Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized,placebo-controlled study in patients with congestive heart failure

Background We sought to investigate whether β-blockers exert a presynaptic effect in the myocardium as measured by ¹²³I-metaiodobenzylguanidine. Methods The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters. Results We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 ± 11 mm to 67 ± 10 mm (P < .05, within-group comparison) and LVEF increased from 25.3% ± 7.4% to 32.6% ± 9.6% (P < .05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2). Conclusions This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy. (Am Heart J 2002;144:e3.)     

Implantation of CD133 Stem Cells in Patients Undergoing Coronary Bypass Surgery: IMPACT-CABG Pilot Trial

Background

The Implantation of Autologous CD133⁺ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial injections of autologous CD133⁺ stem cells during coronary artery bypass grafting (CABG) in patients with chronic ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.

Methods

Bone marrow was harvested from iliac crests and stem cells were isolated using the CliniMACS CD133⁺ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received CABG, followed by CD133⁺ cellular injection in the revascularized hypokinetic myocardium.

Results

Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment in CD133⁺ cells, with 92 ± 11% recovery after selection. Mean number of CD133⁺ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications during the 18-month follow-up and all patients improved to NYHA class I. Six-month echocardiography showed no significant improvement in left ventricular ejection fraction (34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).

Conclusions

This work represents the first Canadian experience with CD133⁺ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients are now being randomized to receive either CD133⁺ stem cell or placebo.     

Echocardiography-derived variables predict outcome in patients with nonischemic dilated cardiomyopathy with or without a restrictive filling pattern

Background Despite recent therapeutic advances, patients with heart failure caused by dilated cardiomyopathy (DCM) still have high morbidity and mortality rates. In this study, we sought to assess the prognostic value of echocardiographic variables in patients with DCM and to assess the impact of a restrictive left ventricle filling pattern. Design We conducted a retrospective cohort study of 337 patients with DCM, using the Royal Brompton Hospital Echocardiography database for the years 1994 to 1998. Methods and Results There were 337 patients with a mean age of 53 ± 15 years. One hundred ninety-five patients (58%) had a restrictive left ventricle filling pattern (RFP). There was a total of 74 deaths (22%) during the follow-up period (43 ± 25 months). RFP more than tripled the risk of death (adjusted hazard ratio 3.2, 95% CI 1.8-5.7, P = .003). RFP is correlated with isovolumic relaxation time, incoordinate wall-motion, amplitude of right ventricular long axis excursion on M-mode echocardiography, and mitral regurgitation. Conclusion RFP is a powerful independent predictor of mortality in patients with nonischemic DCM. The risk associated with RFP is greatest among patients who had short isovolumic relaxation time, mitral regurgitation, incoordinate wall-motion, and depressed amplitude of right ventricular long axis excursion. Thus, echocardiography-derived variables may stratify patients with heart failure with DCM who are at high risk, for whom aggressive medical treatment or heart transplantation should be considered early. (Am Heart J 2002;144:343-50.)     

Heart failure after myocardial infarction: prevalence of preserved left ventricular systolic function in the community

Background Studies have reported that a large proportion of the cases of congestive heart failure (CHF) with mixed etiologies have preserved left ventricular systolic function. Whether this is the case in subjects with CHF after myocardial infarction (MI) is not known. This study was undertaken to examine the prevalence and characteristics associated with CHF in patients who had preserved ejection fraction (LVEF) after MI. Methods Clinical characteristics and LVEF were ascertained in a population-based cohort of patients with CHF after incident MI in Olmsted County, Minn. All MIs were validated by use of standardized epidemiological criteria, and all episodes of CHF were validated by use of Framingham criteria. Results Between 1979 and 1994, 1658 patients had an MI, and 644 of these patients (38%) had CHF during 7.4 ± 5.4 years of follow-up. Of these patients, 395 (61%) underwent LVEF assessment. Preserved LVEF (ie, ≥50%) was present in 30% of cases, and this proportion did not change with time. The proportion of women with CHF and preserved LVEF (37%) was greater than the proportion of men (23%, P = .002). The positive association between female sex and preserved LVEF remained significant after adjustment (odds ratio 1.97, 95% CI 1.26-3.07, P = .003). The highest tertile of peak creatinine phosphokinase level was negatively associated with preserved LVEF (odds ratio 0.51, 95% CI 0.29-0.89). Conclusion A notable proportion of cases of CHF after MI have preserved LVEF. This underscores the burden of CHF with preserved LVEF in a well-defined group of patients with documented coronary disease. CHF with preserved LVEF after MI is associated with female sex and smaller MI size. (Am Heart J 2003;145:742-8.)     

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.)     

Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease

Background Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men. Methods We used ^99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 ± 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline. Results Serum testosterone increased 137 ± 58% and 488 ± 113%, and estradiol levels increased 27 ± 46% and 76 ± 57%, (P < .001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression. Conclusions Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD. (Am Heart J 2002;143:249-56.)     

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.)     

Statins do not significantly affect muscle sympathetic nerve activity in humans with nonischemic heart failure: a double-blind placebo-controlled trial

Background

Hydroxymethylglutaryl–coenzyme A reductase inhibitors (statins) have been shown to reduce sympathetic nervous system (SNS) activation in experimental heart failure (HF). However, this potential mechanism of action of statins in HF has not been well studied in humans.

Methods and Results

Twenty-six patients with nonischemic systolic HF (left ventricular ejection fraction [LVEF] ≤35%) were randomized to atorvastatin (10 mg) or placebo for 3 months. Pre- and posttreatment testing included echocardiography, laboratory assays, quality of life (QOL) questionnaires, and peroneal nerve muscle sympathetic nerve activity (MSNA) via microneurography. Eighteen subjects had technically adequate MSNA tracings before and after treatment. The cohort was 65% male, 81% New York Heart Association functional class II, LVEF 26 ± 6%, and low-density lipoprotein cholesterol (LDL-C) 108 ± 26 mg/dL. Baseline MSNA was 41 ± 2 bursts/min. LDL-C significantly decreased in the atorvastatin (−36.8%) versus the placebo (−0.1%) group (P < .0001). However, there was no significant change in MSNA (−16.2% vs −2.5%), LVEF, B-type natriuretic peptide, or QOL score in the atorvastatin compared with the placebo group.

Conclusions

Short-term statin therapy in patients with nonischemic HF does not result in a significant decrease in SNS activation as measured by MSNA. These findings are consistent with the neutral outcomes of large clinical trials of statins in HF.     

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirty-one healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p = 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p = 0.04). Carotid plaques were also more common (p = 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease.     

The relative importance of left atrial function versus dimension in predicting atrial fibrillation after coronary artery bypass graft surgery

Background Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. The purpose of this study was to determine whether pre-existing left atrial dysfunction is a predictor of postoperative AF compared with other clinical predictors. Methods Ninety-three patients undergoing CABG were prospectively studied. Intraoperatively, transesophageal echocardiography was performed to measure left atrial size, transmitral flow velocity, and other routine parameters. Left atrial function was estimated by the following formula: Atrial index = Transmitral VTI total × LAEF/Left atrial maximal area (where VTI = velocity time integral of E and A waves, LAEF = left atrial ejection fraction). The association of potential clinical predictors with the occurrence of postoperative AF was evaluated by χ² or Fisher exact tests, followed by stepwise multivariate logistic regression model. P values and odds ratios (OR) with 95% CIs were reported. Significance was set at P < .05. Results Postoperative AF occurred in 28 of 93 patients (30.1%). Patients with postoperative AF were older (67.0 ± 8.3 vs 61.5 ± 9.6 years, P = .0075), had larger left atrial maximal area (14.3 ± 4.6 cm² vs 10.9 ± 4.3 cm², P < .001), lower atrial index (0.54 ± 0.56 vs 0.82 ± 0.64, P = .008), larger body surface area (BSA) (OR 57, 95% CI 3.97-827), longer aortic cross-clamp time (OR 1.03, 95% CI 1.00-1.05), and more likely to have a postoperative myocardial infarction (OR 3.28, 95% CI 0.99-10.87) compared with those without AF. By multivariate analysis, only age (OR 1.11, 95% CI 1.04-1.19, P = .002) and atrial dimension (OR 1.75, 95% CI 1.03-2.96, P = .038) were significant independent predictors of postoperative AF. Body surface area also increased the odds of postoperative AF, but the CI was wide (OR 114, 95% CI 4.65-2810, P = .004). Conclusions Our results demonstrate that age and atrial enlargement, rather than atrial function, were independent predictors of postoperative AF. (Am Heart J 2002;143:181-6.)     

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).     

Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction

Background Mitral regurgitation (MR) and tricuspid regurgitation (TR) frequently develop in patients with left ventricular systolic dysfunction (LVSD). Ventricular volume overload that occurs in patients with MR and TR may lead to progression of myocardial dysfunction. We hypothesized that MR and TR would provide markers of risk in patients with LVSD. Methods We reviewed clinical, electrocardiographic, and echocardiographic data on 1421 consecutive patients with LVSD (left ventricular ejection fraction ≤35%). Predictors of survival (freedom from death or United Network for Organ Sharing [UNOS]-1 transplantation) were identified in a multivariable analysis with a Cox proportional hazards analysis. The impact of MR and TR (none to mild, moderate, or severe) then was assessed separately with Kaplan-Meier survival analysis. Results During the follow-up period (mean ± SD, 365 ±364 days), death occurred in 435 study subjects (31%) and UNOS-1 transplantation in 28 subjects (2%). Multivariable predictors of poor outcome included increasing MR and TR grade, cancer, coronary artery disease, and absence of an implantable cardiac defibrillator. Relative risk was 1.84 (95% CI 1.43-2.38) for severe MR and 1.55 (95% CI 1.14-2.11) for severe TR. Survival with Kaplan-Meier analysis related inversely to MR grade (none to mild 1004 ±31 days, moderate 795 ±34 days, severe 628 ±47 days, P < .0001) and TR grade (none to mild 977 ±28 days, moderate 737 ±40 days, severe 658 ±55 days, P = .0001). Conclusion Patients with severe MR or TR represent high-risk subsets of patients with LVSD. Future study is warranted to determine whether pharmaceutical or surgical strategies to relieve MR and TR have a favorable impact on survival. (Am Heart J 2002;144:524-9.)     

Altered coronary flow properties in diffuse coronary artery ectasia

Objectives The purpose of this study was to investigate coronary blood flow properties in patients with diffuse coronary artery ectasia (CAE) associated with exercise-induced myocardial ischemia.Methods Seventeen patients with diffuse CAE and without coexisting coronary artery stenosis were enrolled in the study (CAE group). CAE was defined as luminal dilatation 1.5 to 2 times that of the adjacent normal coronary artery segment or the diameter of the corresponding coronary artery of the control group when there was no normal segment. The age- and sex-matched control group (n = 20) comprised patients with normal epicardial coronary arteries. Coronary blood flow velocities were obtained invasively by use of Doppler scanning flow wire. Coronary flow reserve (CFR) was measured by administration of intracoronary papaverine as the hyperemic stimulus. Volumetric coronary blood flow was estimated by multiplying the velocity time integral of coronary blood flow with the cross-sectional area of the coronary artery and the heart rate.Results Fifteen patients with CAE, but none of the patients in the control group, had electrocardiographic signs of myocardial ischemia at peak exercise on ergometry. Baseline average peak velocities (APVs) of coronary blood flow were similar in the 2 groups. Peak hyperemic APVs of coronary blood flow were lower in the CAE group than in the control group (17.5 ± 7.4 cm/s vs 41.5 ± 12.6 cm/s, respectively, P < .001). Volumetric coronary blood flow was significantly higher in the CAE group than in the control group, both at rest and at hyperemia (146.3 ± 71.2 cm³/min vs 45.1 ± 16.1 cm³/min, respectively, P < .001, and 202 ± 87.3 cm³/min vs 104.1 ± 37.6 cm³/min, respectively, P < .003). The mean CFR of the CAE group was significantly reduced compared with that of the control group (1.51 ± 0.31 vs 2.67 ± 0.52, respectively, P < .001).Conclusions The CFR is significantly reduced in patients with diffuse CAE compared to a matched control group. Although volumetric coronary blood flow is significantly higher in CAE, microcirculatory dysfunction that is reflected as depressed CFR may be the underlying cause of exercise-induced myocardial ischemia. (Am Heart J 2003;145:66-72.)     

A new thrombolytic agent,monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial

Background Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. Methods This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. Results Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 ± 4 vs 20 ± 2 ng/mL, P < .01) and in Group II (36 ± 3 vs 27 ± 2 ng/mL, P < .05). In the high PAI-1 level subgroup (≥27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P < .01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald χ²= 3.94, P = .02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. Conclusion Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI. (Am Heart J 2002;144:e5.)     

Impact of geographic miss on adjacent coronary artery segments in diffuse in-stent restenosis with beta-radiation therapy: angiographic and intravascular ultrasound analysis

Background The impacts of geographic miss on edge restenosis have not been sufficiently evaluated. Methods β-Radiation therapy with rhenium 188-filled balloon after rotational atherectomy for diffuse in-stent restenosis was performed in 50 patients. We evaluated the impacts of geographic miss on adjacent coronary artery segments beyond the stent by angiographic (QCA) and intravascular ultrasound (IVUS) analysis in 50 irradiated lesions and 100 edges. Serial IVUS and QCA comparisons between postradiation and 6 months' follow-up were available in 44 and 47 of 50 patients, respectively. QCA measurements of minimal lumen diameter (MLD) and IVUS analysis were performed in the reference and radiation segments. Edges that were touched by the angioplasty balloon but were not adequately covered by radiation constituted the geographic miss edges. Results Geographic miss was observed in 55.6% and 52.6% in QCA and IVUS analysis, respectively. Edge restenosis after radiation therapy in 3 patients was associated with geographic miss. In contrast to uninjured edges (postradiation 2.9 ± 0.6 mm to follow-up 2.8 ± 0.6 mm, P = .292), MLD in the radiation segment by QCA analysis significantly decreased from 2.7 ± 0.4 mm to 2.4 ± 0.6 mm in geographic miss edges (P = .002). IVUS analysis showed that significant positive remodeling in the radiation segment occurred in uninjured edges (vessel area from 15.4 ± 4.4 mm² to 15.8 ± 4.4 mm², P = .001) but not in geographic miss edges (vessel area from 12.8 ± 3.6 mm² to 13.0 ± 3.6 mm², P = .119). Conclusion The geographic miss might be one of the predictors, which resulted in decreased MLD at follow-up in β-radiation therapy. Sufficient lesion coverage with radiation might be associated with positive remodeling in the radiation segment. (Am Heart J 2002;143:327-33.)     

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.)     

No effect of an L-arginine-enriched medical food (HeartBars) on endothelial function and platelet aggregation in subjects with hypercholesterolemia

Background Providing l-arginine as a precursor for nitric oxide has been proposed to improve endothelial function in populations at high risk for cardiovascular events. We studied the effects of dietary l-arginine supplementation with HeartBars (a medical food rich in L-arginine, Cooke Pharma, Belmont, Calif) on flow-mediated dilation and markers of endothelial function in subjects with hypercholesterolemia. Methods We randomly assigned 47 subjects with hypercholesterolemia to receive one HeartBar containing 3.3 g l-arginine each, or a placebo bar, consumed twice daily for 2 weeks. Flow-mediated dilation, platelet aggregation studies, and soluble levels of endothelial and platelet adhesion molecules were obtained before and after the 2-week treatment period. Results Baseline and follow-up levels of l-arginine were 78.5 ± 28.2 μmol/L and 80.7 ± 26.7 μmol/L, respectively (P = .54). The HeartBar group had no improvement in flow-mediated dilation; changes in brachial artery diameter at baseline and follow-up were 5.52% ± 3.32% and 4.96% ± 2.39%, respectively. There were also no changes in the soluble levels of E-selectin and P-selectin by treatment group. Conclusions In our study, 2 weeks of HeartBar supplementation in subjects with hypercholesterolemia showed no favorable effects on endothelial or platelet function. (Am Heart J 2003;145:e15.)     

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.)     

Potential contributing factors to noncompliance with dietary sodium restriction in patients with heart failure

Background Although sodium restriction is considered essential in the management of patients with chronic heart failure (CHF), there are no data available regarding patients awareness of and ability to comply with the sodium restriction guideline. Methods Between May 1999 and August 2000, 50 patients referred to the Parkland Memorial Hospital CHF clinic were assessed by a registered dietitian for (1) awareness of the sodium restriction guideline, (2) ability to read the sodium content from a Nutrition Facts label, and (3) ability to sort 12 food containers, all bearing a Nutrition Facts label, into high- and low-sodium groups. A global measure of dietary sodium knowledge was calculated (“sodium knowledge score,” range 0-10). These tests were repeated after the patient completed one or more educational sessions (mean 2.8 ± 1.5) with the dietitian. Results The proportion of patients aware of the sodium restriction guideline was 14% at baseline and 42% at follow-up (P < .01). The proportion of patients able to read the sodium content from the Nutrition Facts label was 58% at baseline and 92% at follow-up (P < .01). The sodium knowledge score was 3.8 ± 3.4 at baseline and 5.8 ± 3.2 at follow-up (P < .01). The proportion of subjects who achieved a perfect sodium knowledge score of 10 was 8% at baseline and 26% at follow-up (P < .05). The number of food containers sorted accurately was 10.6 ± 1.5 at baseline and 11.3 ± 1.1 at follow-up, P = .09. Conclusions On referral to a specialty CHF clinic, many patients had severe deficiencies in their knowledge base regarding dietary sodium intake that would preclude compliance with the sodium restriction guideline. Directed education focusing on sodium intake corrected many of these deficiencies. (Am Heart J 2002;143:29-33.)     

The cardiac component of cardiac cachexia

Background Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. Methods Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 ± 13 vs 67 ± 8 years, P = .07; New York Heart Association class 2.9 ± 0.7 vs 2.6 ± 0.6, P = .08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. Results Cardiac dimensions including LV diastolic (69 ± 9 mm vs 67 ± 13 mm) and systolic cavity diameter (58 ± 11 mm vs 55 ± 15 mm), LV mass (480 ± 180 g vs 495 ± 190 g), and LV systolic and diastolic function including fractional shortening (16% ± 10% vs 18% ± 10%), isovolumic relaxation time (29 ± 22 ms vs 36 ± 27 ms), and E/A ratio (2.7 ± 1.6 vs 3.3 ± 2.9) did not differ between cachectic and noncachectic patients (all P > .1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (χ² test, P < .05). Conclusions Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia. (Am Heart J 2002;144:45-50.)