Selective low-level leg muscle training alleviates dyspnea in patients with heart failure.

OBJECTIVES: The purpose of this study was to demonstrate in patients with moderate to severe heart failure that exertional dyspnea can be alleviated by improving muscle function. BACKGROUND: Dyspnea is a frequent limiting symptom in patients with chronic heart failure (CHF). This sensation may originate from activation of receptors in the musculature rather than the lung. METHODS: To investigate whether dyspnea could be alleviated by selective changes in leg muscle function, we performed isolated lower-limb training in 17 patients with severe CHF. Eight patients learned guided imagery relaxation techniques and served as an active control group. Exercise training consisted of three months of low-level bicycle and treadmill exercise such that minute ventilation was <25 l/min. Leg calisthenics were also performed. Maximal and submaximal exercise performance, respiratory and quadriceps muscle strength and endurance and quality-of-life and dyspnea scales were measured before and after each intervention. Metabolic stress testing (VO(2)), pulmonary function tests and isokinetic strength testing were also performed. RESULTS: In the active control group, no changes in leg muscle function, pulmonary function, maximal and submaximal exercise performance or quality-of-life questionnaires were observed. In the training group, peak torque of leg flexors (pre: 39 +/- 15 ft-lb; post: 50 +/- 13 ft-lb; p < 0.002) increased and the fatigue ratio decreased, indicating improved strength and endurance of the leg muscles. Maximal inspiratory and expiratory mouth pressures and maximum voluntary ventilation were unchanged. Peak VO(2) was increased (pre:12 +/- 2.2 ml/kg/min; post: 14 +/- 2.6 ml/kg/min) as well as the duration of exercise at 70% peak VO(2) increased (pre: 11.5 +/- 3.1 min; post: 21.5 +/- 5.4 min; p < 0.003). Perceived dyspnea during the submaximal testing was decreased. Minnesota Living with Heart Failure Score, Guyatt Dyspnea Scale, and the Transitional Dyspnea Index were all improved with training (all p < 0.05). CONCLUSIONS: We concluded that improvement of limb muscle function alleviates dyspnea and improves exercise performance in patients with CHF.

Interleukin-2 receptor blockade in cardiac transplantation: influence of HLA-DR locus incompatibility on treatment efficacy.

BACKGROUND: Because allograft rejection results from specific T-cell activation by donor human leukocyte antigens (HLA), new immunomodulatory therapies for organ-transplant recipients are used to selectively block T-cell activity without global immunosuppression. We investigated whether blockade of the high-affinity interleukin (IL)-2 receptor effectively prevented T-cell alloreactivity in cardiac transplantation. METHODS AND RESULTS: A study of a humanized monoclonal antibody against the high-affinity IL-2 receptor (daclizumab) was performed in 70 adult, cardiac-transplant recipients. Patients were stratified based on the degree of donor-recipient HLA-DR matches. Primary and secondary endpoints were incidence and frequency of high-grade allograft rejections, IL-2-dependent, T-cell outgrowth from biopsy sites as measured by lymphocyte growth assay, and production of anti-HLA antibodies. Treatment with daclizumab significantly prevented development of high-grade acute rejection in recipients with at least one donor HLA-DR locus match during the first 3 months posttransplantation; in this group 0 of 13 (0%) treated with daclizumab experienced at least one high-grade rejection versus 3 of 13 (23%) controls (P=0.05). In addition, 1 of 12 (9%) daclizumab-treated patients experienced one or more episodes of IL-2-dependent, T-cell outgrowth versus 5 of 12 (42%) patients in the untreated group (P=0.05). In contrast, daclizumab used at the same dose and schedule was not as effective in fully HLA-DR-mismatched recipients. After cessation of daclizumab, allograft rejection increased to levels seen in controls. CONCLUSIONS: IL-2-receptor blockade is effective for preventing alloreactivity and high-grade rejection in cardiac transplantation; however, its efficacy seemed to be influenced by the degree of donor-recipient, HLA-DR locus mismatching.

Morbidity and mortality in diabetic patients following cardiac transplantation.

BACKGROUND: Diabetes remains a relative contraindication to cardiac transplantation. Previous reports have described small numbers of diabetic patients without end-organ damage who have undergone successful cardiac transplantation. METHODS: A retrospective analysis of diabetic patients transplanted and their outcome in a single large center from 1/1/95 to 12/31/99 was performed. Diabetes was defined as "medium risk" by the presence of any of the following parameters: duration of therapy >10 years; use of insulin; serum creatinine >2 mg/dl; urinary protein >300 mg per 24 hours; presence of peripheral vascular disease (ankle:brachial ratio <1.0); and documentation of other diabetic comorbidity (retinopathy, neuropathy, gastroparesis). RESULTS: During this time period, 374 adult cardiac transplants were performed. Seventy-six patients (20%) were diabetic with 33 patients (43%) requiring insulin. Forty-two of the patients had moderate disease. Survival of the diabetic and non-diabetic recipients was comparable (1- and 3-year survival of 86% and 85%. vs 87% and 84%, respectively, p = NS). No difference in survival between "medium-risk" and "low-risk" diabetics was observed. The incidence of acute rejection in the first year, graft vasculopathy and infection, was comparable between diabetic and non-diabetic patients. In both diabetic and non-diabetic patients, there was a similar and small insignificant increase in serum creatinine. CONCLUSIONS: More patients with advanced diabetes are undergoing cardiac transplantation and the early and mid-term survival remains comparable to non-diabetic recipients. Future liberalization of transplantation in diabetics appears likely.

Partial loading of the left ventricle during mechanical assist device support is associated with improved myocardial function, blood flow and metabolism and increased exercise capacity.

BACKGROUND: Myocardial recovery has been observed after placement of left ventricular assist devices in some patients awaiting cardiac transplantation. Left ventricular assist devices provide profound volume and pressure unloading while restoring systemic blood flow. However, the optimal degree of left ventricular unloading during left ventricular assist device support is unknown. The purpose of this study was to assess the effect of the degree of left ventricular decompression, during left ventricular assist device support, on myocardial function and exercise capacity. METHODS: Twenty patients with a left ventricular assist device performed cardiopulmonary exercise testing with simultaneous echocardiographic and hemodynamic measurements during full, and then partial, device support. Eleven patients underwent positron emission tomographic scanning for measurement of myocardial blood flow and oxygen consumption. RESULTS: Patients were divided into two groups based on the degree of left ventricular decompression as assessed by echocardiographic measurements. Patients with partially decompressed ventricles (n = 13, LVEDD = 4.8 +/- 1.0 cm) as compared to those with fully decompressed ventricles (n = 10, LVEDD = 3.0 +/- 0.3 cm) demonstrated significant improvements in: peak oxygen consumption (16.8 +/- 4.3 versus 12.8 +/- 3.0 ml/kg.min), native left ventricular index during exercise (2.5 +/- 1.4 versus 0.8 +/- 0.8 liters/min.m(2)); ability to exercise with the device weaned (10 of 13 versus 1 of 10 patients); resting myocardial blood flow (0.55 +/- 0.11 versus 0.21 +/- 0.13 ml/g.min); and myocardial oxygen consumption (0.04 +/- 0.01 versus 0.02 +/- 0.001 min-1) (all p < 0.05). CONCLUSIONS: These results suggest that partial loading of the left ventricle during left ventricular assist device support may be beneficial. Further study of optimal ventricular decompression during device support is needed, as this may be important in improving myocardial recovery.