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Cachexia is more closely associated with hormonal changes in CHF than conventional measures of the severity of CHF. This study suggests that the syndrome of heart failure progresses to cardiac cachexia if the normal metabolic balance between catabolism and anabolism is altered.

A high VE-VCO2 slope selects patients with more severe heart failure and is an independent prognostic marker. The VE-VCO2 slope may be used as a supplementary index in the assessment of patients with chronic heart failure.

Background-In patients with chronic heart failure (CHF) and preserved exercise tolerance, the value of cardiopulmonary exercise testing for risk stratification is not known. Elevated slope of ventilatory response to exercise (V E/V CO 2 ) predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary reflexes may trigger exercise hyperpnea. We assessed the relationship between cardiopulmonary reflexes and V E/V CO 2 and investigated the prognostic value of V E/V CO 2 in CHF patients with preserved exercise tolerance. Methods and Results-Among 344 consecutive CHF patients, we identified 123 with preserved exercise capacity, defined as a peak oxygen consumption (peak V O 2 ) Ն18 mL · kg Ϫ1 · min Ϫ1 (age 56 years; left ventricular ejection fraction 28%; peak V O 2 23.5 mL · kg Ϫ1 · min Ϫ1 ). Hypoxic and hypercapnic chemosensitivity (nϭ38), heart rate variability (nϭ34), baroreflex sensitivity (nϭ20), and ergoreflex activity (nϭ20) were also assessed. We identified 40 patients (33%) with high V E/V CO 2 (ie, Ͼ34.0). During follow-up (49Ϯ22 months, Ͼ3 years in all survivors), 34 patients died (3-year survival 81%). High V E/V CO 2 (hazard ratio 4.3, PϽ0.0001) but not peak V O 2 (Pϭ0.7) predicted mortality. In patients with high V E/V CO 2 , 3-year survival was 57%, compared with 93% in patients with normal V E/V CO 2 (PϽ0.0001). Patients with high V E/V CO 2 demonstrated impaired reflex control, as evidenced by augmented peripheral (Pϭ0.01) and central (Pϭ0.0006) chemosensitivity, depressed low-frequency component of heart rate variability (PϽ0.0001) and baroreflex sensitivity (Pϭ0.03), and overactive ergoreceptors (Pϭ0.003) compared with patients with normal V E/V CO 2 . Conclusions-In CHF patients with preserved exercise capacity, enhanced ventilatory response to exercise is a simple marker of a widespread derangement of cardiovascular reflex control; it predicts poor prognosis, which peak V O 2 does not. (Circulation. 2001;103:967-972.)

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Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.

There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.

Enhanced hypoxic and central hypercapnic chemosensitivity may play a role in mediating the increased ventilatory response to exercise in chronic heart failure.