Author + information
- Sebastiaan Holverda, MSc,
- C. Tji-Joong Gan, MSc,
- J. Tim Marcus, PhD,
- Pieter E. Postmus, MD, PhD, FCCP,
- Anco Boonstra, MD, PhD and
- Anton Vonk-Noordegraaf, MD, PhD, FCCP⁎ ()
- ↵⁎VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands
To the Editor:Most patients with idiopathic pulmonary arterial hypertension (iPAH) have severe exercise limitation, which can be explained by inefficient lung gas exchange and the inability of the heart to adequately increase pulmonary blood flow during exercise. The latter may be due to an exercise-induced increase in pulmonary artery pressure (Ppa) (1,2). It is unclear, however, to what extent cardiac function is impaired during exercise in iPAH, and whether only right ventricular (RV) function is affected by a sudden increase in Ppa. This study aimed to evaluate the effects of submaximal exercise on stroke volume (SV) and RV and left ventricular (LV) function in iPAH.
The study group consisted of 10 iPAH patients (5 female patients, age 38 ± 16 years, body surface area [BSA] 1.94 ± 0.15 m2) all in New York Heart Association functional class 3, and 10 matched healthy non-smoking control subjects (6 female subjects, age 41 ± 13 years, BSA 1.89 ± 0.16 m2) without a history of cardiopulmonary disease. The iPAH patients were stable on daily treatment at the time of examination (yearly clinical evaluation), which consisted of epoprostenol in four patients and bosentan in six patients. The protocol was approved by the VU University Medical Center Ethics Committee.
All patients underwent right heart catheterization with a Swan-Ganz catheter (131HF7, Baxter Healthcare Corp., Irvine, California). All subjects performed a maximal exercise test within four days of catheterization and magnetic resonance imaging (MRI) measurements.
Cardiac function was assessed by MRI both at rest and during submaximal exercise. The magnetic resonance images and flow measurements were acquired with a 1.5-T Siemens Sonata whole body system (Siemens Medical Solutions, Erlangen, Germany) as previously described (3), with the exception that no breathholds were used and that temporal resolution was increased to 56 ms and 35 ms, respectively, for cine imaging and flow quantification. Left ventricular stroke volume (LVSV) and right ventricular stroke volume (RVSV) were determined by assessing the flow in the aorta and main pulmonary artery, respectively. For the exercise measurements, the number of time phases in the cardiac cycle, and the velocity sensitivity were adjusted to the increased heart rate. The MRI exercise protocol consisted of a 3-min period of cycling in supine position on a recumbent bicycle (Lode, Groningen, the Netherlands). Work rate was increased in the first minute to 40% of maximal workload as previously determined during maximal exercise testing. Occurrence of exercise-induced right-to-left shunting was measured by comparing flow in the aorta and main pulmonary artery. Between exercise measurements was a 5-min resting period.
The Mann-Whitney Utest was applied for between-group analyses. To test for significance within groups between resting and exercise conditions, the Wilcoxon signed rank test was used.
Right heart catheterization in the patient group yielded a right atrial pressure and Ppa of 8 ± 5 mm Hg and 51 ± 18 mm Hg, respectively, a cardiac output (CO) of 5.7 ± 2.2 l/min, and a pulmonary vascular resistance of 720 ± 428 dynes·s−1·cm−5. Resting and exercise cardiac function parameters as measured by MRI are presented in Table 1.Resting RVSV and LVSV were larger in controls (p = 0.06 and p < 0.05, respectively). Within groups, RVSV was not significantly different from LVSV, neither at rest nor during exercise. Left ventricular end-diastolic volume (LVEDV) and right ventricular ejection fraction (RVEF) were significantly lower in iPAH.
Because the MRI exercise measurements were performed at 40% of maximal workload, this resulted in lower exercise levels in the iPAH group (42 ± 21 W) than in the controls (100 ± 37 W). In healthy controls, all cardiac parameters significantly increased to exercise with the exception of right ventricular end-diastolic volume (RVEDV) and LVEDV; iPAH patients were not able to significantly increase SV from rest to exercise (Fig. 1).Only 1 of 10 patients showed a clear increase in SV, and in most patients CO was therefore augmented by an increase in heart rate only. Right ventricular end-diastolic volume tended to increase during exercise whereas LVEDV significantly decreased in the patient group.
The finding that SV is not increased in iPAH is in agreement with an earlier imaging study in 16 patients with pulmonary hypertension in which a decrease in SV to near maximal exercise was observed (4). Another finding that provides strong evidence that SV progression during exercise is impaired in iPAH is given by a recent study showing that these patients have a reduced peak O2pulse during cardiopulmonary exercise testing (5).
Stroke volume is determined by both contractility and end-diastolic volume. In controls, RVEDV and LVEDV remained stable during exercise whereas end-systolic volume decreased, showing that the augmentation of SV in this group was due to increased myocardial contractility. In contrast, the iPAH patients were not able to augment SV to exercise, in spite of a small increase in RVEDV, and a decrease in LVEDV. The decrease in LVEDV can be explained by two mechanisms. First, because the RV and LV are enclosed in a relatively non-distensible pericardium and separated by the interventricular septum, changes in one ventricular volume will directly influence the other (6). Total cardiac end-diastolic blood volume did not change from rest to exercise (250 ± 57 ml and 248 ± 60 ml, respectively). Therefore, exercise-induced changes in RVEDV and pressure-mediated septal curvature will interfere with LV diastolic filling leading to a decrease in LVEDV (7). Second, a reduction of RVEF to exercise in iPAH patients provides evidence that RV failure becomes more manifest during exercise. Forward failure of the RV will also hamper an adequate filling of the LV. In the absence of invasive pressure measurements including pulmonary capillary wedge pressure, it remains unclear which mechanism contributed most to the exercise-induced underfilling of the LV.
We conclude that in patients with iPAH an exercise-induced rise in Ppa results in further impairment of RV function and underfilling of the LV, both leading to a failing SV response to exercise.
- American College of Cardiology Foundation
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