Simultaneous exercise stress cardiac magnetic resonance and cardiopulmonary exercise testing to elucidate the Fick components of aerobic exercise capacity: a feasibility and reproducibility study and pilot study in hematologic cancer survivors.

BACKGROUND: Patients treated for hematologic malignancy often experience reduced exercise capacity and increased fatigue; however whether this reduction is related to cardiac dysfunction or impairment of skeletal muscle oxygen extraction during activity is unknown. Cardiopulmonary exercise testing (CPET) coupled with stress cardiac magnetic resonance (ExeCMR), may provide a noninvasive method to identify the abnormalities of cardiac function or skeletal muscle oxygen extraction. This study was performed to determine the feasibility and reproducibility of a ExeCMR + CPET technique to measure the Fick components of peak oxygen consumption (VO2) and pilot its discriminatory potential in hematologic cancer patients experiencing fatigue. METHODS: We studied 16 individuals undergoing ExeCMR to determine exercise cardiac reserve with simultaneous measures of VO2. The arteriovenous oxygen content difference (a-vO2diff) was calculated as the quotient of VO2/cardiac index (CI). Repeatability in measurements of peak VO2, CI, and a-vO2diff was assessed in seven healthy controls. Finally, we measured the Fick determinants of peak VO2 in hematologic cancer survivors with fatigue (n = 6) and compared them to age/gender-matched healthy controls (n = 6). RESULTS: Study procedures were successfully completed without any adverse events in all subjects (N = 16, 100%). The protocol demonstrated good-excellent test-retest reproducibility for peak VO2 (intraclass correlation coefficient [ICC] = 0.992 [95%CI:0.955-0.999]; P < 0.001), peak CI (ICC = 0.970 [95%CI:0.838-0.995]; P < 0.001), and a-vO2diff (ICC = 0.953 [95%CI:0.744-0.992]; P < 0.001). Hematologic cancer survivors with fatigue demonstrated a significantly lower peak VO2 (17.1 [13.5-23.5] vs. 26.0 [19.7-29.5] mL·kg-1·min-1, P = 0.026) and lower peak CI (5.0 [4.7-6.3] vs. 7.4 [7.0-8.8] L·min-1/m2, P = 0.004) without a significant difference in a-vO2diff (14.4 [11.8-16.9] vs. 13.6 [10.9-15.4] mLO2/dL, P = 0.589). CONCLUSIONS: Noninvasive measurement of peak VO2 Fick determinants is feasible and reliable with an ExeCMR + CPET protocol in those treated for a hematologic malignancy and may offer insight into the mechanisms of exercise intolerance in those experiencing fatigue.

Usefulness of the Duke Activity Status Index to Select an Optimal Cardiovascular Exercise Stress Test Protocol.

Exercise testing represents the preferred stress modality for individuals undergoing evaluation of suspected myocardial ischemia. Patients with limited functional status may be unable to achieve an adequate exercise stress, thus influencing the diagnostic sensitivity of the results. The Duke Activity Status Index (DASI) is a clinically applicable tool to estimate exercise capacity. The purpose of the current study was to assess the utility of the DASI to identify patients unable to achieve an adequate exercise stress result. Patients referred for exercise stress testing were administered the DASI pre-exercise. Baseline characteristics and exercise variables were evaluated including DASI-metabolic equivalents (DASI-METs), peak METs, exercise time (ET), and %-predicted maximal heart rate (%PMHR). Criteria for determining adequate exercise stress was defined as ≥85%PMHR or ≥ 5-METs at peak exercise. In 608 cardiovascular stress tests performed during the study period; 314 were exercise stress. The median DASI-METs (8.4 [interquartile range; 6.7 to 9.9]) was associated with estimated peak exercise METs (R=0.50, p <0.001), ET (R=0.29, p <0.001), and %PMHR (R=0.19, p = 0.003). DASI-METs were different between those with < or ≥85%PMHR (7.9 [6.6-9.0] vs. 8.9 [7.1-9.9], P=0.025) and those with < or ≥5-METs (5.8 [4.6 to 6.6] versus 8.9 [7.3-9.9], p <0.001). Receiver operating characteristic curve analysis identified a DASI-MET threshold of ≤/>7.4 to optimally predict adequate exercise stress (sensitivity=93%, specificity=71%). In conclusion, the DASI correlates with peak METs, ET, and %PMHR among patients referred for exercise testing and can be used to identify patients with an increased likelihood of an inadequate stress test result.

Pilot study: evaluation of the effect of functional electrical stimulation cycling on muscle metabolism in nonambulatory people with multiple sclerosis.

OBJECTIVE: To investigate the changes in muscle oxygen consumption (mV˙O2) using near-infrared spectroscopy (NIRS) after 4 weeks of training with functional electrical stimulation (FES) cycling in nonambulatory people with multiple sclerosis (MS). DESIGN: Four-week before-after trial to assess changes in mV˙O2 after an FES cycling intervention. SETTING: Rehabilitation hospital. PARTICIPANTS: People (N=8; 7 men, 1 women) from a volunteer/referred sample with moderate to severe MS (Expanded Disability Status Scale score>6.0). INTERVENTION: Participants cycled 30 minutes per session, 3d/wk for 4 weeks or a total of 12 sessions. MAIN OUTCOME MEASURES: mV˙O2 of the right vastus lateralis muscle was measured with NIRS before and within 1 week after the intervention. Six bouts of 15-second electrical stimulation increasing from 2 to 7Hz were used to activate the muscle. mV˙O2 was assessed by analyzing the slope of the NIRS oxygen signal during a 10-second arterial occlusion after each electrical stimulation bout. RESULTS: Significant FES training by electrical stimulation frequency level interaction was observed (P=.031), with an average increase in mV˙O2 of 47% across frequencies with a main effect of training (P=.047). CONCLUSIONS: FES cycling for 4 weeks improved mV˙O2, suggesting that FES cycling is a potential therapy for improving muscle health in people with MS who are nonambulatory.

A cross-validation of near-infrared spectroscopy measurements of skeletal muscle oxidative capacity with phosphorus magnetic resonance spectroscopy.

The purpose of this study was to cross-validate measurements of skeletal muscle oxidative capacity made with near-infrared spectroscopy (NIRS) measurements to those made with phosphorus magnetic resonance spectroscopy ((31)P-MRS). Sixteen young (age = 22.5 ± 3.0 yr), healthy individuals were tested with both (31)P-MRS and NIRS during a single testing session. The recovery rate of phosphocreatine was measured inside the bore of a 3-Tesla MRI scanner, after short-duration (∼10 s) plantar flexion exercise as an index of skeletal muscle oxidative capacity. Using NIRS, the recovery rate of muscle oxygen consumption was also measured using repeated, transient arterial occlusions outside the MRI scanner, after short-duration (∼10 s) plantar flexion exercise as another index of skeletal muscle oxidative capacity. The average recovery time constant was 31.5 ± 8.5 s for phosphocreatine and 31.5 ± 8.9 s for muscle oxygen consumption for all participants (P = 0.709). (31)P-MRS time constants correlated well with NIRS time constants for both channel 1 (Pearson's r = 0.88, P < 0.0001) and channel 2 (Pearson's r = 0.95, P < 0.0001). Furthermore, both (31)P-MRS and NIRS exhibit good repeatability between trials (coefficient of variation = 8.1, 6.9, and 7.9% for NIRS channel 1, NIRS channel 2, and (31)P-MRS, respectively). The good agreement between NIRS and (31)P-MRS indexes of skeletal muscle oxidative capacity suggest that NIRS is a valid method for assessing mitochondrial function, and that direct comparisons between NIRS and (31)P-MRS measurements may be possible.