Amy L. Taylor

Left ventricular diastolic dysfunction in children and young adults with Marfan syndrome

Adults with Marfan syndrome (MFS) demonstrate abnormal aortic elastic properties manifest by decreased aortic distensibility and increased aortic stiffness. Left ventricular (LV) diastolic dysfunction has been reported in adults with MFS. The objective of this study was to assess the frequency of LV diastolic dysfunction in a group of children and young adults with MFS and to determine whether diastolic dysfunction is associated with hemodynamic alterations of the aorta. Review of echocardiographic findings in 40 patients with MFS was performed to assess LV size, systolic function, isovolumic relaxation time (IVRT), mitral inflow velocities, deceleration time (DT) of mitral E wave, and aortic root dimension. No patient had significant valvar disease or was on any cardiac medication at the time of study. A group of 40 age and sex-matched healthy subjects undergoing echocardiography served as controls. Significant differences in LV diastolic function were found between MFS patients and controls. MFS patients had prolonged DT and IVRT and decreased mitral E/A ratio, suggesting impaired LV relaxation. No relationship between aortic root dimension and diastolic performance was identified. Left ventricular diastolic dysfunction may be an early marker of myocardial involvement in young MFS patients occurring independently of aortic root dilatation.

Ventilatory efficiency slope correlates with functional capacity, outcomes, and disease severity in pediatric patients with pulmonary hypertension☆ , ☆☆ ,★

BACKGROUND Cardiopulmonary exercise testing is widely used in a variety of cardiovascular conditions. Ventilatory efficiency slope can be derived from submaximal exercise testing. The present study sought to evaluate the relationship between ventilatory efficiency slope and functional capacity, outcomes, and disease severity in pediatric patients with pulmonary hypertension. METHODS Seventy six children and young adults with a diagnosis of pulmonary hypertension (PH) performed 258 cardiopulmonary exercise tests from 2001 to 2011. Each individual PH test was matched to a control test. Ventilatory efficiency slope was compared to traditional measures of functional capacity and disease severity including WHO functional classification, peak oxygen consumption, and invasive measures of pulmonary arterial pressures and pulmonary vascular resistance. RESULTS Ventilatory efficiency slope was significantly higher in patients with pulmonary arterial hypertension, with an estimated increase of 7.2 for each increase in WHO class (p<0.0001), compared with normal control subjects (38.9 vs. 30.9, p<0.001). Ventilatory efficiency slope correlated strongly with invasive measures of disease severity including pulmonary vascular resistance index (r =0.61), pulmonary artery pressure (r =0.58), mean pulmonary artery pressure/mean aortic pressure ratio (r =0.52), and peak VO2 (r=-0.58). Ventilatory efficiency slope in 12 patients with poor outcomes (9 death, 3 lung transplant), was significantly elevated compared to patients who did not (51.1 vs. 37.9, p<0.001). CONCLUSIONS Ventilatory efficiency slope correlates well with invasive and noninvasive markers of disease severity including peak VO2, WHO functional class, and catheterization variables in pediatric patients with PH. Ventilatory efficiency slope may be a useful noninvasive marker for disease severity.

Living at an altitude adversely affects exercise capacity in Fontan patients.

BACKGROUND Data assessing the effect of altitude on Fontan haemodynamics are limited to experimental models and case reports. Both suggest a detrimental impact. This study describes exercise performance in patients with Fontan circulation and matched controls at a low altitude versus at sea level. We sought to assess the impact of increasing altitude on functional capacity in patients with Fontan palliation. METHODS A retrospective review of 22 patients at low altitude (1602 metres) and 119 patients at sea level with Fontan circulation, as well as age-, gender-, and altitude-matched controls, underwent maximal cardiopulmonary exercise testing. Linear regression models were created to determine the influence of altitude on differences in exercise variables between Fontan patients and their matched controls. RESULTS Peak oxygen consumption was 28.4 millilitres per kilogram per minute (72% predicted) for the sea-level cohort and 24.2 millilitres per kilogram per minute (63% predicted) for the moderate altitude cohort. The matched case-control differences for patients at moderate altitude were greater for peak oxygen consumption (-29% against -13%, p = 0.04), anaerobic threshold (-36% against -5%, p = 0.001), and oxygen pulse (-35% against -18%, p = 0.007) when compared with patients living at sea level. When compared to institution-matched controls, the same parameters fell by 3%, 8.9%, and 4.2%, respectively, for each increase of 1000 feet in residential altitude (p = 0.03, p = 0.001, and p = 0.05, respectively). CONCLUSIONS Patients with Fontan circulation at a higher altitude have impairment in aerobic capacity when compared with patients at sea level. Reduction in exercise capacity is associated with a reduction in stroke volume, likely related to increased pulmonary vascular resistance.

Exercise Capacity in Pediatric Heart Transplant Candidates: Is There Any Role for the 14 ml/kg/min Guideline?

A peak oxygen consumption (VO2) of <14 ml/kg/min has been identified as a predictor of l-year mortality in adults with congestive heart failure (CHF) and is used as a criterion for listing for cardiac transplantation (OHT). The role of VO2 measurement in children awaiting OHT has not been thoroughly evaluated. We sought to assess the degree of exercise impairment and the clinical applicability of the 14 ml/kg/min rule in children awaiting OHT. Cardiopulmonary exercise test (CPT) and cardiac catheterization data in all patients listed for OHT during the period of 1995–2003 were reviewed. Fourteen patients with a mean age of 15.5 ± 2.9 years underwent CPT with no serious adverse events at an interval of 6.6 ± 5.1 months prior to OHT. The etiology of CHF was multifactorial. Patients had impaired aerobic capacity with a mean peak VO2 of 20.4 ± 6.8 ml/kg/min. Eleven of 14 patients (79%) had a peak VO2 higher than the adult cutoff value of 14 ml/kg/min. Pediatric ambulatory patients with CHF can safely undergo CPT. Because of age-related differences in oxygen consumption and varied etiologies of CHF a peak VO2 of <14 ml/kg/min is not a useful criterion for listing for OHT in this population.

The clinical translation gap in child health exercise research: a call for disruptive innovation.

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health.

Evaluation of predictive models for six minute walk test among children with pulmonary hypertension.

BACKGROUND Existing six minute walk distance (6MWD) prediction equations were developed using healthy children and include relatively small sample sizes. Children with congenital heart disease and pulmonary hypertension (PH) are often small-for-age, so the existing pediatric prediction equations are likely a poor fit for children with PH. Currently, there are no equations for 6MWD among children with PH. OBJECTIVES Evaluate the validity of five existing pediatric prediction equations among the 6MWD of children with PH, including for each World Health Organization (WHO) class. Develop a validated predictive equation for use in children with PH. METHODS/RESULTS The 6MWDs from 711 six minute walk tests (6MWTs) of children aged four through 18years with PH were analyzed retrospectively and were evaluated against existing pediatric prediction equations. Existing pediatric prediction equations overestimated the walk distance among our population. The predicted distances versus actual distances were significantly different for each WHO class, with higher class associated with greater difference. A new prediction equation for 6MWD among children with PH was developed and validated with 65 additional 6MWTs. Our prediction equation demonstrates higher goodness of fit for all WHO classes than the preexisting pediatric equations. CONCLUSIONS Existing prediction equations for 6MWD among healthy children are not accurate for children with PH, particularly for children with more advanced stages of the disease (WHO classes III and IV). We present a new prediction equation for children with PH (WHO classes I through IV) that provides reference for medical care and management.