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Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?

ABSTRACT: Background Patients with a Fontan circulation achieve lower peak heart rates ( HR ) during exercise. Whether this impaired chronotropic response reflects pathology of the sinoatrial node or is a consequence of altered cardiac hemodynamics is uncertain. We evaluated the adequacy of HR acceleration throughout exercise relative to metabolic demand and cardiac output in patients with a Fontan circulation relative to healthy controls. Methods and Results Thirty subjects (20 healthy controls and 10 Fontan patients) underwent cardiac magnetic resonance imaging with simultaneous invasive pressure recording via a pulmonary and radial artery catheter during supine bicycle exercise to near maximal exertion. Adequacy of cardiac index, stroke volume, and HR reserve was assessed by determining the exercise-induced increase (?) in cardiac index, stroke volume, and HR relative to the increase in oxygen consumption ( VO 2). HR reserve was lower in Fontan patients compared with controls (71±21 versus 92±15 bpm; P=0.001). In contrast, increases in HR relative to workload and VO 2 were higher than in controls. The change in cardiac index relative to the change in VO 2 (?cardiac index/? VO 2) was similar between groups, but Fontan patients had increased ? HR /? VO 2 and reduced ? stroke volume/? VO 2 compared with controls. There was an early and marked reduction in stroke volume during exercise in Fontan patients corresponding with a plateau in cardiac output at a low peak HR . Conclusions In Fontan patients, the chronotropic response is appropriate relative to exercise intensity, implying normal sinoatrial function. However, premature reductions in ventricular filling and stroke volume cause an early plateau in cardiac output beyond which further increases in HR would be physiologically implausible. Thus, abnormal cardiac filling rather than sinoatrial node dysfunction explains the diminished HR reserve in Fontan patients.

SUBMITTER: Claessen G

PROVIDER: S-EPMC6512107 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?

Claessen Guido G La Gerche Andre A Van De Bruaene Alexander A Claeys Mathias M Willems Rik R Dymarkowski Steven S Bogaert Jan J Claus Piet P Budts Werner W Heidbuchel Hein H Gewillig Marc M

Journal of the American Heart Association 20190501 9

Background Patients with a Fontan circulation achieve lower peak heart rates ( HR ) during exercise. Whether this impaired chronotropic response reflects pathology of the sinoatrial node or is a consequence of altered cardiac hemodynamics is uncertain. We evaluated the adequacy of HR acceleration throughout exercise relative to metabolic demand and cardiac output in patients with a Fontan circulation relative to healthy controls. Methods and Results Thirty subjects (20 healthy controls and 10 Fo ...[more]

PMID: 31041880

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Project description:BackgroundPulmonary vascular disease, pulmonary endothelial dysfunction, liver fibrosis, renal disease, and exercise intolerance are common in adults with Fontan physiology. Although the pathophysiologic mechanisms linking these phenomena have been studied, certain aspects are not well understood.ObjectivesThis study hypothesized that impaired pulmonary vascular reserve (VR) plays a central role linking these abnormalities, and that patients with abnormal pulmonary VR with exercise, compared with patients with normal VR, would display poorer pulmonary endothelial function, greater liver stiffness, more renal dysfunction, and poorer exercise capacity.MethodsSymptomatic adults with the Fontan palliation (n = 29) underwent invasive cardiopulmonary exercise testing, echocardiography, and assessment of microvascular function. Abnormal pulmonary VR was defined by the slope of increase in pulmonary pressure relative to cardiac output with exercise >3 mm Hg/l/min. Pulmonary endothelial function was assessed using reactive hyperemia index. End-organ function was assessed using magnetic resonance elastography-derived liver stiffness, glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and peak oxygen consumption (Vo2).ResultsCompared with individuals with normal VR (n = 8), those with abnormal VR (n = 21) displayed higher central and pulmonary venous pressures, and more severely impaired cardiac output and stroke volume responses to exertion, but similar pulmonary vascular resistance at rest. Patients with abnormal VR displayed more severely impaired reactive hyperemia index, increased liver stiffness, lower glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and lower peak Vo2. As compared to pulmonary vascular resistance at rest, slope of increase in pulmonary pressure relative to cardiac output displayed stronger correlations with reactive hyperemia index (r = -0.63 vs. r = -0.31; Meng test p = 0.009), magnetic resonance elastography-derived liver stiffness (r = 0.47 vs. r = 0.29; Meng test p = 0.07), glomerular filtration rate (r = -0.52 vs. r = -0.24; Meng test p = 0.03), N-terminal pro-B-type natriuretic peptide (r = 0.56 vs. r = 0.17; Meng test p = 0.02), and peak Vo2 (r = -0.63 vs. r = -0.26; Meng test p = 0.02).ConclusionsPulmonary vascular limitations in Fontan physiology are related to pulmonary endothelial and end-organ dysfunction, suggesting a mechanistic link between these commonly observed findings, and these abnormalities are more apparent during exercise testing, with little relationship at rest.

Project description:People with schizophrenia die on average 15-20 years earlier than age and gender matched controls in the general population. An essential part of this excess mortality in people with schizophrenia is caused by physical illnesses. Among the physical illnesses, cardiovascular disease (CVD) has been identified as the most common natural cause of death in up to 40-45% of the cases. Chronotropic incompetence (CI) is defined as the inability of the heart to increase its beating frequency in proportion to increased physical activity or higher metabolic demand. It is an established independent cardiovascular risk factor for major cardiac events and overall mortality and might explain adaptation intolerance of the cardiovascular system to even minor exercise courses. CI needs objective exercise testing for definitive diagnosis and therefore represents a biological marker indicating the integrity of the cardiovascular system. It was recently described in patients with schizophrenia and might help explain the reduced physical fitness in these patients and the inability of a subgroup of patients to benefit from exercise interventions. In this study, we tried to replicate the occurrence of CI in an independent sample of patients with schizophrenia and evaluated whether CI can be influenced by a continuous endurance training of 12 weeks. Therefore, we re-analyzed the fitness testing data of 43 patients with schizophrenia and 22 aged and gender matched healthy controls. Parameters of aerobic fitness and chronotropic response to exercise were calculated. Patients with schizophrenia were less physically fit than the healthy controls and displayed a significantly higher heart rate at rest. 10 of 43 patients with schizophrenia and no healthy control subject were classified as chronotropically incompetent. Chronotropic response to exercise did not change significantly after 12 weeks of continuous aerobic exercise training. No differences were observed for baseline heart rate and peak heart rate in both subgroups of schizophrenia patients. Aerobic fitness did not improve significantly in the patients with schizophrenia classified as chronotropically incompetent. Our results confirm the occurrence of CI in patients with multi-episode schizophrenia. This should be taken into account when planning an exercise or lifestyle intervention studies in this population. Schizophrenia patients with CI do not seem to benefit as well as schizophrenia patients without CI from aerobic exercise training interventions. Larger, prospective randomized controlled clinical trials with different training interventions are urgently needed to address the topic of schizophrenia patients not responding to exercise and the relationship to the illness itself.

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Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?

Publications

Heart Rate Reserve in Fontan Patients: Chronotropic Incompetence or Hemodynamic Limitation?

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