Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

Are dynamic measurements of central venous pressure in Fontan circulation during exercise or volume loading superior to resting measurements?

Venna A, Deshpande S, Downing T, John A, d’Udekem Y. Cardiol Young. 2023 Nov 20:1-12. doi: 10.1017/S1047951123003797. Online ahead of print. PMID: 37981897

Take Home Points:

  • Predicting morbidity and mortality in patients with a Fontan circulation is challenging and imprecise, with limited data regarding dynamic Fontan pressure measurements and outcomes
  • In the current review, 26 studies were identified to have sufficient data to investigate the relationship between elevated resting central venous or pulmonary pressures after Fontan completion and adverse outcomes, while a further 10 studies examined the relationship between exercise or volume loading and outcomes
  • Nine studies observed significantly higher central venous pressures in patients with worse outcomes, supporting the belief that central venous and pulmonary pressures will rise during failure of the Fontan circulation; however, we are yet to identify useful cut-off values above which long-term adverse outcomes can be predicted
  • The additional use of dynamic testing demonstrates a great variation in the slope of increase of central pressures under these conditions but may have the potential to unmask patients with occult diastolic dysfunction or increasing pulmonary vascular resistance and warrants further prospective studies.
Dr Timothy Roberts

Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:

The aim of the current paper was to review published literature evaluating the relationship between resting pressure in the Fontan circuit and outcomes related to Fontan failure. Furthermore, the review sought to explore the relationship between dynamic measurement by volume loading or exercise and outcomes, which may have the potential to improve identification of those at greater risk.

A PubMed search was performed, and studies were considered eligible if analysis was performed between post-operative resting central venous pressure or pulmonary artery pressure and markers of Fontan failure, or between exercise or volume load on the heart and measured central venous pressure or pulmonary artery pressure following a Fontan operation. All articles between 1976 and January 2023 were included. Non-English studies, those who had not yet reached Fontan completion, and case reports or review papers were excluded.

A total of 441 articles were reviewed for eligibility, of which 26 met inclusion criteria for resting evaluation; only two of these 26 were prospective studies. Ten articles were identified to correlate exercise or volume loading to outcomes, seven of these being prospective.

Elevated central venous pressure/pulmonary artery pressure and risk of mortality or heart transplant

  • Nine studies examined this relationship with only three clearly identifying elevated pressures being predictive of premature death; one of these studies found that central venous pressure ³16 mmHg was an independent predictor of death, but only in patients with a median follow-up time of 1 year.
  • Another study showed higher pulmonary artery pressure was predictive of need for heart transplantation.
  • Two implied better outcomes in patients with lower central venous pressures.

Elevated central venous pressure/pulmonary artery pressure and protein-losing enteropathy

  • Six studies analyzed this relationship and only one positively identified elevated central venous pressure as a risk factor for developing protein-losing enteropathy; in this study of 26 patients with PLE out of a cohort of 354 patients, CVP ³ 12 mmHg measured one-year post-operatively was associated with a 39 times greater risk of developing PLE.
  • Four studies observed elevated systemic venous pressures in patients already diagnosed with protein-losing enteropathy.

Elevated central venous pressure/pulmonary artery pressure and Fontan-associated liver disease

  • Ten studies identified a relationship between elevated systemic venous pressures and symptoms related to liver failure, but only two demonstrated a predictive relationship.

Exercise and central venous pressure/pulmonary artery pressure

  • Two retrospective and three prospective studies assessed central venous pressure or pulmonary artery pressure during various exercise stress tests
    • Mean PA pressure increased from 16 mmHg at rest to 25 mmHg at peak exercise in one group of six patients with Fontan circulation (p=0.001).
    • Mean PA pressure rose from 9 to 21 mmHg in another cohort of Fontan circulation patients, while healthy controls had higher resting and exercise pressure.
    • A wide variation in systemic venous pressures between controls and patients with a Fontan circulation was observed by another group with even a minimal amount of exercise; an increase in central venous pressure of 5-10 mmHg with exercise was observed in controls while elevations were significantly more pronounced in patients with Fontan circulation
    • One study of 29 symptomatic patients with Fontan circulation analyzed hemodynamic parameters during exercise and constructed a “vascular reserve index,” extracted from the change during exercise in the ratio between pulmonary artery pressures and cardiac output; pulmonary vascular reserve was impaired in these patients during exercise, and the exercise limitations were associated with end-organ dysfunction.

Volume loading and central venous pressure/pulmonary artery pressure

  • Four prospective and one retrospective study investigated this relationship.
  • A significant increase in pressure following rapid volume loading was generally observed, but with notable variability in individual responses.
  • One group labelled those with a baseline systemic ventricular end-diastolic pressure less than 15 mmHg that increased above 15 mmHg after volume loading as having occult diastolic dysfunction; subsequent evaluation of these patients found occult diastolic dysfunction to be associated with late adverse outcomes related to Fontan failure.

Cumulatively, nine studies observing significantly higher central venous pressures in patients with worse outcomes strongly supports the belief that central venous and pulmonary pressures will rise during failure of the Fontan circulation; confounders including general anesthesia during catheterization, fasting status, use of contrast agents and medications could contribute to variations between study findings reported, as well as many studies having very small patient numbers which limits statistical analysis. Nonetheless, we are yet to identify useful cut-off values above which long-term adverse outcomes can be predicted. The additional use of dynamic testing has demonstrated a great variation in the slope of increase of central pressures under these conditions but has the potential to unmask patients who have occult diastolic dysfunction or increasing pulmonary vascular resistance and warrants further prospective studies.