Effects of doxorubicin on diastolic function, contractile reserve, and ventricular-vascular coupling in piglets.

The use of doxorubicin as an anticancer drug is limited by its cardiac toxicity. To examine the adverse effects of doxorubicin on cardiac function and ventricular-vascular coupling in piglets, eight piglets received five doses of intravenous doxorubicin, 1.5 mg/kg/dose, every 4-7 days starting at 3 weeks of age. A control group consisted of eight normal piglets. Using conductance and manometric catheters, indices of cardiac function, including end systolic elastance (Ees), preload-recruitable stroke work, dP/dtmax, tau, dP/dtmin, dV/dtmax, and end systolic stiffness, were calculated from volume and pressure measurements at rest and during infusion of isoproterenol. Ventricular-vascular coupling was examined by measuring arterial elastance (Ea) and Ea/Ees. Significant differences in relaxation were found between groups. Indices of diastolic stiffness and of contractile function were not different between groups. Baseline contractile efficiency was increased in the doxorubicin group. Ea and Ea/Ees were lower in the doxorubicin group. Ea/Ees was near 1 at baseline in the doxorubicin group, indicating that conditions were optimized for performance of external stroke work. Therefore, the reserve to increase external cardiac work was diminished. The finding of altered diastolic function suggests the importance of screening of diastolic indices to detect the earliest disturbances in cardiac function caused by doxorubicin.

Oral fluid therapy. A promising treatment for vasodepressor syncope.

OBJECTIVE: To investigate the predictive value of an intravenous fluid bolus during tilt table testing on clinical outcome and to evaluate of oral therapy is an effective treatment for patients with vasodepressor syncope. DESIGN: Retrospective cohort. SETTING: Regional pediatric cardiology outpatient clinic. PATIENTS: Patients (N = 58) with a positive baseline tilt table testing result who were treated with oral fluid therapy between February 1991 and March 1996. INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients with a positive tilt table test result were given an intravenous bolus of isotonic saline solution. Responders were identified as having a negative tilt table test result after the bolus. Patients were prescribed a protocol of oral fluid therapy. Data were obtained from the medical record and a mailed survey. RESULTS: Of the 58 subjects, 90% had no recurrent syncope while receiving oral fluid therapy. During tilt table testing, the mean decrease in mean arterial pressure seen with symptomatic events was lower after the intravenous fluid. The heart rate, which dropped during the initial test, increased during the rests after the intravenous bolus. In the nonresponders, symptomatic episodes occurred significantly later in the tilt table test when given fluids. The response to intravenous fluid bolus had positive predictive value of 92% and negative predictive value of 11% of clinical outcome. CONCLUSIONS: Our data suggest that oral fluid therapy is an effective treatment for vasodepressor syncope in our population. Fluid bolus response during tilt table testing has a high positive but a low negative predictive value of response to oral fluid therapy. We now recommend oral fluid therapy as a primary intervention and reserve tilt table testing for oral fluid therapy failures.

Reopening after successful coil occlusion for patent ductus arteriosus.

OBJECTIVES: This study was performed to determine the frequency of patent ductus arteriosus (PDA) reopening and the factors that may predict reopening after successful coil occlusion. BACKGROUND: Transcatheter coil occlusion is a widely used and accepted method to close a PDA. After documented successful coil occlusion, we found PDAs that reopened. We hypothesized that specific factors are involved in those that reopened. METHODS: All patients who underwent percutaneous transarterial PDA coil occlusion were studied. Successful coil occlusion was documented. PDA reopening was determined when Doppler-echocardiography (DE) performed after the procedure was negative for PDA flow but at follow-up demonstrated PDA shunting. Patients with a reopened PDA were compared with all other patients in evaluating independent variables. RESULTS: Coil occlusion for PDA was attempted in 22 patients. Clinical success was achieved in 20 patients (91%), and DE was negative for PDA shunting in 19 patients (90%). At follow-up, five patients demonstrated reopening. The PDA minimal diameter was 1.4 +/- 0.5 mm (mean +/- SD) for the reopened group and 1.2 +/- 0.7 mm for the other patients. The PDA length was 2.9 +/- 1.9 mm for the reopened group and 7.1 +/- 3.2 mm for all other patients. All those with type B PDA were in the reopened group. When independent variables were compared between groups, only PDA length and type B PDA predicted reopening (p < 0.05). CONCLUSIONS: PDA reopening may occur after successful coil occlusion. Short PDA length and type B PDA are associated with reopening. The data suggest that in such anatomy, alternative strategies to the current coil occlusion technique should be considered.

Left ventricular systolic function, arterial elastance, and ventricular-vascular coupling: a developmental study in piglets.

Circulatory changes occur during perinatal life that increase cardiac output and left ventricular contractile reserve. To examine postnatal changes in left ventricular systolic function and ventricular-vascular coupling, piglets underwent cardiac catheterization at 1, 2, 4, and 6 wk of age. We measured end-systolic elastance (Ees), preload-recruitable stroke work, dP/dt(max), the dP/dt(max) end-diastolic volume relation, cardiac index, heart rate, arterial elastance (Ea), and the ratio Ea/Ees, at rest, during isoproterenol infusions (0.05-1.0 microg/kg/min), and after propranolol (1 mg/kg i.v.). Resting heart rate and cardiac index decreased between 1 and 6 wk. In 1 wk olds, resting Ees was at maximum and was unchanged during isoproterenol infusion; isoproterenol increased other contractility indices. Two, 4, and 6 wk olds demonstrated reserve using all contractility indices. Contractile efficiency was not different between ages. In 1 wk olds, Ea decreased during isoproterenol infusion; isoproterenol did not change Ea at 6 wk. Ea/Ees was higher at rest at 6 wk than at 1 wk, and fell significantly on isoproterenol; isoproterenol did not change Ea/Ees at 1 wk. With beta-adrenergic stimulation, 1 wk olds increased cardiac index by increasing heart rate and decreasing afterload, 6 wk olds increased cardiac index by increasing heart rate and contractility; no change in contractile efficiency was found in either group. In summary, contractile reserve is limited at 1 wk when measured by Ees, but other indices demonstrated reserve. Indexed Ea falls in response to beta-adrenergic stimulation in all ages but 6 wk. Ventricular-vascular coupling is optimized at 1 wk even under baseline conditions.

Left ventricular pressure and volume data acquisition and analysis using LabVIEW.

To automate analysis of left ventricular pressure-volume data, we used LabVIEW to create applications that digitize and display data recorded from conductance and manometric catheters. Applications separate data into cardiac cycles, calculate parallel conductance, and calculate indices of left ventricular function, including end-systolic elastance, preload-recruitable stroke work, stroke volume, ejection fraction, stroke work, maximum and minimum derivative of ventricular pressure, heart rate, indices of relaxation, peak filling rate, and ventricular chamber stiffness. Pressure-volume loops can be graphically displayed. These analyses are exported to a text-file. These applications have simplified and automated the process of evaluating ventricular function.

Effects of commonly used adrenergic agonists on left ventricular function and systemic vascular resistance in young piglets.

This study compared the effects of high-dose infusions of various adrenergic agonists on cardiovascular function in piglets. We hypothesized that agonists would have different effects on systolic, diastolic, and vascular functions. Nine anesthetized 3-week-old piglets underwent cardiac catheterization. Manometric and conductance catheters measured pressures and volumes. Data were acquired at rest and during infusions of epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, and phenylephrine. End-systolic elastance, preload-recruitable stroke work, cardiac output, the maximum and minimum derivatives of left ventricular pressure, the relaxation constant tau, peak filling rate, and end-diastolic stiffness were obtained. Contractile efficiency and the cardiac output/pressure-volume area ratio were calculated. Regression was used for analysis of variance; p < 0.05 was considered significant. All agonists increased indexes of contractility. beta-Adrenergic agonists enhanced relaxation. Isoproterenol and dopamine increased efficiency. No drug changed diastolic stiffness. Therefore both alpha-adrenergic and beta-adrenergic agonists have inotropic effects in the 3-week-old piglet. Some beneficial effects of beta-agonists on cardiac output may be due to enhancement of relaxation and to afterload reduction. Various agents exert different effects on the cardiovascular system, and these differences may be clinically important.

Serum lidocaine concentrations after subcutaneous administration in patients undergoing cardiac catheterization in a pediatric institution.

OBJECTIVE: We wished to determine serum lidocaine concentrations after subcutaneous injection during cardiac catheterization. METHOD: Serum lidocaine concentrations were measured in 50 patients during catheterization. RESULTS: Serum concentration was linearly related to dose per kilogram of body weight. Lidocaine concentrations were therapeutic in 38% of patients. CONCLUSION: Lidocaine dose must be considered when the drug is used for local anesthesia in children.

Coronary artery fistula in the pediatric age group: a 19-year institutional experience.

Ten patients with coronary artery fistulae were identified from records at Columbus Children's Hospital between 1974 and 1993. Clinical presentations of patients were quite variable, from 1 day to 20 years of age. Symptoms ranged from none to severe cardiorespiratory failure requiring extracorporeal membrane oxygenation. Long term follow-up revealed one sudden death and one spontaneous closure of the fistula. This lesion should be ruled out in patients who present as extracorporeal membrane oxygenation candidates. Patients with mild forms of this lesion may be followed up medically if the left to right shunt is inconsequential, because spontaneous closure is a possibility. Because of the risk of sudden death, close long-term follow-up is mandatory even for operated patients, and antiplatelet therapy should be considered for these patients.

Use of cardiac catheterization in pediatric cardiac surgical decisions.

Current practice patterns relating to pediatric cardiac catheterization (Cath) have considerable economic implications. The decreased cost and risk of noninvasive methods such as echocardiography (ECHO) and magnetic resonance imaging (MRI) make them attractive alternative diagnostic methods if they can sufficiently define cardiac anatomy and the need for surgical intervention. We reviewed a recent cardiac surgical series of 465 cases in 1.5 years to determine how often a Cath was performed prior to surgery. Overall, 59.4% of the procedures were preceded by a Cath (76% of open heart operations, and 26.7% of closed heart operations). We specify the situations where we feel enough information is available for preoperative decision making from non-invasive testing, and we present some diagnostic pitfalls that have been encountered.

Pulmonary valve eccentricity in d-transposition of the great arteries and implications for the arterial switch operation.

Neoaortic valve regurgitation is a known complication of the arterial switch operation for d-transposition. Its etiology and long-term effects are undetermined. Observations of pathologic specimens from 67 patients with d-transposition of the great arteries with or without ventricular septal defects demonstrated that the pulmonary valve leaflets had unequal cusp sizes leading to eccentric closure. The posterior cusp was usually the largest and was anatomically related to the membranous ventricular septum and the anterior leaflet of the mitral valve. The right cusp was usually the smallest. Differences in cusp sizes were unrelated to age at death, sex or presence of a ventricular septal defect. To determine if eccentricity could be clinically detected, the pulmonary valves in 24 sequential patients with d-transposition were studied echocardiographically and angiographically. Aortic valves were studied for comparison. All pulmonary valves demonstrated eccentric closure in the long-axis echo plane, posterior in 15 patients and anterior in 9. Only 1 aortic valve showed eccentricity. Angiographic findings correlated with echo findings. Sixteen patients underwent arterial switch operations; 3 died. Twelve had angiography at 1 year. Eleven had neoaortic valve regurgitation: 5 grade I, 4 grade II and 2 grade III.

The end-systolic pressure-volume relationship in young animals using the conductance technique.

Evaluation of ventricular performance by the end-systolic pressure-volume relationship (ESPVR) has been extensively performed in the adult heart using the conductance technique. We undertook this study to validate the conductance technique and to generate ESPVRs in the small heart. To validate the technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets during changes in volume and contractility. Raw conductance volumes correlated highly with cineangiographic volumes (R = 0.97), and the slope was near identity (1.11 +/- 0.04). However, 'alpha Vc-corrected' volumes correlated less well (R = 0.85), probably because of errors induced by the saline technique for alpha Vc. We evaluated the ESPVR in nine lambs by inferior vena cava (IVC) occlusion, aortic occlusion, and volume infusion at rest and during changes in contractility. Reliable and linear ESPVRs were obtained in almost all IVC and aortic occlusions but not in volume infusions. Neither slope (Ees) nor position (V14) significantly changed over time or with dobutamine, but both changed after propranolol, supporting studies showing a limited contractile reserve in the newborn. However, Ees was 25% less steep when generated by IVC occlusion as compared to aortic occlusion. We conclude that the ESPVR can be reliably generated in the small heart using the conductance technique, but that it is sensitive to the loading technique.

Complications of pediatric cardiac catheterization: a 3-year study.

To determine the current risk of pediatric cardiac catheterization, the complications and incidents of all catheterizations performed in a pediatric laboratory between January 1986 and October 1988 were prospectively recorded and compared with results from a 1974 study from the same institution. In the current study 1,037 catheterizations, 885 diagnostic and 152 diagnostic/interventional procedures, were performed in 888 patients (aged 1 day to 27 years, median 15.6 months). There were 15 major complications (1.4%), 70 minor complications (6.8%) and 30 incidents (2.9%). Two patients died as a result of the procedure and two as a result of pericatheterization clinical deterioration caused by the cardiac abnormality. The great majority of complications were successfully treated or were self-limited and the patients had no residua. Of patients with 13 nonfatal major complications and 70 minor complications, residua were evident in 7 patients and 3 without evident residua had the potential for sequelae (0.7% and 0.3% of catheterizations). A comparison of the diagnostic and balloon atrial septostomy cases in the present study with similar cases in the 1974 study shows that the incidence of major complications has decreased from 2.9% to 0.9% (p less than 0.0001); minor complications and incidents have decreased from 11.7% to 7.9% (p less than 0.006) and pericatheterization deaths not attributable to catheterization have decreased from 2.8% to 0.2% (p less than 0.0001). Changes in pericatheterization medical management, patient selection for catheterization and catheterization techniques probably account for these improvements.

The conductance volume catheter technique for measurement of left ventricular volume in young piglets.

The conductance catheter has been used extensively in the adult for instantaneous and continuous measurement of left ventricular volumes, but has not been validated for use in the small heart. To determine the accuracy of this technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets (2-5 wk of age) over a wide range of volumes experimentally altered by volume infusion, hemorrhage, inferior vena caval occlusion, or administration of phenylephrine, isoproterenol, or propranolol. We performed 110 comparisons and determined parallel conductance of contiguous structures (alpha Vc) for each comparison using the saline technique. End-systole and end-diastole volumes were estimated by angiography using Simpson's rule. Raw and alpha Vc-corrected conductance volumes were compared to simultaneously obtained angiographic volumes by multiple regression analyses, using dummy variable coding for the effects of the interanimal variability and the phase of the cardiac cycle. Raw conductance volumes correlated highly with the cineangiographic volumes (r = 0.97), and the coefficient of angiographic volumes was near identity (1.11 +/- 0.04). The phase of the cardiac cycle did not have a significant effect. However, alpha Vc-corrected conductance volumes correlated less (well (r = 0.85), probably related to the fact that estimated alpha Vc was found to vary with ventricular volume. Thus, the conductance catheter affords a very accurate technique for measuring instantaneous changes in ventricular volume in the small heart, although correction to absolute volumes using the saline technique for estimation of alpha Vc may induce some inaccuracy.

In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep.

In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.

Balloon pulmonary valvuloplasty: results of the Valvuloplasty and Angioplasty of Congenital Anomalies Registry.

Eight hundred twenty-two balloon pulmonary valvuloplasties were reported to the Valvuloplasty and Angioplasty of Congenital Anomalies Registry. Before and after systolic outflow gradients were recorded in 784 valvuloplasties, and the gradient decreased from 71 +/- 33 to 28 +/- 21 mm Hg. The sites of residual obstructions could be ascertained in 196 patients. In these, the total systolic outflow gradients decreased from 85 +/- 41 mm Hg to 33 +/- 27 mm Hg. Of this total residual gradient, 16 +/- 15 mm Hg was transvalvar and 18 +/- 24 mm Hg was infundibular. The degree to which infundibular obstruction subsequently resolved was not determined in this study. The procedure was less effective in reducing outflow gradients in patients with dysplastic valves with or without Noonan's syndrome. There were 5 major complications (0.6%), including 2 deaths (0.2%), a cardiac perforation with tamponade (0.1%) and 2 tricuspid insufficiencies (0.2%). There were 11 minor complications (1.3%) and 21 incidents (2.6%). The incidence of major complications, minor complications and incidents was inversely related to age; it was substantially higher in infants and, in particular, neonates. Balloon pulmonary valvuloplasty is a safe and effective method of lowering pulmonary outflow gradients in infants, children and adults. Small transvalvar and varied infundibular gradients commonly are present at the end of the procedure. Assessing the full effect of the procedure requires intermediate-term follow-up and assessing the duration of relief requires long-term follow-up.

Doubly committed subarterial ventricular septal defects: echocardiographic features and surgical implications.

Doubly committed subarterial (supracristal, subpulmonary) ventricular septal defects are often complicated by aortic regurgitation resulting from aortic valve herniation into the defect. The clinical, echocardiographic and catheterization findings in 48 patients aged 0.3 to 46.4 years (median 9.5) with a doubly committed subarterial ventricular septal defect were reviewed. Aortic valve herniation was present in 38 (79%) and 55% of these had aortic regurgitation. The prevalence of both findings increased gradually with advancing age. The defect was closed surgically in 41 patients. Surgery during the first 2 years of life (median 0.4 year) was performed in 13 patients (group I), mainly because of a large shunt with a pulmonary to systemic flow ratio (Qp/Qs) 3.8 +/- 1.4 (mean +/- SD). Aortic regurgitation was present preoperatively in two patients (15%), persisted postoperatively in one patient and did not develop in any after repair (median duration of follow-up 2.3 years, range 0.1 to 7.4). In the other 28 patients (group II) surgery was performed between 4.8 and 46.4 years of age (median 11.5). These patients were generally less symptomatic and had a smaller shunt (Qp/Qs 1.5 +/- 0.5, p less than 0.001). Preoperative aortic regurgitation was present in 18 (64%). It persisted in 15 postoperatively, but in 13 of these it had diminished. Two-dimensional echocardiography in multiple views identified the site of the ventricular septal defect in all patients. Serial echocardiographic examinations demonstrated the progressive nature of aortic valve herniation, the partial occlusion of the defect by the herniated sinus and the development of aortic regurgitation. These findings suggest that timely surgical closure of these defects may prevent aortic regurgitation.

Color Doppler flow mapping in the ultrasound diagnosis of total anomalous pulmonary venous connection.

With color Doppler flow mapping (CFM), we studied 16 children with total anomalous pulmonary venous connection (TAPVC), which was confirmed at cardiac catheterization, surgery, or autopsy in all but one case. The drainage was supracardiac in nine children, cardiac in four, and infracardiac in three. Obstruction to pulmonary venous return was present in seven children. Increased variance, reflecting disturbed blood flow, as well as increased velocities and aliasing were present in all patients. In patients without obstruction turbulence was present in the right atrium and throughout the common pulmonary venous structures. In patients with obstruction a discrete site of increased turbulence and velocity was identified at the site of obstruction. CFM allows rapid differentiation between normal and abnormal venous and arterial structures in TAPVC. In patients suspected of having TAPVC with obstruction, CFM complemented by pulsed Doppler facilitates the determination of the site of obstruction. CFM allows a more rapid appreciation of the anatomy in TAPVC than can be achieved by two-dimensional imaging alone.