Background
Some patients with markedly reduced ejection fractions (EFs) (<35%) have preserved exercise performance greater than predicted for age and gender. Because diastolic function may be a determinant of exercise performance, this study was conducted to test the hypothesis that patients with preserved exercise tolerance despite EFs < 35% may have relatively normal diastolic function.
Methods
Sixty-five subjects with EFs < 35% who underwent exercise Doppler echocardiography and had no inducible ischemia were retrospectively examined. Forty-five subjects with normal EFs (>60%) and preserved exercise capacity were analyzed as a control group.
Results
Sixteen of 65 patients with EFs < 35% had greater than predicted normal exercise capacity for their age and gender, and the remaining 49 patients had reduced exercise capacity. Patients with reduced EFs and preserved exercise capacity had E/e′ ratios (mean, 10 ± 4) similar to those of control subjects (mean, 10 ± 3) and lower than those with reduced exercise tolerance (mean, 16 ± 8) ( P < .01). In addition, they had better diastolic filling patterns and smaller left atrial sizes than patients with EFs < 35% and reduced exercise capacity. Multivariate logistic regression analyses indicated that E/e′ ratio was an independent predictor of preserved exercise capacity in patients with reduced EFs.
Conclusions
Relatively intact diastolic function contributes to preserved exercise capacity in patients with reduced EFs (<35%).
Reduced exercise tolerance is a key symptom of patients with heart failure (HF) and is common among those with HF with reduced ejection fractions (EFs). Normally, during exercise, an increase in left ventricular (LV) suction allows a larger stroke volume (SV) to fill the left ventricle without an increase in left atrial pressure to abnormal levels. This normal response is reduced in the presence of HF, either with a reduced or with a preserved EF. This suggests that diastolic dysfunction may be one of the factors that contribute to exercise intolerance in patients with HF with reduced EF (HFrEF).
Some patients with reduced EFs have preserved exercise capacity. Furthermore, some patients with reduced EFs have no clinical manifestations of HF (i.e., stage B HF). We hypothesized that if LV diastolic function is an important determinant of exercise tolerance, relatively normal diastolic function is necessary for patients with reduced EFs to have preserved exercise capacity.
Methods
Patients
This study was approved by the institutional review board at Wake Forest School of Medicine. We retrospectively analyzed patients with LV EFs < 35% who underwent clinically indicated treadmill exercise stress echocardiography between June 2006 and March 2011 at Wake Forest Baptist Medical Center. Patients with inducible ischemia, mitral stenosis, severe mitral regurgitation, prosthetic mitral valves, histories of mitral valve repair, or aortic stenosis were excluded. Sixty-five subjects met our criteria and were included in this study. Forty-five subjects who underwent exercise echocardiography during the same period with normal EFs (>60%) and preserved age- and gender-predicted exercise capacity were studied as the control group. They underwent exercise echocardiography to evaluate chest pain but were found to have no inducible ischemia. These subjects were similar in age (mean, 61 ± 9 years) and gender (31% men) to the patients with reduced EFs.
Echocardiography
Patients underwent symptom-limited treadmill exercise stress echocardiography using the modified Bruce incremental exercise protocol. The predicted exercise capacity on the basis of age and gender in metabolic equivalents was calculated according to a previous report. The exercise capacity of the patients in metabolic equivalents from the stage reached was compared with predicted exercise capacity. Preserved exercise capacity was defined as ≥100% of predicted exercise capacity on the basis of age and gender.
A complete two-dimensional (2D) Doppler echocardiographic examination was performed before exercise using an iE33 ultrasound system with a multiple-frequency transducer (Philips Medical Systems, Andover, MA). An experienced cardiologist (T.O.) measured the images without knowledge of clinical or exercise data. The grade of mitral regurgitation was evaluated qualitatively (none, trace, mild, moderate, or severe). LV end-systolic and end-diastolic volumes, SV and EF were calculated using a modified Simpson method. Transmitral and tissue Doppler parameters were measured from the apical four-chamber view using standard American Society of Echocardiography criteria. Doppler gain and filter settings were optimized to facilitate the clearest demarcation of velocity profiles. Mitral annular peak velocities at early (e′) and late (a′) diastole and systole (s′) were measured using pulsed-wave tissue Doppler as the mean of septal and lateral values. Diastolic function was assessed as grade 1 (impaired relaxation), 2 (pseudonormal filling), or 3 (restrictive filling) using the e′ and E/e′ values according to American Society of Echocardiography and European Association of Echocardiography guidelines. LV chamber stiffness ( K LV ) was calculated using mitral inflow deceleration time as previously reported :
K LV ( mm Hg/mL ) = ( Deceleration time − 0.02 s 0.07 ) − 2
LV mass was calculated using 2D parameters. To evaluate right ventricular function, tricuspid annular plane systolic excursion (TAPSE) was measured using the 2D frames of the apical four-chamber view at end-diastole and end-systole.
Hemodynamics
Heart rate and noninvasively measured systolic and diastolic blood pressure (BPs) were recorded just before exercise and during exercise. Systemic vascular resistance was estimated using the formula
Systemic vascular resistance = Mean BP × 80 / Cardiac output ( dyne · sec · cm − 5 ) ,
The ratio of SV to brachial pulse pressure was used as an indirect measure of total systemic arterial compliance, which is indicative of a pulsatile component of LV afterload :
Systemic arterial compliance = SV / Pulse pressure ( mL / mm Hg ) .
Effective aortic elastance, a measure of pulsatile and nonpulsatile LV afterload, was estimated using the formula
Effective aortic elastance = End – systolic BP / SV ( mm Hg / mL ) ,
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