Parental factors impacting the enrollment of children in cardiac critical care clinical trials.

Clinical trials are abundant in adult cardiovascular medicine; however, they are rare in pediatric cardiology. Pediatric cardiac trial design may be impacted by the heterogeneous nature of the underlying cardiac defects, as well as by a strong emotional response from parents whose child will undergo a surgical intervention. The purpose of this study was to assess factors that may have an impact on parents considering enrollment of their child in a clinical trial at the time of surgical intervention. A voluntary, self-administered questionnaire (14 questions) was provided to parents of children 16 years of age or younger during the preadmission testing period. Demographic and procedure-related variables were collected for each patient. A total of 119 surveys were analyzed over a 1.5-year period. Only 8% of the parents had their child participate in a clinical trial in the past. Fifty-six percent of the parents preferred that their child's cardiologist or surgeon explain clinical trial details, with 23% preferring the principal investigator and 3% preferring the research coordinator. Fifty percent of the parents were favorably disposed to participate in a clinical trial if the drug or device was currently used by their child's doctor, and 19% were encouraged to participate if the drug or device was approved for use in adults. The majority of parents (64%) preferred to be asked about participating in a trial within 1 month prior to the planned procedure, and 40% preferred to discuss trial details at a remote time in an outpatient location. Sixty-three percent of parents believed that most of the medications currently used in children were already approved by the Food and Drug Administration. Most parents (91%) believed that clinical trials conducted in children will help improve pediatric health care; 74% believed that their child may receive potential benefit from enrolling in a trial. Finally, 43% believed that funding for trials should come from government and health care agencies, as opposed to pharmaceutical companies (24%). This survey reveals the importance of the attending physician and timing in educating parents regarding a cardiac critical care clinical trial. These data may impact the design and successful conduct of future trials.

Nitric oxide in the evaluation of congenital heart disease with pulmonary hypertension: factors related to nitric oxide response.

Inhaled nitric oxide (NO) has been used in the preoperative evaluation of patients with congenital heart disease and pulmonary hypertension. The purpose of this study was to characterize responses in pulmonary vascular resistance (PVR) to oxygen and increasing doses of NO during cardiac catheterization and to determine if any related factors affect the response of the pulmonary vascular bed to NO. A prospective analysis of 42 patients (median age, 3.0 years) with congenital heart disease and pulmonary hypertension who underwent NO testing was performed. Systemic vascular resistance (SVR) and PVR were assessed in room air, 100% oxygen, and oxygen plus 20, 40, and 80 parts per million (ppm) NO. Changes in pulmonary artery pressure, PVR, and SVR were assessed. The response to NO was then correlated to individual patient's age, gender, type of heart defect, the presence of trisomy 21, and baseline PVR/SVR. There was a greater decrease in PVR and PVR/SVR with 20 ppm NO than with oxygen alone. There was no additional decrease at 40 or 80 ppm NO. There was no correlation between age, gender, type of congenital heart disease, and baseline PVR/SVR ratio with the degree of response to NO. Patients with trisomy 21 had less of a response to NO (p = 0.017) than patients without trisomy 21. There is no difference in determining PVR response with doses of NO beyond 20 ppm during cardiac catheterization. Age, gender, and baseline PVR/SVR ratio are not associated with responsiveness to NO. Patients with trisomy 21 may be less responsive to NO.

Natural history of growth of secundum atrial septal defects and implications for transcatheter closure.

OBJECTIVE: To investigate the natural history of secundum atrial septal defects (ASDs) over several years using serial echocardiographic studies. METHODS: All patients with isolated secundum ASDs who had serial transthoracic echocardiograms at Texas Children's Hospital, Houston, Texas, from January 1991 to December 1998 were identified. Patients with fenestrated or multiple ASDs, other congenital heart defects, or less than a six month interval between echocardiograms were excluded. There were 104 patients eligible for inclusion in the study. Studies were reviewed by two echocardiographers (blinded) and the maximal diameter was recorded. Defects were defined as small (> 3 mm to < 6 mm), moderate (> or = 6 mm to < 12 mm), or large (> or = 12 mm). ASDs that grew > or = 20 mm were defined as having outgrown transcatheter closure with the device available to the authors' institution. RESULTS: ASD diameter increased in 68 of 104 patients (65%), including 31 patients (30%) with a > 50% increase in diameter. Spontaneous closure occurred in four patients (4%). Thirteen defects (12%) increased to > or = 20 mm. One fifth of the patients studied had an insufficient atrial rim by transthoracic echocardiogram to hold an atrial septal occluder. The only factor associated with significant growth of ASDs was initial size of the defect. ASD growth was independent both of age at diagnosis and when indexed to body surface area. CONCLUSIONS: Two thirds of secundum ASDs may enlarge with time and there is the potential for secundum ASDs to outgrow transcatheter closure with specific devices. Further development in devices and general availability of devices capable of closing larger ASDs should circumvent this problem.

Perioperative care of the adult with congenital heart disease in a free-standing tertiary pediatric facility.

Adult patients with congenital heart disease are presenting more frequently for cardiac surgery. Frequently, pediatric congenital heart surgeons perform these procedures at pediatric hospitals. Between July 1995 and June 2000, a retrospective review of adult patients (> or = 18 years old) who had undergone cardiothoracic operations was performed. A total of 112 operations were performed and divided into two groups--81 cardiac operations in 79 patients and 31 noncardiac operations in 23 patients. One patient had a cardiac and noncardiac operation performed. The overall early operative mortality was 6% (6/101). There were 3 late deaths. New-onset cardiac arrhythmias requiring treatment were diagnosed after 5/81 (6%) cardiac operations. Six of 79 (7%) patients were diagnosed with postoperative clinical depression. An acceptable mortality can be achieved when adult patients undergo cardiothoracic operations at a pediatric facility. New-onset arrhythmias necessitating treatment are relatively common, and postoperative clinical depression should be anticipated.

The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The aim of this study was to determine the effect of prophylactic immune suppression on the incidence and severity ofpostpericardiotomy syndrome (PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND: Prophylactic suppression of the inflammatory response has an unknown effect on the incidence and severity of PPS in children undergoing surgery with CPB. METHODS: This randomized double-blind placebo controlled trial included two study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg) plus four additional intravenous doses over 24 h, and Group B received intravenous saline placebo at identical intervals. Data included patient demographics, cardiac diagnosis/operation, CPB time, incidence and severity of PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub, patient irritability, small pericardial +/- pleural effusion. Complicated PPS--noncomplicated PPS plus hospital readmission +/- pericardiocentesis or thoracentesis. RESULTS: We randomized 266 children: 20 exclusions (6 perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n = 126) and Group B (n = 120). There were no significant group differences in gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and was treated as a covariate with no substantive outcome effect. In total, 39/246 children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There was no inter-group difference in overall PPS incidence (p = 0.73). However, Group A had a marginally significant increase in complicated PPS (p = 0.05). CONCLUSIONS: Intravenous methylprednisolone at a standard anti-inflammatory dose administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in children. Short-term pre-CPB and post-CPB methylprednisolone treatment may complicate PPS.

Respiratory syncytial virus in patients with congenital heart disease: a contemporary look at epidemiology and success of preoperative screening.

Awareness of respiratory syncytial virus (RSV) as a serious pathogen in the child with congenital heart disease is increasing. We studied the impact of RSV lower respiratory tract disease on patients in a large academic pediatric cardiology practice. We found that RSV disease necessitating hospitalization occurs in congenital heart disease patients well into the second year of life. Although pulmonary hypertension remains a significant risk factor for morbidity in these patients, it does not appear to be as much of a factor as in the past. By implementing a nasopharyngeal RSV enzyme-linked immunoassay screening of young patients prior to cardiac surgery we found a reduction in community-acquired postoperative RSV disease. We postulate this will lead to a reduction in nosocomial disease in the postoperative care unit.

Early initiation of peritoneal dialysis after surgical repair of congenital heart disease.

The mortality rate of infants who require renal replacement therapy after surgical repair of congenital heart disease has been reported to be 30%-79%. We report our experience with early initiation of continuous manual peritoneal dialysis (CPD) to treat fluid overload in 20 consecutive critically ill children who underwent CPD post cardiotomy. CPD catheters were inserted at the discretion of the cardiothoracic surgeon. CPD was started for evidence of total body fluid overload with inadequate urine output, and stopped when negative fluid balance was achieved and urine output improved. Median age was 10 days (range 3-186 days), mean time to start CPD post-operatively was 22 h (range 5-40 h), and mean duration of CPD was 50 h (range 13-92 h). CPD resulted in mean ultrafiltration of 93 ml/kg per day (range 43-233 ml/kg per day). Net negative fluid balance was 106 ml/kg per day (range 49-273 ml/kg per day). During CPD, the mean number of inotropes decreased from 2.2 to 1.6 (P<0.05) and urine output increased from 2.2 to 3.9 ml/kg per hour (P<0.01). No patient died during CPD or had CPD discontinued due to adverse hemodynamic effects. The overall mortality rate was 20%. We conclude that early initiation of CPD can safely and effectively promote fluid removal in infants after repair of congenital heart disease, with a lower mortality rate than has previously been reported.

Development of advanced pulmonary vascular disease in D-transposition of the great arteries after the neonatal arterial switch operation.

We report the case of a neonate with D-transposition of the great arteries who, after undergoing an uneventful arterial switch operation at the age of 4 days, was found at the age of 42 months to have developed advanced pulmonary vascular disease. Because the arterial switch operation was performed when our patient was only 4 days old, this case challenges the hypothesis that postnatal hemodynamics alone dictate the development of advanced pulmonary vascular disease in infants and children with transposition of the great arteries.

Left ventricular performance following the arterial switch operation: use of noninvasive wall stress analysis in the postoperative period.

OBJECTIVE: To determine postoperative left ventricular mechanics following the arterial switch operation (ASO). DESIGN: Prospective, cohort study. SETTING: Pediatric cardiac recovery room. PATIENTS: Nine neonates with transposition of the great arteries undergoing the ASO within the first week of life. INTERVENTIONS: Noninvasive ejection phase indices: shortening fraction (% SF), corrected mean velocity of circumferential shortening (VCFc), and wall stress analysis were used to calculate indices of specific left ventricular systolic mechanics. The % SF and VCFc were respectively adjusted for left ventricular afterload (end-systolic wall stress) to derive an index for left ventricular performance (stress-shortening relation) and contractility (stress-velocity relation). Left ventricular preload was assessed as the variance between the performance and contractility indices. All indexed data are reported as mean Zscore (i.e., number of standard deviations from the mean of a normal age- and body surface area-adjusted population). A mean Zscore of < -2 or > 2 was regarded as a significant variance from normal. Transmitral Doppler flow patterns were recorded at each postoperative interval and analyzed for isovolumic relaxation time (IVRT) as an index of left ventricular compliance. MEASUREMENTS AND MAIN RESULTS: All nine patients did well clinically and completed the study. Noninvasive parameters were measured at mean intervals of 3 (early), 23 (intermediate), and 48 hrs (late postoperative) relative to the time of arrival in the cardiac recovery room. Postoperative left ventricular performance was decreased throughout the early (-4.0 +/- 1.5 SD), intermediate (-4.1 +/- 2.8), and late (-3.5 +/- 1.3) phases of recovery. In contrast, the overall left ventricular contractility remained normal throughout the three postoperative intervals (0.2 +/- 1.8, -1.2 +/- 1.9, and -1.0 +/- 1.6, respectively), although three of the nine patients had a diminished stress-velocity index during the study period. Left ventricular afterload was within normal range in the early (0.1 +/- 1.7) and intermediate (1.5 +/- 1.9) phases of recovery, but increased in the late postoperative period (2.5 +/- 2.9). Left ventricular preload was decreased significantly throughout the early (-4.2 +/- 1.3), intermediate (-2.8 +/- 2.0), and late (-2.5 +/- 1.0) postoperative phases. All nine patients demonstrated decreased preload during the recovery period. IVRT was decreased in the post-ASO patients at each phase of recovery compared with normal data (p < .001). CONCLUSIONS: Left ventricular performance is impaired in infants during the period immediately following the ASO. A persistent preload deficit closely matches the pattern of impaired ventricular performance. Decreased IVRT points to impaired ventricular compliance as the etiology of the altered preload. In contrast, left ventricular contractility remains normal in the majority of post-ASO patients. Decreased contractility may account for impaired ventricular performance in selected cases.

Risk factors for life-threatening cavopulmonary thrombosis in patients undergoing bidirectional superior cavopulmonary shunt: an exploratory study.

We have observed six patients with life-threatening superior vena caval or pulmonary thrombosis after bidirectional superior cavopulmonary shunt. With the use of a case control study we sought to identify perioperative risk factors for this thrombotic complication. Medical records of six patients with cavopulmonary thrombosis and those of 24 patients in a control group were reviewed to abstract data for potential risk factors. Contingency tables and univariate logistic regression were used to determine associations between various perioperative parameters and occurrence of cavopulmonary thrombosis. Preoperative variables associated with thrombosis included bilateral superior vena cavae, odds ratio: 23, p = 0.02, increased age at surgery (p = 0.05), and female sex (odds ratio: 7, p = 0.05). The McGoon Ratio (index of relative pulmonary artery branch diameter) was inversely related to thrombosis risk (p = 0.08). Two torr increases in mean right atrial (p = 0.08) or ventricular end-diastolic (p = 0.05) pressures were associated with approximately 70% increases in thrombosis risk. Intraoperative prolongation of aortic cross-clamp time related directly to thrombosis risk (p = 0.06). Postoperative variables associated with thrombosis included increased superior vena caval pressure within 12 hours after surgery (odds ratio > or = 10 for 5 torr increase in pressure, p = 0.02) and poor ventricular function (odds ratio: 9, p = 0.06) We conclude that high risk variables for patients undergoing a cavopulmonary shunt include bilateral superior vena cavae, female sex, increasing age, decreased McGoon Ratio, and elevated right atrial and ventricular end-diastolic pressure (before surgery), patients with prolonged aortic cross-clamp time (during surgery), and patients with elevated superior vena caval pressure and poor ventricular function (after surgery).

The rare association of tetralogy of Fallot with hypertrophic cardiomyopathy. Report of 2 neonatal patients.

Although tetralogy of Fallot is commonly associated with other congenital heart defects, it is rarely found in conjunction with hypertrophic cardiomyopathy. We describe the cases of 2 neonates with this rare condition, both of whom required surgical intervention during infancy. Because hypertrophic cardiomyopathy is frequently familial, and tetralogy of Fallot is commonly found in patients diagnosed with chromosomal anomalies, we speculate about a possible genetic cause for this association.

Peritoneal dialysis. An adjunct to pediatric postcardiotomy fluid management.

Patients requiring cardiopulmonary bypass for congenital heart surgery commonly exhibit impaired renal function and extravascular fluid retention. These conditions contribute to early postoperative fluid overload, which may result in significant morbidity and mortality. We examined the safety and efficacy of peritoneal dialysis in removing extravascular fluid from critically ill postcardiotomy patients. A retrospective case review from July of 1995 through April of 1996 was conducted. All patients undergoing peritoneal dialysis achieved a net negative fluid balance. Average urine output increased from 2.1 cc/kg/hr to 3.9 cc/kg/hr (P < 0.01) during the pre-peritoneal dialysis to post-peritoneal dialysis period, and the mean number of inotropic agents decreased from 2.2 to 1.7 (P < 0.05). Controlled comparison revealed that the peritoneal dialysis cohort more rapidly achieved a negative weight-adjusted fluid balance throughout the early postoperative course. The peritoneal dialysis group's illness severity decreased more rapidly within the 24-hour period after initiation of peritoneal dialysis than did that of the control cohort over the same period of time. No difference in postoperative morbidity or mortality existed between the study groups. Complications from the catheter placement were minimal, and no patient experienced peritonitis or metabolic or hemodynamic instability during peritoneal dialysis catheter placement, usage, or removal. Peritoneal dialysis is a safe and effective form of renal replacement therapy, even among critically ill pediatric postcardiotomy patients. Early postsurgical institution of peritoneal dialysis may hasten early postoperative recovery. We speculate that intraoperative catheter placement reduces the complication rate associated with this treatment modality.

Nitric oxide for the evaluation and treatment of pulmonary hypertension in congenital heart disease.

The use of inhaled nitric oxide as a selective pulmonary vasodilator has expanded to include patients with congenital heart disease and pulmonary hypertension. The therapeutic and diagnostic roles of inhaled nitric oxide offer additional alternatives and benefits to these patients with pulmonary hypertension, particularly in the postoperative setting. This article reviews the background, mechanism of action, toxicities, and current clinical applications of inhaled nitric oxide in the child with congenital heart disease and pulmonary hypertension.

Fatal myocardial infarction in an 8-year-old girl with systemic lupus erythematosus, Raynaud's phenomenon, and secondary antiphospholipid antibody syndrome.

An 8-year-old black girl with a 5 month history of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) developed Raynaud's phenomenon, marked hemolytic anemia, and a fatal myocardial infarction (MI). Pathologic evaluation of the heart demonstrated a transmural acute MI associated with a recent thrombus of the circumflex coronary artery, thrombosis of small intramural arteries, and a coronary arteriopathy resembling fibromuscular dysplasia. Inflammatory or atherosclerotic changes of the coronary arteries were distinctly absent. This case represents the youngest reported patient with SLE, MI, and pathologic confirmation of nonatheromatous coronary artery disease. The observed coronary pathological findings may have accentuated the thrombogenic potential of the APS, resulting in coronary thrombosis. Cardiac lesions in SLE and APS are reviewed, and pathogenetic considerations for the coronary vasculopathy are discussed.

Lifelong management of patients with a single functional ventricle: a protocol.

Of the wide variety of congenital heart defects, the single functional ventricle continues to be one of the most enigmatic. Compared with patients who have complex congenital heart defects and 2 functional ventricles, patients with a single functional ventricle have greater surgical and long-term morbidity and mortality, and use more medical resources. Recent investigations have shown that patients with a single functional ventricle often have very satisfactory hemodynamics soon after a modified Fontan repair but then develop dilated cardiomyopathy during the subsequent decade. The cause and pathogenesis of the cardiomyopathy have not yet been determined. Many publications have examined individual aspects of the care of these patients based on retrospective reviews, but very few have provided comprehensive prospective methods for managing patients with a single functional ventricle. We hypothesized that a comprehensive management protocol with regular review of the results would provide a better understanding of the problems encountered in these patients and thus improve long-term outcome. Herein, we present our initial protocol for the lifelong management of patients with a single functional ventricle.

Transesophageal echocardiographic detection of atrial thrombi in patients with nonfibrillation atrial tachyarrhythmias and congenital heart disease.

OBJECTIVES: We hypothesized an association between atrial thrombi and nonfibrillation atrial tachyarrhythmias in patients with congenital heart disease. BACKGROUND: We observed a fatal thromboembolus after direct current cardioversion in an adolescent with atrial flutter and repaired tetralogy of Fallot. METHODS: Using transesophageal echocardiography, we prospectively studied 19 consecutive patients with congenital heart disease with nonfibrillation atrial tachyarrhythmia (atrial flutter in 18, primary atrial tachycardia in 1) undergoing electrophysiologic procedures (median age 19.6 years, range 7.0 to 53.8; 11 male, 8 female). Transthoracic echocardiograms were available for 17 patients. RESULTS: All transesophageal examinations were performed without incident. No atrial thrombi were detected in 11 patients who subsequently had uncomplicated direct current cardioversion. Eight solitary atrial thrombi were detected (incidence 42%). Six thrombi were located in the right atrium (Fontan repair in four patients, Ebstein's malformation repair in two), and two were noted in the left atrium (congenital hypertrophic cardiomyopathy and atrial septal defect repair in one patient each). Transthoracic echocardiograms were available in seven of eight patients with thrombus detected by transesophageal echocardiography, with only one study conclusive for an atrial thrombus. Cardioversion was deferred in six of eight patients with thrombus, and anticoagulation therapy was initiated. Uncomplicated electrophysiologic procedures were conducted in two patients at the time of detection of right atrial thrombus (atrioventricular node ablation in one patient, direct current cardioversion in the other). CONCLUSIONS: Prothrombin conditions exist in patients with congenital heart disease with nonfibrillation atrial tachyarrhythmias, as indicated by a significant incidence of transesophageally detected atrial thrombi. The need for prophylactic anticoagulation and the safety of pharmacologic or direct current cardioversion are issues that remain unresolved.

Quantitated left ventricular systolic mechanics in children with septic shock utilizing noninvasive wall-stress analysis.

OBJECTIVE: To quantitate ventricular systolic mechanics in septic children. DESIGN: Prospective wall-stress analysis was compared to standard ejection phase indices. SETTING: University-based pediatric intensive care unit. PATIENTS: Fifteen children with sepsis (hemodynamically stable, n = 5; in shock, n = 10). MEASUREMENTS AND MAIN RESULTS: Left ventricular ejection phase indices: shortening fraction (shortening) and corrected mean velocity of circumferential shortening (velocity) were adjusted for end-systolic wall stress (stress). Ejection phase, performance (stress-shortening relation), contractility (stress-velocity relation), and afterload (stress) were indexed to age-corrected normal means, with variance of > or = 2 SD regarded as significant. Preload index represented variance between performance and contractility indices. All hemodynamically stable septic patients had normal performance, contractility, and preload. Afterload was increased in three of five patients. Of the patients with septic shock, six of ten had decreased performance (decreased contractility and increased afterload, n = 4; decreased afterload, n = 1; and severe preload deficit, n = 1). Despite aggressive volume resuscitation, six of ten children in septic shock had evidence of diminished preload. Follow-up studies in the septic shock patients demonstrated reversal of depressed ventricular contractility within 3 to 6 days in all four patients initially affected (p < .05). One patient developed late decreased performance and contractility in association with multiple organ failure. Ventricular loading abnormalities persisted in a follow-up study of these patients including a preload deficit in five of ten patients in shock. CONCLUSIONS: The frequency rate (40%) of reversible impaired ventricular contractility in children with septic shock is significant. Afterload is normal or increased in the majority of septic subjects, possibly due to acute ventricular dilation. Decreased preload contributes to altered ventricular performance in the majority of children with septic shock, persisting days after the initiation of therapy. Wall-stress analysis provided detailed information regarding ventricular mechanics that was not otherwise obtainable by standard ejection phase indices.