Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure: implications for outpatient monitoring with B-type natriuretic peptide

Background B-natriuretic peptide (BNP), a neurohormone secreted from the cardiac ventricles, reflects left ventricular pressure and correlates to disease severity and prognosis. The fact that BNP levels can now be measured by a rapid assay suggests its potential usefulness in the outpatient clinic. However, if patient activity were to markedly alter BNP levels, its use would be less attractive for monitoring patients in the outpatient clinical setting. Methods A total of 30 patients (10 normal, 10 New York Heart Association [NYHA] class I-II, 10 NYHA class III-IV) exercised with an upright bicycle protocol. Exercise was carried out to 75% of maximum heart rate, and venous blood was sampled before, immediately after, and 1 hour after completion of exercise. Plasma levels of BNP, epinephrine, and norepinephrine were measured. Results BNP levels at baseline were 29 ± 11 pg/mL for normal subjects, 126 ± 26 pg/mL for NYHA I-II subjects, and 1712 ± 356 pg/mL for NYHA III-IV subjects. The change in BNP levels with exercise was significantly lower than the change in epinephrine and norepinephrine (P < .001). In normal subjects, BNP increased from 29 pg/mL to 44 pg/mL with peak exercise, still within the range of normal (<100 pg/mL) . This is compared with larger increases of norepinephrine (716 pg/mL to 1278 pg/mL) and epinephrine (52 pg/mL to 86 pg/mL) with exercise in normal subjects. There were also only small increases in BNP with exercise in patients with congestive heart failure (NYHA I-II, 30%; NYHA III-IV, 18%). For the same groups, epinephrine levels increased by 218% and 312%, respectively, and norepinephrine levels increased by 232% and 163%, respectively. One hour after completion of exercise, there were only minimal changes in BNP levels from baseline state in normal subjects (+0.9%) and patients with NYHA I-II (3.8%). In patients with NYHA III-IV, there was a 15% increase from baseline 1 hour after exercise. Conclusions BNP levels show only minor changes with vigorous exercise, making it unlikely that a normal patient would be classified as having congestive heart failure based on a BNP level obtained after activity. Prior activity should not influence BNP levels in patients with congestive heart failure. Therefore, when a patient presents to clinic with a marked change in their BNP level, it may reflect a real change in their condition. (Am Heart J 2002;143:406-11.)     

Effects of exercise training on left ventricular volumes and function in patients with nonischemic cardiomyopathy: application of magnetic resonance myocardial tagging

Background Exercise training is now an accepted component of the therapeutic regimen in patients with heart failure and underlying ischemia, but few data are available on the effects of training in patients with nonischemic dilated cardiomyopathy. Methods Twenty-four patients (mean age 55 ± 9 years, mean ejection fraction 26.6% ± 10%) were randomized to an exercise (n = 12) or a control (n = 12) group. Patients in the exercise group underwent 5 45-minute sessions of supervised training per week. Before and after the 2-month study period, exercise testing with respiratory gas exchange and lactate analysis was performed, left ventricular volumes and ejection fraction were measured with magnetic resonance imaging, and left ventricular rotation and relaxation velocities were measured with a novel magnetic resonance imaging tagging technique. Results Training resulted in increases in peak oxygen uptake (VO₂) (21.7 ± 4 mL/kg/min to 25.3 ± 5 mL/kg/min, P < .05) and VO₂ at the lactate threshold (12.8 ± 4 mL/kg/min to 19.0 ± 5 mL/kg/min, P < .01). No differences were observed within or between groups in left ventricular end-diastolic volume, end-systolic volume, or ejection fraction. Velocity of left ventricular rotation during systole was unchanged in both groups, and relaxation velocity was higher after training in the exercise group (21.2 ± 5 degrees/s versus 29.7 ± 12 degrees/s, P < .05). Conclusion Training resulted in increases in peak VO₂ and VO₂ at the lactate threshold. Left ventricular volumes and systolic function (ie, ejection fraction and rotation velocity) were unchanged with training, suggesting that training in patients with dilated cardiomyopathy does not lead to further myocardial damage. However, the increase in relaxation velocity after exercise training indicates an improvement in diastolic function. The latter finding suggests an additional potential benefit of exercise training in patients with dilated cardiomyopathy. (Am Heart J 2002;144:719-25.)     

Heart rate recovery after exercise is related to the insulin resistance syndrome and heart rate variability in elderly men

Objective We investigated the associations between heart rate recovery after exercise (as a suggested measure of vagal activity), heart rate variability, and measurements of the insulin resistance syndrome. Material and Methods Seventy men aged 70 years were examined with a symptom-limited bicycle exercise test, a 24-hour heart rate variability test, and different measurements of different components of the insulin resistance syndrome. Results Heart rate recovery after exercise (mean ± SD 20 ± 9 beats during the first minute) was related to both the SD of the R-R interval and the low frequency power at the heart rate variability analyses (r = 0.39, P < .002 for both). Furthermore, heart rate recovery after exercise was related to insulin sensitivity at the hyperinsulinemic eugleucemic clamp (r = 0.28, P < .03), and to high-density lipoprotein cholesterol and exercise capacity, and inversely to obesity and insulin and glucose levels 2 hours after an oral glucose load (P < .05 for all). Heart rate recovery after exercise was not related to left ventricular mass measured by means of echocardiography or to the number of ventricular premature complexes at a 24-hour Holter recording. Conclusion Heart rate recovery 1 minute after exercise was related to measurements of 24-hour heart rate variability. Furthermore, heart rate recovery after exercise was related to several of the major components of the insulin resistance syndrome, thereby establishing a link between this syndrome and cardiac autonomic nervous activity. (Am Heart J 2002;144:666-72.)     

Effects of cardiac rehabilitation and exercise training on autonomic regulation in patients with coronary artery disease

Background Although cardiovascular rehabilitation and exercise training have substantial benefits in various ischemic heart disease (IHD) risk factors and subsequent prognosis after major IHD events, there is a paucity of information about its effects on autonomic regulation (such as heart rate variability [HRV] and baroreflex gain), particularly considering its arterial and cardiopulmonary components. Methods We studied 40 patients (aged 60 ± 6 y) after major IHD events, including 29 who underwent a comprehensive phase II cardiac rehabilitation and exercise training program and 11 controls who did not attend cardiac rehabilitation. Specifically, we determined whether active training improves prognostic indices of autonomic regulation of the SA node and whether changes in baroreflex gain could be ascribed to the arterial or to the cardiopulmonary component of the overall arterial pressure/heart period baroreflex. Results Only patients with IHD undergoing active rehabilitation demonstrated a significant increase in R-R interval, in its variance, in overall gain of arterial pressure/heart period baroreflex (7.44 ± 1.20 ms/mm Hg to 12.12 ± 1.48 ms/mm Hg, P < .001) and in peak oxygen consumption (Δ = 2.45 mL/kg/min, P < .001). Separate examination of the selective arterial and cardiopulmonary components showed that only the latter increased significantly (6.17 ± 1.09 ms/mm Hg to 10.62 ± 1.56 ms/mm Hg; P < .01). Conclusions Cardiac rehabilitation is associated with significant improvements in autonomic markers of neural regulation of the SA node, such as increases in R-R variance and the gain of the overall spontaneous baroreflex, with specific improvements in the cardiopulmonary component as opposed to the arterial baroreflex component of this system. These improvements may further explain the reduction in morbidity and mortality noted after formal cardiac rehabilitation and exercise training programs. (Am Heart J 2002;143:977-83.)     

Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy

Background Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC). Methods Serum levels of tumor necrosis factor-α (TNF-α), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% ± 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo₂max) was also used to evaluate the functional status of patients with IDC. Results Treatment with GH produced a significant reduction in serum levels of TNF-α (8.2 ± 1.2 vs 5.7 ± 1.1 pg/mL, P < .05), sTNF-RI (3.9 ± 0.4 vs 3.2 ± 0.3 ng/mL, P < .05), sTNF-RII (2.6 ± 0.3 vs 2.2 ± 0.2 ng/mL, P < .05), IL-6 (5.5 ± 0.6 vs 4.4 ± 0.4 pg/mL, P = .05), sIL-6R (32.7 ± 3.0 vs 28.2 ± 3.0 ng/mL, P < .05), sFas (4.4 ± 0.8 vs 3.1 ± 0.6 ng/mL, P < .05), and sFasL (34.2 ± 11.7 vs 18.8 ± 7.3 pg/mL, P < .01). A significant improvement was also observed in Vo₂max after the completion of 3 months' treatment with GH (15.0 ± 0.8 vs 17.2 ± 1.0 mL/kg/min, P < .05). Good correlations were found between GH-induced reduction in TNF-α levels and increase in Vo₂max (r = −0.64, P < .05) as well as between GH-induced reduction in sFasL and increase in Vo₂max (r = −0.56, P = .08). Conclusions GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC. (Am Heart J 2002;144:359-64.)     

Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT)

Background The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure. Methods One hundred eighty-one patients in New York Heart Association class I to III, with ejection fraction <40% and 6-minute walk distance <500 meters, were recruited into a randomized, controlled, single-blind trial comparing 3 months of supervised training, then 9 months of home-based training with usual care. Results There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences. Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months (0.104 ± 0.026 L/min vs 0.025 ± 0.023 L/min; P = .026) and 12 months (0.154 ± 0.074 L/min vs 0.024 ± 0.027 L/min; P = .081). Compared with the control group, significant increases were observed in the exercise group for arm and leg strength. No significant changes were observed in cardiac function or quality of life. Adherence to exercise was good during supervised training but reduced during home-based training. Conclusions Exercise training improves peak oxygen uptake and strength during supervised training. Over the final 9 months of the study, there was little further improvement, suggesting that some supervision is required for these patients. There were no adverse effects on cardiac function or clinical events. (Am Heart J 2002;144:23-30.)     

运动对高血压心力衰竭患者血清肌钙蛋白Ⅰ的影响

目的观察症状限制性运动试验和运动训练对高血压心力衰竭患者心肌肌钙蛋白I（cTnI）的影响。方法30例高血压中度心力衰竭患者[NYHA分级Ⅱ～Ⅲ级,射血分数（1．7±9.3）％]与15例轻度心力衰竭患者及10例无心力衰竭受试者进行对比观察。患者均进行症状限制性运动试验和单期运动训练（达最大心率的80％以上,持续时间30min）,分别测定基础cTnI值、症状限制性试验后和运动训练后1～6h时的cTnI值。结果症状限制性运动试验后,中度心力衰竭患者cTM值由（37±21）pg／ml增加到（77±24）pg／d,其中9例中度心力衰竭患者和4例轻度心力衰竭患者的cTnI值升高到100pg／ml以上。无心力衰竭的受试者无论是静息时或是运动后,cTnI值均较低（P〈0．05）。结论高血压心力衰竭患者在症状限制性运动试验后cTnI值增加,其水平达到轻微的心肌损伤水平。这一现象对患者预后的影响值得进一步研究。     

Beta blockers normalize QT hysteresis in long QT syndrome

Objectives This study was performed to evaluate the impact of beta blockers on QT adaptation to heart rate during the exercise and recovery phases of exercise testing in long QT syndrome. Background Long QT syndrome is characterized by familial syncope and sudden death in the context of sudden heart rate changes. QT hysteresis has been proposed as a phenotypic marker of long QT syndrome, suggesting altered QT adaptation to changes in heart rate. Methods Fourteen patients with long QT syndrome (aged 26 ± 16 years, 6 male) and 10 healthy volunteers (aged 37 ± 11 years, 9 male) underwent graded exercise testing with continuous lead II electrocardiographic monitoring. Long QT patients underwent repeat assessment after 1 month of beta blockade. QT intervals at matching heart rates were compared during exercise and recovery to determine the effect of beta blockade on QT hysteresis, defined as the recovery QT peak interval subtracted from the exercise QT peak interval. Results In the 14 long QT syndrome patients, beta blockers slowed the resting heart rate without affecting the corrected QT interval (502 ± 52 ms baseline vs 481 ± 40 ms beta blocker, P = .17). The increase in heart rate with exercise was similar in the 3 groups (P = .73). Exaggerated hysteresis of the QT interval was seen in the patients with long QT syndrome at baseline compared with controls (46 ± 19 ms vs 19 ± 11 ms 1 minute into recovery, P = .006). Beta blockers had minimal effect on the QT interval but markedly reduced hysteresis with minimal separation of the exercise and recovery QT/RR curves (25 ± 35 ms 1 minute into recovery, P = .027). The combined curve separation at all 6 time points analyzed was 165 ± 95 ms in patients with long QT syndrome at baseline, 40 ± 131 ms after beta blockade, and 29 ± 30 ms in control subjects (P = .002). Comparison of the beta blocker effect on hysteresis in the 2 genotypes suggested a greater reduction in hysteresis in the 3 patients with long QT syndrome 1 compared with the 11 patients with long QT syndrome 2. Conclusions Beta blockers reduce QT hysteresis in patients with long QT syndrome to values seen in normal patients. This improved QT adaptation to changes in heart rate may explain the clinical benefit of beta blockers in long QT syndrome. (Am Heart J 2002;143:528-34.)     

Effects of bisoprolol fumarate on left ventricular size, function, and exercise capacity in patients with heart failure: analysis with magnetic resonance myocardial tagging

Background Recent data suggest that beta-blockers can be beneficial in subgroups of patients with chronic heart failure (CHF). For metoprolol and carvedilol, an increase in ejection fraction has been shown and favorable effects on the myocardial remodeling process have been reported in some studies. We examined the effects of bisoprolol fumarate on exercise capacity and left ventricular volume with magnetic resonance imaging (MRI) and applied a novel high-resolution MRI tagging technique to determine myocardial rotation and relaxation velocity. Methods Twenty-eight patients (mean age, 57 ± 11 years; mean ejection fraction, 26 ± 6%) were randomized to bisoprolol fumarate (n = 13) or to placebo therapy (n = 15). The dosage of the drugs was titrated to match that of the the Cardiac Insufficiency Bisoprolol Study protocol. Hemodynamic and gas exchange responses to exercise, MRI measurements of left ventricular end-systolic and end-diastolic volumes and ejection fraction, and left ventricular rotation and relaxation velocities were measured before the administration of the drug and 6 and 12 months later. Results After 1 year, heart rate was reduced in the bisoprolol fumarate group both at rest (81 ± 12 before therapy versus 61 ± 11 after therapy; P < .01) and peak exercise (144 ± 20 before therapy versus 127 ± 17 after therapy; P < .01), which indicated a reduction in sympathetic drive. No differences were observed in heart rate responses in the placebo group. No differences were observed within or between groups in peak oxygen uptake, although work rate achieved was higher (117.9 ± 36 watts versus 146.1 ± 33 watts; P < .05) and exercise time tended to be higher (9.1 ± 1.7 minutes versus 11.4 ± 2.8 minutes; P = .06) in the bisoprolol fumarate group. A trend for a reduction in left ventricular end-diastolic volume (−54 mL) and left ventricular end-systolic volume (−62 mL) in the bisoprolol fumarate group occurred after 1 year. Ejection fraction was higher in the bisoprolol fumarate group (25.0 ± 7 versus 36.2 ± 9%; P < .05), and the placebo group remained unchanged. Most changes in volume and ejection fraction occurred during the latter 6 months of treatment. With myocardial tagging, insignificant reductions in left ventricular rotation velocity were observed in both groups, whereas relaxation velocity was reduced only after bisoprolol fumarate therapy (by 39%; P < .05). Conclusion One year of bisoprolol fumarate therapy resulted in an improvement in exercise capacity, showed trends for reductions in end-diastolic and end-systolic volumes, increased ejection fraction, and significantly reduced relaxation velocity. Although these results generally confirm the beneficial effects of beta-blockade in patients with chronic heart failure, they show differential effects on systolic and diastolic function. (Am Heart J 2002;143:676-83.)     

Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity

Background Peak oxygen consumption (VO₂) has an important prognostic role in chronic heart failure (CHF), but its discriminatory power is limited in patients with intermediate exercise capacity (peak VO₂ between 10-18 mL/kg/min). Thus, supplementary exertional indexes are greatly needed. Methods Six hundred patients with CHF with left ventricular ejection fraction (LVEF) ≤40% who performed a symptom-limited cardiopulmonary exercise testing were screened and followed up for 780 ± 450 days. Results Eighty-seven patients had major cardiac events (77 cardiac deaths and 10 urgent heart transplantations). Multivariate analysis revealed the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO₂ slope) (χ², 79.3, P < .0001), LVEF (χ², 24.6, P < .0001), and peak VO₂ (χ², 9.4, P < .0001) as independent and additional predictors of major cardiac events. VE/VCO₂ slope was the strongest independent predictor of outcome (χ², 20.9, P = .0001) in patients with intermediate peak VO₂ (n = 403), and the best cutoff value was 35 (χ², 25.8; relative risk = 3.2, 95% CI 2.0-5.1, P < .0001). Total mortality rate was 30% in patients with VE/VCO₂ slope ≥35 (n = 103, 26%) and 10% in those with VE/VCO₂ slope <35 (n = 300, 74%) (P < .0001). Patients with VE/VCO₂ slope ≥35 had a similar total mortality rate to those with peak VO₂ ≤10 mL/kg/min (30% vs 37%, P not significant). Conclusions A rational and pragmatic risk stratification process with symptom-limited cardiopulmonary exercise testing in CHF should include both peak VO₂ and VE/VCO₂ slope, the latter index effectively predicting outcome in almost one fourth of patients with intermediate exercise capacity. (Am Heart J 2002;143:418-26.)     

Improvements in blood rheology after cardiac rehabilitation and exercise training in patients with coronary heart disease

Objectives Our purpose was to examine the effect of cardiac rehabilitation and exercise training on blood rheology in patients with coronary heart disease (CHD). Although increased blood and plasma viscosity have been associated with an increased risk of CHD, the effects of cardiac rehabilitation and exercise training on blood rheology in patients with CHD are uncertain. Methods We assessed whole blood effective viscosity (μ), hematocrit standardized blood viscosity (μ₄₅), red blood cell transport efficiency (τ_rbc), and plasma viscosity (PV) in 23 nonsmoking patients with CHD before and after a phase II cardiac rehabilitation and exercise training program. In addition, we compared the group data with the data of a healthy reference group of 10 subjects. Results Patients with CHD had significantly elevated μ (3.35 ± 0.35 cp vs 3.06 ± 0.19 cp, P < .05) and μ₄₅ (3.51 ± 0.29 cp vs 3.12 ± 0.06 cp, P < .001) and reduced τ_rbc (12.7% ± 1.0% · cp^-1 vs 14.2% ± 0.7% · cp^-1, P < .001) compared with healthy subjects. After rehabilitation, patients with CHD had reductions in PV (1.85 ± 0.18 cp vs 1.77 ± 0.11 cp, P < .01) and μ₄₅ (3.58 ± 0.22 cp vs 3.39 ± 0.22 cp, P < .0001) and an increase in τ_rbc (12.4% ± 0.8% · cp^-1 vs 13.2% ± 0.9% · cp^-1, P < .0001). Conclusions Cardiac rehabilitation improves blood rheology in patients with CHD by reducing μ₄₅ and PV and elevating τ_rbc. These improvements may contribute to the increased functional capacity and reduced morbidity and mortality that is associated with participation in cardiac rehabilitation and exercise programs. (Am Heart J 2002;143:349-55.)     

Reduction of oxidative stress augments natriuretic effect of furosemide in moderate heart failure

Background The significance of antioxidant therapy in heart failure has not been fully examined. This study evaluated whether vitamin C has beneficial effects on renal function or augments the renal effects of furosemide in patients with heart failure.Methods There were 2 protocols. In protocol 1, plasma level of thiobarbituric acid-reactive substances (TBARS) and renal function were assessed before and after intravenous infusion of vitamin C or placebo in 8 patients with moderate congestive heart failure (CHF) treated with enalapril. In protocol 2, a randomized crossover study was performed in patients with moderate CHF treated with either an ACE inhibitor (enalapril) (n = 10) or an angiotensin II receptor antagonist (losartan) (n = 9) and in asymptomatic patients with impaired left ventricular function treated with enalapril (n = 8). TBARS and renal function were assessed before and after intravenous infusion of furosemide alone, coinfusion of furosemide with placebo and vitamin C, or coinfusion of furosemide with vitamin C and a kallikrein inhibitor (nafamostat mesilate).Results In protocol 1, although vitamin C reduced TBARS, it did not affect renal function. In protocol 2, TBARS was higher in patients with moderate CHF than in asymptomatic patients. Vitamin C augmented natriuretic effect of furosemide (from 179 ± 98 to 192 ± 104 μmol/min, P < .01) only in patients with moderate CHF treated with enalapril but not in the other 2 groups. Nafamostat mesilate prevented this augmentation.Conclusions In patients with CHF treated with enalapril, counteraction of the increased oxidative stress by vitamin C may contribute to the augmented natriuretic effect of furosemide through the renal kinin-nitric oxide pathway. (Am Heart J 2003;145:e2.)     

Treatment of acromegaly improves myocardial abnormalities

Background Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. Methods In 15 patients with active acromegaly (age range, 33.4 ± 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 ± 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. Results Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 ± 21 g/m² × 87 ± 21 g/m²; P <.01), LV relative wall thickness (0.40 ± 0.06 × 0.35 ± 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 ± 0.33 × 1.49 ± 0.34; P <.001), and isovolumetric relaxation period (126 ± 18 ms × 113 ± 13 ms; P <.05). Conclusion Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible. (Am Heart J 2002;143:873-6).     

Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion

Background In a randomized study, we recently documented that a vigorous, hospital-based exercise training (ET) program improves coronary endothelial function in coronary artery disease. The aim of this consecutive study was to assess whether a home-based exercise program with reduced average training duration can sustain previously achieved effects on coronary endothelial function.Methods Nineteen patients with coronary endothelial dysfunction documented by acetylcholine-induced vasoconstriction were randomly assigned to a training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital training (60 min of bicycle ergometry per day), all training patients were enrolled in a 5-month home-based program of 20 minutes' ergometry training per day and 1 group training session per week. At baseline, after 4 weeks and 6 months, endothelium-mediated vasodilation was assessed by quantitative coronary angiography after intracoronary infusions of acetylcholine. Average peak velocity (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated by multiplying vascular cross-sectional area and APV.Results CBF increased in response to 7.2 μg/min acetylcholine, from 27% ± 11% at the beginning of the study to 110% ± 24% after 4 weeks (P < .01 vs control group). After 6 months, the increase in CBF was lower versus inhospital training (67% ± 18%, P < .05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily training durations (r = 0.65, P = .03).Conclusions Home-based ET sustained part of the effects of hospital-based ET on endothelium-dependent vasodilation in coronary artery disease. However, acetylcholine-induced increases in CBF were lower after home-based ET, suggesting a relation between daily training duration and improvement of coronary vasomotion. (Am Heart J 2003;145:e3.)     

Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing

Background Transmyocardial and percutaneous laser revascularization (TMR, PTMR) may reduce angina and increase exercise tolerance in otherwise untreatable angina patients, although the mechanism is unknown and the placebo effect may be significant. One other proposed mechanism is cardiac denervation leading to silent ischemia. Methods Electrocardiograms obtained during symptom-limited exercise (ETT, modified Bruce protocol) at baseline and 12 months were analyzed (blinded core laboratory) from 182 patients randomized to TMR (n = 92) or medical therapy alone (MED_TMR, n = 90) and 219 patients randomized to PTMR (n = 109) or medical therapy alone (MED_PTMR, n = 110). Results Exercise duration increased 1 year after TMR or PTMR relative to medically treated patients (6.8 ± 3.4 min vs 8.6 ± 3.5 min for TMR; 7.3 ± 3.1 min vs 9.1 ± 3.6 min for PTMR, P < .05). At baseline, 20% of TMR and MED_TMR subjects had ST depression >1.0 mm, >80% had angina during exercise, but only 3% had ST changes without chest pain (silent ischemia). This did not change after TMR. In the PTMR group, more subjects exercised to >1.0 mm ST depression (from 17% to 34%, P < .05), with no change in MED_PTMR, but the proportion with silent ischemia did not change in either group. Conclusion Exercise tolerance improved after TMR and after PTMR. Relative to PTMR, TMR more effectively suppressed pain during exercise and ischemic ST depression. However, neither TMR nor PTMR induced significant silent ischemia. These results suggest that denervation may not be a significant factor contributing to angina relief after these procedures. The contribution of the placebo effect was not determined by these results. (Am Heart J 2002;143:1052-7.)     

Marked improvement in left ventricular ejection fraction during long-term beta-blockade in patients with chronic heart failure: clinical correlates and prognostic significance

Background Some patients with heart failure (HF) may have a marked improvement in left ventricular ejection fraction (LVEF) after long-term β-blockade. We compared the clinical characteristics and the prognosis of these patients with those of other patients. Methods One hundred seventy-one patients with chronic HF were assessed before and after 9 to 12 months of maintenance therapy with metoprolol or carvedilol. Results Thirty-eight patients (22%) showed an increase in their LVEF ≥15 units (from 20% ± 8% to 43% ± 10%). Compared with the other patients (LVEF change from 21% ± 7% to 26% ± 9%, P < .0001 for differences between groups), these patients also had a greater decline in the left ventricular end-diastolic volume (from 175 ± 74 mL/m² to 113 ± 36 mL/m²) and in the right atrial, mean pulmonary artery, and pulmonary wedge pressures, with a greater increase in the cardiac index, stroke volume index, stroke work index, and maximal functional capacity. Their long-term prognosis was excellent, with a 2-year cumulative survival rate of 95%, versus 81% for the other patients, and a hospitalization-free survival rate of 73%, versus 50% for the other patients (all P < .05). By means of multivariate analysis, only the nonischemic cause of HF and the mean arterial pressure at baseline were independently associated with an increase of ≥0.15 in LVEF. Conclusions Patients who show a marked improvement in their LVEF after long-term β-blockade have an excellent prognosis and have a high prevalence of nonischemic HF and a higher blood pressure at baseline. (Am Heart J 2003;145:292-9.)     

Sex differences in QTc interval and QT dispersion: dynamics during exercise and recovery in healthy subjects

Background Sex differences have been described in resting cardiac repolarization and susceptibility to torsade de pointes in humans. This study compares the QT-interval and QT-dispersion dynamics during exercise and recovery between healthy men and women.Methods Twenty healthy subjects (10 males aged 30 ± 4 years, 10 females aged 31 ± 11 years) underwent symptom-limited bicycle ergometry followed by a 10-minute recovery period. Digital 12-lead electrocardiograms (ECG) were recorded every 10 seconds during exercise and recovery. For each lead, the QTp interval (Q onset to T peak) was automatically measured by use of QT Guard (GE Marquette, Milwaukee, Wis). QTp dispersion was defined as the difference between the maximum and minimum QTp for each ECG. To quantify QT dynamics, we fit the QTp in lead V₃ (QTpV₃) versus cycle length (CL) relationship to a quadratic function during exercise and recovery with nonlinear regression analy- sis. Similar regression analysis was performed for the QTp dispersion versus CL relationship.Results At baseline, QTpcVs was longer in women than in men (338 ± 25 vs 278 ± 15 ms, P < .0001), but QTp dispersion was similar (35 ± 18 vs 41 ± 19 ms). At peak exercise, QT dispersion decreased compared with baseline in both men and women. During exercise and recovery, women had a steeper QTpVs-CL relationship. QTpVs hysteresis, a measure of the exercise and recovery QTpVs-CL curve separation, was greater in women than in men when measured 1 minute into recovery (33 ± 20 vs 6 ± 8 ms, P < .001). No sex difference in QTp-dispersion-rate adaptation was observed during exercise or recovery.Conclusions Healthy women exhibit greater QT-interval-rate adaptation during both exercise and recovery than men, resulting in more QT-interval hysteresis. Greater QT prolongation during decelerating heart rates in recovery may play a role in increasing proarrhythmia risk in women.     

Intravenous prostaglandin E1 reduces monocyte chemoattractant protein-1 levels in peripheral arterial obstructive disease

Objectives Blood monocytes are the precursors of the lipid-laden foam cells that are the hallmark of early atherosclerotic lesions, and monocyte chemoattractant protein-1 (MCP-1) plays important roles in their recruitment to the vessel wall. In this study, we measured serum levels of MCP-1 in patients with peripheral arterial obstructive disease (PAOD) and investigated whether intravenous prostaglandin E1 (PGE1) treatment, which produces clinical benefits in PAOD, might decrease such levels. Methods Eight patients with PAOD at Fontaine stage II to IV were treated with a daily intravenous infusion of 10 μg of PGE1 for 7 consecutive days. Blood samples before and after 7-day PGE1 treatment were used for assays of MCP-1, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), von Willebrand factor (vWF), and endothelin-1 (ET-1). Results Serum MCP-1 levels in patients with PAOD were significantly higher than those in healthy control subjects (263.8 ± 52.8 vs 136.5 ± 15.0 pg/mL, P = .002). PGE1 administration for 7 days resulted in a significant decrease in the MCP-1 level, from 263.8 ± 52.8 to 196.1 ± 25.5 pg/mL (P = .02), whereas levels of IL-6, hs-CRP, and ET-1 and the activity of vWF were not affected. Conclusions Serum MCP-1 levels were elevated in patients with PAOD, indicating the involvement of activation of monocytes in the pathogenesis of this disorder. Parenteral administration of PGE1 appeared to decrease circulating MCP-1 levels, which might lead to the suppression of the development of atherosclerotic lesions in patients with PAOD. (Am Heart J 2003;145:330-3.)     

Effects of oral soy protein on markers of inflammation in postmenopausal women with mild hypercholesterolemia

Background Nitric oxide (NO) may protect arteries against atherosclerosis, as suggested by experimental studies. Estrogen therapy enhances the bioactivity of NO in the vasculature of healthy postmenopausal women, but is not acceptable for long-term use by many women. Observational studies have demonstrated beneficial cardiovascular effects of soy protein in premenopausal and postmenopausal women. We examined whether the consumption of isolated soy protein may improve markers of vascular inflammation in postmenopausal women with hypercholesterolemia. Methods and Results In a randomized, double-blind, placebo-controlled, crossover study, 24 postmenopausal women with hypercholesterolemia received 25 g of soy protein or a placebo daily for 6 weeks, with treatment periods separated by 1 month. Markers of vascular inflammation were measured by enzyme-linked immunosorbent assay methods, including: soluble interleukin-2 receptor (sIL-2r), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). There was no effect of soy protein in comparison with placebo on the inflammatory markers: the sIL-2r level was 942.2 ± 335.3 pg/mL with soy protein and 868.5 ± 226.9 pg/mL with placebo (P = .311); E-selectin was 39.6 ± 16.5 ng/mL with soy protein and 42.1 ± 17.6 ng/mL with placebo (P = .323); P-selectin was 157.9 ± 67.9 ng/mL with soy protein and 157.5 ± 47.6 ng/mL with placebo, (P = .977); ICAM-1 was 266.0 ± 81.3 ng/mL with soy protein and 252.5 ± 82.7 ng/mL with placebo (P = .435); VCAM-1 was 402.7 ± 102.1 ng/mL with soy protein and 416.4 ± 114.8 ng/mL with placebo (P = .53). Conclusions Consumption of 25 g of isolated soy protein daily for 6 weeks does not substantially affect markers of vascular inflammation in postmenopausal women with hypercholesterolemia. (Am Heart J 2003;145:e7.)     

Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis

Background Although a high incidence of myocardial adrenergic denervation has been reported in patients with familial amyloid polyneuropathy, assessment of cardiac sympathetic nerve function has not been available in patients with AL (primary) amyloidosis. Methods To test the hypothesis that myocardial sympathetic nerve innervation might be impaired and variable according to the presence or absence of clinical autonomic abnormalities and congestive heart failure in AL amyloidosis, we examined 25 patients by use of iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy. Results Ten of the 16 patients without autonomic symptoms and 5 of the 9 patients with autonomic neuropathy showed congestive heart failure. The heart/mediastinal activity (H/M) ratio (1.53 ± 0.06 vs 1.29 ± 0.05 at 3 hours, P < .001) and myocardial washout ratio (41.5% ± 4.8% vs 30.8% ± 4.0%, P < .001) of MIBG were significantly increased in patients without autonomic symptoms compared with patients showing autonomic neuropathy. In patient groups with and without autonomic dysfunction, patients demonstrating congestive heart failure exhibited a significantly decreased H/M ratio and increased washout compared with patients with no heart failure, and left ventricular fractional shortening was positively correlated with the H/M ratio and inversely correlated with the washout ratio. There were significant correlations between the low-frequency component of the heart rate variability and the H/M ratio and washout ratio in the entire patient population. Conclusions Patients with AL amyloidosis and no autonomic dysfunction showed variable degrees of enhanced cardiac adrenergic neuronal activity with presynaptic sympathetic dysfunction. In contrast, patients with AL amyloidosis and autonomic neuropathy exhibited prominent myocardial adrenergic denervation with normal or impaired sympathetic neural function of the heart. This study demonstrates that myocardial uptake and turnover of MIBG in patients with AL amyloidosis are heterogeneous and dependent on the presence or absence of congestive heart failure and cardiac autonomic dysfunction. (Am Heart J 2002;144:122-9.)