Inotropic agents improve the peripheral microcirculation of patients with end-stage chronic heart failure.

BACKGROUND: Skeletal muscle microcirculation impairment in patients with chronic heart failure (CHF) seems to correlate with disease severity. We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion. METHODS: We evaluated 25 patients with stable CHF, 30 patients with end-stage CHF (ESCHF) receiving treatment with intermittent infusion of inotropic agents, and 12 healthy subjects. Thenar muscle tissue oxygen saturation (StO(2)%) was measured noninvasively by NIRS before, during, and after 3-minute occlusion of the brachial artery (occlusion technique) in all subjects and in patients with ESCHF before and after 6 hours of inotropic infusion (dobutamine and/or levosimendan) or placebo (N = 5). RESULTS: Patients with ESCHF or CHF presented significantly lower StO(2)% than healthy subjects (74.5% +/- 7%, 78.6% +/- 6%, and 85% +/- 5%, respectively; P = .0001), lower oxygen consumption rate during occlusion (24.6% +/- 8%/min, 28.6% +/- 10%/min, and 38.1% +/- 11.1%/min, respectively; P = .001), and lower reperfusion rate (327% +/- 141%/min, 410% +/- 106%/min, and 480% +/- 133%/min, respectively; P = .002). After 6 hours of inotropic infusion, patients with ESCHF showed significantly increased StO(2)% (74.5% +/- 7% to 82% +/- 9%, P = .001), oxygen consumption rate (24.6% +/- 8%/min to 29.3% +/- 8%/min, P = .009), and reperfusion rate (327% +/- 141%/min to 467% +/- 151%/min, P = .001). No statistical difference was noted in the placebo group. CONCLUSION: Peripheral muscle microcirculation as assessed by NIRS is impaired in patients with CHF. This impairment is partially reversed by infusion of inotropic agents in patients with ESCHF.

Bone mass loss in chronic heart failure is associated with secondary hyperparathyroidism and has prognostic significance.

AIMS: Chronic heart failure (CHF) is associated with increased risk of osteoporosis. We investigated the relationship between severity of CHF and bone loss, underlying pathophysiological mechanisms, and the prognostic significance of bone mass changes in heart failure. METHODS AND RESULTS: Total body (TB) and femoral (F) bone mineral density (BMD), and T- and Z-scores in the femur were measured in 60 men with CHF (56 ± 11 years) and 13 age-matched men free from CHF. The composite study endpoint was death, implantation of a left ventricular assist device (LVAD), or inotrope dependency during a median 2-year follow-up. Parathyroid hormone (PTH) and vitamin D were measured in all subjects. TBBMD, FBMD, T-score, and Z-score were significantly lower in men with CHF. Their PTH levels were also significantly increased (111 ± 59 vs. 39 ± 14; P < 0.001). Patients in New York Heart Association classes III-IV compared with those in classes I-II demonstrated significantly lower TBBMD, FBMD, T-score, and Z-score, and higher PTH (136 ± 69 vs. 86 ± 31; P= 0.001). Increased PTH levels were correlated with reduced TBBMD (P = 0.003), FBMD (P = 0.002), and femur T-score (P = 0.001), reduced cardiac index (P = 0.01) and VO(2) peak (P < 0.0001), and increased wedge pressure (P = 0.001). Low TBBMD [hazard ratio (HR) 0.003, 95% confidence interval (CI) 0.00-0.58; P = 0.03] and Z-score (HR 0.56, 95% CI 0.35-0.90; P = 0.017) were associated with adverse outcome. CONCLUSIONS: Secondary hyperparathyroidism and reduction in bone density occur in CHF patients and are associated with disease severity. Increased bone mass loss in CHF has prognostic significance.

Anemia in heart failure: pathophysiologic insights and treatment options.

Anemia has been recognized as a very common and serious comorbidity in heart failure, with a prevalence ranging from 10 to 79%, depending on diagnostic definition, disease severity and patient characteristics. A clear association of anemia with worse prognosis has been confirmed in multiple heart failure trials. This finding has recently triggered intense scrutiny in order to identify the underlying pathophysiology and the best treatment options. Etiology is multifactorial, with iron deficiency and cytokine activation (anemia of chronic disease) playing the most important roles. Treatment is aimed at not only restoring hemoglobin values back to normal, but also at improving the patient's symptoms, functional capacity and hopefully the outcome. Iron supplementation and erythropoietin-stimulating agents have been used for this purpose, either alone or in combination. In this review, the recent advances in elucidating the mechanisms leading to anemia in the setting of heart failure are presented and the evidence supporting the use of different treatment approaches are discussed.

The effects of exercise training on the kinetics of oxygen uptake in patients with chronic heart failure.

BACKGROUND: Prolonged oxygen uptake kinetics (O2 kinetics), following the onset of a constant workload of exercise has been associated with a poor prognosis in patients with chronic heart failure. This study aimed to determine both continuous and interval training effects on the different O2-kinetics phases in these patients. DESIGN: Twenty-one patients (60+/-8 years) with stable chronic heart failure participated in a 36-session exercise rehabilitation program (three times weekly). Patients were randomly assigned to interval training (n=11; 100% of peak work rate for 30 s, alternating with 30 s-rest) and to continuous training (n=10; 50% of peak work rate). METHODS: Before and after the completion of the program, all patients performed both incremental symptom-limited and constant workload submaximal cardiopulmonary exercise tests. Phase I O2-kinetics was evaluated by time (t), from the start of exercise until the onset of decreased respiratory exchange ratio and phase II by the time constant (tau) of the response from the end of phase I until steady state. RESULTS: After training, there was a significant increase in peak oxygen uptake and peak work rate in both continuous (15.3+/-4.4 vs. 16.6+/-4.5 ml/kg per min; P=0.03 and 81.8+/-40.1 vs. 94.7+/-46.1 W; P=0.03) and interval training groups (14.2+/-3.1 vs. 15.4+/-4.2 ml/kg per min; P=0.03 and 82.5+/-24.1 vs. 93.7+/-30.1 W; P=0.04). Patients who underwent interval training had a significant decrease in t (39.7+/-3.7 to 36.1+/-6.9 s; P=0.05), but not tau (59.6+/-9.4 to 58.9+/-8.5 s; P=ns), whereas those assigned to continuous training had a significant decrease in both t (40.6+/-6.1 to 36.4+/-5.4 s; P=0.01) and tau (63.3+/-23.6 to 42.5+/-16.7 s; P=0.03). CONCLUSIONS: Exercise training improves O2 kinetics in chronic heart failure patients. Both continuous and interval training improve phase I O2-kinetics, but continuous training results in superior improvement of the phase II O2-kinetics, an indirect index of muscle oxidative capacity.