patients with ACMD, treatment with G-CSF to mobilize ABMC is feasible and safe and seems to be effective under clinical conditions. The therapeutic effect might be attributed to ABMC-associated promotion of myocardial regeneration and neovascularization.

Longevity of the Placebo Effect in the Therapeutic Angiogenesis and Laser Myocardial Revascularization Trials in Patients With Coronary Heart Disease

The long-term beneficial effects of placebo therapy were evaluated in angiogenesis and laser myocardial revascularization trials in patients who had end-stage coronary heart disease. Improvements in mean angina class, exercise treadmill time, and quality of life were mostly maintained at 30 +/- 6 months of follow-up. Persistence of effect cannot be used as evidence of efficacy, and double-blinded trials are essential in this patient population.

Enhanced external counterpulsation does not alter arterial stiffness in patients with angina

Enhanced external counterpulsation (EECP) is a noninvasive treatment for angina that acutely augments diastolic pressure and reduces cardiac afterload. However, the mechanism of the sustained clinical benefit seen with this therapy is not known. The study aimed to determine whether EECP leads to an improvement in arterial stiffness. In all, 22 men and 1 woman with angina (age 63.6 +/- 6.7 years, mean +/- SD) were studied prior to and after 35 h of EECP therapy over 7 weeks. We measured carotid-radial (C-R) pulse wave velocity (PWV), and aortic augmentation index (AI) was derived from radial and carotid artery waveforms using applanation tonometry. Seventeen patients underwent treadmill exercise testing before and after the 7 weeks of EECP. After EECP therapy, despite a significant improvement in treadmill exercise time and a reduction in systolic and diastolic blood pressures, there was no significant change in any arterial stiffness parameters: Mean C-R PWV was 8.4 +/- 0.8 m/s at baseline and 8.0 +/- 1.2 m/s after 7 weeks of EECP, mean change: -0.4, 95% confidence interval (CI): -1.0, + 0.2, p = 0.17. Mean radial-derived AI was 25.7 +/- 10.4% before and 24.6 +/- 10.8% after, mean change: +1.1%, 95% CI: -2.3, +4.5, p = 0.53. Median AI-carotid was 31.5% before and 28.7% after; median change: -0.5, interquartile range: -9.5, +3.5, p = 0.32. Nineteen patients returned for 6-month recordings; neither blood pressure nor arterial stiffness readings were significantly different from baseline. Enhanced external counterpulsation therapy does not significantly alter arterial stiffness. Other than an initial reduction in blood pressure, the sustained clinical benefit seen with this therapy is unlikely to be effected through alterations in arterial wall mechanical properties.

Effect of Simvastatin Versus Placebo on Treadmill Exercise Time Until the Onset of Intermittent Claudication in Older Patients With Peripheral Arterial Disease at Six Months and at One Year After Treatment

The authors conducted a study to investigate the effect of simvastatin after 6 months and 1 year on the time to onset of intermittent claudication during treadmill exercise in patients with peripheral arterial disease. Thirty-four patients were randomized to simvastatin, 35 were randomized to placebo. Simvastatin therapy resulted in a 24% increased treadmill exercise time until onset of intermittent claudication from baseline at 6 months and by 42% at 1 year.

Autologous Bone Marrow Cells for Treatment of Myocardial Infarction in Colombia.

Experimental studies in animals demonstrate the ability of the bone marrow stem cells to differentiate in cardiomyocytes, vascular endothelium cells and smooth muscle cells. There is evidence that these cells can regenerate infarcted myocardium and induce myogenesis and angiogenesis. Clinical studies in humans suggest the feasibility and safety of the utilization of the stem cells to recovery the ventricular function in patients with acute myocardial infarction. We report the first experience in Colombia using autologous bone marrow cells for cardiomyoplasty in isquemic heart disease.This report shows the two months follow-up of four patients, three with acute myocardial infarction of the anterior myocardial wall and one patient with severe chronic isquemic heart disease. Extensive myocardial damage demonstrated by absence of viability in scintigraphic images and ejection fraction less than 40%. The patients received an optimum postinfarction medical treatment, successful coronary percutaneous intervention (three patients) or direct intramyocardial injection (one patient) to transfer of autologous bone marrow cells mobilised with granulocyte-colony stimulating factor during five days.Demographics and resultsThe exercise capacity improve importantly, evidenced by increase in contractility, the six minutes test, the treadmill exercise time and the functional capacity in METS. There were not changes in the myocardial perfusion at two months follow-up, there were not complications related to the cellular transplant or the utilization of the granulocyte-colony stimulating factor. This is the first experience in Colombia with the bone marrow cells and selective intracoronary transplantation for myocardial regeneration and angiogenesis. We observed functional recovery of the left ventricle, improvement in the exercise capacity without adverse effects or complications related to the therapy.Patient #1234Age/sex51/M23/M59/M53/MDiagnosisacute MIacute MIacute MIchronic IHDDiagnosis to transplant3 weeks2 weeks4 weeks> 1 yearCD34 dose19.7x10(6)16.8x10(6)19.5x10(6)21.7x10(6)EF% B/A36/4326/4040/4145/55ESV (cc) B/A80/60116/10365/70101/84METS B/A4/144/175/125/146-min test (mts) B/A420/540216/462260/450414/727MI= myocardial infarction, IHD= isquemic heart disease, B/A= before/after 2 months, EF= eyection fraction, ESV=end systolic volume

Effects of intracoronary infusion of peripheral blood stem-cells mobilised with granulocyte-colony stimulating factor on left ventricular systolic function and restenosis after coronary stenting in myocardial infarction: the MAGIC cell randomised clinical trial

Bone-marrow stem-cell transplantation has been shown to improve cardiac function in patients with myocardial infarction. We examined the feasibility and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy and subsequent intracoronary infusion of collected peripheral blood stem-cells (PBSCs) in such patients. We prospectively randomised 27 patients with myocardial infarction who underwent coronary stenting for the culprit lesion of infarction into three groups; cell infusion (n=10), G-CSF alone (n=10), and control group (n=7). Changes in left ventricular systolic function and perfusion were assessed after 6 months. By December, 2003, seven patients from the cell infusion group, three from the G-CSF group, and one from the control group had been assessed. G-CSF injection and intracoronary infusion of the mobilised PBSC did not aggravate inflammation and ischaemia during the periprocedural period. Exercise capacity (mean treadmill exercise time: 450 s [SD 178] at baseline vs 578 s [168] at 6 months' follow-up, p=0.004), myocardial perfusion (perfusion defect 11.6% [9.6] vs 5.3% [5.0], p=0.020) and systolic function (left ventricular ejection fraction 48.7% [8.3] vs 55.1% [7.4], p=0.005) improved significantly in patients who received cell infusion. However, we noted an unexpectedly high rate of in-stent restenosis at culprit lesion in patients who received G-CSF, and therefore we stopped enrollment. G-CSF therapy with intracoronary infusion of PBSC showed improved cardiac function, and promoted angiogenesis in patients with myocardial infarction. However, aggravation of restenosis could be a serious problem. In future studies with G-CSF based stem-cell therapy, patients should be carefully monitored for unexpected effects.

Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease

Background—Cholesterol modification reduces cardiovascular events in patients with atherosclerosis, including those with peripheral arterial disease. The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication. Methods and Results—This randomized, double-blind, parallel-design study included 354 persons with claudication attributable to peripheral arterial disease. Patients were treated with placebo, atorvastatin (10 mg per day), or atorvastatin (80 mg per day) for 12 months. The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on questionnaires. Maximal walking time after 12 months of treatment with atorvastatin did not change significantly. However, there was improvement in pain-free walking time after 12 months of treatment for the 80-mg (P0.025) group compared with placebo. A physical activity questionnaire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups (P0.011), whereas 2 quality of life instruments, the Walking Impairment Questionnaire and Short Form 36 Questionnaire, did not show significant change. Conclusions—Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication. When treated with atorvastatin, patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins. (Circulation. 2003;108:1481-1486.)