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Commentary on Claessen et al. (2019): “Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?” (PMID: 31041880)

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Claessen et al. (1) suggest that the apparent chronotropic incompetence in Fontan patients may be secondary to a reflex mechanism that diminishes the heart rate increase rather than due to SA nodal dysfunction.  Claessen et al. evoke the reverse Bainbridge reflex (heart rate response to a fall in CVP back toward baseline CVP) as a possible explanation for the lower peak heart rate in Fontan patients (1).  This is quite possible if central venous pressure were elevated at baseline, and indeed fell during exercise in the Fontan patients in this study.  The Bainbridge reflex is noted to be independent of autonomic innervation (1).  To clarify, the Bainbridge reflex is abolished by vagotomy, so it is neurally mediated. (2)

In the study by Claessen et al (1), data in Tables 1 and 3 suggest that ventricular end-diastolic volume (EDV) during supine bicycling exercise did not fall critically relative to baseline; thus, a Bezold-Jarisch reflex (3) evoked by a hypercontracting poorly filled ventricle seems less likely to explain the lower peak heart rate in patients with Fontan physiology.

However, arterial O2 saturation dropped during exercise to 94.3 +/- 1.2% [mean (1 SD)] in patients with Fontan physiology (1, data in Tables 1 and 3). Therefore, based on the normal relationship between PaO2 and percentage saturation of hemoglobin with oxygen, at least some Fontan patients must have had an exercise PaO2 < 70 mm Hg, a PaO2 at which activation of the systemic arterial chemoreceptor reflex evokes vasoconstriction and a vagally mediated lowering of heart rate, though the heart rate response to hypoxemia is also affected by the prevailing ventilation (4).  Although the mean systemic arterial pressure (mSAP) in Fontan patients during exercise was 106 mm Hg, significantly greater than the pre-exercise mean, this does not rule out the possibility of a transient fall in mSAP during exercise due to a drop in systemic vascular resistance from actions of products of metabolism and possibly arterial hypoxemia.  Thus, it would be useful to know what continuous systemic BP measurements during exercise indicated in this regard in Fontan patients.  Some studies (example, ref. 5) have documented arterial desaturation during peak exercise in patients with Fontan physiology.  If transient hypotension, arterial hypoxemia, and or acidosis occurred during exercise in Fontan patients in this study, the interaction of the systemic arterial chemoreceptor reflex (which induces vasoconstriction and a decrease in heart rate) and the arterial baroreceptor reflex (which induces vasoconstriction and an increase in heart rate) under these circumstances might at least in part underlie the lower maximal heart rate observed during exercise in patients with Fontan physiology.

E.S.Prakash, MBBS

Conflict of interests: None

References:

  1. Claessen G, La Gerche A, Van De Bruaene A, Claeys M, Willems R, Dymarkowski S, et al. Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation? J Am Heart Assoc 2019 May 7; 8(9). Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512107/ 
  2. Bainbridge FA. The influence of venous filling upon the rate of the heart. J Physiol [Internet]. 1915 Dec 24;50(2):65–84. Available from: http://doi.wiley.com/10.1113/jphysiol.1915.sp001736
  3. Warltier DC, Campagna JA, Carter C. Clinical Relevance of the Bezold–Jarisch Reflex: Anesthesiology [Internet]. 2003 May [cited 2019 May 19];98(5):1250–60. Available from: http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1943118 
  4. Daly M de B, Scott MJ. The cardiovascular responses to stimulation of the carotid body chemoreceptors in the dog. J Physiol [Internet]. 1963 Jan 1 [cited 2019 May 19];165(1):179–97. Available from: http://doi.wiley.com/10.1113/jphysiol.1963.sp007051
  5. Troutman WB, Barstow TJ, Galindo AJ, Cooper DM. Abnormal Dynamic Cardiorespiratory Responses to Exercise in Pediatric Patients After Fontan Procedure. J Am Coll Cardiol [Internet]. 1998 Mar [cited 2019 May 19];31(3):668–73. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0735109797005457