Derivation and Validation of a General Predictive Model for Long Term Risks for Mortality and Invasive Cardiovascular Interventions in Congenital Heart Disease

Introduction. Accurate assessment of prognosis is a key driver of clinical decision making in congenital heart disease (CHD), but is complicated because CHD represents such a diverse collection of conditions. The aim of this investigation is to derive, validate, and calibrate multivariable predictive models for time to surgical or catheter-mediated intervention (INT) in CHD and for time to death in CHD. Methods. 4108 unique subjects were prospectively and consecutively enrolled, and randomized to derivation and validation cohorts. Total follow up was 26,578 patient-years, with 102 deaths and 868 INTs. Accelerated failure time multivariable predictive models for the outcomes, based on primary and secondary diagnoses, pathophysiologic severity, age, gender, genetic comorbidities, and prior interventional history, were derived using piecewise exponential methodology. The model predictions were validated, calibrated, and evaluated for sensitivity to changes in the independent variables. Results. Model validity was excellent for prediction of both mortality and INT at 4 months, 1 year, 5 years, 10 years, and 22 years (areas under receiver operating characteristic curves ranged from 0.809 to 0.919), and predictions calibrated well with observed outcomes. Although age, gender, secondary diagnoses, and genetic comorbidities were significant independent contributors to the survival and/or freedom from intervention models, predicted outcomes were most sensitive to variations in a composite predictor incorporating primary diagnosis, pathophysiologic severity, and history of prior intervention. An active cohort effect is identified in which predicted mortality and intervention both increased throughout the 22 years of study. Conclusions. Time to INT and time to death in CHD can be predicted with accuracy based on clinical variables. The objective predictions available through these models could educate both patient and provider, and inform clinical decision making in CHD

Subspecialty surveillance of long-term course of small and moderate muscular ventricular septal defect: heterogenous practices, low yield.

BACKGROUND: No expert consensus guides practice for intensity of ongoing pediatric cardiology surveillance of hemodynamically insignificant small and moderate muscular ventricular septal defect (mVSD). Therefore, despite the well-established benign natural history of mVSD, there is potential for widely divergent follow up practices. The purpose of this investigation was to evaluate (1) variations in follow up of mVSD within an academic children\u27s hospital based pediatric cardiology practice, and (2) the frequency of active medical or surgical management resulting from follow up of mVSD. METHODS: We retrospectively reviewed records of 600 patients with isolated mVSD echocardiographically diagnosed between 2006 and 2012. Large mVSD were excluded (n = 4). Patient age, gender, echocardiographic findings, provider, recommendations for follow up, and medical and surgical management were tabulated at initial and follow up visits. Independent associations with follow up recommendations were sought using multivariate analysis. RESULTS: Initial echocardiography showed small single mVSD in 509 (85%), multiple small mVSD in 60 (10%), and small-to-moderate or moderate single mVSD in 31 (5%). The mean age at diagnosis was 15.9 months (0-18.5 years) and 25.7 months (0-18.5 years) at last follow up. There was slight female predominance (56.3%). Fourteen pediatric cardiology providers recommended 316 follow up visits, 259 of which were actually accomplished. There were 37 other unplanned follow up visits. No medical or surgical management changes were associated with any of the follow up visits. The proportion of patients for whom follow up was advised varied among providers from 11 to 100%. Independent associations with recommendation for follow up were limited to the identity and clinical volume of the provider, age of the patient, and the presence of multiple, small-to-moderate, or moderate mVSD. CONCLUSIONS: In this large series of moderate or smaller mVSD, pediatric cardiology follow up was commonly recommended but resulted in no active medical or surgical management. Major provider based inconsistency in intensity of follow up of mVSD was identified, but is difficult to justify

Mortality-related resource utilization in the inpatient care of hypoplastic left heart syndrome.

BACKGROUND: Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF). METHODS: A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children\u27s hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of stay (LOS) were recorded. RESULTS: In all, 11,122 HLHS admissions were identified which account for total LOS of 277,027 inpatient-days and $3,928,794,660 in BC. There were 1145 inpatient deaths (10.3%). LOS was greater among inpatient deaths than among patients discharged alive (median 17 vs. 12, p \u3c 0.0001). BC were greater among inpatient deaths than among patients discharged alive (median 4.09 × 10(5) vs. 1.63 × 10(5), p \u3c 0.0001). 16% of all LOS and 21% of all BC were accrued by patients who did not survive their hospitalization. These proportions showed no significant change year-by-year. The highest volume institutions had lower mortality rates, but there was no relation between institutional volume and the MRRUF. CONCLUSIONS: These data should alert providers and consumers that current practices often result in major resource expenditure for inpatient care of HLHS that does not result in survival to hospital dismissal. They highlight the need for data-driven critical review of standard practices to identify patterns of care associated with success, and to modify approaches objectively

Depressed Left and Right Ventricular Cardiac Output in Fetuses of Diabetic Mothers

INTRODUCTION: We compared right and left ventricular cardiac output (RVCO and LVCO) in fetuses of diabetic mothers (FDM) to a large normal cohort. METHODS: We prospectively enrolled 264 normal fetuses and 30 FDM. Fetal CO parameters: semilunar valve velocity time integrals (AVVTI, PVVTI), ventricular outflow diameters (LVOTD, RVOTD), stroke volumes (AVSV, PVSV) were measured, and LVCO and RVCO calculated. These were normalized using nonlinear regression to estimated fetal weight (EFW) to provide means and standard deviations. Among FDMs, mean Z-scores and 95% confidence limits (CL) were calculated, and compared to zero. RESULTS: LVCO, RVCO, and parameters they were calculated from, increased predictably and non-linearly with increasing EFW. In FDM, LVCO was depressed (mean Z -1.679, 95% CL -2.404, -0.955, p CONCLUSION: Normal biventricular stroke volumes and outputs follow a nonlinear regression with EFW. FDM have significantly lower right and left heart stroke volumes and outputs for weight than do normal fetuses

Prevention of arteriovenous shunt occlusion using microbubble and ultrasound mediated thromboprophylaxis.

BACKGROUND: Palliative shunts in congenital heart disease patients are vulnerable to thrombotic occlusion. High mechanical index (MI) impulses from a modified diagnostic ultrasound (US) transducer during a systemic microbubble (MB) infusion have been used to dissolve intravascular thrombi without anticoagulation, and we sought to determine whether this technique could be used prophylactically to reduce thrombus burden and prevent occlusion of surgically placed extracardiac shunts. METHODS AND RESULTS: Heparin-bonded ePTFE tubular vascular shunts of 4 mm×2.5 cm (Propaten; W.L Gore) were surgically placed in 18 pigs: a right-sided side-to-side arteriovenous (AV, carotid-jugular) shunt, and a left-sided arterio-arterial (AA, carotid-carotid) interposition shunt in each animal. After shunt implantation, animals were randomly assigned to one of 3 groups. Transcutaneous, weekly 30-minute treatments (total of 4 treatments) of either guided high MI US+MB (Group 1; n=6) using a 3% MRX-801 MB infusion, or US alone (Group 2; n=6) were given separately to each shunt. The third group of 6 pigs received no treatments. The shunts were explanted after 4 weeks and analyzed by histopathology to quantify luminal thrombus area (mm2) for the length of each shunt. No pigs received antiplatelet agents or anticoagulants during the treatment period. The median overall thrombus burden in the 3 groups for AV shunts was 5.10 mm2 compared with 4.05 mm(2) in AA (P=0.199). Group 1 pigs had significantly less thrombus burden in the AV shunts (median 2.5 mm2) compared with Group 2 (median 5.6 mm2) and Group 3 (median 7.5 mm2) pigs (P=0.006). No difference in thrombus burden was seen between groups for AA shunts. CONCLUSION: Transcutaneous US with intravenous MB is capable of preventing thrombus accumulation in arteriovenous shunts without the need for antiplatelet agents, and may be a method of preventing progressive occlusion of palliative shunts