K. Gauvreau

Surgical outcome for patients with the mitral stenosis–aortic atresia variant of hypoplastic left heart syndrome

OBJECTIVE We sought to identify and characterize a subgroup of patients with hypoplastic left heart syndrome who might be at higher risk for stage I failure. METHODS From January 2001 through December 2006, all patients with hypoplastic left heart syndrome who underwent stage I palliation at Childrens Hospital Boston were retrospectively reviewed. The subgroup with the mitral stenosis-aortic atresia variant was studied separately. We evaluated preoperative echocardiographic data, operative characteristics, and postoperative factors associated with death or the need for transplantation. The Kaplan-Meier method was used to assess survival. RESULTS Thirty-eight (23%) of 165 patients had mitral stenosis-aortic atresia. Hospital mortality or need for transplantation for patients with mitral stenosis-aortic atresia was significantly higher than for other anatomic subgroups (29% vs 7.9%, P = .002). Left ventricle-subepicardial coronary artery communications were present in 20 (53%) patients with mitral stenosis-aortic atresia and were associated with a significantly higher hospital mortality (50% vs 6%, P = .004). No difference in outcome was demonstrated between different sources of pulmonary blood flow. A longer cardiopulmonary bypass time (P = .02) and the need for postoperative extracorporeal membrane oxygenation support (P < .001) were associated with a higher mortality rate. CONCLUSIONS With improved outcomes in the management of neonates with hypoplastic left heart syndrome, those with the mitral stenosis-aortic atresia variant and left ventricle-subepicardial coronary artery fistulae have emerged as a higher-risk subgroup for failure of stage I palliation. Further investigation is required, and a change in clinical management strategy for this particular subgroup might be warranted.

The Barth Syndrome Registry: Distinguishing disease characteristics and growth data from a longitudinal study

Barth syndrome (BTHS); MIM accession # 302060) is a rare X‐linked recessive cardioskeletal mitochondrial myopathy with features of cardiomyopathy, neutropenia, and growth abnormalities. The objectives of this study were to further elucidate the natural history, clinical disease presentation, and course, and describe growth characteristics for males with BTHS. Patients with a confirmed genetic diagnosis of BTHS are referred to the BTHS Registry through the Barth Syndrome Foundation, self‐referral, or physician referral. This study is based on data obtained from 73 subjects alive at the time of enrollment that provided self‐reported and/or medical record abstracted data. The mean age at diagnosis of BTHS was 4.04 ± 5.45 years. While the vast majority of subjects reported a history of cardiac dysfunction, nearly 6% denied any history of cardiomyopathy. Although most subjects had only mildly abnormal cardiac function by echocardiography reports, 70% were recognized as having cardiomyopathy in the first year of life and 12% have required cardiac transplantation. Of the 73 enrolled subjects, there have been five deaths. Growth curves were generated demonstrating a shift down for weight, length, and height versus the normative population with late catch up in height for a significant percentage of cases. This data also confirms a significant number of patients with low birth weight, complications in the newborn period, failure to thrive, neutropenia, developmental delay of motor milestones, and mild learning difficulties. However, it is apparent that the disease manifestations are variable, both over time for an individual patient and across the BTHS population.

Acute Outcomes after Introduction of a Standardized Clinical Assessment and Management Plan (SCAMP) for Balloon Aortic Valvuloplasty in Congenital Aortic Stenosis

INTRODUCTION Standardization of care can reduce practice variation, optimize resource utilization, and improve clinical outcomes. We have created a standardized clinical assessment and management plan (SCAMP) for patients having balloon aortic valvuloplasty (BAV) for congenital aortic stenosis (AS). This study compares acute outcomes of BAV at our institution before and after introduction of this SCAMP. METHODS In this retrospective matched cohort study, each SCAMP patient was matched to four historical controls. Outcomes were categorized based on the combination of residual AS and aortic regurgitation (AR) as: (1) Optimal: gradient ≤ 35 mm Hg and trivial or no AR; (2) Adequate: gradient ≤ 35 mm Hg and mild AR; (3) Inadequate: gradient > 35 mm Hg and/or moderate or severe AR. RESULTS All 23 SCAMP patients achieved a residual AS gradient ≤ 35 mm Hg; the median residual AS gradient for the SCAMP group was lower (25 [10-35] mm Hg) than in matched controls (30 [0-65] mm Hg; P = 0.005). The two groups did not differ with regard to degree of AR grade after BAV. Compared with controls, SCAMP patients were more likely to have an optimal result and less likely to have an inadequate result (52% vs. 34% and 17% vs. 45%, respectively; P = 0.02) CONCLUSIONS: A SCAMP for BAV resulted in optimal acute results in half of the initial 23 patients enrolled, and outcomes in this group were better than those of matched historical controls. Whether these improved acute outcomes translate into better long-term outcomes for this patient population remains to be seen.

Coronary Artery Aneurysms in Kawasaki Disease: Risk Factors for Progressive Disease and Adverse Cardiac Events in the US Population

Background The natural history of coronary artery aneurysms (CAA) after intravenous immunoglobulin (IVIG) treatment in the United States is not well described. We describe the natural history of CAA in US Kawasaki disease (KD) patients and identify factors associated with major adverse cardiac events (MACE) and CAA regression. Methods and Results We evaluated all KD patients with CAA at 2 centers from 1979 to 2014. Factors associated with CAA regression, maximum CA z‐score over time (zMax), and MACE were analyzed. We performed a matched analysis of treatment effect on likelihood of CAA regression. Of 2860 KD patients, 500 (17%) had CAA, including 90 with CAA z‐score >10. Most (91%) received IVIG within 10 days of illness, 32% received >1 IVIG, and 27% received adjunctive anti‐inflammatory medications. CAA regression occurred in 75%. Lack of CAA regression and higher CAA zMax were associated with earlier era, larger CAA z‐score at diagnosis, and bilateral CAA in univariate and multivariable analyses. MACE occurred in 24 (5%) patients and was associated with higher CAA z‐score at diagnosis and lack of IVIG treatment. In a subset of patients (n=132) matched by age at KD and baseline CAA z‐score, those receiving IVIG plus adjunctive medication had a CAA regression rate of 91% compared with 68% for the 3 other groups (IVIG alone, IVIG ≥2 doses, or IVIG ≥2 doses plus adjunctive medication). Conclusions CAA regression occurred in 75% of patients. CAA z‐score at diagnosis was highly predictive of outcomes, which may be improved by early IVIG treatment and adjunctive therapies.

Idiopathic Pericarditis and Pericardial Effusion in Children: Contemporary Epidemiology and Management

Background Multicenter studies on idiopathic or viral pericarditis and pericardial effusion (PPE) have not been reported in children. Colchicine use for PPE in adults is supported. We explored epidemiology and management for inpatient hospitalizations for PPE in US children and risk factors for readmission. Methods and Results We analyzed patients in the Pediatric Health Information System database for (1) a code for PPE; (2) absence of codes for underlying systemic disease (eg, neoplastic, cardiac, rheumatologic, renal); (3) age ≥30 days and <21 years; and (4) discharge between January 1, 2007, and December 31, 2012, from 38 hospitals contributing complete data for each year of the study period. Among 11 364 hospitalizations with PPE codes during the study period, 543 (4.8%) met entry criteria for idiopathic or viral PPE. Significantly more boys were noted, especially among adolescents. No temporal trends were noted. Median age was 14.5 years (interquartile range 7.3 to 16.6 years); 78 patients (14.4%) underwent pericardiocentesis, 13 (2.4%) underwent pericardiotomy, and 11 (2.0%) underwent pericardiectomy; 157 (28.9%) had an intensive care unit stay, including 2.0% with tamponade. Median hospitalization was 3 days (interquartile range 2 to 4 days). Medications used at initial admission were nonsteroidal anti‐inflammatory drugs (71.3%), corticosteroids (22.7%), aspirin (7.0%), and colchicine (3.9%). Readmissions within 1 year of initial admission occurred in 46 of 447 patients (10.3%), mostly in the first 3 months. No independent predictors of readmission were noted, but our statistical power was limited. Practice variation was noted in medical management and pericardiocentesis. Conclusions Our report provides the first large multicenter description of idiopathic or viral PPE in children. Idiopathic or viral PPE is most common in male adolescents and is treated infrequently with colchicine.

Echocardiographic Predictors of Left Ventricular Dysfunction after Aortic Valve Surgery in Children with Chronic Aortic Regurgitation

OBJECTIVE Postoperative left ventricular dysfunction is associated with poor prognosis in adults with severe chronic aortic regurgitation and published practice guidelines aim to minimize this risk. However, only limited information exists in pediatrics. The goal of this study was to define preoperative risk factors for postoperative left ventricular dysfunction in children with chronic aortic regurgitation. METHODS Patients fulfilling the following criteria were included in this study: (1) age at preoperative echocardiogram ≤18 years; (2) ≥moderate aortic regurgitation; (3) ≤mild aortic valve stenosis; (4) no additional valve disease/shunt; (5) underwent aortic valve surgery for aortic regurgitation; and (6) available preoperative and ≥6-month postoperative echocardiograms with adequate information. Primary outcome was postoperative left ventricular dysfunction defined as ejection fraction z-score < -2. RESULTS Median ages at diagnosis and surgery of the 53 eligible patients were 6.9 (0.04-17.2) and 13 years (1.2-22.4), respectively. Compared with patients whose postoperative left ventricular ejection fraction was normal, those with left ventricular ejection fraction z-score < -2 (n = 10) had significantly higher preoperative left ventricular end-diastolic and systolic volumes and dimensions and lower indices of systolic function. Preoperative left ventricular ejection fraction z-score < -1 was the most sensitive (89%; confidence interval [CI] 52, 100) but least specific (58%; CI 41, 73), whereas left ventricular end-systolic diameter z-score ≥ 5 was the most specific (95%; CI 84, 99) but least sensitive (60%; CI 26, 88) outcome identifier. A combination of shortening fraction z-score < -1 or end-systolic diameter z-score ≥ 5 best identified postoperative left ventricular dysfunction with an area of 0.819 under the receiver-operator characteristic curve. CONCLUSION Lower indices of left ventricular systolic function and severity of dilation identify children at risk for postoperative left ventricular dysfunction after aortic valve surgery. These identifiers are similar to predictors defined in adult patients albeit with different threshold values.

Safety and Efficacy of Warfarin Therapy in Kawasaki Disease

Objective To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. Study design We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5. Results In 9 patients (5 male), median age 14.4 years (range 7.1–22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3–13.3 years). Goal INR was 2.0–3.0 (n = 6) or 2.5–3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%‐85%), and median percentage of INRs in range was 68% (52%‐87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient‐years (95% CI 0.9–12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients. Conclusions Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two‐thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.

Is Doppler Echocardiography Useful for Estimating Ventricular Filling Pressures in Pediatric Heart Transplant Recipients

We utilized all echocardiograms with TDI performed within 24 hours of a heart catheterization during 2005-2011 (N=751 studies in 122 HT recipients, median 6 per patient). Using age-based normative values in 380 healthy children, we transformed the biventricular and TDI velocities into z-scores. We used univariate and multivariable analyses; and univariable generalized estimating equation (GEE) models were developed to relate mitral inflow and TDI velocities to pulmonary capillary wedge pressure (PCWP) as a continuous variable and as binary (≥12mmHg). A similar analysis was performed for mean right atrial pressure (RAP) using right ventricular (RV) Doppler velocities. Left ventricular (LV) E/E’ ratio the ratio of mitral inflow Doppler E –wave and annular tissue Doppler imaging E’-wave velocitieshas been accepted as a noninvasive and less expensive surrogate for invasively measured LV filling pressure in adults. However, this technique has thus far performed poorly in children.

Risk-Stratification in Children with Advanced Heart Failure Using Hemodynamic Data

Results: Overall, 109 children (median age 10.6 yrs, 56% male; 61% dilated cardiomyopathy, 21% congenital heart disease, 18% other) underwent 134 catheterizations during the study period. Median CIx (ml/min/m2) was 2.7 (interquartile range [IQR] 2.1, 3.4) and median PCWP (mm Hg) was 18 (IQR 13, 24). Children with CIx ≤ 2.3 (cold) were at higher risk of death or deterioration (HR 2.25, 95% confidence interval [CI] 1.38, 3.67; p = 0.001) compared to children with CIx > 2.3 (warm). Children with PCWP > 21 (wet) were at higher risk of death or deterioration (HR 1.81, 95% CI 1.10, 2.98; p = 0.02) compared to those with PCWP ≤ 21 (dry). Compared to warm-dry children, cold-wet children (HR 3.19, 95% CI 1.75, 5.82; p < 0.001) were at higher risk of death or deterioration but not warm-wet (HR 1.16, 95% CI 0.53, 2.55; p= 0.71) or cold-dry children (HR 1.66, 95% CI 0.84, 3.28; p= 0.14). Conclusion: While low cardiac output and congestion are both associated with higher risk of death or deterioration, low cardiac output is a more sinister prognostic sign among children being evaluated for HT.