Peter C. Frommelt

Recommendations for Quantification Methods During the Performance of a Pediatric Echocardiogram: A Report From the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council

n Society of Echocardiography designates this educational activity for of 1.5 AMA PRA Category 1 Credits . Physicians should only claim credit te with the extent of their participation in the activity. CCI recognize the ASE’s certificates and have agreed to honor the credit their registry requirements for sonographers. n Society of Echocardiography is committed to ensuring that its educan and all sponsored educational programs are not influenced by the special y corporation or individual, and itsmandate is to retain only those authors ial interests can be effectively resolved to maintain the goals and educaty of the activity. Although amonetary or professional affiliationwith a cors not necessarily influence an author’s presentation, the Essential Areas and e ACCME require that any relationships that could possibly conflict with al value of the activity be resolved prior to publication and disclosed to . Disclosures of faculty and commercial support relationships, if any, dicated. ience: is designed for all cardiovascular physicians and cardiac sonographers with erest and knowledge base in the field of echocardiography; in addition, reschers, clinicians, intensivists, and other medical professionals with a spein cardiac ultrasound will find this activity beneficial.

Comparison of shunt types in the Norwood procedure for single-ventricle lesions.

BACKGROUND The Norwood procedure with a modified Blalock-Taussig (MBT) shunt, the first palliative stage for single-ventricle lesions with systemic outflow obstruction, is associated with high mortality. The right ventricle-pulmonary artery (RVPA) shunt may improve coronary flow but requires a ventriculotomy. We compared the two shunts in infants with hypoplastic heart syndrome or related anomalies. METHODS Infants undergoing the Norwood procedure were randomly assigned to the MBT shunt (275 infants) or the RVPA shunt (274 infants) at 15 North American centers. The primary outcome was death or cardiac transplantation 12 months after randomization. Secondary outcomes included unintended cardiovascular interventions and right ventricular size and function at 14 months and transplantation-free survival until the last subject reached 14 months of age. RESULTS Transplantation-free survival 12 months after randomization was higher with the RVPA shunt than with the MBT shunt (74% vs. 64%, P=0.01). However, the RVPA shunt group had more unintended interventions (P=0.003) and complications (P=0.002). Right ventricular size and function at the age of 14 months and the rate of nonfatal serious adverse events at the age of 12 months were similar in the two groups. Data collected over a mean (+/-SD) follow-up period of 32+/-11 months showed a nonsignificant difference in transplantation-free survival between the two groups (P=0.06). On nonproportional-hazards analysis, the size of the treatment effect differed before and after 12 months (P=0.02). CONCLUSIONS In children undergoing the Norwood procedure, transplantation-free survival at 12 months was better with the RVPA shunt than with the MBT shunt. After 12 months, available data showed no significant difference in transplantation-free survival between the two groups. (ClinicalTrials.gov number, NCT00115934.)

Initiation and Use of Propranolol for Infantile Hemangioma: Report of a Consensus Conference

Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in nature and anticipate that they will be revised as more data are made available.

Home surveillance program prevents interstage mortality after the Norwood procedure

OBJECTIVE To determine whether early identification of physiologic variances associated with interstage death would reduce mortality, we developed a home surveillance program. METHODS Patients discharged before initiation of home surveillance (group A, n = 63) were compared with patients discharged with an infant scale and pulse oximeter (group B, n = 24). Parents maintained a daily log of weight and arterial oxygen saturation according to pulse oximetry and were instructed to contact their physician in case of an arterial oxygen saturation less than 70% according to pulse oximetry, an acute weight loss of more than 30 g in 24 hours, or failure to gain at least 20 g during a 3-day period. RESULTS Interstage mortality among infants surviving to discharge was 15.8% (n = 9/57) in group A and 0% (n = 0/24) in group B (P =.039). Surveillance criteria were breached for 13 of 24 group B patients: 12 patients with decreased arterial oxygen saturation according to pulse oximetry with or without poor weight gain and 1 patient with poor weight gain alone. These 13 patients underwent bidirectional superior cavopulmonary connection (stage 2 palliation) at an earlier age, 3.7 +/- 1.1 months of age versus 5.2 +/- 2.0 months for patients with an uncomplicated interstage course (P =.028). A growth curve was generated and showed reduced growth velocity between 4 and 5 months of age, with a plateau in growth beyond 5 months of age. CONCLUSION Daily home surveillance of arterial oxygen saturation according to pulse oximetry and weight selected patients at increased risk of interstage death, permitting timely intervention, primarily with early stage 2 palliation, and was associated with improved interstage survival. Diminished growth identified 4 to 5 months after the Norwood procedure brings into question the value of delaying stage 2 palliation beyond 5 months of age.

Consensus Statement on Diagnostic Criteria for PHACE Syndrome

OBJECTIVES: A subgroup of patients with infantile hemangiomas have associated structural anomalies of the brain, cerebral vasculature, eyes, sternum, and/or aorta in the neurocutaneous disorder known as PHACE syndrome. The diagnosis has been broadly inclusive by using a case definition of a facial hemangioma plus ≥1 extracutaneous features, leading to numerous reports of potential associated disease features, many of uncertain significance. This consensus statement was thus developed to establish diagnostic criteria for PHACE syndrome. METHODS: A multidisciplinary group of specialists with expertise in PHACE syndrome drafted initial diagnostic criteria on the basis of review of published, peer-reviewed medical literature and clinical experience. The group then convened in both executive and general sessions during the PHACE Syndrome Research Conference held in November 2008 for discussion and used a consensus method. All conflicting recommendations were subsequently reconciled via electronic communication and teleconferencing. RESULTS: These criteria were stratified into 2 categories: (1) PHACE syndrome or (2) possible PHACE syndrome. Major and minor criteria were determined for the following organ systems: cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline. Definite PHACE requires the presence of a characteristic segmental hemangioma or hemangioma >5 cm on the face or scalp plus 1 major criterion or 2 minor criteria. Possible PHACE requires the presence of a hemangioma >5 cm on the face or scalp plus 1 minor criterion. The group recognized that it may be possible to have PHACE syndrome with a hemangioma affecting the neck, chest, or arm only or no cutaneous hemangioma at all. In such cases, fulfillment of additional required criteria would also lead to a possible PHACE diagnosis. CONCLUSIONS: These criteria represent current knowledge and are expected to enhance future assessments of PHACE syndrome. It is understood that modifications are to be expected over time to incorporate new research findings.

Hypoglycemia in Children Taking Propranolol for the Treatment of Infantile Hemangioma

BACKGROUND Propranolol hydrochloride has been prescribed for decades in the pediatric population for a variety of disorders, but its effectiveness in the treatment of infantile hemangiomas (IHs) was only recently discovered. Since then, the use of propranolol for IHs has exploded because it is viewed as a safer alternative to traditional therapy. OBSERVATIONS We report the cases of 3 patients who developed symptomatic hypoglycemia during treatment with propranolol for their IHs and review the literature to identify other reports of propranolol-associated hypoglycemia in children to highlight this rare adverse effect. CONCLUSIONS Although propranolol has a long history of safe and effective use in infants and children, understanding and recognition of deleterious adverse effects is critical for physicians and caregivers. This is especially important when new medical indications evolve as physicians who may not be as familiar with propranolol and its adverse effects begin to recommend it as therapy.

Prospective echocardiographic diagnosis and surgical repair of anomalous origin of a coronary artery from the opposite sinus with an interarterial course

OBJECTIVES In this study, we sought to describe the mode of presentation, anatomic features, diagnostic techniques, and surgical outcome in a group of patients with anomalous origin of a coronary artery from the opposite sinus with an interarterial course between the great arteries (AOCA). BACKGROUND Anomalous origin of a coronary artery from the opposite sinus with an interarterial course is associated with myocardial ischemia and sudden cardiac death, particularly in adolescents and young adults. METHODS The cardiology database at Childrens Hospital of Wisconsin was reviewed to identify all patients diagnosed with AOCA. RESULTS From September 1997 to August 2002, 10 patients were identified with AOCA; all were children/adolescents (age range, 3 months to 20 years; weight range, 4.7 to 72 kg), and nine were diagnosed prospectively by transthoracic echocardiography (TTE). Symptoms of cardiac ischemia initiated investigation in 4/10 patients at a mean age of 16 +/- 2.8 years; the other six had TTE for suspected congenital heart disease/musculoskeletal chest pain. The left coronary artery originated from the right sinus in six patients, and the right coronary artery originated from the left sinus in four patients. An intramural course of the AOCA within the anterior aortic wall was found in 9/10 patients and was reliably identified by TTE; the other patient had an intramyocardial course of the anomalous coronary. Surgical repair was performed in 8/10 patients at a mean age of 13 +/- 4.7 years. Unroofing of the intramural portion of the AOCA to relocate the ostia in the appropriate sinus was successfully performed in seven patients. All patients status post unroofing were asymptomatic with patent coronary flow by Doppler and normal exercise treadmill testing at a median follow-up interval of 1.5 years. CONCLUSIONS Anomalous origin of a coronary artery from the opposite sinus with an interarterial course is frequently characterized by an intramural course, which can be prospectively identified by TTE. Unroofing the intramural segment without bypass grafting can reliably repair the intramural form of AOCA.

Transplantation-Free Survival and Interventions at 3 Years in the Single Ventricle Reconstruction Trial

Background— In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle–to–pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups. Methods and Results— Vital status and medical history were ascertained from annual medical records, death indexes, and phone interviews. The cohort included 549 patients randomized and treated in the SVR trial. Transplantation-free survival for the RVPAS versus MBTS groups did not differ at 3 years (67% versus 61%; P=0.15) or with all available follow-up of 4.8±1.1 years (log-rank P=0.14). Pre-Fontan right ventricular ejection fraction was lower in the RVPAS group than in the MBTS group (41.7±5.1% versus 44.7±6.0%; P=0.007), and right ventricular ejection fraction deteriorated in RVPAS (P=0.004) but not MBTS (P=0.40) subjects (pre-Fontan minus 14-month mean, −3.25±8.24% versus 0.99±8.80%; P=0.009). The RVPAS versus MBTS treatment effect had nonproportional hazards (P=0.004); the hazard ratio favored the RVPAS before 5 months (hazard ratio=0.63; 95% confidence interval, 0.45–0.88) but the MBTS beyond 1 year (hazard ratio=2.22; 95% confidence interval, 1.07–4.62). By 3 years, RVPAS subjects had a higher incidence of catheter interventions (P<0.001) with an increasing HR over time (P=0.005): <5 months, 1.14 (95% confidence interval, 0.81–1.60); from 5 months to 1 year, 1.94 (95% confidence interval, 1.02–3.69); and >1 year, 2.48 (95% confidence interval, 1.28–4.80). Conclusions— By 3 years, the Norwood procedure with RVPAS compared with MBTS was no longer associated with superior transplantation-free survival. Moreover, RVPAS subjects had slightly worse right ventricular ejection fraction and underwent more catheter interventions with increasing hazard ratio over time. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00115934.

Intermediate-term mortality and cardiac transplantation in infants with single-ventricle lesions: Risk factors and their interaction with shunt type

OBJECTIVE The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt. METHODS We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. RESULTS Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (P = .01), obstructed pulmonary venous return (P < .001), smaller ascending aorta (P = .02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P < .001) and lower gestational age (P < .001). The right ventricle-to-pulmonary artery shunt demonstrated better survival in the 51% of subjects who were full term with aortic atresia (P < .001). The modified Blalock-Taussig shunt was better among the 4% of subjects who were preterm with a patent aortic valve (P = .003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P < .03), but shunt type was not (P = .43). CONCLUSIONS Independent risk factors for intermediate-term mortality include lower socioeconomic status, anatomy, genetic syndrome, and lower gestational age. Term infants with aortic atresia benefited from a right ventricle-to-pulmonary artery shunt, and preterm infants with a patent aortic valve benefited from a modified Blalock-Taussig shunt. Right ventricular function and anatomy, but not shunt type, were associated with transplantation.

Design and rationale of a randomized trial comparing the Blalock-Taussig and right ventricle-pulmonary artery shunts in the Norwood procedure

OBJECTIVE The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two techniques. METHODS The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for subjects undergoing a Norwood procedure with either the right ventricle-pulmonary artery or modified Blalock-Taussig shunt. Infants with a diagnosis of single, morphologically right ventricle anomaly who are undergoing a Norwood procedure are eligible for inclusion in this study. The primary outcome is death or cardiac transplant 12 months after random assignment. Secondary outcomes include postoperative morbidity after Norwood and stage II palliation procedures, right ventricular function and pulmonary arterial growth at stage II palliation, and neurodevelopmental outcomes at 14 months old. Incidence of adverse events will also be compared between treatment groups. CONCLUSION This study will make an important contribution to the care of patients with hypoplastic left heart syndrome and related forms of single, morphologically right ventricle. It also establishes a model with which other operative interventions for patients with congenital cardiovascular malformations can be evaluated in the future.