Jain CC, Egbe AC, Allison TG, van de Bruaene A, Borlaug BA, Connolly HM, Burchill LJ, Miranda WR. Am J Cardiol. 2024 Dec 1;232:82-88. doi: 10.1016/j.amjcard.2024.09.005. Epub 2024 Sep 6.PMID: 39245333
Take-home Points:
- In patients with Fontan physiology, lower peak heart rate, peak VO2 and %predicted VO2 on CPET were associated with worse hemodynamics
- Oxygen pulse on CPET correlated with invasively measured stroke volume but not AVO2 difference
- There was no association between VE/VCO2 slope and invasive hemodynamics
- Peak VO2 ≤ 19.2mL/kg/min and %predicted VO2 ≤ 48% had sensitivity and specificity of roughly 81% and 75% respectively for abnormal exercise hemodynamics.
Commentary by Dr. Joshua Price (Vermont, USA), section editor of ACHD Journal Watch:
Introduction: The authors note that exercise limitation is nearly universal in adults after Fontan palliation and that cardiopulmonary exercise test (CPET) is increasingly being utilized for prognostic guidance and management decisions. In acquired heart disease there is ample evidence describing the correlation between invasive hemodynamics and CPET data, but the same information is not available for patients with Fontan physiology. This study aims to correlate CPET data with invasive exercise hemodynamics in adults after Fontan palliation and identify cut off values for peak oxygen consumption (pVO2) that correlates with abnormal invasive exercise hemodynamics.
Study Design: This is a retrospective single center review of all patients over the age of 18 with Fontan palliation who had treadmill CPET prior to invasive exercise cardiac catheterization between November 2018 and April 2023. Correlations between CPET and invasive hemodynamics were performed with linear regression and optimal peak VO2 for diagnosis of abnormal exercise hemodynamics were assessed with receiving operator curves.
Key Findings:
- 55 patients with mean age of 32 were included, including 8 patients with atriopulmonary Fontan. 19 patients had NYHA functional class II or IV. 13 has at least moderate AV valve regurgitation. 20 patients had previously undergone pacemaker placement.
- Invasive hemodynamics at rest showed a mean PA pressure of 13.7mmHg and PAWP of 9mmHg. Cardiac index at rest was 2.8 l/min/m2. With exercise, mean PA pressure increased to 26, PAWP increased to 20. Peak heart rate was 110 bpm and stroke volume index were 45mL/m2 with Vo2 of 1004 mL/min.
- CPET data showed a mean RER of 1.13 with exercise time of 7.1 minutes. Peak heart rate of 140 bpm with peak VO2 of 19ml/kg/min, 47% predicted. VO2/HR was 10.5 (ml/kg/min)/bpm and VE/VCO2 slope was 33.
- Peak heart rate and peak VO2 from CPET correlated well exercise PA pressure and PAWP. VO2/heart rate (oxygen pulse) correlated well with stroke volume index, but not with invasive AVO2 difference.
- A peak VO2 of less than 19.1 mL/kg/min and peak VO2 less than 48% predicted had a sensitivity of roughly 81% and specificity of 75% (area under the curve of approximately 0.8) for predicting abnormal exercise hemodynamics.
Strengths:
- Comprehensive evaluation of both CPET parameters and invasive hemodynamics in patients with Fontan physiology.
- Hypothesis generating for potential mechanisms of exercise intolerance in Fontan patients and potential future targets for intervention.
Limitations:
- Single center study, retrospective design with relatively small number of subjects
- 15% of subjects had history of atriopulmonary Fontan connection which is less commonly seen in modern cohorts.
Discussion:
This important work is the first study to describe both CPET parameters and invasive exercise hemodynamics in patients with Fontan physiology. Many theories have been proposed for mechanisms of exercise intolerance in these patients and this study starts to lend evidence for and against these theories. In this cohort, peak heart rate has the strongest correlation with invasive hemodynamics. In preload starved Fontan patients, the ability to augment stroke volume is impaired making heart rate an important driver of overall exercise capacity. Paradoxically, however, further increased heart rate may lead to further reduction in stroke volume leaving total cardiac output unchanged and further work will be needed to investigate this further.
This work also shows that several parameters known to have prognostic importance in acquired heart disease, do not correlate well with invasive hemodynamics in this patient population. VE/VCO2 slope, often considered a marker of pulmonary vascular dysfunction and pulmonary congestion in acquired heart disease, did not correlate with exercise pulmonary artery pressures or pulmonary artery wedge pressures. Similarly, the oxygen uptake efficiency slope (OUES) and VO2 at anaerobic threshold did not correlate with hemodynamics which was perhaps unexpected.
Finally, using receiving operator curves, the authors demonstrate that a peak VO2 ≤ 19.2mL/kg/min and %predicted VO2 ≤ 48% had sensitivity and specificity of roughly 81% and 75% respectively for abnormal exercise hemodynamics. This corresponds with an area under the curve of approximately 0.8. Cutoffs for abnormal pVO2 are not well defined in Fontan patients in this study adds to the growing body of literature around this topic.
Conclusion:
Acknowledging limitations inherent to single center retrospective study designs and the inability to show causal relationships, this is an important work to better understand hemodynamics associated with exercise intolerance in patients with Fontan physiology. Further work will be needed to confirm these findings and potentially identify targets to improve exercise capacity in these complex individuals.
