Timothy M. Hoffman

Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease

Background—Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results—The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-&mgr;g/kg bolus over 60 minutes followed by a 0.25-&mgr;g/kg per min infusion for 35 hours; high dose, 75-&mgr;g/kg bolus followed by a 0.75-&mgr;g/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P =0.023) in 238 treated patients and 64% (P =0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P =0.049). Conclusions—The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

Hybrid Approach for Hypoplastic Left Heart Syndrome: Intermediate Results After the Learning Curve

BACKGROUND Lessons learned during the development of a novel hybrid approach have resulted in a reliable, reproducible alternative treatment for hypoplastic left heart syndrome (HLHS). Herein we report our results using this hybrid approach in a uniform risk cohort. METHODS This is a review of prospectively collected data on patients treated for HLHS using a hybrid approach (n = 40) between July 2002 and June 2007. The hybrid approach includes pulmonary artery bands, a ductal stent, and atrial septostomy as a neonate, comprehensive stage 2 procedure resulting in Glenn shunt physiology at six months and Fontan completion at two years. RESULTS Forty patients had a hybrid stage 1 with 36 undergoing a comprehensive stage 2 procedure. Fifteen patients have completed the Fontan procedure with 17 pending. Overall survival was 82.5% (33 of 40). The seven deaths included one at stage 1, two between stages 1 and 2, three at stage 2, and one between stages 2 and 3. One patient had successful heart transplantation during the interstage period. CONCLUSIONS The hybrid approach can yield acceptable intermediate results that are comparable with a traditional Norwood strategy. Potential advantages of the hybrid approach include the avoidance of circulatory arrest and shifting the major surgical stage to later in life. These data provide the platform for a prospective trial comparing these two surgical options to assess whether there is less cumulative impact with the hybrid approach, thereby improving end organ function, quality, and quantity of life.

Recommendations for the Use of Mechanical Circulatory Support: Device Strategies and Patient Selection A Scientific Statement From the American Heart Association

The era of mechanical circulatory support (MCS) began in 1953 with the development of cardiopulmonary bypass to facilitate open heart surgery.1 In 1964, the National Heart Institute (now the National Heart, Lung, and Blood Institute) funded the Artificial Heart Program and became actively involved in MCS development. This led to requests for Proposals issued in 1977 and 1980, which laid the foundation for the development of implantable MCS for long-term use, including devices capable of hospital discharge, in the 1990s. Although heart transplantation is now commonplace at many hospitals, the inadequate supply of donor hearts and patient contraindications to transplantation continue to severely restrict its application. As the demand for long-term replacement of diseased hearts increases, there is a clear need for innovative, safe, and durable MCS to treat the growing population of patients with advanced heart failure (HF). Many exciting changes in the field of MCS have occurred in the past few years, including the development of smaller portable pumps and the concept of destination therapy (DT), or permanent pump placement as an alternative to heart transplantation. Currently, there are no published guidelines for the use of MCS. Thus, it is our intent that this statement will provide the contemporary cardiologist and other HF providers with an understanding of general considerations when determining the appropriateness of MCS. There is little hope that complete consensus will ever be reached on the definition of advanced HF, but most physicians caring for such patients on a regular basis readily identify the characteristics of these patients. Advanced HF patients are those with clinically significant circulatory compromise who require special care, including consideration for heart transplantation, continuous intravenous inotropic therapy, MCS, or hospice.2,3 Typically, such patients have symptoms at rest or with minimal exertion and cannot perform many activities of …

Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient

Objective: Hyperglycemia in critical care populations has been shown to be a risk factor for increased morbidity and mortality. Minimal data exist in postoperative pediatric cardiac patients. The goal of this study was to determine whether hyperglycemia in the postoperative period was associated with increased morbidity or mortality. Design: Retrospective chart review. Setting: Tertiary care, free-standing pediatric medical center with a dedicated cardiac intensive care unit. Patients: We included 184 patients <1 yr of age who underwent cardiac surgery requiring cardiopulmonary bypass from October 2002 to August 2004. Patients with a weight <2 kg, a preoperative diagnosis of diabetes, preoperative extracorporeal membrane oxygenation support, solid organ transplant recipients, and preoperative renal or liver insufficiency were excluded. Interventions: None. Measurements and Main Results: Age was 4.3 ± 3.2 months and weight was 4.9 ± 1.7 kg at surgery. Duration of hyperglycemia was significantly longer in patients with renal insufficiency (p = .029), liver insufficiency (p = .006), infection (p < .002), central nervous system event (p = .038), extracorporeal membrane oxygenation use (p < .001), and death (p < .002). Duration of hyperglycemia was also significantly associated with increased intensive care (p < .001) and hospital (p < .001) stay and longer ventilator use (p < .001). Peak glucose levels were significantly different in patients with renal insufficiency (p < .001), infection (p = .002), central nervous system event (p = .01), and mortality (p < .001). Conclusions: Hyperglycemia in the postoperative period was associated with increased morbidity and mortality in postoperative pediatric cardiac patient. Strict glycemic control may improve outcomes in this patient population.

Postoperative junctional ectopic tachycardia in children : Incidence, risk factors, and treatment

BACKGROUND Junctional ectopic tachycardia (JET) occurs commonly after pediatric cardiac operation. The cause of JET is thought to be the result of an injury to the conduction system during the procedure and may be perpetuated by hemodynamic disturbances or postoperative electrolyte disturbances, namely hypomagnesemia. The purpose of this study was to determine perioperative risk factors for the development of JET. METHODS Telemetry for each patient admitted to the cardiac intensive care unit from December 1997 through November 1998 for postoperative cardiac surgical care was examined daily for postoperative JET. A nested case-cohort analysis of 33 patients who experienced JET from 594 consecutively monitored patients who underwent cardiac operation was performed. Univariate and multivariate analyses were conducted to determine factors associated with the occurrence of JET. RESULTS The age range of patients with JET was 1 day to 10.5 years (median, 1.8 months). Univariate analysis revealed that dopamine or milrinone use postoperatively, longer cardiopulmonary bypass times, and younger age were associated with JET. Multivariate modeling elicited that dopamine use postoperatively (odds ratio, 6.2; p = 0.01) and age less than 6 months (odds ratio, 4.0; p = 0.02) were associated with JET. Only 13 (39%) of the patients with JET received therapeutic interventions. CONCLUSIONS Junctional ectopic tachycardia occurred in 33 (5.6%) of 594 patients who underwent cardiac operation during the study period. Postoperative dopamine use and younger age were associated with JET. It may be speculated that dopamine should be discontinued in the presence of postoperative JET.

Cardiovascular Function and Treatment in β-Thalassemia Major A Consensus Statement From the American Heart Association

This aim of this statement is to report an expert consensus on the diagnosis and treatment of cardiac dysfunction in β-thalassemia major (TM). This consensus statement does not cover other hemoglobinopathies, including thalassemia intermedia and sickle cell anemia, in which a different spectrum of cardiovascular complications is typical. There are considerable uncertainties in this field, with a few randomized controlled trials relating to treatment of chronic myocardial siderosis but none relating to treatment of acute heart failure. The principles of diagnosis and treatment of cardiac iron loading in TM are directly relevant to other iron-overload conditions, including in particular Diamond-Blackfan anemia, sideroblastic anemia, and hereditary hemochromatosis. Heart failure is the most common cause of death in TM and primarily results from cardiac iron accumulation. The diagnosis of ventricular dysfunction in TM patients differs from that in nonanemic patients because of the cardiovascular adaptation to chronic anemia in non-cardiac-loaded TM patients, which includes resting tachycardia, low blood pressure, enlarged end-diastolic volume, high ejection fraction, and high cardiac output. Chronic anemia also leads to background symptomatology such as dyspnea, which can mask the clinical diagnosis of cardiac dysfunction. Central to early identification of cardiac iron overload in TM is the estimation of cardiac iron by cardiac T2* magnetic resonance. Cardiac T2* <10 ms is the most important predictor of development of heart failure. Serum ferritin and liver iron concentration are not adequate surrogates for cardiac iron measurement. Assessment of cardiac function by noninvasive techniques can also be valuable clinically, but serial measurements to establish trends are usually required because interpretation of single absolute values is complicated by the abnormal cardiovascular hemodynamics in TM and measurement imprecision. Acute decompensated heart failure is a medical emergency and requires urgent consultation with a center with expertise in its management. The first principle of management of acute heart failure is control of cardiac toxicity related to free iron by urgent commencement of a continuous, uninterrupted infusion of high-dose intravenous deferoxamine, augmented by oral deferiprone. Considerable care is required to not exacerbate cardiovascular problems from overuse of diuretics or inotropes because of the unusual loading conditions in TM. The current knowledge on the efficacy of removal of cardiac iron by the 3 commercially available iron chelators is summarized for cardiac iron overload without overt cardiac dysfunction. Evidence from well-conducted randomized controlled trials shows superior efficacy of deferiprone versus deferoxamine, the superiority of combined deferiprone with deferoxamine versus deferoxamine alone, and the equivalence of deferasirox versus deferoxamine.

The Incidence of Arrhythmias in a Pediatric Cardiac Intensive Care Unit

A pediatric cardiac intensive care unit (CICU) manages critically ill children and adults with congenital or acquired heart disease. These patients are at increased risk for arrhythmias. The purpose of this study was to prospectively evaluate the incidence of arrhythmias in a pediatric CICU patient population. All patients admitted to the CICU at the Cardiac Center at The Childrens Hospital of Philadelphia between December 1, 1997, and November 30, 1998, were evaluated prospectively from CICU admission to hospital discharge via full disclosure telemetry reviewed every 24 hours. Arrhythmias reviewed included nonsustained and sustained ventricular tachycardia (VT), nonsustained and sustained supraventricular tachycardia (SVT), atrial flutter and fibrillation, junctional ectopic tachycardia, and complete heart block. We reviewed 789 admissions consisting of 629 patients (age range, 1 day–45.5 years; median, 8.1 months). Hospital stay ranged from 1 to 155 days (total of 8116 patient days). Surgical interventions (n = 602) included 482 utilizing cardiopulmonary bypass. During the study period, there were 44 deaths [44/629 patients (7.0%)], none of which were directly attributable to a primary arrhythmia. The operative mortality was 5.1%. Overall, 29.0% of admissions had one or more arrhythmias the most common arrhythmia was nonsustained VT (18.0% of admissions), followed by nonsustained SVT (12.9% of admissions). Patients admitted to a pediatric CICU have a high incidence of arrhythmias, most likely associated with their underlying pathophysiology and to the breadth of medical and surgical interventions conducted.

Outcome of Pediatric Patients With Dilated Cardiomyopathy Listed for Transplant: A Multi-institutional Study

BACKGROUND The course of dilated cardiomyopathy (DCM) leading to heart failure in children varies; survival with conventional treatment is 64% at 5 years. Heart transplantation (HTx) enables improved survival; however, outcomes from listing for transplant are not well described. This study reports survival of patients with DCM from listing with the availability of mechanical bridge to transplant. METHODS Patients with a primary diagnosis of DCM (n = 1,098) were identified from a multi-institutional, prospective, registry of patients aged < 18 years listed for HTx from January 1, 1993, to December 31, 2006. RESULTS Characteristics of DCM patients at listing included a mean age of 7.3 years; 51% male, 64% white ethnicity, 77% United Network for Organ Sharing status I, 66% on inotropic support, 28% mechanically ventilated, and 15% on mechanical support. Waitlist mortality was 11%, and 75% underwent HTx at 2 years after listing. Overall 10-year survival after listing was 72%, with higher risk of death associated with arrhythmias, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO) support, but not ventricular assist device (VAD) support. Survival at 10 years post-HTx was 72%, with a higher risk of death associated with black race, older age, mechanical ventilation, longer ischemic time, and earlier era of transplant. CONCLUSIONS Transplantation for DCM in the pediatric population offers enhanced survival compared with the natural history. Overall waitlist mortality for DCM is low, with the exception of patients on ECMO, mechanically ventilated, or with arrhythmias. DCM patients fared well after transplant, making HTx a key therapeutic intervention.

Report of the Pediatric Heart Network and National Heart, Lung, and Blood Institute Working Group on the Perioperative Management of Congenital Heart Disease

The survival of patients with congenital heart disease (CHD) has significantly improved during the past several decades (the Figure). This accomplishment is directly attributable to the net effect of individual therapeutic successes from the innovative work of surgeons and cardiologists and the courageous devotion of patients and families. However, as the field moves forward, the need for evidence-based medicine derived from multi-institutional collaborations to address more subtle and complex questions such as functional outcome and quality of life and to provide data to guide individual practitioners has become paramount. Recognizing this, the National Heart, Lung, and Blood Institute (NHLBI) established the Pediatric Heart Network (PHN) in 2001 to provide a collaborative platform for conducting clinical studies. The need for evidence-based care and the ability of the PHN to provide this evidence were demonstrated by recent developments in the surgical management of hypoplastic left heart syndrome. Hypoplastic left heart syndrome was a uniformly fatal defect before Norwood’s innovative surgical approach in which the diminutive aorta is reconstructed using the pulmonary artery trunk and pulmonary blood flow is provided by a Blalock-Taussig shunt. 2 Recently, a previously described modification to this procedure in which pulmonary blood flow is provided by a right ventricle to pulmonary artery shunt has seen renewed interest. 3 This modification has been widely adopted but has yielded conflicting results. 4–7 In May 2005, the PHN launched the Single Ventricle Reconstruction (SVR) trial, a randomized trial comparing these 2 surgical strategies. 8 In just over 3 years, 555 infants were

A Population Pharmacokinetic Analysis of Milrinone in Pediatric Patients After Cardiac Surgery

The purpose of this study was to ascertain the optimal pharmacokinetic model for milrinone in pediatric patients after cardiac surgery when milrinone was administered as a slow loading dose followed by a constant-rate infusion. The data used for pharmacokinetic analysis were collected in a prospective, randomized, placebo-controlled multi-center trial of milrinone as prophylaxis for the development of low cardiac output syndrome after surgery for repair of complex congenital cardiac defects. Two blood samples were randomly collected from each patient for determination of plasma milrinone concentrations with subsequent population pharmacokinetic modeling. The pharmacokinetics of milrinone in pediatric patients under 6years age were best described by a weight-normalized one compartment model after a slow loading dose followed by a constant-rate infusion. The volume of distribution was 482mlkg−1, and was independent of age. Clearance was a linear function of age given by Cl=2.42mlkg−1min−1[1+0.0396*age].