Surgical management of pediatric renin-mediated hypertension secondary to renal artery occlusive disease and abdominal aortic coarctation.

BACKGROUND: Renovascular hypertension (RVH) associated with renal artery and abdominal aortic narrowings is the third most common cause of pediatric hypertension. Untreated children may experience major cardiopulmonary complications, stroke, renal failure, and death. The impetus of this study was to describe the increasingly complex surgical practice for such patients with an emphasis on anatomic phenotype and contemporary outcomes after surgical management as a means of identifying those factors responsible for persistent or recurrent hypertension necessitating reoperation. METHODS: A retrospective analysis was performed of consecutive pediatric patients with RVH undergoing open surgical procedures at the University of Michigan from 1991 to 2017. Anatomic phenotype and patient risk factors were analyzed to predict outcomes of blood pressure control and the need for secondary operations using ordered and binomial logistic multinomial regression models, respectively. RESULTS: There were 169 children (76 girls, 93 boys) who underwent primary index operations at a median age of 8.3 years; 31 children (18%) had neurofibromatosis type 1, 76 (45%) had abdominal aortic coarctations, and 28 (17%) had a single functioning kidney. Before treatment at the University of Michigan, 51 children experienced failed previous open operations (15) or endovascular interventions (36) for RVH at other institutions. Primary surgical interventions (342) included main renal artery (136) and segmental renal artery (10) aortic reimplantation, renal artery bypass (55), segmental renal artery embolization (10), renal artery patch angioplasty (8), resection with reanastomosis (4), and partial or total nephrectomy (25). Non-renal artery procedures included patch aortoplasty (32), aortoaortic bypass (32), and splanchnic arterial revascularization (30). Nine patients required reoperation in the early postoperative period. During a mean follow-up of 49 months, secondary interventions were required in 35 children (21%), including both open surgical (37) and endovascular (14) interventions. Remedial intervention to preserve primary renal artery patency or a nephrectomy if such was impossible was required in 22 children (13%). The remaining secondary procedures were performed to treat previously untreated disease that became clinically evident during follow-up. Age at operation and abdominal aortic coarctation were independent predictors for reoperation. The overall experience revealed hypertension to be cured in 74 children (44%), improved in 78 (46%), and unchanged in 17 (10%). Children undergoing remedial operations were less likely (33%) to be cured of hypertension. There was no perioperative death or renal insufficiency requiring dialysis after either primary or secondary interventions. CONCLUSIONS: Contemporary surgical treatment of pediatric RVH provides a sustainable overall benefit to 90% of children. Interventions in the very young (<3 years) and concurrent abdominal aortic coarctation increase the likelihood of reoperation. Patients undergoing remedial surgery after earlier operative failures are less likely to be cured of hypertension. Judicious postoperative surveillance is imperative in children surgically treated for RVH.

Natural History of Iatrogenic Pediatric Femoral Artery Injury.

BACKGROUND: Iatrogenic femoral artery trauma complicates the course of critically ill neonates and children. Complications from persistent arterial occlusion may include claudication and limb length discrepancies. Data supporting risk factors for such and need for revascularization are lacking. METHODS: Review of a prospectively maintained database at a tertiary institution of iatrogenic pediatric femoral artery injuries incurred between 2013 and 2014 was performed. Additional injuries were identified by review of pediatric arterial duplex performed between 2008 and 2013. Demographics, risk factors, and outcomes were queried. Data analysis utilized Fischer's exact t-test and logistic regression. RESULTS: Seventy-six patients were identified of which 68 presented with acute limb ischemia (ALI) and 8 with chronic iliofemoral arterial occlusion resulting in claudication (n = 6) or limb length discrepancy (n = 2). Mean weight at injury was 6.3 kg; mean age at injury was 49 weeks (50% aged <3 months). Mean follow-up was 14 months (out to 11 years). Six patients required surgery for ALI, and 6 required delayed operation for limb length discrepancy (n = 4) or for persistent external iliac artery (EIA) occlusion. Mean age at delayed revascularization was 6 years (range: 2-13 years). Vasopressor use, mechanism/location of injury, and concomitant venous thrombosis were not significantly correlated with need for operation; trends suggested that cardiac catheterization and EIA thrombosis may correlate with chronic disease. Increased age at injury was associated with need for operation. CONCLUSIONS: Although a majority of children with ALI may be successfully treated medically, 9% will require operation for ALI and 16% ultimately required revascularization during follow-up. Persistent iliofemoral arterial thrombosis is a likely risk factor for limb length discrepancy with growth; identifying risk factors for this and improved methods for surveillance requires ongoing investigation.

Apixaban Versus Warfarin for Mechanical Heart Valve Thromboprophylaxis in a Swine Aortic Heterotopic Valve Model.

OBJECTIVE: Warfarin is the current standard for oral anticoagulation therapy in patients with mechanical heart valves, yet optimal therapy to maximize anticoagulation and minimize bleeding complications requires routine coagulation monitoring, possible dietary restrictions, and drug interaction monitoring. As alternatives to warfarin, oral direct acting factor Xa inhibitors are currently approved for the prophylaxis and treatment of venous thromboembolism and reduction of stroke and systemic embolization. However, no in vivo preclinical or clinical studies have been performed directly comparing oral factor Xa inhibitors such as apixaban to warfarin, the current standard of therapy. APPROACH AND RESULTS: A well-documented heterotopic aortic valve porcine model was used to test the hypothesis that apixaban has comparable efficacy to warfarin for thromboprophylaxis of mechanical heart valves. Sixteen swine were implanted with a bileaflet mechanical aortic valve that bypassed the ligated descending thoracic aorta. Animals were randomized to 4 groups: control (no anticoagulation; n=4), apixaban oral 1 mg/kg twice a day (n=5), warfarin oral 0.04 to 0.08 mg/kg daily (international normalized ratio 2-3; n=3), and apixaban infusion (n=4). Postmortem valve thrombus was measured 30 days post-surgery for control-oral groups and 14 days post-surgery for the apixaban infusion group. Control thrombus weight (mean) was significantly different (1422.9 mg) compared with apixaban oral (357.5 mg), warfarin (247.1 mg), and apixiban 14-day infusion (61.1 mg; P<0.05). CONCLUSIONS: Apixaban is a promising candidate and may be a useful alternative to warfarin for thromboprophylaxis of mechanical heart valves. Unlike warfarin, no adverse bleeding events were observed in any apixaban groups.

Circulating and vein wall P-selectin promote venous thrombogenesis during aging in a rodent model.

INTRODUCTION: The objective of this study was to identify the direct relationship between aging and selectin activation during acute venous thrombosis in mice of varying ages. We hypothesized that older animals would have increased venous thrombus formation as a result of age associated-increases of pro-inflammatory molecules within the vein wall when compared to younger animals. MATERIALS AND METHODS: Deep venous thrombosis (DVT) was induced in 4 and 18month old C57BL/6 mice using the electrolytic inferior vena cava model (EIM) of DVT. Blood and tissue samples were collected at baseline (TC), 6hours, and 2days post-thrombosis induction. RESULTS: Older mice had significantly larger thrombi versus younger mice at 6H (18.4±6.21 vs. 13.0±4.29×10(-3) grams, p=0.0033) and 2D (18.4±4.27 vs. 13.0±5.01×10(-3) grams, p=0.0005), higher soluble P-selectin levels at 6H (13±2.5 vs. 8.4±2.7ng/mg p=0.0010) and 2D (12.7±5.0 vs. 5.9±1.3ng/mg p=0.0020), and higher vein wall P-selectin levels at 6H (1.94×10(5)±3.56×10(4) vs. 4.81±2.29×10(4) pg/mg p=0.0001) and 2D (1.38×10(5)±5.65×10(4) vs. 3.73±1.66×10(4) pg/mg p=0.0177). Older animals also had significantly higher platelet numbers at 6H (841±203.8 vs. 564±164.8K/µL p=0.0001), and 2D (1002±342.9 vs. 690±186.1K/µL p=0.0003), with corresponding increases in mean platelet volume versus younger mice post thrombosis (p≤0.01). CONCLUSIONS: Older animals had significantly larger venous thrombi versus younger animals post-thombosis, as a result of high levels of P-selectin both in the circulation and locally at the level of the vein wall. Expression of local and soluble P-selectin increased with age, resulting in a pro-thrombotic environment not represented in younger mice.