Safety of Simultaneous Coronary Artery Bypass Grafting and Carotid Endarterectomy Versus Isolated Coronary Artery Bypass Grafting: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: The optimal operative strategy in patients with severe carotid artery disease undergoing coronary artery bypass grafting (CABG) is unknown. We sought to investigate the safety and efficacy of synchronous combined carotid endarterectomy and CABG as compared with isolated CABG. METHODS: Patients with asymptomatic high-grade carotid artery stenosis ≥80% according to ECST (European Carotid Surgery Trial) ultrasound criteria (corresponding to ≥70% NASCET [North American Symptomatic Carotid Endarterectomy Trial]) who required CABG surgery were randomly assigned to synchronous carotid endarterectomy+CABG or isolated CABG. To avoid unbalanced prognostic factor distributions, randomization was stratified by center, age, sex, and modified Rankin Scale. The primary composite end point was the rate of stroke or death at 30 days. RESULTS: From 2010 to 2014, a total of 129 patients were enrolled at 17 centers in Germany and the Czech Republic. Because of withdrawal of funding after insufficient recruitment, enrolment was terminated early. At 30 days, the rate of any stroke or death in the intention-to-treat population was 12/65 (18.5%) in patients receiving synchronous carotid endarterectomy+CABG as compared with 6/62 (9.7%) in patients receiving isolated CABG (absolute risk reduction, 8.8%; 95% confidence interval, -3.2% to 20.8%; PWALD=0.12). Also for all secondary end points at 30 days and 1 year, there was no evidence for a significant treatment-group effect although patients undergoing isolated CABG tended to have better outcomes. CONCLUSIONS: Although our results cannot rule out a treatment-group effect because of lack of power, a superiority of the synchronous combined carotid endarterectomy+CABG approach seems unlikely. Five-year follow-up of patients is still ongoing. CLINICAL TRIAL REGISTRATION: URL: https://www.controlled-trials.com. Unique identifier: ISRCTN13486906.

Complete interventional heart repair of multiple concomitant cardiac pathologies in a staged approach.

OBJECTIVES AND BACKGROUND: The evidence of multiple percutaneous cardiac procedures in patients with numerous concomitant cardiac pathologies is limited. METHODS AND RESULTS: We report on the case of a 90-year-old male patient presenting with advanced heart failure because of degenerative aortic valve stenosis and degenerative mitral valve regurgitation. Moreover, significant coronary artery disease and intolerance of anticoagulation in atrial fibrillation were present. The patient was rejected from surgery because of age and frailty and underwent a staged interventional procedure with percutaneous coronary intervention, followed by transfemoral aortic valve implantation with Edwards Sapien XT, percutaneous mitral valve repair with MitraClip, and left atrial appendage closure with Amplatzer Cardiac Plug. The last procedure was complicated by pericardial tamponade necessitating pericardial drainage. Eight weeks later, the patient reported on the absence of dyspnea in activities of daily living and a significant gain in quality of live. CONCLUSIONS: The case demonstrates feasibility of a staged interventional approach in a select high-risk patient.

A Monoclonal Human Alveolar Epithelial Cell Line ("Arlo") with Pronounced Barrier Function for Studying Drug Permeability and Viral Infections.

In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well as toxicological responses in humans. Models based on human cells and tissues are potential alternatives to animal experimentation allowing for the isolation of essential processes of human biology and making them accessible in vitro. Here, the generation of a novel monoclonal cell line "Arlo," derived from the polyclonal human alveolar epithelium lentivirus immortalized cell line hAELVi via single-cell printing, and its characterization as a model for the human alveolar epithelium as well as a building block for future complex in vitro models is described. "Arlo" is systematically compared in vitro to primary human alveolar epithelial cells (hAEpCs) as well as to the polyclonal hAELVi cell line. "Arlo" cells show enhanced barrier properties with high transepithelial electrical resistance (TEER) of ≈3000 Ω cm2 and a potential difference (PD) of ≈30 mV under air-liquid interface (ALI) conditions, that can be modulated. The cells grow in a polarized monolayer and express genes relevant to barrier integrity as well as homeostasis as is observed in hAEpCs. Successful productive infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a proof-of-principle study offers an additional, attractive application of "Arlo" beyond biopharmaceutical experimentation.

CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in right atrial myocardium of patients with atrial fibrillation.

RATIONALE: Although research suggests that diastolic Ca(2+) levels might be increased in atrial fibrillation (AF), this hypothesis has never been tested. Diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) might increase diastolic Ca(2+) levels and play a role in triggering or maintaining AF by transient inward currents through Na(+)/Ca(2+) exchange. In ventricular myocardium, ryanodine receptor type 2 (RyR2) phosphorylation by Ca(2+)/calmodulin-dependent protein kinase (CaMK)II is emerging as an important mechanism for SR Ca(2+) leak. OBJECTIVE: We tested the hypothesis that CaMKII-dependent diastolic SR Ca(2+) leak and elevated diastolic Ca(2+) levels occurs in atrial myocardium of patients with AF. METHODS AND RESULTS: We used isolated human right atrial myocytes from patients with AF versus sinus rhythm and found CaMKII expression to be increased by 40+/-14% (P<0.05), as well as CaMKII phosphorylation by 33+/-12% (P<0.05). This was accompanied by a significantly increased RyR2 phosphorylation at the CaMKII site (Ser2814) by 110+/-53%. Furthermore, cytosolic Ca(2+) levels were elevated during diastole (229+/-20 versus 164+/-8 nmol/L, P<0.05). Most likely, this resulted from an increased SR Ca(2+) leak in AF (P<0.05), which was not attributable to higher SR Ca(2+) load. Tetracaine experiments confirmed that SR Ca(2+) leak through RyR2 leads to the elevated diastolic Ca(2+) level. CaMKII inhibition normalized SR Ca(2+) leak and cytosolic Ca(2+) levels without changes in L-type Ca(2+) current. CONCLUSION: Increased CaMKII-dependent phosphorylation of RyR2 leads to increased SR Ca(2+) leak in human AF, causing elevated cytosolic Ca(2+) levels, thereby providing a potential arrhythmogenic substrate that could trigger or maintain AF.

Indications for reoperation late after correction of tetralogy of Fallot.

OBJECTIVE: Correction of tetralogy of Fallot has excellent long-term results. The present retrospective study investigates the indications for reoperation late after corrective surgery. METHODS: Data from 914 consecutive cases who underwent correction of tetralogy of Fallot in our department between 1960 and 2002 were retrospectively reviewed and analysed. In 91 patients, a total of 102 reoperations were performed late after repair. RESULTS: The mean time interval between corrective surgery and the first reoperation was 12.8 years. The main indication for reoperation was residual ventricular septal defect in nearly half of the cases, mostly isolated, but also in combination with a right ventricular outflow tract aneurysm or pulmonary stenosis. One-fourth of reoperated patients underwent a procedure on their pulmonary artery or pulmonary valve: replacement of pulmonary valve, replacement of primary implanted pulmonary artery conduits with or without concomitant surgery, and surgery for isolated peripheral pulmonary stenosis. The remaining indications were right ventricular outflow tract aneurysms and others. Aneurysms of the right ventricular outflow tract were seen mostly after the use of autologous - untreated - pericardial patch in 18 of 21 cases. CONCLUSION: The number of reoperations for residual ventricular septal defect decreased during the study period. The primary use of conduits led to an increased number of reoperations for conduit exchange due to degeneration or failure. Use of an untreated autologous pericardial patch for enlargement of the right ventricular outflow tract should be avoided due to increased risk for aneurysm formation.

Partial Anomalous Pulmonary Venous Return Diagnosed by Central Catheter Misplacement.

Anomalous venous connections of the left lung can either affect all of the veins or only the upper lobe. They mostly drain into the innominate vein. We present the case of a patient who underwent a coronary bypass operation and was prepared with insertion of central lines including Swan-Ganz catheter through both the internal jugular veins. Blood gas analysis obtained from these catheters suggested the presence of a left-to-right shunt. CT (computed tomography) imaging confirmed a pulmonary venous anomaly with misplacement of the left-sided catheter in an abnormal pulmonary vein. Such a rare condition can be suspected by obtaining arterialized blood samples and measuring the mean pressure through central catheters.

Extravascular perivenous fibrin support leads to aneurysmal degeneration and intimal hyperplasia in arterialized vein grafts in the rat.

BACKGROUND AND AIMS: External support of vein grafts by fibrin glue possibly prevents overdistension, vascular remodeling, and neointimal hyperplasia. Previous animal models of neointimal hyperplasia showed conflicting results. Here, long-term effects of external fibrin glue support were studied in a new rat model of jugular vein to abdominal aorta transposition. MATERIALS AND METHODS AND METHODS: In male Wistar rats (250-300 g) right jugular vein (1.0-1.5 cm) was transposed to the infrarenal aorta. Fibrin glue (0.25 ml) covered the vein before releasing the vascular clamps (n = 6). Control vein grafts were exposed directly to blood pressure. After 16 weeks vein grafts were pressure-fixed for histology. Intima thickness, luminal and intimal area were measured by planimetry and elastic fibers demonstrated by Elastica van Giesson staining. RESULTS: Intimal thickness (74.04 +/- 6.7 microm vs 1245 +/- 187 microm, control vs fibrin treatment; p < 0.001), intimal area (2517.16 +/- 355 mm(2) vs 18424 +/- 4927 mm(2), control vs fibrin treatment; p < 0.05) and luminal area (2184.75 +/- 347 mm(2) vs 7231.85 +/- 1782 mm(2), control vs fibrin treatment; p < 0.05) were significantly increased, elastic fibers in the vessel wall were diminished and the vessel wall infiltrated by mononuclear cells in fibrin glue supported veins. CONCLUSION: External support of vein grafts by fibrin glue leads to aneurysmal degeneration and intimal hyperplasia, thereby possibly jeopardizing long-term graft patency.

Bronchial Fistula and Pneumomediastinum after EBUS-TBNA Following Mediastinoscopy.

Background Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a very useful diagnostic tool for the assessment of enlarged mediastinal and hilar lymph nodes. It is a safe procedure with a low risk of complications. Case Description We report a case of bronchial fistula and pneumomediastinum after EBUS-TBNA, which was performed shortly after a mediastinoscopy. Due to the extent of the bronchial lesion, a surgical closure of the bronchial fistula was necessary. The patient recovered completely. Conclusion The performance of EBUS-TBNA shortly after a mediastinoscopy should not be recommended to avoid possible procedure-related complications.

Impact of endothelin-1 Lys198Asn polymorphism on coronary artery disease and endorgan damage in hypertensives.

OBJECTIVE: Endothelin is the most potent endogenous vasoconstrictor and is involved in several vascular disorders such as arterial hypertension. Its intense interaction with other vasoactive hormone systems revealed the consideration about the endothelin gene as an interesting candidate for influencing the development of essential hypertension and hypertensive endorgan damage. The purpose of this study was to investigate the role of endothelin-1 Lys198Asn polymorphism in patients with severe arterial hypertension as well as associated endorgan damages. METHODS: In 400 hypertensive patients and 150 normotensive controls we examined the endothelin-1 Lys198Asn polymorphism by DNA sequencing and patients were divided according to their genotype (GG, GT, and TT). Moreover, the frequency of endothelin-1 Lys198Asn polymorphism was investigated with respect to the prevalence of several actual or historical endorgan damages (renal disorder, coronary artery disease, vascular events, vascular damage, and congestive heart failure) in hypertensive patients. RESULTS: Genotype distribution for endothelin-1 Lys198Asn polymorphism was 57.3% (GG), 41.3% (GT), and 1.43% (TT) in normotensive individuals; and in hypertensive individuals was 54.75% (GG), 43% (GT) and 2.25% (TT). Genotype distribution was unaffected in patients with severe hypertension, renal disorder, vascular events, vascular damage, and congestive heart failure. We, however, found a significant difference in hypertensive individuals with coronary artery disease and TT genotype (P=0.004). CONCLUSION: Homozygous TT carrier contributes to a higher prevalence of coronary artery disease, especially for three-vessel disease in hypertensive individuals. Thus, the polymorphism at position 198 could serve as a possibility to differentiate high-risk subgroups in the heterogeneous population of hypertensive patients.

Hypothermic renal protection using cold histidine-tryptophan-ketoglutarate solution perfusion in suprarenal aortic surgery.

We examined data of 21 patients who were treated with selective perfusion of both renal arteries with 500 mL of 8 degrees C histidine-tryptophan-ketoglutarate (HTK) solution each for renal protection during aortic surgery. Only the data from aortic surgeries with unavoidable suprarenal aortic cross-clamping for juxtarenal or suprarenal abdominal aortic aneurysms (AAAs) or high Leriche syndrome accompanied with stenosis of renal arteries are presented. Five patients underwent immediate surgery because of perforation of an AAA; the other 16 patients went through elective surgeries. In three cases (14%) stenosis of the renal arteries was diagnosed; nevertheless, implantation of an aortorenal bypass was necessary in seven patients. In total, 14 aortorenal bypasses were implanted (five venous grafts and nine prosthesis grafts). Four (19%) patients needed catecholaminergic support to establish stable circulatory conditions; in two (9%) of these cases additional ischemia of the colon was observed and sigmoidectomy was performed. All of these four patients underwent immediate surgery, and one died after surgery because of severe sepsis. In four cases postsurgical renal insufficiency was observed. Three of these patients were admitted for emergency surgery because of their hemodynamic situation due to perforation of the AAA. None of the patients needed chronic dialysis after surgery. Whereas in all patients who underwent elective surgery the renal function remained stable as judged by postoperative serum creatinine values, in five out of seven patients with aortorenal bypass surgery the renal function improved. Perfusion with cold HTK solution offers an additional procedure to protect renal function in patients undergoing elective surgery with suprarenal cross-clamping of the aorta.

[Norman Edward Shumway - pioneer of cardiac surgery (February 9, 1923 to February 10, 2006)]. / Norman Edward Shumway - Pionier der Herzchirurgie (9. Februar 1923 bis 10. Februar 2006).

After a fulfilled life, Norman E. Shumway, the great pioneer of cardiac transplantation, died of lung cancer 1 day after his 83rd birthday in Palo Alto, California, USA. Already at the beginning of the 1960s, he and his colleague Richard R. Lower did revolutionary experimental work on developing and establishing the technique of orthotopic cardiac transplantation in dogs. Several studies on cardiac transplantation were carried out in his department and a few years later, Shumway and his team were on their way to perform the worldwide first human-to-human cardiac transplantation. On December 3, 1967, Christiaan Neethling Barnard, a cardiac surgeon from South Africa, forestalled Shumway and performed this operation in Cape Town, South Africa. This event initiated a global boom of cardiac transplantations in the following years." Many heart centers started their own cardiac transplant programs but high mortality rates led again to stagnancy of transplant activities. Shumway remained stable in believing in good results of cardiac transplantation and continued his program steadily. At the beginning of the 1970s, he and his group were responsible for most cardiac transplantations worldwide.

Topical VEGF enhances healing of thoracic aortic anastomosis for coarctation in a rabbit model.

BACKGROUND: Recurrent stenosis after extended end-to-end anastomosis for aortic coarctation is the primary indication for further interventions in children. Tension because of the extended resection and local arterial wall hypoxia are possible pathogenetic mechanisms. We hypothesized that (1) tension interferes with healing and (2) that vascular endothelial growth factor (VEGF), a hypoxia sensitive angiogenic inducer, may enhance healing of the vascular anastomosis. METHODS AND RESULTS: In a model of coarctation repair, rabbits underwent thoracic aortic end-to-end anastomosis after transection (no-tension; n=15), resection of an aortic ring (tension; n=14) or resection and topical VEGF treatment (0.75 microg VEGF165; tension+VEGF; n=14). Gross and histologic characteristics of the aortic wall were assessed at 1 week, 1 and 2 months. In the tension only group at 1 month, the severity of vascular remodeling was increased with fibrosis and calcification compared with controls. At 2 months, this group also revealed more luminal stenosis (29% versus 19%; P<0.001). Exogenous VEGF resulted in significantly less fibrosis, calcification and chondroid metaplasia at 1 month (P<0.05) and luminal area was only reduced 3% at 2 months (P<0.001 versus tension group). CONCLUSIONS: In a rabbit model of coarctation repair, the addition of tension on the vascular anastomosis resulted in poor healing and luminal stenosis. Topical VEGF maintained luminal integrity by decreasing fibrosis and calcification. These findings suggest that topical VEGF may be a promising new strategy to enhance healing and improve the outcome of vascular anastomoses for coarctation of the aorta.

Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children.

OBJECTIVES: We sought to determine the effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children and to assess whether such changes are associated with morbidity. METHODS: At 6 perioperative time points in 25 patients, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and guanosine 3', 5'-monophosphate were measured, and the biologic activity of the natriuretic hormone system was quantified. Relationships were sought between changes in brain natriuretic peptide levels, biologic activity, and a number of morbidity indicators. RESULTS: There was a significant change in atrial natriuretic peptide levels (P = .037), brain natriuretic peptide levels (P = .001), and biologic activity of the natriuretic hormone system (P = .009) over the first 4 time points in the study. Atrial natriuretic peptide levels transiently decreased from baseline to 12 hours after surgical intervention. Compared with baseline values, brain natriuretic peptide levels were increased at 12 hours after surgical intervention and on postoperative day 1. The increase in brain natriuretic peptide levels from baseline to 12 hours after surgical intervention was associated with cardiopulmonary bypass time (r(s) = 0.4, P = .047). The biologic activity transiently decreased from baseline to intensive care unit admission but was not associated with any morbidity indicators. CONCLUSIONS: Increased postoperative brain natriuretic peptide levels are associated with longer bypass times. The biologic activity of the natriuretic hormone system is transiently impaired. Larger studies should investigate brain natriuretic peptide as a predictor of postoperative morbidity and the potential for natriuretic hormone infusions to improve postoperative hemodynamics and urine output.

Local delivery of osteopontin attenuates vascular remodeling by altering matrix metalloproteinase-2 in a rabbit model of aortic injury.

OBJECTIVE: Vascular remodeling, often accelerated after cardiovascular procedures, may result in stenosis or aneurysm formation. The bone-associated protein osteopontin has been suggested to be involved in vascular remodeling, yet the effect of locally applied osteopontin in an acute vascular injury model of aortic calcification has not been examined. METHODS: Vascular healing of rabbit thoracic aortas treated locally with recombinant osteopontin (dose: 1 microg; n = 16) or albumin (control, n = 16) after acute injury created by end-to-end anastomosis was evaluated. Matrix metalloproteinase-2 level was quantified by gelatin zymography. Proliferation of smooth muscle cells was detected by immunostaining for proliferative cell nuclear antigen. RESULTS: Osteopontin-treated aortas showed significantly diminished vascular remodeling with less calcification (P = .001) and reduced anastomotic luminal stenosis (4% vs 28%, P = .002) compared with controls 2 months postsurgery. Moreover, osteopontin-treated aortas revealed a thickened adventitia with increased fibrosis (P = .006). Matrix metalloproteinase-2 level was up-regulated 2-fold with osteopontin treatment compared with control at 1 week, returning to baseline by 1 month. Staining for proliferation cell nuclear antigen disclosed an increase in proliferation cell nuclear antigen-positive smooth muscle cells in the media of osteopontin-treated aortas at 1 week, normalizing by 1 month. CONCLUSIONS: These data suggest a beneficial effect of locally applied osteopontin after acute injury possibly by altering matrix metalloproteinase-2 activity and smooth muscle cell proliferation. Brief application of osteopontin may effectively enhance vascular healing by reducing calcification and thus maintaining luminal integrity. The role of the osteopontin-related increase in adventitial fibrosis on vascular healing has to be explored.

Osteopontin expression and adventitial angiogenesis induced by local vascular endothelial growth factor 165 reduces experimental aortic calcification.

BACKGROUND: Vascular calcification is a common pathologic and precisely regulated process involving bone-associated proteins such as osteopontin. In this study, we investigated mechanisms by which recombinant human vascular endothelial growth factor 165 protects the arterial wall from severe vascular remodeling, including calcification, a newly discovered biologic action of vascular endothelial growth factor. METHODS: In a rabbit model of thoracic aortic end-to-end anastomosis that simulates cardiovascular intervention, recombinant human vascular endothelial growth factor 165 at a dose of 0.75 mug (n = 19) or albumin (control; n = 19) was delivered intraluminally and on the serosal surface. Animals were killed, and aortic tissue was evaluated by Western blotting, immunohistochemistry, and immunofluorescence at 4, 8, and 24 hours; 1 week; and 1 month after surgery. RESULTS: All controls revealed extensive aortic medial calcification at 1 month, whereas calcification was significantly reduced or absent with vascular endothelial growth factor treatment. Compared with controls, vascular endothelial growth factor treatment resulted in an earlier infiltration of macrophages in the vessel media (at 8 hours: 5.7 +/- 2.3 macrophages per high-power field in control vs 32.1 +/- 7.5 in vascular endothelial growth factor-treated aortas; P < .001), whereas controls showed an increase in macrophages starting at 1 week (24.1 +/- 6.9 vs 4.3 +/- 1.8; P < .001). Osteopontin expression was transiently increased and detected in macrophages and endothelial cells in vascular endothelial growth factor-treated vessels, and adventitial microvascular density was significantly increased by 1 week (9.5 +/- 0.43 vs 25.0 +/- 1.3; P < .001). CONCLUSIONS: Our data suggest that exogenous vascular endothelial growth factor is capable of increasing adventitial angiogenesis and shifting macrophage infiltration and osteopontin expression in the media to an earlier time point, thereby promoting prompt repair and diminishing vascular remodeling and calcification after acute vascular injury.

Neointimal inflammation and adventitial angiogenesis correlate with severity of cardiac allograft vasculopathy in pediatric recipients.

BACKGROUND: Chronic inflammation and angiogenesis have been implicated in the pathogenesis of both cardiac allograft vasculopathy (CAV) and age-related vasculopathy. Because concurrent atherosclerosis does not complicate assessment of CAV in children, we sought to characterize the spectrum of coronary lesions in this population and determine whether inflammatory infiltrates and angiogenesis correlate with severity of CAV. METHODS: In 18 pediatric heart specimens CAV was graded 1 to 4 (none to severe). Each case was assigned to either: Group I, no inflammation; Group II, perivascular inflammation; or Group III, perivascular and neointimal inflammation. Inflammatory infiltrates were immunophenotyped using anti-CD3, anti-CD20 and HAM 56. Angiogenesis was assessed by determining microvascular density (MVD) in 5 high-power fields (HPFs) per section. RESULTS: CAV was evident in 94% of cases, and inflammation in 61%. Cases with neointimal inflammation had significantly more severe CAV compared with cases without inflammation (2.7 +/- 0.16 vs 1.9 +/- 0.2, p = 0.002). MVD was significantly higher in both inflammation groups (Groups II and III) compared with Group I (4.1 +/- 0.5 per HPF and 5.9 +/- 0.5 vs 3.1 +/- 0.7, p = 0.018 and p = 0.002) and correlated with the degree of CAV (p = 0.007). The perivascular infiltrates (Group II, n = 5) contained lymphocytes, macrophages and plasma cells, and 67% of neointimal infiltrates (Group III, n = 6) also contained eosinophils. CONCLUSIONS: CAV in children is more common than previously reported. Our data indicate that CAV is often associated with inflammation and that adventitial angiogenesis correlated with the severity of CAV.

Hemodynamic and gas transfer properties of a compliant thoracic artificial lung.

A compliant thoracic artificial lung (TAL) has been developed for acute respiratory failure or as a bridge to transplantation. The development goal was to increase TAL compliance, lower TAL impedance, and improve right ventricular function during use. Prototypes were tested in vitro and in vivo in eight pigs between 67 and 79 kg to determine hemodynamic and gas transfer properties. The in vitro compliance was 16.2 +/- 4.4 ml/mm Hg at pressures < 7.8 mm Hg and 4.3 +/- 1.1 ml/mm Hg above 7.8 mm Hg. In vivo, this compliance significantly reduced blood flow pulsatility from 1.7 at the inlet to 0.36 at the outlet. Device resistance was 1.9 and 1.8 mm Hg/(L/min) at a flow rate of 4 L/min in vitro and in vivo, respectively. Approximately 75% of the resistance was at the inlet and outlet. In vivo TAL O2 and CO2 transfer rates were 188 and 186 ml/min, respectively, at 4 L/min of blood and gas flow, and average outlet O2 saturations exceeded 98% for average flow rates up to and including the maximum tested, 5.3 L/min. The new design has a markedly improved compliance and excellent gas transfer but also possesses inlet and outlet resistances that must be reduced in future designs.

Hypercholesterolemia is common after pediatric heart transplantation: initial experience with pravastatin.

BACKGROUND: Coronary allograft vasculopathy (CAV) is a progressive complication after cardiac transplantation and limits survival. Hyperlipidemia is a known risk factor for CAV, and pravastatin is effective in decreasing cholesterol levels in adults after transplantation. However, few data exist regarding lipid profiles and statin use after pediatric heart transplantation. We evaluated the prevalence of hyperlipidemia in pediatric heart transplant recipients and assessed the efficacy and safety of pravastatin therapy. METHODS: We performed a retrospective chart review of lipid profiles > or =1 year after surgery in 50 pediatric cardiac transplant recipients to assess the incidence of hyperlipidemia. Twenty of these patients received pravastatin for hypercholesterolemia. Their primary immunosuppression therapy was cyclosporine/prednisone plus either azathioprine or mycophenolate mofetil. We reviewed serial lipid profiles, creatinine phosphokinase, and liver enzymes. RESULTS: Overall, 36% of the patients (n = 50) had total cholesterol (TC) concentrations > 200 mg/dl and 52% had low-density lipoprotein (LDL) >110 mg/dL beyond 1 year after transplantation. Of the 20 treated with pravastatin, TC (236 +/- 51 vs 174 +/- 33 mg/dl) and LDL levels (151 +/- 32 vs 99 +/- 21 mg/dl) decreased significantly with therapy (p <.0001). We found no symptoms; however, 1 patient had increased creatinine phosphokinase. Liver enzyme concentrations remained normal in all. CONCLUSIONS: Hypercholesterolemia is prevalent in pediatric cardiac transplant recipients. Pravastatin therapy is effective in decreasing TC and LDL levels, seems to be safe, and is tolerated well. Further studies are necessary to determine whether pravastatin treatment is beneficial in decreasing CAV.

Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches.

BACKGROUND: Although patients after Fontan procedure have a high incidence of thromboembolic complications, anticoagulant therapy is not handled uniformly. We analyzed the frequency and clinical relevance of thromboembolism after Fontan procedure and compared different therapeutic approaches. METHODS: From 1986 to 1998, 101 patients (mean age, 7.3 +/- 8.1 years) underwent Fontan type procedure (modified Fontan, n = 40; total cavopulmonary connection, n = 61). In 85 of 87 survivors, transthoracic echocardiography was performed; and in 31 transesophageal echocardiography and/or angiography was performed. Mean follow-up was 5.7 +/- 3.5 years. Three groups with different anticoagulant regimen were compared: group I without medication (n = 45), group II with acetylsalicylic acid therapy (n = 14) and group III with Coumadin (n = 26). RESULTS: Thromboembolic events occurred in 13 of 85 patients (15.3%; 3.3 events/100 patient-years). Type of operation as well as other known risk factors had no influence on the rate of thromboembolism. Within the first postoperative year, seven of 13 events occurred. A second peak developed beyond 10 years of follow-up. Patients benefit significantly from Coumadin compared with those who did not receive any medication, with similar results in the entire population and the subgroup of patients with total cavopulmonary connection (log-rank, p = 0.031 and p = 0.033, respectively). With 4.2 events/100 patient-years, the cumulative event rate was substantially higher in group I than with 1.6 in group II and with 1.1 in group III. No relevant bleeding complications occurred. CONCLUSIONS: Thromboembolism is frequent after Fontan procedure with a peak during the first postoperative year and another peak beyond 10 years of follow-up. Coumadin is the most effective prophylactic therapy in preventing thromboembolism. Therefore, we suggest initial oral anticoagulation therapy in patients with Fontan type operation.

Antegrade palliation for diminutive pulmonary arteries in Tetralogy of Fallot.

OBJECTIVES: The purpose of this study was to evaluate the outcome following palliative reconstruction of right ventricular outflow tract in Tetralogy of Fallot (TOF) with diminutive pulmonary arteries with central and peripheral stenosis. METHODS: Between 1986 and 1999 in 15 children with the diagnosis of TOF palliative reconstruction of the right ventricular outflow tract without closure of the ventricular septal defect (VSD) was performed. All patients were not suitable for an AP-Shunt because of a diminutive pulmonary vascular bed. Six patients were younger than 1 year at operation. RESULTS: There was one hospital death (6.7%) in a child with additional aortic valve insufficiency in multi-organ failure. Although the postoperative course was prolonged (median duration on ICU: 8 days) and complicated by congestive heart failure, clinically the 14 patients discharged improved significantly. The arterial oxygen saturation increased from 67 to 93% (P<0.001), the hemoglobin decreased from 16.1 to 13.3g/l (P=0.02) and hematocrit from 0.52 to 0.40 (P=0.06). In control angiography, the McGoon Index increased in the average from 1.01 to 1.95 (P<0.001). VSD closure was performed in 12 patients (median: 2.5 years after initial operation) with one perioperative death. A homograft had to be implanted in seven patients and a mechanical prosthesis in the right ventricular outflow tract in one. One late death occurred due to ventricular arrhythmia 12 years after antegrade palliation (11 years after corrective operation). CONCLUSIONS: The antegrade palliation seems to be an adequate strategy for the treatment of selected children with diminutive pulmonary arteries in TOF, who were not candidates for primary correction or an AP-Shunt.