Corey R. Tomczak

Determinants of Exercise Intolerance in Patients with Heart Failure and Reduced or Preserved Ejection Fraction

This mini-review summarizes the literature regarding the mechanisms of exercise intolerance in patients with heart failure and reduced or preserved ejection fraction (HFREF and HFPEF, respectively). Evidence to date suggests that the reduced peak pulmonary oxygen uptake (pulm V̇o₂) in patients with HFREF compared with healthy controls is due to both central (reduced convective O₂ transport) and peripheral factors (impaired skeletal muscle blood flow, decreased diffusive O₂ transport coupled with abnormal skeletal morphology, and metabolism). Although central and peripheral impairments also limit peak pulm V̇o₂ in HFPEF patients compared with healthy controls, emerging data suggest that the latter may play a relatively greater role in limiting exercise performance in these patients. Unlike HFREF, currently there is limited evidence-based therapies that improve exercise capacity in HFPEF patients, therefore future studies are required to determine whether interventions targeted to improve peripheral vascular and skeletal muscle function result in favorable improvements in peak pulm and leg V̇o2 and their determinants in HFPEF patients.

Cardiac Reserve and Pulmonary Gas Exchange Kinetics in Patients With Stroke

Background and Purpose— Cardiovascular and pulmonary factors contributing to impaired peak oxygen uptake (&OV0312;O2) in patients with stroke (SP) are not well known. We assessed cardiovascular function, pulmonary gas exchange, and ventilation in SP and healthy age, gender, and activity-matched control subjects. Methods— Ten hemiparetic SP and 10 control subjects were enrolled. Subjects completed cycle ergometry testing to assess peak and reserve &OV0312;O2, carbon dioxide production, ventilation (tidal volume; breathing frequency; minute ventilation), and cardiac output. &OV0312;O2, carbon dioxide production, and minute ventilation were measured throughout peak exercise recovery (off-kinetics) and at exercise onset (on-kinetics) along with heart rate during low-level exercise. Results— Peak &OV0312;O2 was 43% lower (P<0.001) in SP secondary to reduced peak and reserve cardiac output and minute ventilation. The impaired cardiac output reserve (P<0.001) was due to a 34% lower heart rate reserve (P=0.001). The impaired minute ventilation reserve (P=0.013) was due to a 41% lower tidal volume reserve (P=0.009). Stroke volume and breathing frequency reserve were preserved. &OV0312;O2 off-kinetics were 29% slower in SP (P<0.001) and related to peak &OV0312;O2 (R=−0.72, P<0.001) and peak cardiac output (R=−0.75, P<0.001) for the study group. Additionally, carbon dioxide production (P=0.016) and minute ventilation (P=0.023) off-kinetics were prolonged in SP. &OV0312;O2 on-kinetics were 29% slower (P=0.031) during low-level exercise in SP. Conclusions— The impaired peak &OV0312;O2 in SP is secondary to a decline in peak and reserve cardiac output and ventilation. Prolonged &OV0312;O2 kinetics in SP are associated in part with deconditioning and may be mediated by reduced O2 availability and/or the rate of muscle O2 use.

Effect of acute high-intensity interval exercise on postexercise biventricular function in mild heart failure

We studied the acute effect of high-intensity interval exercise on biventricular function using cardiac magnetic resonance imaging in nine patients [age: 49 ± 16 yr; left ventricular (LV) ejection fraction (EF): 35.8 ± 7.2%] with nonischemic mild heart failure (HF). We hypothesized that a significant impairment in the immediate postexercise end-systolic volume (ESV) and end-diastolic volume (EDV) would contribute to a reduction in EF. We found that immediately following acute high-intensity interval exercise, LV ESV decreased by 6% and LV systolic annular velocity increased by 21% (both P < 0.05). Thirty minutes following exercise (+30 min), there was an absolute increase in LV EF of 2.4% (P < 0.05). Measures of preload, left atrial volume and LV EDV, were reduced immediately following exercise. Similar responses were observed for right ventricular volumes. Early filling velocity, filling rate, and diastolic annular velocity remained unchanged, while LV untwisting rate increased 24% immediately following exercise (P < 0.05) and remained 18% above baseline at +30 min (P < 0.05). The major novel findings of this investigation are 1) that acute high-intensity interval exercise decreases the immediate postexercise LV ESV and increases LV EF at +30 min in patients with mild HF, and this is associated with a reduction in LV afterload and maintenance of contractility, and 2) that despite a reduction in left atrial volume and LV EDV immediately postexercise, diastolic function is preserved and may be modulated by enhanced LV peak untwisting rate. Acute high-intensity interval exercise does not impair postexercise biventricular function in patients with nonischemic mild HF.

Use of the Continuous Scale Physical Functional Performance Test in Stroke Survivors

OBJECTIVE To (1) determine the feasibility of the continuous scale physical functional performance 10-item test (CS-PFP10) for the measurement of physical function in stroke survivors, (2) characterize physical functional performance of stroke survivors and their matched controls, and (3) explore the associations among physical functional performance, ambulatory activity, and peak oxygen uptake (VO2peak). DESIGN Case control. SETTING University research setting. PARTICIPANTS Ten participants with stroke and 10 healthy controls matched for age, sex, and physical activity. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES The CS-PFP10 test was used to measure functional ability. The test requires performance of 10 serial tasks that range from low to high difficulty. The step activity monitor was used to measure absolute ambulatory activity and was reported as the average number of steps a day over a 4-day period. VO2peak was determined using a metabolic cart and a recumbent cycle ergometer. RESULTS Stroke survivors scored lower than healthy controls on all individual tasks, domains, and the total score on the CS-PFP10. Higher VO2peak was associated with higher total scores on the CS-PFP10 in both stroke survivors and controls. In stroke survivors, lower levels of impairment (as indicated by the Chedoke-McMaster stroke assessment) were associated with higher total CS-PFP10 scores. CONCLUSIONS The CS-PFP10 is a measure of physical performance that is feasible to use with ambulatory participants with stroke. Future investigations with people with stroke should explore the ability of the CS-PFP10 to provide meaningful information about change in CS-PFP10 subscales with interventions that target items on the subscales, such as balance or upper extremity strength.

Oxygen uptake kinetics: associations with ambulatory activity and physical functional performance in stroke survivors.

OBJECTIVE To explore the associations amongst the on-and-off kinetics time constants, ambulatory activity outcomes, and physical functional performance in stroke survivors. DESIGN Cross-sectional, case control study. SUBJECTS Ten stroke survivors (time since stroke: mean 7.5 years (standard deviation 8.3); gender: 4 males, 6 females) and 10 control subjects matched for age and physical activity level. METHODS Oxygen uptake kinetics (on-and-off kinetics) were measured using a submaximal exercise test with a recumbent cycle. The continuous-scale physical functional performance test was used to measure functional ability. Ambulatory activity outcomes including steps per day, number of activity bouts and length of activity bouts were measured using a Step Activity Monitor. RESULTS AND CONCLUSION Shorter activity bouts were significantly associated with longer off-kinetics time constants in stroke survivors (or longer time to recover from an exercise bout). Future research may test the effect of activity interventions designed to increase the length of activity bouts on-kinetics outcomes and functional ability.

Exercise training improves aerobic capacity, muscle strength, and quality of life in renal transplant recipients

Renal transplant recipients (RTR) have reduced peak aerobic capacity, muscle strength, arterial function and an unfavorable cardiovascular disease risk (CVD) profile. This study compared the effects of 12 weeks of supervised endurance and strength training (EST, n = 16) versus usual care (UC, n = 15) on peak aerobic capicity, cardiovascular and skeletal muscle function, CVD risk profile, and quality of life (QOL) in RTR (55 ± 13 years). Peak aerobic capacity and exercise hemodynamics, arterial compliance, 24-h blood pressure, muscle strength, lean body mass, CVD risk score, and QOL were assessed before and after 12 weeks. The change in peak aerobic capacity (EST: 2.6 ± 3.1 vs. UC: -0.5 ± 2.5 mL/(kg·min)), cardiac output (EST: 1.7 ± 2.6 vs. UC: -0.01 ± 0.8 L/min), leg press (EST: 48.7 ± 34.1 vs. UC: -10.5 ± 37.7 kg) and leg extension strength (EST: 9.5 ± 10.3 vs. UC: 0.65 ± 5.5 kg) improved significantly after EST compared with UC. The overall change in QOL improved significantly after 12 weeks of EST compared with UC. No significant difference was found between groups for lean body mass, arterial compliance, 24-h blood pressure or CVD risk score. Supervised EST is an effective intervention to improve peak exercise aerobic capacity and cardiac output, muscle strength and QOL in clinically stable RTR.

Pulmonary Oxygen Uptake and Heart Rate Kinetics During the Six-Minute Walk Test in Transplant Recipients

Background. The effect of organ transplantation on arterial compliance, pulmonary oxygen uptake (&OV0312;O2p) and heart rate kinetics during the 6-minute walk test (6-MWT) remains unknown. Methods. Twenty-two thoracic (heart and/or lung) organ transplant recipients (TOTR, 51±12 years) and 30 abdominal (kidney, kidney-pancreas, or liver) organ transplant recipients (AOTR, 46±11 years) from the 2006 Canadian Transplant Games, and 37 healthy controls (HC) completed a 6-MWT. &OV0312;O2p, heart rate kinetics, and arterial compliance were determined. Results. The 6-MWT distance and highest &OV0312;O2p were significantly lower in TOTR and AOTR versus HC. The highest 6-MWT heart rate was lower in TOTR (11%) and AOTR (13%) versus HC. &OV0312;O2p kinetics were slower in TOTR (52±11 sec, P≤0.001) and AOTR (45±24 sec, P≤0.001) versus HC (28±9 sec). Heart rate kinetics were slower in TOTR (100±49 sec) versus AOTR (41±21 sec, P≤0.001) and HC (34±21 sec, P≤0.001), but not between AOTR and HC. Small and large artery compliance were 26% (P=0.007) and 19% (P=0.004) lower, respectively, in TOTR versus HC. Large artery compliance was 14% lower in TOTR versus AOTR (P=0.017). 6-MWT distance was significantly related to &OV0312;O2p kinetics (r=−0.35) and the highest 6-MWT &OV0312;O2p (r=0.72). Conclusions. TOTR and AOTR have abnormal &OV0312;O2p kinetics, which is secondary to prolonged heart rate kinetics and impaired vascular function in TOTR, but not AOTR.

LV hypertrophy in resistance or endurance trained athletes: the Morganroth hypothesis is obsolete, most of the time

A widely accepted principle in sport cardiology is that the pattern of LV hypertrophy that occurs with athletic training is related to the type of exercise performed. This principle is based largely on the nearly four-decade-old seminal echocardiographic study by Morganroth et al who reported that the increased LV mass in highly trained (collegiate or world class) male long distance runners or swimmers compared with age-matched and sex-matched non-athlete controls was primarily due to increased LV end-diastolic volume with little or no increase in LV wall thickness ( eccentric LV hypertrophy pattern ).1 In contrast, the increased LV mass in highly trained wrestlers and shot-putters was solely due to an increased LV wall thickness as LV end-diastolic volume was normal ( concentric LV hypertrophy pattern ).1 Based on the divergent LV remodelling patterns observed, Morganroth et al 1 ,2 hypothesised that the haemodynamic burden ( volume overload ) associated with endurance exercise training (ET) may be similar to that which occurs in patients with …

Cardiac resynchronization therapy modulation of exercise left ventricular function and pulmonary O2 uptake in heart failure

To better understand the mechanisms contributing to improved exercise capacity with cardiac resynchronization therapy (CRT), we studied the effects of 6 mo of CRT on pulmonary O(2) uptake (Vo(2)) kinetics, exercise left ventricular (LV) function, and peak Vo(2) in 12 subjects (age: 56 ± 15 yr, peak Vo(2): 12.9 ± 3.2 ml·kg(-1)·min(-1), ejection fraction: 18 ± 3%) with heart failure. We hypothesized that CRT would speed Vo(2) kinetics due to an increase in stroke volume secondary to a reduction in LV end-systolic volume (ESV) and that the increase in peak Vo(2) would be related to an increase in cardiac output reserve. We found that Vo(2) kinetics were faster during the transition to moderate-intensity exercise after CRT (pre-CRT: 69 ± 21 s vs. post-CRT: 54 ± 17 s, P < 0.05). During moderate-intensity exercise, LV ESV reserve (exercise - resting) increased 9 ± 7 ml (vs. a 3 ± 9-ml decrease pre-CRT, P < 0.05), and steady-state stroke volume increased (pre-CRT: 42 ± 8 ml vs. post-CRT: 61 ± 12 ml, P < 0.05). LV end-diastolic volume did not change from rest to steady-state exercise post-CRT (P > 0.05). CRT improved heart rate, measured as a lower resting and steady-state exercise heart rate and as faster heart rate kinetics after CRT (pre-CRT: 89 ± 12 s vs. post-CRT: 69 ± 21 s, P < 0.05). For peak exercise, cardiac output reserve increased significantly post-CRT and was 22% higher at peak exercise post-CRT (both P < 0.05). The increase in cardiac output was due to both a significant increase in peak and reserve stroke volume and to a nonsignificant increase in heart rate reserve. Similar patterns in LV volumes as moderate-intensity exercise were observed at peak exercise. Cardiac output reserve was related to peak Vo(2) (r = 0.48, P < 0.05). These findings demonstrate the chronic CRT-mediated cardiac factors that contribute, in part, to the speeding in Vo(2) kinetics and increase in peak Vo(2) in clinically stable heart failure patients.

Making the Case for Skeletal Muscle Myopathy and Its Contribution to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

See Article by Weiss et al Thirty-five years ago, Robert Luchi provided the first description of heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is now the most common form of HF in older adults, particularly women, and its prevalence is increasing and its prognosis is worsening. The primary symptom in chronic HFpEF, even when patients are well compensated and nonedematous, is severe exercise intolerance, characterized by exertional fatigue and dyspnea, associated with reduced quality of life.1 Thus, understanding the pathophysiology of exercise intolerance in HFpEF is critical for improving patient-centered outcomes. Exercise intolerance can be objectively and reproducibly measured as reduced peak exercise oxygen consumption (VO2) by expired gas analysis. Using this technique, we and others have shown that the reduction in peak VO2 in HFpEF is at least as severe as in age-matched people with HF with severely reduced ejection fraction (HFrEF; mean ejection fraction, 30%).1 By the Fick equation, reduced peak VO2 must be because of either reduced cardiac output (CO), reduced arteriovenous oxygen content difference (A-VO2Diff), or a combination of these factors.2 It has conventionally been assumed that reduced exercise CO is the sole driver of exercise intolerance in HFpEF. However, we showed that reduced exercise A-VO2Diff accounts for at least 50% of the reduction in peak VO2 and is a stronger independent predictor of peak VO2 than exercise CO,3 results confirmed by several others.4 Reduced A-VO2Diff during exercise can be caused by reduced convective and diffusive oxygen delivery to exercising skeletal muscle, impaired oxygen utilization by the exercising skeletal muscle, or a combination of these factors.2 Indeed, it is now known that, as has been previously established in HFrEF, there are multiple skeletal muscle abnormalities in HFpEF …