Wayne A. Mays

Persistent hyperdynamic cardiovascular state at rest and during exercise in children after successful repair of coarctation of the aorta

OBJECTIVESnThe purposes of this study were to evaluate left ventricular performance and contractility at rest and during exercise to determine mechanisms and correlates for alterations in performance and blood pressure in pediatric patients after successful repair of coarctation of the aorta.nnnBACKGROUNDnBlood pressure and left ventricular function are elevated in children despite successful repair. The mechanisms for these changes are not understood.nnnMETHODSnThirty asymptomatic pediatric patients with successful coarctation repair (mean age [+/- SD] 12.5 +/- 4 years) underwent echocardiographic determination of left ventricular mass, performance (shortening fraction), preload (indexed diastolic dimension), afterload (end-systolic wall stress), contractility (velocity of circumferential fiber shortening/wall stress relation) and Doppler gradient at rest and during exercise. Data were compared with those of 24 control subjects (mean age 21.0 +- 4 years). Because of the age discrepancy between groups, age-dependent echocardiographic data were indexed by body surface area.nnnRESULTSnThe mean age at operation was 5 +/- 4 years, and the average follow-up period was 7.5 +/- 3 years. The average blood pressure gradient between upper and lower limbs was 4 mm Hg. Left ventricular mass was higher in the postoperative group than in the control group (1.58 vs. 1.31 g/ht2.7, p = 0.04), as were values at rest for performance (44% vs. 31%, p = 0.0001), preload (3.9 vs. 3.7 cm/body surface area0.5), indexes systolic blood pressure (1.05 vs. 0.91, p = 0.0001) and contractility (0.23 vs. -0.05 circumferences/s, p= 0.001). Afterload was lower at rest (36 vs. 52 g/cm2, p = 0.0004). These differences between groups persisted during and after exercise. Contractility underwent an exaggerated increase after exercise in the postoperative group.nnnCONCLUSIONSnLeft ventricular performance in children after coarctation repair is higher at rest and during exercise than in control subjects as a result of higher preload and contractility and lower afterload. These changes may be due to associated hypertrophy. Persistent postoperative hypertension may be due to a hyperdynamic, hypercontractile state caused by residual gradients manifested only during exertion.

Cardiovascular physiology during supine cycle ergometry and dobutamine stress.

PURPOSEnThis study compared cardiac hemodynamics during supine cycle ergometry and dobutamine stress.nnnMETHODSnThirty-two healthy volunteers (19 female, 13 male, 23.5 +/- 3.5 yr old) completed respective tests on separate days and in random order. Heart rate, blood pressure, and cardiac output were recorded at baseline and peak stress. Echocardiographic measures included left ventricular end-diastolic dimension, fractional shortening, heart rate corrected velocity of circumferential fiber shortening, end-systolic wall stress, and the difference between measured and predicted fiber shortening for measured wall stress.nnnRESULTSnCompared with peak exercise, dobutamine infusion resulted in lower cardiac output (12 +/- 2 vs 16 +/- 4 l x min(-1), P < 0.0001), heart rates (163 +/- 7 vs 175 +/- 12 beats x min(-1), P < 0.0001), and systolic blood pressure (160 +/- 22 vs 185 +/- 20 mm Hg, P < or = 0.0001). Echocardiography demonstrated smaller left ventricular end-diastolic dimension (4.2 +/- 0.7 vs 4.5 +/- 0.7 cm, P = 0.013), higher fractional shortening (0.55 +/- 0.07 vs 0.50 +/- 0.06%, P < 0.001), higher VCFc (2.07 +/- 0.36 vs 1.54 +/- 0.20 circs x s(-1), P < 0.001) higher VCFdiff (0.94 +/- 0.35 vs 0.48 +/- 0.20 circs x s(-1), P < 0.001), and lower end-systolic wall stress (25 +/- 11 vs 42 +/- 16 g x cm(-2), P < 0.001). The stress-velocity relationship during dobutamine demonstrated higher y-intercept and steeper slope, indicating greater load-independent contractility.nnnCONCLUSIONnThe cardiovascular adaptation to exercise and dobutamine stress differ significantly. Cardiac output during peak exercise is greater than during peak dobutamine secondary to increased heart rate and stroke volume. Despite a greater increase in contractility and decrease in afterload, a smaller increase in cardiac output during dobutamine stress may be secondary to limited ventricular preload.

A controlled study of type a behavior and psychophysiologic responses to stress in anorexia nervosa

Adolescents and young adults meeting DSM-III criteria for anorexia nervosa (n = 13) and atypical eating disorders (n = 7) were compared with weight-recovered anorectics (n = 6) and normal weight controls (n = 11) using a type-A structured interview and a computerized stress procedure. Heart rate, blood pressure, and electrocardiographic changes were monitored. Anorexia nervosa subjects demonstrated significantly more type-A characteristics than controls. The emaciated and weight-recovered anorectics had elevated hostility scores on the type-A interview, which has been shown in recent studies of type-A behavior to be a risk factor for cardiovascular disease. This pilot study is the first to demonstrate a significant relationship between anorexia and the type-A behavioral pattern. Also the anorectic subjects showed significantly more cardiovascular reactivity than controls as measured by failure of stressed anorectic subjects to lower their systolic blood pressure to baseline levels as controls did. These results support the importance of monitoring stress reactions and personality traits as well as traditional biological measures.

Exercise Capacity Improves after Transcatheter Closure of the Fontan Fenestration in Children

OBJECTIVESnThis study evaluated the aerobic capacity, exercise capacity, and arterial oxygen saturation (O(2)Sat) in children before and after transcatheter Fontan fenestration closure.nnnDESIGNnObservational study comparing exercise parameters and hemodynamics before and after transcatheter fenestration closure in Fontan patients.nnnOUTCOME MEASURESnWorking capacity, exercise duration, oxygen consumption (VO(2)), and arterial O(2)Sat were evaluated during aerobic exercise.nnnRESULTSnTwenty patients (mean age 11.4 years) underwent standardized exercise testing before and after fenestration closure. Twelve patients underwent cycle ergometry testing (mean age 14.8 years) (group 1), and eight younger patients (mean age 6.4 years) underwent Bruce treadmill testing (group 2). The same exercise protocol was used in each patient before and after fenestration closure (interval between tests: 118 +/- 142 days). Immediately following fenestration closure at cardiac catheterization, cardiac index decreased (3.0 to 2.1 L/minute/m(2)) and Fontan pressure increased (11 +/- 2 to 12 +/- 2 mm Hg) with an increased arterial saturation (92 to 96%) (P < .001). The total group demonstrated no significant change in pre- and postclosure maximal heart rates (164 +/- 21 and 169 +/- 19 bpm). Rest and exercise O(2)Sat increased (89 and 82 to 95 and 92%) (P < .0001). Exercise duration increased (7.7 +/- 1.9 to 9.2 +/- 2.4 minutes) (P < .0005). Maximal VO(2), indexed maximal VO(2), and total working capacity in kilopond-meters (kpm) increased (1.2 +/- 0.5, 27 +/- 7 and 2466 +/- 1012 to 1.3 +/- 0.4 L/minute, 31 +/- 9 mL/kg/minute and 2869 +/- 1051 kpm, respectively) (P < .005).nnnCONCLUSIONnIn children with a univentricular heart after Fontan palliation, transcatheter fenestration closure improves exercise arterial O(2)Sat and aerobic capacity despite a restricted resting cardiac output documented by catheterization immediately after the closure procedure.

Usefulness of Ventricular Premature Complexes in Asymptomatic Patients ≤21 Years as Predictors of Poor Left Ventricular Function

Although ventricular premature complexes (VPCs) have been shown to correlate with decreased cardiac function in adults, the correlation of left ventricular (LV) function to VPCs in asymptomatic children remains unclear. The aim of this study was to determine the correlation of VPC burden with LV function in asymptomatic pediatric patients with structurally normal hearts. This was a retrospective analysis of patients aged ≤21 years with echocardiograms and 24-hour Holter monitors with ≥0.5% VPCs completed within 60 days of each other. LV fractional shortening (FS) was compared with VPC burden and VPC characteristics. Normal LV function was defined as FS ≥28%. Correlation between VPC burden and LV function was determined by regression analysis. Wilcoxons rank-sum test was used to compare LV function with VPC characteristics. This study included 123 patients (77 male [63%]). The median age was 11.6 years (interquartile range 5.8 to 14.3). The median VPC burden was 11.2% (interquartile range 4.8% to 18.9%), and median FS was 36% (interquartile range 33% to 38%). There was no significant correlation between VPC burden and LV FS (p = 0.50). The presence of uniform versus multiform VPCs (p = 0.29), ventricular couplets (p = 0.37), or runs of ventricular ectopy (p = 0.19) were not associated with a decrease in LV FS. Twenty-two patients (18%) had VPC burden >24%, none of which had decreased LV FS. In conclusion, there was no significant relation between VPC burden or VPC characteristics and LV systolic function in this pediatric population with structurally normal hearts.

Blood pressure and total peripheral resistance in children with chronic kidney disease

We performed a study to assess cardiac output (CO) and total peripheral resistance (TPR) at rest and during peak exercise with the goal to better define the role of these parameters in the development of hypertension in children with chronic kidney disease (CKD) stage 2–4. Fifty-two pediatric patients with CKD (mean age 12.7±3.7xa0years) and 28 healthy individuals of comparable age and sex participated in the study. At rest, children with CKD had a significantly higher systolic and diastolic blood pressure (BP) and calculated mean arterial pressure (MAP) than healthy controls. Total peripheral resistance was significantly higher in children with CKD than in controls (1627.7±534.6 vs 1354.6±338.9xa0dyne×s×cm−5, p =0.02). There was no significant difference in heart rate or CO between the two groups. Children taking antihypertensive medications had lower TPR than children without BP medications (1514.6±439.6 vs 1788.2±505.4xa0dyne×s×cm−5, respectively, p =0.06). At peak exercise, children with CKD had a significant increase in MAP, heart rate and CO and had a significant decrease in TPR (difference between rest and peak exercise: −782.4±375.9xa0dyne×s×cm−5, p <0.001). Children taking BP medications had blunted MAP and CO responses when compared to controls (Δ CO: 6.2±2.8xa0l/min vs 9.8±4.5xa0l/min, respectively, p =0.01; MAP: 13.9±10.2xa0mmHg vs 21.5±11.7xa0mmHg, respectively, p =0.01). Children without BP medications had a similar to controls response to exercise in respect to CO, MAP and TPR. We conclude that increased TPR is a major contributor to elevated blood pressure in children with CKD and suggest that BP medications decreasing vascular resistance should be used as a first line of antihypertensive therapy in these patients.

Endothelial Function and Arterial Stiffness Relate to Functional Outcomes in Adolescent and Young Adult Fontan Survivors

Background Fontan survivors demonstrate diminished vascular function and functional outcomes, but the relationships between these measures have not been established. Methods and Results We performed a cross‐sectional study of 60 Fontan survivors (52% male) with a mean age of 13.9±4.1 years and mean Fontan duration of 9.9±4.2 years. Multimodality assessment of endothelial function (reactive hyperemia index and flow‐mediated dilation) and arterial stiffness (augmentation index and baseline pulse amplitude) was performed with peripheral arterial tonometry and brachial flow‐mediated dilation. Aerobic capacity was determined using cardiopulmonary exercise testing; mean peak and percentage of predicted oxygen consumption (VO2) were 27.8±7.6 mL/kg per minute and 71.0±21.2%, respectively. Quality of life and physical activity were assessed using the Pediatric Quality of Life Inventory (PedsQL) and the Physical Activity Questionnaire. Vascular measures served as predictor variables, whereas functional measures served as outcome variables. In all cases, worse vascular measures were associated with worse functional measures. Flow‐mediated dilation–derived reactive hyperemia index (P<0.05) was positively associated with VO2 at anaerobic threshold. Peripheral arterial tonometry–derived baseline pulse amplitude (P<0.05) was negatively associated with the ratio of minute ventilation to carbon dioxide at anaerobic threshold. Flow‐mediated dilation–derived reactive hyperemia index and peripheral arterial tonometry–derived augmentation index (P<0.05) were positively and negatively associated, respectively, with peak VO2. Maximum flow‐mediated dilation (P<0.05) was positively associated with Physical Activity Questionnaire score. Peripheral arterial tonometry–derived augmentation index and baseline pulse amplitude (P<0.05) were negatively associated with parent‐reported PedsQL total and physical heath summary scores. Conclusions Increased arterial stiffness and decreased endothelial function are associated with lower aerobic capacity, physical activity, and quality of life in adolescent and young adult Fontan survivors. Understanding the cause–effect relationship between vascular function and functional outcomes is an important next step.

Cardiac Rehabilitation Improves Cardiometabolic Health in Young Patients with Nonischemic Dilated Cardiomyopathy

Nonischemic dilated cardiomyopathy is deadly and costly, and treatment options are limited. Cardiac rehabilitation has proved safe and beneficial for adults with various types of heart failure. Therefore, we retrospectively evaluated the hypothesis that rehabilitation is safe and improves cardiometabolic health in young patients with nonischemic dilated cardiomypathy. From 2011 through 2015, 8 patients (4 males) (mean age, 20.6 ± 6.6 yr; range, 10-31 yr) underwent rehabilitation at our institution. They were in American Heart Association class C or D heart failure and were on maximal medical therapy. Their mean left ventricular ejection fraction at baseline was 0.26 ± 0.15. Two patients had a left ventricular assist device, and 2 were inpatients. To evaluate safety, we documented adverse events during rehabilitation sessions. Clinical endpoints were measured at baseline, immediately after completing rehabilitation, and after one year. Patients attended 120 of 141 possible sessions (85%), with no adverse events. There were no marked changes in mean left ventricular ejection fraction or body mass index. The patients mean waist circumference decreased by 1.37 ± 0.6 in (n=5; 95% CI, -2.1 to -0.63). Their 6-minute walk distance increased by a mean of 111 ± 75 m (n=5; 95% CI, 18-205). In our small sample of young patients with nonischemic dilated cardiomyopathy, cardiac rehabilitation was feasible and was associated with minimal risk. Our findings suggest that prospective studies in this population are warranted.

Cardiopulmonary fitness assessment on maximal and submaximal exercise testing in patients with Fabry disease

The cardiopulmonary exercise test (CPET) is a valuable tool to assess a patients aerobic fitness and cardiac function, including the response to stress. There have been few studies using CPET to evaluate cardiopulmonary exercise capacity in patients with Fabry disease. We performed a retrospective chart review of patients with Fabry disease from 2001 to 2016, compared to age, gender, and size‐matched normal controls. A total of 18 patients were evaluated using the Bruce protocol (treadmill) and 11 patients were evaluated with the ramp protocol (cycle ergometer). The Fabry group demonstrated significantly lower heart rate at peak exercise (151.2 ± 22.5 vs. 178.6 ± 16.2, p < .05), max indexed VO2 (23.7 ± 7 vs. 33.9 ± 8.4, p < .05), and peak index oxygen pulse (12.1 ± 3 vs. 15.2 ± 4.2, p < .05). When the groups were further separated into treadmill or cycle ergometry testing only, there remained statistically significant differences in peak indexed oxygen pulse, heart rate at peak exercise, and max indexed VO2. There was a statistically significant difference between the Fabry patients evaluated by treadmill testing for systolic blood pressure at peak exercise that was not seen in the cycle ergometry group. Additionally, when looking at the patients who had concurrent cardiac MRI (cMRI) with their CPET, there was a positive correlation with max indexed VO2 and right ventricular end‐diastolic volume (r = .55, p = .007) and end‐systolic volume (r = .59, p = .007). Patients with Fabry disease have impaired cardiopulmonary exercise capacity as measured by CPET. Additionally, in patients with Fabry disease there is a positive correlation with functional capacity and right ventricular volumes on cMRI.

A Comparison of Four Submaximal Tests for Evaluating Change in Fitness in Youth With Obesity

Obesity has more than doubled in children and quadrupled in adolescents over the past 30 years. Children with obesity are more likely to become adults with obesity and in conjunction are likely to develop disease and shortened life. In particular, type 2 diabetes mellitus was previously considered an adult disease, but is now increasing among children. Treatment of obesity involves a combination of improved diet and physical activity. However, it has been shown that body weight and activity level are more highly correlated than body weight and food intake. Physical activity also reduces the risk of cardiovascular disease and type 2 diabetes by improving plasma triglyceride levels, total cholesterol, high-density lipoprotein (HDL) cholesterol, and insulin sensitivity. In fact, it has been shown that fitness levels are a more accurate predictor of cardiovascular disease and all-cause mortality than weight status. Typically, youths with obesity have a lower cardiovascular fitness and overall physical ability to tolerate exercise than do lean youth. Low cardiovascular fitness is an important health problem in today’s youth, especially in the obese population. Excess body fat is thought to contribute to exercise intolerance and thus a lower cardiorespiratory fitness. Historically, measuring VO 2 max has been the “gold standard” for assessing the cardiovascular fitness of an individual. VO 2 is the amount of oxygen that a given individual can consume while performing dynamic exercise. VO 2 max, then, is the point at which the VO 2 plateaus and no further increase in consumption is seen with increasing workload. Maximal effort is challenging to obtain in pediatric patients, especially in children and adolescents who are obese due to the higher perceived exhaustion and erratic breathing. Because of this, submaximal measures may be of value to evaluate fitness in children with obesity. Submaximal measures such as heart rate (HR), blood pressure (BP), respiratory rate (RR), rating of perceived exertion (RPE), and breathlessness at a given exercise level have been used for evaluating fitness. Typically, the obese population has a higher submaximal heart rate when compared with that of the leaner population. With increased exercise and improvement in fitness, a decrease in submaximal measures such as VO 2 , HR, BP, and RR are seen. Change in HR (lower HR compared with HR at baseline before a fitness program), for example, has been shown to be a successful measure of cardiovascular fitness in youth and minimizes discomfort in study participants. VO 2 max has also been accurately predicted by measuring VO 2 consumption at submaximum effort. While submaximal testing has potential advantages in fitness testing in children and adolescent with obesity, the best mode of testing is still not clear. In this study, we describe a comparison between 4 submaximal tests in obese youth. Change in HR and VO 2 consumption at 6and 9-minute intervals are compared with change in VO 2 max in youth enrolled in a pediatric weight management program (PWMP).