James E. Potts

Catecholaminergic Polymorphic Ventricular Tachycardia in Children Analysis of Therapeutic Strategies and Outcomes From an International Multicenter Registry

Background—Catecholaminergic polymorphic ventricular tachycardia is an uncommon, potentially lethal, ion channelopathy. Standard therapies have high failure rates and little is known about treatment in children. Newer options such as flecainide and left cardiac sympathetic denervation are not well validated. We sought to define treatment outcomes in children with catecholaminergic polymorphic ventricular tachycardia. Methods and Results—This is a Pediatric and Congenital Electrophysiology Society multicenter, retrospective cohort study of catecholaminergic polymorphic ventricular tachycardia patients diagnosed before 19 years of age. The cohort included 226 patients, including 170 probands and 56 relatives. Symptomatic presentation was reported in 176 (78%). Symptom onset occurred at 10.8 (interquartile range, 6.8–13.2) years with a delay to diagnosis of 0.5 (0–2.6) years. Syncope (P<0.001), cardiac arrest (P<0.001), and treatment failure (P=0.008) occurred more often in probands. &bgr;-Blockers were prescribed in 205 of 211 patients (97%) on medication, and 25% experienced at least 1 treatment failure event. Implantable cardioverter defibrillators were placed in 121 (54%) and was associated with electrical storm in 22 (18%). Flecainide was used in 24% and left cardiac sympathetic denervation in 8%. Six deaths (3%) occurred during a cumulative follow-up of 788 patient-years. Conclusions—This study demonstrates a malignant phenotype and lengthy delay to diagnosis in catecholaminergic polymorphic ventricular tachycardia. Probands were typically severely affected. &bgr;-Blockers were almost universally initiated; however, treatment failure, noncompliance and subtherapeutic dosing were often reported. Implantable cardioverter defibrillators were common despite numerous device-related complications. Treatment failure was rare in the quarter of patients on flecainide. Left cardiac sympathetic denervation was not uncommon although the indication was variable.

Fitness, fatigue, disease activity, and quality of life in pediatric lupus.

OBJECTIVE To measure aerobic fitness (maximum oxygen consumption [VO(2peak)]), fatigue, quality of life (QOL), and disease activity in young persons with systemic lupus erythematosus (SLE), and to determine an equation for predicting VO(2peak) from the distance walked in 6 minutes (6MW). METHODS Fifteen young patients ages 12-19 years with SLE participated. VO(2) was measured by a graded treadmill exercise test. Submaximal exercise intensity was determined from the ventilatory anaerobic threshold. Submaximal aerobic capacity was measured using the 6MW. Patient questionnaires included measures of fatigue, QOL, and physical activity. Physician questionnaires included the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS Compared with age-matched norms, our patients had moderate impairment in aerobic fitness, with a mean +/- SD VO(2peak) of 31.1 +/- 7.9 ml/minute/kg and a mean 6MW distance Z score of -2.4 +/- 2.3. The regression equation to predict VO(2peak) (ml/minute/kg) from 6MW was as follows: 57.1 + [0.038 x distance (meters)] + (-0.35 x maximal heart rate) (R = 0.67, P = 0.027). Ten subjects (67%) reported significant fatigue. There was no significant correlation of fatigue with fitness measures. Neither fatigue nor fitness was significantly correlated with disease activity, disease damage, or QOL measures. CONCLUSION Young SLE patients have lower aerobic fitness than reference norms. The 6MW may be used as a marker of fitness, but it is preferable to determine VO(2) with a graded exercise test. Fatigue is a significant symptom in young SLE patients. The application of fatigue measures in young persons is exploratory. The relationship between fatigue and aerobic fitness is not clear.

A novel doppler echocardiographic method of measuring the biophysical properties of the aorta in pediatric patients

BACKGROUND This study was performed to: (1) assess the feasibility of measuring pulse wave velocity (PWV) from aortic (AO) Doppler flow and deriving AO input and characteristic impedances and the arterial pressure strain elastic modulus; and (2) compare these indices in pediatric patients with arterial disease to control (C) patients. METHODS There were 14 healthy children in the C group, 9 with inflammatory connective tissue diseases (ICTD), and 6 with Marfan syndrome (M). Using standard echocardiographic equipment, the AO annulus, AO root diameter in systole (AO(S)) and diastole (AO(D)), and AO length (L) were measured. The time taken for the Doppler signal to travel from the ascending to descending aorta was measured. AO peak flow was calculated from AO annulus cross-sectional area x peak aortic velocity (AoV); PWV = L/time taken for the Doppler signal to travel from the ascending to descending aorta; input impedance = (systolic - diastolic blood pressure)/(AO cross-sectional area x AoV); characteristic impedance = (PWV x rho)/Ao cross-sectional area (where rho = 1.06); and pressure strain elastic modulus = (systolic - diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)]; beta index = ln (systolic/diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)]. RESULTS Results for PWV were ICTD = M > C (533, 496, 362 cm/s; P <.02); for input impedance were ICTD > M = C (245, 120, 116; P <.03); for characteristic impedance were ICTD < M = C (249, 107, 142; P <.05); for pressure strain elastic modulus were M > ICTD = C (262, 447, 187; P <.003); and for beta index were M > ICTD > C (2.91, 2.51, 2.13; P <.0006). CONCLUSIONS This novel, relatively simple method of assessing the biophysical properties of the aorta shows abnormal function in patients with M and ICTD. This technique may be helpful in the long-term follow up of patients with arterial disease.

The Study of Antiarrhythmic Medications in Infancy (SAMIS) A Multicenter, Randomized Controlled Trial Comparing the Efficacy and Safety of Digoxin Versus Propranolol for Prophylaxis of Supraventricular Tachycardia in Infants

Background—Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergent cardiac care in children, yet its management has never been subjected to a randomized controlled clinical trial. The purpose of this study was to compare the efficacy and safety of the 2 most commonly used medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and propranolol. Methods and Results—This was a randomized, double-blind, multicenter study of infants <4 months with SVT (atrioventricular reciprocating tachycardia or atrioventricular nodal reentrant tachycardia), excluding Wolff-Parkinson-White, comparing digoxin with propranolol. The primary end point was recurrence of SVT requiring medical intervention. Time to recurrence and adverse events were secondary outcomes. Sixty-one patients completed the study, 27 randomized to digoxin and 34 to propranolol. SVT recurred in 19% of patients on digoxin and 31% of patients on propranolol (P=0.25). No first recurrence occurred after 110 days of treatment. The 6-month recurrence-free status was 79% for patients on digoxin and 67% for patients on propranolol (P=0.34), and there were no first recurrences in either group between 6 and 12 months. There were no deaths and no serious adverse events related to study medication. Conclusions—There was no difference in SVT recurrence in infants treated with digoxin versus propranolol. The current standard practice may be treating infants longer than required and indicates the need for a placebo-controlled trial. Clinical Trial Registration Information—http://clinicaltrials.gov; NCT-00390546.

The effect of repeat exercise on pulmonary diffusing capacity and EIH in trained athletes

PURPOSE The purpose of this study was to determine the effects of repeated heavy exercise on postexercise pulmonary diffusing capacity (DL) and the development of exercise induced arterial hypoxemia (EIH). METHODS 13 endurance-trained, male athletes (age = 27+/-3 yr, height = 179.6+/-5.0 cm, weight = 71.8+/-6.9 kg, VO2max = 67.0+/-3.6 mL x kg(-1) x min(-1) performed two consecutive, continuous exercise tests on a cycle ergometer to VO2max, separated by 60 min of recovery. Arterial oxygen saturation (%SaO2) was measured via ear oximetry, and resting DL was measured and partitioned by the single-breath method, before exercise and 60 min after each exercise bout. RESULTS No significant differences resulted in VO2max, VE, peak heart rate (HR), or breathing frequency between exercise bouts (P > 0.05). There was a small but significant decrease (454-446 W; P < 0.05) in peak power output in the second test. %SaO2 decreased from resting values during both exercise tasks, but there was no difference between the minimum saturation achieved in test 1 (91.4) or test 2 (91.6; P > 0.05). After the initial exercise bout, significant decreases (P < 0.05) occurred in DL (11%), membrane diffusing capacity (DM) (11%) and pulmonary capillary volume (VC) (10%). Further decreases occurred in DL (6%; P < 0.05), DM (2%; P > 0.05), and VC (10%; P < 0.05) after the second exercise bout. CONCLUSIONS These observations question the meaning of post exercise measurements of pulmonary diffusion capacity, and its components, relative to pulmonary gas exchange and pulmonary fluid accumulation during exercise. The fact that there was no further change in %SaO2 after the second test suggests that if any interstitial edema developed, it was of no clinical significance; alternatively, the changes in DL(CO) may be related more to redistribution of blood than the development of pulmonary edema.

Early changes in the biophysical properties of the aorta in pre-adolescent children born small for gestational age.

OBJECTIVE To assess the biophysical properties of the aorta in children born small for gestational age (SGA) with an echo-Doppler method and to determine associations with known perinatal risk factors. STUDY DESIGN In this cross-sectional study, 39 SGA and 41 control subjects aged 8 to 13 years were recruited. Perinatal risk factors were recorded. The aortic diameters and pulse wave transit time around the aortic arch were measured with echo-Doppler and the blood pressure recorded. Pulse wave velocity, aortic input impedance (Zi), characteristic impedance (Zc), arterial pressure-strain elastic modulus (Ep), and arterial wall stiffness index (beta-index) were calculated. RESULTS Pulse wave velocity (374 +/- 46 vs 348 +/- 47 cm/sec, P < .02); Zi (177 +/- 39 vs 142 +/- 27 dynes x sec/cm(5), P < .0001); Zc (185 +/- 29 vs 152 +/- 37 dynes x sec/cm(5), P < .0001); Ep (286 +/- 101 vs 216 +/- 41 mm Hg, P < .0001); and beta-index (2.43 +/- 0.32 vs 2.17 +/- 0.15, P < .0001) were all higher in SGA. We found negative associations between the following: birth weight and Zi, Zc, Ep, and beta-index; as well as body mass index and Zi, Zc. CONCLUSION This simple echo-Doppler method demonstrated abnormal biophysical properties of the aorta in a cohort of pre-adolescent patients born SGA who remain small in stature and continue to have normal blood pressure.

Should early extubation be the goal for children after congenital cardiac surgery

OBJECTIVE We sought to determine the feasibility and assess the clinical outcomes associated with an early extubation strategy for all children undergoing congenital heart surgery, including neonates (age, <30 days). METHODS We performed a linked database analysis of all patients undergoing congenital heart surgery from July 1, 2010 to December 31, 2012. We collected data on the cardiac diagnoses, preoperative status, procedure, and postoperative course, including the duration of invasive and noninvasive ventilation, failure of extubation, hemodynamic data, length of stay, complications, and mortality. A multivariable model was used to assess the independent factors associated with an inability to extubate within the operating room and with delayed extubation (>24 hours). RESULTS We operated on 613 children, including 97 neonates. Intraoperative extubation was achieved in 71% of the cases and early extubation (≤ 24 hours) was achieved in 89% of the cases. The overall mortality was 1.5% (9 of 613 patients). Early extubation was associated with lower mortality (1% vs 9%, P < .001) and a lower rate of reintubation (4% vs 23%, P < .001) compared with delayed extubation. Notably, 63% of the neonates were extubated within 24 hours, including 67% of arterial switch operations and 54% of total anomalous pulmonary venous return repairs. Norwood operations were the only procedure in which no patient was extubated within the first 24 hours. Multivariable logistic regression demonstrated that the predictors of delayed extubation included preoperative mechanical ventilation, weight < 5 kg, a longer procedure time, and the need for postoperative inotrope support. Implementation of an early extubation strategy was associated with low rates of complications (5.1 per 10 procedures), short lengths of intensive care unit stay (median, 1 day; interquartile range, 1-3), and short hospital stays (median, 4 days; interquartile range, 3-6). CONCLUSIONS Most children undergoing congenital heart surgery can be extubated in the operating room. Most neonates, including many undergoing complex procedures, can be extubated within the first 24 hours after surgery. Early extubation was associated with low morbidity rates and short lengths of intensive care unit and hospital stays.

The time course of pulmonary diffusing capacity for carbon monoxide following short duration high intensity exercise

We investigated the time course of changes in post-exercise pulmonary diffusing capacity for carbon monoxide (DLCO), membrane diffusing capacity (DM), and pulmonary capillary blood volume (VC) in highly trained (HT), moderately trained (MT) and untrained (UT) male subjects (n = 8/group). Subjects were assigned to groups based on their aerobic capacity from a preliminary VO2max test (HT > or = 65, MT = 50-60, UT < or = 50 ml x kg(-1) x min(-1)). Resting (BASE) DLCO, DM and VC were obtained, then subjects cycled to fatigue at the highest workrate attained during the preliminary tests. Diffusion measurements were then made at 1, 2, 4, 6 and 24 h. DLCO was depressed at 1 h, lowest at 6 h and approached BASE values at 24 h in all groups. The DLCO change was paralleled by a change in VC. Alterations to VC were similar between groups except at 24 h where MT and HT subjects had returned to BASE while UT did not. DM was significantly lower than BASE at 1, 2, 4, and 6 h, and was similar between groups. The changes in DLCO post-exercise appear to be primarily due to a decrease in VC. Comparable diffusion decrements were observed in all subjects. The results of this study suggest that post-exercise alterations in DLCO, DM and VC are not related to aerobic capacity.

A stress echocardiography study of cardiac function during progressive exercise in pediatric oncology patients treated with anthracyclines

Anthracycline‐treated patients (AP) are at risk for cardiac dysfunction years after treatment. Cardiac function has not been evaluated during exercise in AP. The purpose of this study was to assess exercise tolerance, left ventricular (LV) function, and hemodynamics during progressive exercise.

Cardiac responses to progressive exercise in normal children: a synthesis.

UNLABELLED The cardiac responses to exercise are influenced by a complex interplay of changes in diastolic filling, intrinsic myocardial contractility, heart rate, and ventricular afterload. PURPOSE To characterize these responses in children, findings are reported from two studies utilizing Doppler echocardiographic assessment of stroke volume and cardiac output during maximal upright and semisupine cycle exercise. METHODS In study 1, stroke volume, heart rate, and peak aortic velocity were assessed during upright cycle exercise to exhaustion in 39 sixth-grade boys. In study 2, similar methods were used to examine cardiac responses to semisupine exercise with measurement of left ventricular dimensions by two-dimensional echocardiography. RESULTS The findings support patterns similar to that previously described in adults, with an initial rise in stroke volume reaching a plateau at mild-moderate exercise intensities. CONCLUSIONS The observations in these two studies also suggest 1) peripheral vasodilatation plays an important role in the early rise in stroke volume, 2) increasing heart rate acts to maintain a stable stroke volume and left ventricular diastolic dimension at high workloads, and 3) improvements in contractility serve to maintain stroke volume as the systolic ejection period shortens.