Anticoagulation: a practical guide for strabismus surgeons.

An increasing number of surgical strabismus patients are taking oral anticoagulant and antiplatelet agents, with more diverse mechanisms of action than those used in the past. The decision as to whether to continue these drugs throughout the perioperative period is difficult and must be based on the balance between hemorrhagic and thrombotic risk. To help guide strabismus surgeons with clinical management in these cases, we review potential hemorrhagic complications of strabismus surgery and examine the use of anticoagulant and antiplatelet drugs during the perioperative period. Surgical strategies that might help minimize intraoperative hemorrhage in patients on anticoagulant therapy are also discussed.

Cardiovascular biomarkers in acute Kawasaki disease.

BACKGROUND: Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). METHODS: We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. RESULTS: Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst). CONCLUSIONS: NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Coronary artery dilation in acute Kawasaki disease and acute illnesses associated with Fever.

BACKGROUND: In the absence of a specific test, the diagnosis of clinically incomplete Kawasaki disease (KD) can be challenging. The 2004 American Heart Association guidelines state that the diagnosis of KD is supported by the presence of coronary artery dilation documented by echocardiography. However, the specificity of coronary artery dilation and its prevalence in children with other acute illnesses associated with fever has not been studied. METHODS: A 2-center, prospective study compared the internal diameters and Z-scores (standard deviation [SD] units from the mean internal diameter normalized for body surface area) of the proximal left anterior descending and right coronary arteries measured by echocardiography in febrile children (FC) and children with KD. RESULTS: The median Z-score (interquartile range) of the left anterior descending coronary artery was -0.05 (-0.86, 0.62) and 1.06 (0.36, 2.06) SD units for the 45 FC and the 145 KD patients, respectively (P < 0.0001). For the right coronary artery, the median Z-score was 0.21 (-0.20, 0.87) and 1.04 (0.31, 1.85) SD units for the FC and KD patients, respectively (P < 0.0001). There was no correlation between body temperature at the time of echocardiography and coronary artery Z-score. No febrile child had a coronary artery Z-score ≥ 2.5 SD units. CONCLUSIONS: Z-scores ≥ 2.5 SD units were not observed in our cohort of FC. Therefore, echocardiographic evidence of coronary artery dilation can be used to support the diagnosis of KD.

Transforming growth factor-beta signaling pathway in patients with Kawasaki disease.

BACKGROUND: Transforming growth factor (TGF)-ß is a multifunctional peptide that is important in T-cell activation and cardiovascular remodeling, both of which are important features of Kawasaki disease (KD). We postulated that variation in TGF-ß signaling might be important in KD susceptibility and disease outcome. METHODS AND RESULTS: We investigated genetic variation in 15 genes belonging to the TGF-ß pathway in a total of 771 KD subjects of mainly European descent from the United States, the United Kingdom, Australia, and the Netherlands. We analyzed transcript abundance patterns using microarray and reverse transcriptase-polymerase chain reaction for these same genes, and measured TGF-ß2 protein levels in plasma. Genetic variants in TGFB2, TGFBR2, and SMAD3 and their haplotypes were consistently and reproducibly associated with KD susceptibility, coronary artery aneurysm formation, aortic root dilatation, and intravenous immunoglobulin treatment response in different cohorts. A SMAD3 haplotype associated with KD susceptibility replicated in 2 independent cohorts and an intronic single nucleotide polymorphism in a separate haplotype block was also strongly associated (A/G, rs4776338) (P=0.000022; odds ratio, 1.50; 95% confidence interval, 1.25 to 1.81). Pathway analysis using all 15 genes further confirmed the importance of the TGF-ß pathway in KD pathogenesis. Whole-blood transcript abundance for these genes and TGF-ß2 plasma protein levels changed dynamically over the course of the illness. CONCLUSIONS: These studies suggest that genetic variation in the TGF-ß pathway influences KD susceptibility, disease outcome, and response to therapy, and that aortic root and coronary artery Z scores can be used for phenotype/genotype analyses. Analysis of transcript abundance and protein levels further support the importance of this pathway in KD pathogenesis.

Performance of 2004 American Heart Association recommendations for treatment of Kawasaki disease.

OBJECTIVE: The 2004 American Heart Association (AHA) statement included a clinical case definition and an algorithm for diagnosing and treating suspected incomplete Kawasaki disease (KD). We explored the performance of these recommendations in a multicenter series of US patients with KD with coronary artery aneurysms (CAAs). METHODS: We reviewed retrospectively records of patients with KD with CAAs at 4 US centers from 1981 to 2006. CAAs were defined on the basis of z scores of >3 or Japanese Ministry of Health and Welfare criteria. Our primary outcome was the proportion of patients presenting at illness day < or =21 who would have received intravenous immunoglobulin (IVIG) treatment by following the AHA guidelines at the time of their initial presentation to the clinical center. RESULTS: Of 195 patients who met entry criteria, 137 (70%) met the case definition and would have received IVIG treatment at presentation. Fifty-three patients (27%) had suspected incomplete KD and were eligible for algorithm application; all would have received IVIG treatment at presentation. Of the remaining 5 patients, 3 were excluded from the algorithm because of fever for <5 days at presentation and 2 because of <2 clinical criteria at >6 months of age. Two of these 5 patients would have entered the algorithm and received IVIG treatment after follow-up monitoring. Overall, application of the AHA algorithm would have referred > or =190 patients (97%) for IVIG treatment. CONCLUSIONS: Application of the 2004 AHA recommendations, compared with the classic criteria alone, improves the rate of IVIG treatment for patients with KD who develop CAAs. Future multicenter prospective studies are needed to assess the performance characteristics of the AHA algorithm in febrile children with incomplete criterion findings and to refine the algorithm further.

Recognition of a Kawasaki disease shock syndrome.

OBJECTIVE: We sought to define the characteristics that distinguish Kawasaki disease shock syndrome from hemodynamically normal Kawasaki disease. METHODS: We collected data prospectively for all patients with Kawasaki disease who were treated at a single institution during a 4-year period. We defined Kawasaki disease shock syndrome on the basis of systolic hypotension for age, a sustained decrease in systolic blood pressure from baseline of > or =20%, or clinical signs of poor perfusion. We compared clinical and laboratory features, coronary artery measurements, and responses to therapy and analyzed indices of ventricular systolic and diastolic function during acute and convalescent Kawasaki disease. RESULTS: Of 187 consecutive patients with Kawasaki disease, 13 (7%) met the definition for Kawasaki disease shock syndrome. All received fluid resuscitation, and 7 (54%) required vasoactive infusions. Compared with patients without shock, patients with Kawasaki disease shock syndrome were more often female and had larger proportions of bands, higher C-reactive protein concentrations, and lower hemoglobin concentrations and platelet counts. Evidence of consumptive coagulopathy was common in the Kawasaki disease shock syndrome group. Patients with Kawasaki disease shock syndrome more often had impaired left ventricular systolic function (ejection fraction of <54%: 4 of 13 patients [31%] vs 2 of 86 patients [4%]), mitral regurgitation (5 of 13 patients [39%] vs 2 of 83 patients [2%]), coronary artery abnormalities (8 of 13 patients [62%] vs 20 of 86 patients [23%]), and intravenous immunoglobulin resistance (6 of 13 patients [46%] vs 32 of 174 patients [18%]). Impairment of ventricular relaxation and compliance persisted among patients with Kawasaki disease shock syndrome after the resolution of other hemodynamic disturbances. CONCLUSIONS: Kawasaki disease shock syndrome is associated with more-severe laboratory markers of inflammation and greater risk of coronary artery abnormalities, mitral regurgitation, and prolonged myocardial dysfunction. These patients may be resistant to immunoglobulin therapy and require additional antiinflammatory treatment.

Stenting of stenotic or occluded iliofemoral veins, superior and inferior vena cavae in children with congenital heart disease: acute results and intermediate follow up.

OBJECTIVES: To determine the short and intermediate term outcome following systemic venous stent placement in children with congenital heart disease. BACKGROUND: Patients with congenital heart disease are at risk of stenosis or occlusion of systemic veins following indwelling lines or catheterizations. Stent dilation may ameliorate symptoms and open the vessel for use during future procedures. We report our acute and intermediate results. METHODS: All patients with systemic venous stent placement in the iliofemoral veins, inferior or superior vena cava at our institution between 1998 and 2006 were included. Initial and the follow-up catheterization data were reviewed retrospectively. RESULTS: 70 stents were placed in 33 patients (36 vessels). Median age was 2.6 years (0.2-14.2) and weight 11.5 kg (3.8-78.7). 17/36 vessels (47%) were occluded requiring recanalization. Following stent delivery, the mean minimum vessel diameter increased from 3.1 +/- 3.2 to 7.2 +/- 3.0 mm (P < 0.001). There were no major complications. Seventeen patients and vessels had a total of 62 follow-up catheterizations, with median length of follow-up 4.1 years (0.7-9.3). During intermediate follow up, 7/17 vessels (41%) required additional intervention. Six patients had additional balloon dilation of existing stents, and one additional stent was placed. Vessels were further dilated to 8.4 +/- 3.5 mm at the last catheterization. CONCLUSION: Systemic venous stents are safe and effective in recanalizing stenosed or occluded vessels. At follow-up, reocclusion can occur, however, previously placed stents can be safely recanalized if necessary. Future studies will determine if stenting is indicated in a broader population.

The modified Konno procedure for complex left ventricular outflow tract obstruction.

BACKGROUND: Complex left ventricular outflow tract (LVOT) obstruction with normal aortic valve function requires aggressive resection in the subaortic region and preservation of the aortic valve. The modified Konno procedure allows generous exposure of the LVOT from the left ventricular apex to the inter leaflet trigones of the aortic valve. Widespread use of this procedure has been limited by concern over injury to the aortic valve, the conduction system, and possibility of residual ventricular septal defect (VSD). METHODS: Retrospective analysis of pertinent data for all patients undergoing the modified Konno procedure (1994 to 2001) at the University of Iowa were reviewed. RESULTS: The modified Konno procedure was used in 18 patients (age 1 to 31) for LVOT obstruction associated with diffuse narrowing of the LVOT (n = 7), a discrete fibrous ring (n = 7), or a fibrous ring associated with abnormal mitral attachments (n = 4). Eight patients had previously undergone LVOT resection. There were no perioperative deaths. Estimated LVOT peak gradients by echocardiogram were 70.4 +/- 24.2 mm Hg (preoperative) and 19.2 +/- 20.4 mm Hg (postoperative) at most recent followup (p < 0.001 vs preop). Aortic insufficiency was moderate in one patient (present preop) and mild or less in all other patients. There were no cases of permanent heart block. Small residual VSDs were present in five patients (28%). Median follow-up is 3.1 years. CONCLUSIONS: The modified Konno procedure can effectively relieve complex LVOT obstruction and preserve aortic valve function. Extension of this procedure for use in the initial presentation of LVOT may be appropriate in cases at increased risk of recurrent LVOT obstruction.