Author + information
- Received October 9, 2012
- Revision received April 2, 2013
- Accepted April 15, 2013
- Published online August 1, 2013.
- Nir Uriel, MD,
- Jose Gonzalez-Costello, MD,
- Andrea Mignatti, MD,
- Kerry A. Morrison, BA,
- Nadav Nahumi, BA,
- Paolo C. Colombo, MD and
- Ulrich P. Jorde, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Ulrich P. Jorde, Division of Cardiology, College of Physicians and Surgeons, Columbia University, 622 West 168th Street, New York, New York 10032.
Objectives This study sought to investigate plasma levels of glucose and free fatty acids (FFA) and their relationship with adrenergic activation and insulin resistance (IR) in patients with advanced congestive heart failure (CHF).
Background Adrenergic activation and IR are hallmarks of advanced heart failure. The resulting changes in fuel substrate availability and their implications for exercise capacity have not been elucidated.
Methods Subjects with CHF underwent maximal exercise testing. Plasma glucose, FFA, insulin, and norepinephrine (NE) levels were measured at rest and at peak exercise. Beta-receptor sensitivity to NE was assessed using the Chronotropic Responsiveness Index (CRI). Homeostasis Model Assessment Index >2.5 defined IR. Left ventricular ejection fraction was estimated by 2-dimensional echocardiography.
Results Ninety-six subjects were enrolled. CHF subjects without IR (CHF/No-IR), but not those with IR (CHF/IR), significantly increased glucose and insulin in response to exercise. Only CHF/No-IR subjects increased FFA in response to exercise (0.14 ± 0.27 mmol/l; p = 0.027). NE increased significantly less with exercise, and CRI was lower in CHF/IR subjects compared with CHF/No-IR subjects (1.3 ± 1.4 vs. 2.5 ± 2.1; 6.4 ± 2.6 vs. 8.5 ± 3.4; p = 0.069). CRI correlated with the exercise-induced increase in FFA (r = 0.41; p < 0.005). These results stayed the same after excluding diabetic patients from the CHF/IR group.
Conclusions Circulating FFA levels increased during exercise in CHF subjects without IR, but not in those with IR or DM. Increased FFA availability during exercise may represent a catecholamine-dependent compensatory fuel shift in CHF.
This study was supported by National Institutes of Health grants R01HL45095 (to Dr. Jorde) and 1K23HL103795-01A1 (to Dr. Uriel). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 9, 2012.
- Revision received April 2, 2013.
- Accepted April 15, 2013.
- 2013 American College of Cardiology Foundation