Utility of apical four-chamber longitudinal strain in the assessment of childhood cancer survivors: A multicenter study.

BACKGROUND: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population. METHODS: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated. RESULTS: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations. CONCLUSION: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories.

Rationale and design of the Children's Oncology Group study AAML1831 integrated cardiac substudies in pediatric acute myeloid leukemia therapy.

Background: Pediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML. Methods/design: Children (age <22 years) with newly diagnosed AML were enrolled and randomized to CPX-351-containing induction 1 and 2 (Arm A) or standard daunorubicin and dexrazoxane-containing induction (Arm B). Embedded cardiac correlative studies aim to compare the efficacy of this liposomal anthracycline formulation to dexrazoxane for primary prevention of cardiotoxicity by detailed core lab analysis of standardized echocardiograms and serial cardiac biomarkers throughout AML therapy and in follow-up. In addition, AAML1831 will assess the ability of early changes in sensitive echo indices (e.g., global longitudinal strain) and cardiac biomarkers (e.g., troponin and natriuretic peptides) to predict subsequent LVSD. Finally, AAML1831 establishes expert consensus-based strategies in cardiac monitoring and anthracycline dose modification to balance the potentially competing priorities of cardiotoxicity reduction with optimal leukemia therapy. Discussion: This study will inform diagnostic, prognostic, preventative, and treatment strategies regarding cardiotoxicity during pediatric AML therapy. Together, these measures have the potential to improve leukemia-free and overall survival and long-term cardiovascular health in children with AML. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT04293562.

Challenges associated with retrospective analysis of left ventricular function using clinical echocardiograms from a multicenter research study.

BACKGROUND: Retrospective multicenter research using echocardiograms obtained for routine clinical care can be hampered by issues of individual center quality. We sought to evaluate imaging and patient characteristics associated with poorer quality of archived echocardiograms from a cohort of childhood cancer survivors. METHODS: A single blinded reviewer at a central core laboratory graded quality of clinical echocardiograms from five centers focusing on images to derive 2D and M-mode fractional shortening (FS), biplane Simpson's ejection fraction (EF), myocardial performance index (MPI), tissue Doppler imaging (TDI)-derived velocities, and global longitudinal strain (GLS). RESULTS: Of 535 studies analyzed in 102 subjects from 2004 to 2017, all measures of cardiac function could be assessed in only 7%. While FS by 2D or M-mode, MPI, and septal E/E' could be measured in >80% studies, mitral E/E' was less consistent (69%), but better than EF (52%) and GLS (10%). 66% of studies had ≥1 issue, with technical issues (eg, lung artifact, poor endocardial definition) being the most common (33%). Lack of 2- and 3-chamber views was associated with the performing center. Patient age <5 years had a higher chance of apex cutoff in 4-chamber views compared with 16-35 years old. Overall, for any quality issue, earlier era of echo and center were the only significant risk factors. CONCLUSION: Assessment of cardiac function using pooled multicenter archived echocardiograms was significantly limited. Efforts to standardize clinical echocardiographic protocols to include apical 2- and 3-chamber views and TDI will improve the ability to quantitate LV function.

Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors.

BACKGROUND: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. OBJECTIVES: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development. METHODS: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.

Traditional Cardiovascular Risk Factors and Individual Prediction of Cardiovascular Events in Childhood Cancer Survivors.

BACKGROUND: Childhood cancer survivors have an increased risk of heart failure, ischemic heart disease, and stroke. They may benefit from prediction models that account for cardiotoxic cancer treatment exposures combined with information on traditional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes. METHODS: Childhood Cancer Survivor Study participants (n = 22 643) were followed through age 50 years for incident heart failure, ischemic heart disease, and stroke. Siblings (n = 5056) served as a comparator. Participants were assessed longitudinally for hypertension, dyslipidemia, and diabetes based on self-reported prescription medication use. Half the cohort was used for discovery; the remainder for replication. Models for each outcome were created for survivors ages 20, 25, 30, and 35 years at the time of prediction (n = 12 models). RESULTS: For discovery, risk scores based on demographic, cancer treatment, hypertension, dyslipidemia, and diabetes information achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater in 9 and 10 of the 12 models, respectively. For replication, achieved areas under the receiver operating characteristic curve and concordance statistics 0.70 or greater were observed in 7 and 9 of the models, respectively. Across outcomes, the most influential exposures were anthracycline chemotherapy, radiotherapy, diabetes, and hypertension. Survivors were then assigned to statistically distinct risk groups corresponding to cumulative incidences at age 50 years of each target outcome of less than 3% (moderate-risk) or approximately 10% or greater (high-risk). Cumulative incidence of all outcomes was 1% or less among siblings. CONCLUSIONS: Traditional cardiovascular risk factors remain important for predicting risk of cardiovascular disease among adult-age survivors of childhood cancer. These prediction models provide a framework on which to base future surveillance strategies and interventions.

Improving paediatric cardiologists' awareness about the needs of childhood cancer survivors: results of a single-centre directed educational initiative.

BACKGROUND: Cardiovascular disease is a leading cause of morbidity and mortality in childhood cancer survivors. Cardiologists must be aware of risk factors and long-term follow-up guidelines, which have historically been the purview of oncologists. Little is known about paediatric cardiologists' knowledge regarding the cardiotoxicity of cancer treatment and how to improve this knowledge. METHODS: A total of 58 paediatric cardiologists anonymously completed a 21-question, web-based survey focused on four cardio-oncology themes: cancer treatment-related risk factors (n = 6), patient-related risk factors (n = 6), recommended surveillance (n = 3), and cardiac-specific considerations (n = 6). Following the baseline survey, a multi-disciplinary team of paediatric cardiologists and cancer survivor providers developed an in-person and web-based educational intervention. A post-intervention survey was conducted 5 months later. RESULTS: The response rate was 41/58 (70.7%) pre-intervention and 30/58 (51.7%) post-intervention. On the baseline survey, the percentage of correct answers was 68.8 ± 10.3%, which improved to 79.2 ± 16.2% after the intervention (p = 0.009). The theme with the most profound knowledge deficit was surveillance; however, it also had the greatest improvement after the intervention (49.6 ± 26.7 versus 66.7 ± 27.7% correct, p = 0.025). Individual questions with the largest per cent improvement pertained to risk of cardiac dysfunction with time since treatment (52.4 versus 93.1%, p = 0.002) and the role of dexrazoxane (48.8 versus 82.8%, p = 0.020). CONCLUSION: Specific knowledge deficits about the care of paediatric cancer survivors were identified amongst cardiologists using a web-based survey. Knowledge of surveillance was initially lowest but improved the most after an educational intervention. This highlights the need for cardio-oncology-based educational initiatives among paediatric cardiologists.

The landscape of cardiovascular care in pediatric cancer patients and survivors: a survey by the ACC Pediatric Cardio-Oncology Work Group.

OBJECTIVE: To enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors. STUDY DESIGN: A 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC. RESULTS: Sixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%, p < 0.01). The most common indications for referral to cardiology at pediatric centers were abnormal test results (n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%). CONCLUSIONS: The survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.

Preoperative echocardiographic measures in interrupted aortic arch: Which ones best predict surgical approach and outcome?

OBJECTIVE: It is unclear whether neonates with interrupted aortic arch (IAA) and a smaller left ventricular outflow tract may have improved outcomes with a Yasui operation (ventricular outflow bypass procedure) over a primary complete repair. This study sought to identify preoperative echocardiographic parameters to differentiate which neonates may have improved outcomes with a primary vs Yasui operation. DESIGN: Patient demographics, cardiac surgery type, complications, need for reoperation and/or interventional catheterization, and date of last follow-up were collected on neonates who underwent a biventricular repair for IAA from 2003 to 2014. Preoperative echocardiograms were analyzed for: IAA type, valve annulus size, aortic valve morphology, ventricular size and aortic arch anatomy. RESULTS: Seventy-seven neonates underwent IAA repair between 2003 and 2013. 60 neonates had a primary repair and 17 a Yasui operation. Neonates that underwent a Yasui operation had significantly smaller mitral and aortic valves with aortic arch hypoplasia. Within the primary repair group, a decreasing aortic root z-score on univariate analysis increased the odds of reoperation by twofold [OR = 1.98, 95% CI: (1.15-3.42), P = .014]. A significant interaction between repair type and aortic root z-score was identified on multivariable analysis (P = .039), for neonates with aortic root z-scores less than -2.5, the probability of reoperation during the follow up time period [mean 4.5 years (3.3 months-10 year)] was significantly higher in the primary repair group compared to the Yasui group (64.3% vs 37.5%). CONCLUSIONS: Neonates with IAA and an aortic root z-score less than -2.5 have lower odds of subsequent reoperations with a Yasui operation compared to a primary repair over the follow up period. These findings suggest a Yasui operation should be considered if the preoperative aortic root z-score is less than -2.5. Careful evaluation of these morphologic predictors on preoperative echocardiograms can be helpful in surgical planning in neonates with IAA.

Prediction of Ischemic Heart Disease and Stroke in Survivors of Childhood Cancer.

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children's Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were < 5%, compared with approximately 20% for high-risk groups ( P < .001); cumulative incidence was only 1% for siblings ( P < .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.

Cardio-oncology Related to Heart Failure: Pediatric Considerations for Cardiac Dysfunction.

Although tremendous advances in pediatric cancer treatment have improved the survival of many children, these patients remain at increased risk of early morbidity and mortality with cardiovascular disease as a leading cause of death. Heightened awareness in providers with increased surveillance and improvement in cardiovascular imaging modalities have led to earlier detection of cardiac dysfunction, but the outcomes remain poor once this has dysfunction developed. A great deal of work remains to be done to refine screening and identify high-risk patients more precisely, and to develop more evidence-based strategies for effective primary and secondary cardioprotection and treatment.

Yield of screening echocardiograms during pediatric follow-up in survivors treated with anthracyclines and cardiotoxic radiation.

BACKGROUND: Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms. PROCEDURE: Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy. Descriptive statistics and logistic regressions were performed and the yield of screening echocardiograms was calculated. RESULTS: Of 853 patients, 1,728 screening echocardiograms were performed, and 37 patients had an abnormal echocardiogram (overall yield 2.1%). Yields were only somewhat higher in more frequently screened patients. Risk factors for an abnormal result included anthracycline dose of ≥300 mg/m2 (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI]: 1.3-7.2; P < 0.01) with a synergist relationship in patients who also received radiation doses ≥30 Gy (aOR 7.0; 95% CI: 1.6-31.9; P = 0.01), as well as autologous bone marrow transplant (OR 3.3; 95% CI: 1.3-8.5; P = 0.01). Sex, race, age at diagnosis, and cyclophosphamide exposure were not statistically significant risk factors, and no patient receiving <100 mg/m2 anthracycline dose without concomitant radiation had an abnormal echocardiogram. CONCLUSIONS: Dose-dependent and synergist anthracycline and cardiotoxic radiotherapy risks for developing cardiomyopathy were confirmed. However, previously identified risk factors including female sex, black race, and early age at diagnosis were not replicated in this cohort. The yields showed weak correlation across frequency categories. Echocardiographic screening recommendations for low-risk pediatric patients may warrant re-evaluation.

Echocardiographic Predictors of Left Ventricular Outflow Tract Obstruction following Repair of Atrioventricular Septal Defect.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is a common complication following surgical repair of atrioventricular septal defect (AVSD). OBJECTIVE: We sought to determine predictors of LVOTO based on echocardiograms performed prior to initial repair of AVSD. METHODS: Of the 415 children that had repair of AVSD from 2003 to 2012, 17 children were identified with LVOTO that required surgical intervention. Thirty-four patients with repaired AVSD and no LVOTO served as controls. Patient demographics, cardiac surgery type, and echocardiogram results at last follow-up were collected. Off-line analysis of the echocardiogram prior to AVSD repair was done to obtain: left ventricular outflow tract (LVOT) and interventricular septal diameter, chordae across LVOT, aortoseptal angle, left ventricular (LV) inflow/outflow length ratio, inferior displacement of the atrioventricular (AV) valve, atrioventricular valve index (AVVI) and presence of coarctation of the aorta. RESULTS: The LVOTO group had significantly smaller indexed LVOT diameters (P < .001), increased likelihood of chordae crossing the LVOT (P = .010), decreased LV inflow/outflow length ratio (P < .001), decreased AVVI (P = .014) and increased presence of coarctation of the aorta (P = .003) compared to control patients. A multiple logistic regression model including presence of chordae in the LVOT [OR 5.32, 95% CI: (1.24-22.78, P = .024] and an indexed LVOT diameter ≤2.5 cm/m2 [OR 5.41, 95% CI: (1.15-25.39) P = .032] demonstrated each to be independently associated with the development of LVOT obstruction (area under the receiving operating curve = 0.77). CONCLUSIONS: Chordae across the LVOT and an indexed LVOT diameter of ≤2.5 cm/m2 are associated with a higher risk of development of LVOTO following repair of AVSD. Identification of these risk factors on echocardiogram prior to initial AVSD repair can be useful in evaluating for future risk of LVOTO and the need for closer clinical follow-up.

Pediatric quality of life in long-term survivors of childhood cancer treated with anthracyclines.

BACKGROUND: Anthracyclines are a common class of drugs used to treat pediatric cancer. While much attention is given to their cardiotoxicity, little is known about the relationship between the use of anthracyclines and health-related quality-of-life (HRQoL) outcomes. This study examines the association of anthracycline cardiotoxicity risk status and Pediatric Quality-of-Life (PedsQL) InventoryTM scores in childhood cancer METHODS: Pediatric cancer survivors aged 8-21 who were at least 5 years posttreatment were recruited from a Cancer Survivor Clinic. Participants completed the PedsQL 4.0 Generic Core Scales and a health behavior survey. Linear regression was used to evaluate the association between PedsQL scores and anthracycline cardiotoxicity risk status and to assess whether self-reported physical activity modified the association. RESULTS: Eighty survivors participated and were characterized by cardiotoxicity risk status (high: 12; moderate: 23, low: 24, no risk: 21) as defined by the Children's Oncology Group (COG). Measures in all PedsQL domains tended to be slightly lower for survivors exposed to anthracyclines as compared to the unexposed. The largest difference in unadjusted mean scores was for social functioning (96.0% for unexposed vs. 91.3% for exposed, P = 0.0068). There was also an inverse dose-response relation between adjusted PedsQL scores and increasing anthracycline cardiotoxicity risk; this association was not modified by physical activity level. CONCLUSION: These data indicate that regular psychosocial assessments, such as those currently recommended by the COG, may be especially important for survivors treated with anthracyclines.

Fetal Diagnostics and Fetal Intervention.

Advances in ultrasound technology and specialized training have allowed clinicians to diagnose congenital heart disease in utero and counsel families on perinatal outcomes and management strategies, including fetal cardiac interventions and fetal surgery. This article gives a detailed approach to fetal cardiac assessment and provides the reader with accompanying figures and video clips to illustrate unique views and sweeps invaluable to diagnosing congenital heart disease. We demonstrate that using a sequential segmental approach to evaluate cardiac anatomy enables one to decipher the most complex forms of congenital heart disease. Also provided is a review of fetal cardiac intervention and surgery from the fetal cardiologist's perspective.

Heterotaxy Syndrome: Proceedings From the 10th International PCICS Meeting.

A session dedicated to heterotaxy syndrome was included in the program of the Tenth International Conference of the Pediatric Cardiac Intensive Care Society in Miami, Florida in December 2014. An invited panel of experts reviewed the anatomic considerations, surgical considerations, noncardiac issues, and long-term outcomes in this challenging group of patients. The presentations, summarized in this article, reflect the current approach to this complex multiorgan syndrome and highlight future areas of clinical interest and research.

Assessing anthracycline-treated childhood cancer survivors with advanced stress echocardiography.

BACKGROUND: Surveillance for anthracycline cardiotoxicity in cancer survivors typically utilizes resting M-mode and two-dimensional echocardiography, which are insensitive to detection of subtle myocardial changes. We examined childhood cancer survivors treated with anthracyclines during exercise using various echocardiography techniques to investigate if these tools can better detect subclinical cardiac dysfunction. PROCEDURE: We recruited asymptomatic survivors at least five years post treatment. Echocardiography was performed at rest and at termination of exercise utilizing tissue Doppler techniques and strain rate imaging. RESULTS: Eighty participants were characterized by cardiotoxicity risk status (high [12], moderate [23], low [24], no risk [21]) as defined by the Children's Oncology Group Long Term Follow-Up Guidelines v3.0. The high-risk group had a higher resting heart rate than controls (100 vs. 88 bpm [P for trend = 0.049]). Peak aerobic capacity in all groups was similar. Compared to controls at rest, the high-risk group had evidence of diastolic dysfunction with lower E/A ratios (1.4 vs. 2.0, P = 0.008) and higher septal early diastolic velocities (E/E') of 11.7 versus 9.9 (P = 0.165). With exercise, this difference resolved and myocardial contractile reserve was preserved. CONCLUSIONS: Asymptomatic, pediatric cancer survivors at high-risk for anthracycline cardiotoxicity have some evidence of diastolic filling abnormalities at rest. With exercise, they augment their systolic and diastolic function to achieve normal maximal aerobic capacity suggesting they are able to compensate for mild cardiac dysfunction in the early years after exposure. Additionally, findings suggest that routine exercise echocardiography may not be a useful surveillance tool to assess anthracycline cardiotoxicity.

Individual prediction of heart failure among childhood cancer survivors.

PURPOSE: To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer. PATIENTS AND METHODS: Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models. RESULTS: Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%). CONCLUSION: Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions.

Low-weight infants are at increased mortality risk after palliative or corrective cardiac surgery.

BACKGROUND: Low weight is an established risk factor for mortality after congenital cardiac surgery. Given the advances in the care of neonates and infants after surgery, we sought to examine the effect of low weight on outcomes in the current era. METHODS: From 2002 to 2012, 2051 infants aged 90 days or less underwent cardiac surgery including 534 (26.0%) with single-ventricle pathology. Regression models examined the effect of low weight (≤ 2.5 kg; n = 274, 13.4%) on early and late outcomes. RESULTS: Overall, the incidence of prematurity, associated chromosomal/extracardiac abnormalities was higher in infants who weighed 2.5 kg or less than in those who weighed more than 2.5 kg; the incidence of single-ventricle pathology was comparable between the 2 groups. In addition, infants who weighed 2.5 kg or less underwent more palliation and had a higher proportion of STAT (Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery) risk category 4 and 5 procedures. Adjusted regression models showed that low weight (≤ 2.5 kg) did not increase unplanned reoperation (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.48-1.67; P = .73) or extracorporeal membrane oxygenation requirement (OR, 1.23; 95% CI, 0.68-2.22; P = .49), however it was associated with significant increase in hospital mortality (OR, 2.15; 95% CI, 1.33-3.50; P = .002). In addition, there was a significant association between low weight and increased duration of postoperative mechanical ventilation and intensive care unit and hospital stays. Adjusted hazard analysis showed that weight equal to or less than 2.5 kg was associated with diminished late survival (hazard ratio, 1.89; 95% CI, 1.39-2.55; P < .001) and that was evident in all patients subgroups (P < .001 for all). CONCLUSIONS: In a large single-center series, low weight continues to be associated with increased early mortality risk and resource utilization after palliative and corrective cardiac surgery. The hazard of death in low-weight patients continues beyond the perioperative period for at least 1 year before normalizing. Strategies to improve outcomes for this high-risk population must address perioperative care, outpatient surveillance, and management.

Doppler flow patterns in the right ventricle-to-pulmonary artery shunt and neo-aorta in infants with single right ventricle anomalies: impact on outcome after initial staged palliations.

BACKGROUND: A Pediatric Heart Network trial compared outcomes in infants with single right ventricle anomalies undergoing Norwood procedures randomized to modified Blalock-Taussig shunt (MBTS) or right ventricle-to-pulmonary artery shunt (RVPAS). Doppler patterns in the neo-aorta and RVPAS may characterize physiologic changes after staged palliations that affect outcomes and right ventricular (RV) function. METHODS: Neo-aortic cardiac index (CI), retrograde fraction (RF) in the descending aorta and RVPAS conduit, RVPAS/neo-aortic systolic ejection time ratio, and systolic/diastolic (S/D) ratio were measured early after Norwood, before stage II palliation, and at 14 months. These parameters were compared with transplantation-free survival, length of hospital stay, and RV functional indices. RESULTS: In 529 subjects (mean follow-up period, 3.0 ± 2.1 years), neo-aortic CI and descending aortic RF were significantly higher in the MBTS cohort after Norwood. The RVPAS RF averaged <25% at both interstage intervals. Higher pre-stage II descending aortic RF was correlated with lower RV ejection fraction (R = -0.24; P = .032) at 14 months for the MBTS cohort. Higher post-Norwood CI (5.6 vs 4.4 L/min/m(2), P = .04) and lower S/D ratio (1.40 vs 1.68, P = .01) were correlated with better interstage transplantation-free survival for the RVPAS cohort. No other Doppler flow patterns were correlated with outcomes. CONCLUSIONS: After the Norwood procedure, infants tolerated significant descending aortic RF (MBTS) and conduit RF (RVPAS), with little correlation with clinical outcomes or RV function. Neo-aortic CI, ejection time, and S/D ratios also had limited correlations with outcomes or RV function, but higher post-Norwood neo-aortic CI and lower S/D ratio were correlated with better interstage survival in those with RVPAS.