Hemodynamic causes of exercise intolerance in Fontan patients.

Exercise intolerance is frequent among Fontan patients and an important determinant for quality of life. This study investigated the hemodynamic causes of impaired exercise capacity in Fontan patients with particular focus on the influence of stroke volume index (SVI) and heart rate (HR). In 38 Fontan patients, peak oxygen consumption (VO2), SVI and HR were recorded during incremental load exercise test and compared with 19 age and gender matched controls. SVI (ml/m(2)) was lower in patients than controls during warm-up (28[26-31] vs. 35[30-39], p=0.0093), at submaximal (40[37-43] vs. 55[51-59], p<0.0001) and at maximal exercise (38[35-40] vs. 54[51-58], p<0.0001). Similarly, HR (% of expected maximum) was lower in patients at warm-up (45[43-48]% vs. 64[57-64]%, p<0.0001), submaximal (71[68-75]% vs 85[82-88]%, p<0.0001) and maximal exercise (84[80-88]% vs. 97[95-99]%, p<0.0001). Furthermore, SVI dropped 14% (from 44[41-48] to 38[35-40] ml/m(2)) in Fontan patients from the peak plateau to maximal exercise vs. 5% (from 57[53-61] to 54[51-58] ml/m(2)) in controls, p<0.0001. The low SVI and HR explained 67% and 20% of the difference in peak VO2 between Fontan patients and controls respectively. SVI decreased significantly in Fontan patients near the end of maximal effort exercise. The low SVI at maximal exercise was the most important hemodynamic factor limiting exercise capacity in Fontan patients, whereas chronotropic impairment had a smaller impact. The low SVI and HR at maximal exercise accounted for the difference in peak VO₂ between Fontan patients and controls in this study. http://www.cvk.sum.dk/CVK/Home/English.aspx (protocol nr: H-3-2010-045).

Hebert A ，Jensen AS ，Mikkelsen UR ，Idorn L ，Sørensen KE ，Thilen U ，Hanseus K ，Søndergaard L ... -  《-》

Relation of systemic venous return, pulmonary vascular resistance, and diastolic dysfunction to exercise capacity in patients with single ventricle receiving fontan palliation.

Fontan patients have a reduced exercise capacity, primarily owing to limitations in the ability to augment pulmonary blood flow and stroke volume. To date, the mechanism of peak exercise pulmonary blood flow restriction has not been elucidated. We performed a single-center, prospective, crossover trial of supine and upright exercise in Fontan patients and healthy controls to determine the mechanisms of exercise limitation in the Fontan-palliated patient. A total of 29 Fontan patients and 16 control subjects completed the protocol. The duration of exercise, percentage of predicted peak oxygen consumption (VO(2)) and peak work were reduced in the Fontan group, regardless of posture (p < or = 0.03). The percentage of predicted oxygen pulse, a surrogate for pulmonary stroke volume, was not increased with supine posture in the Fontan cohort (upright, 82.3 + or - 18.8% vs supine, 82.4 + or - 19.7%; p = 0.6). In both groups, the percentage of predicted peak VO(2) was lower with supine exercise than with upright exercise (p < or =0.002). Diastolic dysfunction was present in 57% of the Fontan patients and was associated with a reduced percentage of predicted peak VO(2) (p = 0.04) and supine peak work (p = 0.008). Six Fontan patients who underwent supine exercise with indwelling catheters failed to demonstrate the expected decrease in pulmonary vascular resistance characteristically seen with peak exercise (at rest, 2.8 + or - 0.7 mm Hg/L/min/m(2) vs at peak, 2.8 + or - 0.9 mm Hg/L/min/m(2); p = 0.9). In conclusion, supine exercise in Fontan patients does not result in an increased VO(2) or oxygen pulse, suggesting that inadequate venous return might not be the primary limitation of exercise capacity in this population. Diastolic dysfunction and relatively excessive peak exercise pulmonary vascular resistance might be more important factors in Fontan exercise limitation.

Goldstein BH ，Connor CE ，Gooding L ，Rocchini AP ... -  《-》

Usefulness of stroke volume monitoring during upright ramp incremental cycle exercise in young patients with Fontan circulation.

Aerobic capacity (VO2 max) of patients with Fontan circulation (FC) is lowest within patients with congenital heart disease. The reasons have not been completely elucidated. Twenty five young patients with non-failing FC underwent a cardiopulmonary test during an upright ramp cycling. By using a signal morphology impedance cardiography device (physioflow®), stroke volume (SV) was evaluated along with effort. The results were compared with paired healthy controls. FC patients had lower VO2 max (24 vs 32ml/Kg/min) and maximal cardiac index (CI) (6.4 vs 9.9l/min/m2) than controls, due to impaired maximal SV (42 vs 54ml/m2) and maximal Heart Rate (HR) (154 vs 184/min) (p<0.001). No correlation between SV and HR at peak was found. At ventilatory threshold, SV continued to rise in a part of FC patients. Other FC patients showed an almost a "plateau" as in controls. The more maximal CI was impaired, the more was maximal arterio-venous difference (r=-0.6, p=0.001). Compared to controls, stroke work was lower in FC patients (p<0.01) even though maximal vascular resistance was higher in them (p<0.001). Impaired SV and chronotropic incompetence are both independently responsible for impaired CI at peak. The increase in arteriovenous difference appeared to be an adaptive response. As the stroke work was low among FC patients, high systemic vascular resistance does not appear to be the cause of SV impairment but rather a consequence. SV monitoring at effort evidences heterogeneous SV profiles among FC patients that could be considered for the management of patients.

Legendre A ，Guillot A ，Ladouceur M ，Bonnet D ... -  《-》

Mechanism for temporal changes in exercise capacity after Fontan palliation: Role of Doppler echocardiography.

The objective was to better understand Doppler hemodynamics and exercise capacity in patients with Fontan palliation by delineating the hemodynamic mechanism for temporal changes in their peak oxygen consumption (V̇o2). We performed a retrospective review of adult Fontan patients with systemic left ventricle (LV) who underwent serial transthoracic echocardiograms (TTE) and cardiopulmonary exercise tests (CPET) at Mayo Clinic in 2000-2015. TTE and CPET data were used (1) to determine agreement between V̇o2 and Doppler-derived LV function indices (eg, stroke volume index [SVI] and cardiac index [CI]) and (2) to determine agreement between temporal changes in peak V̇o2 and LV function indices. Seventy-five patients (44 men; 59%) underwent 191 pairs of TTE and CPET. At baseline, mean age was 24±3 years, peak V̇o2 was 22.9±4.1 mL/kg/min (63±11 percent predicted), SVI was 43±15 mL/m2, and CI was 2.9±0.9 L/min/m2. Peak V̇o2 correlated with SVI (r=0.30, P<.001) and with CI (r=0.45, P<.001) in the 153 pairs of TTE and CPET in patients without cirrhosis. Temporal changes in percent predicted peak V̇o2 correlated with changes in SVI (r=0.48, P=.005) and CI (r=0.49, P=.004) among the 33 patients without interventions during the study. In the 19 patients with Fontan conversion, percent predicted peak V̇o2 and chronotropic index improved. Overall, there was a temporal decline in peak V̇o2 that correlated with decline in Doppler SVI. In the patients who had Fontan conversion operation, there was a temporal improvement in peak V̇o2 that correlated with improvement in chronotropic index.

Egbe A ，Khan AR ，Miranda WR ，Ammash NM ，Warnes CA ，Said SS ，Taggart NW ，Akintoye E ，Veldtman GR ，Connolly HM ... -  《-》

Effect of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension on stroke volume response to exercise.

In pulmonary hypertension, exercise is limited by an impaired right ventricular (RV) stroke volume response. We hypothesized that improvement in exercise capacity after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is paralleled by an improved RV stroke volume response. We studied the extent of PEA-induced restoration of RV stroke volume index (SVI) response to exercise using cardiac magnetic resonance imaging (cMRI). Patients with CTEPH (n = 18) and 7 healthy volunteers were included. Cardiopulmonary exercise testing and cMRI were performed before and 1 year after PEA. For cMRI studies, pre- and post-operatively, all patients exercised at 40% of their preoperative cardiopulmonary exercise testing-assessed maximal workload. Post-PEA patients (n = 13) also exercised at 40% of their postoperative maximal workload. Control subjects exercised at 40% of their predicted maximal workload. Preoperatively, SVI (n = 18) decreased during exercise from 35.9 ± 7.4 to 33.0 ± 9.0 ml·m(2) (p = 0.023); in the control subjects, SVI increased (46.6 ± 7.6 vs 57.9 ± 11.8 ml·m(-2), p = 0.001). After PEA, the SVI response (ΔSVI) improved from -2.8 ± 4.6 to 4.0 ± 4.6 ml·m(2) (p <0.001; n = 17). On exercise at 40% of the postoperative maximal workload, SVI did not increase further and was still significantly lower compared with controls. Moreover, 4 patients retained a negative SVI response, despite (near) normalization of their pulmonary hemodynamics. The improvement in SVI response was accompanied by an increased exercise tolerance and restoration of RV remodeling. In conclusion, in CTEPH, exercise is limited by an impaired stroke volume response. PEA induces a restoration of SVI response to exercise that appears, however, incomplete and not evident in all patients.

Surie S ，van der Plas MN ，Marcus JT ，Kind T ，Kloek JJ ，Vonk-Noordegraaf A ，Bresser P ... -  《-》