Management and Outcomes of Patients with Occlusive Thrombosis after Pediatric Cardiac Surgery.

OBJECTIVES: To evaluate management and outcomes of thrombosis after pediatric cardiac surgery and stratify thrombi according to risk of short- and long-term complications to better guide therapeutic choices. STUDY DESIGN: Retrospective review was performed of 513 thrombi (400 occlusive) diagnosed after 213 pediatric cardiac operations. Long-term outcomes over time were assessed with the use of parametric hazard regression models. RESULTS: Serious complications and/or high-intensity treatment occurred with 17%-24% of thrombi depending on location, most commonly in thrombi affecting the cardiac and cerebral circulation. Bleeding complications affected 13% of patients; associated factors included thrombolytics (OR 8.7, P < .001), greater daily dose of unfractionated heparin (OR 1.25 per 5 U/kg/day, P = .03), and extracorporeal support (OR 4.5, P = .007). Radiologic thrombus persistence was identified in 30% ± 3% at 12 months; associated factors included extracorporeal support (hazard ratio [HR] 1.9, P = .003), venous (HR 1.7, P = .003), and occlusive thrombi at presentation (HR 1.8, P = .001); greater oxygen saturation before surgery (HR 1.13/10%, P = .05) and thrombi in femoral veins (HR 1.9, P = .001) were associated with increased hazard of resolution. Freedom from postthrombotic syndrome was 83% ± 4% at 6 years, greater number of persistent vessel segment occlusions (HR 1.8/vessel, P = .001) and greater fibrinogen at diagnosis (HR 1.1 per g/L, P = .02) were associated with increased hazard. CONCLUSIONS: Thrombosis outcomes after pediatric cardiac surgery remain suboptimal. Given that more intensive treatment would likely increase the risk of bleeding, the focus should be on both thrombosis-prevention strategies, as well as in tailoring therapy according to a thrombosis outcome risk stratification approach.

Variability in Response to Intravenous Immunoglobulin in the Treatment of Kawasaki Disease.

OBJECTIVES: To characterize the pattern of temperature response to intravenous immunoglobulin (IVIG) infusion in patients with Kawasaki disease (KD). STUDY DESIGN: Patients nonresponsive to IVIG (axillary temperature ≥37.5°C >24 hours after end of IVIG) were identified. Each patient with IVIG-nonresponsive KD was matched to a control patient with IVIG-responsive KD of the same age, sex, and duration of fever before IVIG. Hourly temperature profiles were obtained from immediately before the start of IVIG infusion until complete defervescence. RESULTS: A total of 182 patients nonresponsive to IVIG were matched (total n = 364). Nonresponders were further classified as partial nonresponders (68%) (axillary temperature decreased to <37.5°C but fever recurred) and complete nonresponders (32%) (axillary temperature consistently ≥37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between responders and partial nonresponders (EST: -0.061 [0.007]°C/h, P < .001 for responders vs EST: -0.027 (0.012)°C/h, P = .03 for partial nonresponders [responders vs partial nonresponders, P = .65]), where EST is the parameter estimate from the regression model, representing the change in degrees Celsius for each hour since start of IVIG. In complete nonresponders, IVIG was not associated with significant decreases in temperature (EST: -0.008 [0.010]°C, P = .42). Factors associated with complete (vs partial) nonresponse included laboratory-confirmed infection, greater C-reactive protein, and IVIG brand. Defervescence in partial nonresponders was achieved with a second IVIG dose for 72% of patients compared with 58% of complete nonresponders (P = .001). Complete nonresponders were more likely to develop coronary artery aneurysms vs partial nonresponders (OR: 2.4 [1.1-5.4], P = .03) or responders (OR: 3.2 [1.5-6.9], P = .002). CONCLUSIONS: Nonresponse to initial IVIG can be further characterized by temperature profile, and complete nonresponders may require more aggressive second-line therapy.

Factors associated with development of coronary artery aneurysms after Kawasaki disease are similar for those treated promptly and those with delayed or no treatment.

BACKGROUND: While the risk is reduced, patients may develop coronary artery (CA) aneurysms after Kawasaki disease (KD) despite receiving intravenous immunoglobulin (IVIG) within 10days of symptom onset. Risk factors for CA aneurysms may differ compared to those patients with delayed or no treatment. METHODS: Patients diagnosed with KD between 1990 and 2013 were included. Patients with maximum coronary artery z-scores>5 were classified as having CA aneurysms. Separate multivariable regression models were used to determine factors associated with CA aneurysms for those with versus without prompt treatment. RESULTS: Of 1358 patients included, 83% (n=1126) were treated with IVIG within 10days and 5% (n=53) developed CA aneurysms. Patients who had delayed (>10days) or no IVIG treatment were at increased odds of developing CA aneurysms (OR: 3.1,95% CI: 1.9-5.1, p<0.001). For patients with prompt treatment with IVIG, factors associated with increased odds of CA aneurysms were: longer duration of fever prior to treatment (OR: 1.2/day, p=0.04), age<1year (OR: 3.9, p=0.001), higher pre-IVIG white blood cell count (OR: 1.05/×109/L, p=0.007), lower hemoglobin (OR: 1.4/g/L, p=0.004) and non-response to initial IVIG treatment (OR: 2.5, p<0.001). For patients with delayed or no treatment, factors associated with increased odds of CA aneurysms were: males (OR: 5.4, p=0.009), age<1year (OR: 29.9, p<0.001), and higher platelet count (OR: 1.4/100×1012/L, p=0.001). Delayed treatment with IVIG did not reduce the risk of CA aneurysms (OR: 1.9, p=0.28), and total duration of fever was not associated with CA aneurysms for this group (OR: 1.04/day, p=0.16). CONCLUSIONS: Factors associated with the development of CA aneurysms are generally similar for those treated promptly versus those with delayed or no treatment. For those with delayed diagnosis, treatment with IVIG does not appear to be effective to prevent CA aneurysms.