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Background: Transcatheter aortic valve implantation (TAVI) has recently developed into an acceptable alternative to conventional surgery in high-risk patients. However, information on the identification of patients gaining most benefit from this procedure is still limited. The aim of this study was to evaluate safety and efficacy of TAVI in different patient cohorts., Methods: Between August 2008 and December 2010, 180 high-risk patients underwent TAVI at our institution (97 transapical and 83 transfemoral approaches). Periprocedural complications as well as mortality and incidence of MACCE during follow-up were recorded., Results: Mean age was 82 ± 5 years, and mean logistic EuroScore 27 ± 14%. In the total cohort, 30-day mortality was 8.9% and 12-month survival (according to Kaplan-Meier-analysis) 72%, with no significant differences between the two approaches. However, a significant difference in survival was obvious after stratification of patients according to logistic EuroScore mortality estimates. Survival proportions at 1 year were 62% in patients with logistic EuroScore >40%, 71% in patients with EuroScore 20-40% and 80% in octogenarians with EuroScore <20% (P = 0.009). Furthermore, the observed median event-free survival as an indicator for morbidity ranged between 315 days in the first, 442 days in the second and 710 days in the third group (P = 0.1)., Conclusions: TAVI proved to be feasible with reproducible results. However, mortality and rehospitalization rates were considerably high in specific patient cohorts, suggesting that the risk-to-benefit ratio of TAVI should be validated individually. In the present study, octogenarians with logistic EuroScore <20% could be identified as candidates apparently gaining high benefit from the procedure.

We report on three out of 270 consecutive patients (1.1%) suffering from coronary artery obstruction or occlusion at the end of transcatheter aortic valve implantation (TAVI). The partial or total obstruction of the coronary artery seen in the post-implantation aortography was accompanied by haemodynamic instability and electrocardiographic changes typical for myocardial ischaemia. Immediate percutaneous coronary intervention with stent implantation was successful in two cases, while in the third case it was not possible to cross the occluded right coronary artery. Emergency coronary artery bypass grafting was performed resulting in uneventful myocardial recovery. All patients were discharged home. These cases highlight the awareness of this rare, life-threatening complication of TAVI, which is in need of a dedicated heart team involved not only in decision-making, but also in the procedure itself.

Aim: Minimally invasive approaches for repair of congenital heart defects have gained in popularity. Aim of the study was to evaluate the safety and efficiency of the partial inferior sternotomy approach to repair various congenital heart defects., Methods: Since 1998, 100 children (55 males; mean age: 3.8 ± 3.7; mean weight: 15.1 ± 8.7 kg) were operated on via a limited median vertical skin incision and partial inferior sternotomy. Preoperative diagnoses were: ASD II (N.=46), sinus venosus defect with partial anomalous pulmonary venous connection (N.=12), partial AV-canal (N.=4), VSD (N.=35), tetralogy of Fallot (N.=2), and double chambered right ventricle (N.=1). Cannulation was always performed via the chest incision., Results: There were no deaths. Mean cross-clamp time was 49.9 ± 30.6 minutes, and mean operation time 192 ± 46 minutes. Mean postoperative mechanical ventilation time, Intensive Care Unit stay and hospital stay were 9.7 ± 10.4 hours, 1.8 ± 0.7 days, and 12 ± 3.0 days, respectively. Complications included pneumothorax requiring drainage in 2 patients, atrioventricular block necessitating a permanent pacemaker in 1 patient. The incisions healed properly. All patients are in excellent condition after a mean follow-up of 32 ± 25 months. On echocardiography no residual defect was evident in 98 patients, and a mild mitral insufficiency in two patients operated on partial atrioventricular canal., Conclusion: The partial inferior sternotomy approach to congenital heart operations is less invasive than and cosmetically superior to full sternotomy with reduced postoperative pain and discomfort for the patients. This approach ensures a safe procedure with excellent exposure without additional incisions. It is our standard approach in infants/children with septal defects.

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.

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.

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.

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.

This study examined changes in the natriuretic hormone system in five infants with congestive heart failure (CHF) due to intracardiac left-to-right shunting who were exposed to cardiopulmonary bypass (CPB) during surgical repair. Plasma concentrations of three hormones [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and dendroaspis natriuretic peptide (DNP)] and their secondary messenger, guanosine 3',5'-monophosphate (cGMP), were measured, and the biological activity of the system was quantified. At baseline, BNP and DNP concentrations were normal in our patients, a finding that is strikingly different from that of adult CHF patients, whereas ANP concentrations were elevated. Following CPB, ANP concentrations decreased (median, 175 vs 44 pg/ml; p = 0.043) and BNP concentrations increased (median, 25 vs 66 pg/ ml; p = 0.043), whereas DNP concentrations did not change. Following modified ultrafiltration, BNP concentrations increased (p = 0.043), but other natriuretic peptide concentrations did not change. The calculated biological activity of the natriuretic hormone system decreased following CPB [molar ratio, cGMP / (ANP + BNP + DNP); median, 213 vs 127; p = 0.043)]. Additional studies are needed to expand on these findings and identify patients with other types of congenital heart disease who have perioperative disturbances in the natriuretic hormone system and thus might benefit from pharmacologic intervention.

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.

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.

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.

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.

Introduction and Objectives: Patients with combined mitral valve operation and coronary artery surgery represent a high risk group. The aim of this retrospective study was to evaluate which factors affect early and late postoperative results in this particular group of considered high risk patients. PATIENTS AND METHOD. Between 1984 and 1997, 264 patients (mean age: 63 +/- 7.3 years) underwent mitral valve surgery (199 patients; 75% mitral valve replacement, 25% mitral valve repair) in combination with coronary revascularization (mean 2.4 +/- 1.3 grafts). Follow-up comprised a mean of 69 +/- 42 months and was 98.3% complete., Results: Early mortality was 10.6% (28/264). Ischemic mitral regurgitation operated on in emergent status, moderate to severe reduced left ventricular function and advanced age (> 60 years) were independently associated with early hospital mortality (p < 0.05). Ischemic etiology of mitral valve disease (emergency and elective operations), severity of mitral regurgitation and New York Heart Association (NYHA) functional class IV were related to early hospital mortality, only with univariate statistics. Actuarial survival was 86, 69 and 48% at 1, 5 and 10 years, respectively. The preoperative NYHA functional class was the only variable independently related to late survival. Eighty-five percent of the surviving patients were in NYHA functional class I and II., Conclusions: Mitral valve operation combined with coronary artery bypass grafting is associated with a high early hospital mortality. Independent risk factors of early mortality are emergency operation of ischemic mitral valve disease, reduced left ventricular function and advanced age. Long term survival is independently influenced only by preoperative NYHA functional class IV.

Background: The Silzone-coated St. Jude Medical valve (SJM "Silzone" valve), developed to reduce prosthetic valve endocarditis (PVE), was recalled by SJM due to a higher rate of paravalvular leaks. The aim of this study was to determine the efficacy of the SJM "Silzone" valve in avoiding PVE and to evaluate the frequency of paravalvular leaks, when the valve was used exclusively for active bacterial endocarditis., Methods: From January 1998 to December 1999, the SJM "Silzone" valve was implanted in 40 consecutive patients with active endocarditis (20 aortic, 14 mitral, and 6 both valves). Late transesophageal echocardiography was performed in 87% of survivors, and transthoracic echocardiography in the remaining 13%. Follow-up was 100%., Results: Hospital mortality was 17.5%. Early PVE occurred in 2 of 40 patients (5%). There were two late deaths without signs of recurrent PVE. A hemodynamic relevant paravalvular leak necessitating reoperation was seen in 2 patients within 6 months after operation. The rate of a minor paravalvular leak was 13% (4 of 31 patients)., Conclusions: The SJM "Silzone" valve when implanted for active bacterial endocarditis does not give better results than other mechanical prostheses with regard to early recurrence of endocarditis. The rate of a hemodynamic relevant paravalvular leak requiring reoperation seems rather high during the early postoperative period, whereas the occurrence of minor paravalvular leaks is comparable with that of other mechanical prostheses. Routine observation, recommended for all patients with mechanical heart valves, is also sufficient for patients with the SJM "Silzone" valve.

Objectives: Mitral valve combined with coronary artery surgery is associated with a higher hospital mortality than each operation in particular. Controversy exists regarding the predictive value of ischemic mitral valve disease (MVD) on outcome., Methods: Between 1984 and 1997, 262 patients underwent mitral valve operations (replacement, n = 198; repair, n = 64) in combination with coronary revascularization. The etiology of MVD was secondary to ischemic heart disease (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups were similar in age, cardiac risk factors and pulmonary artery pressure. Patients of group I had significantly more severe coronary artery disease, more often an impaired left ventricle and myocardial infarction, and were in a worse functional condition. The mean number of bypass grafts was significantly higher in group I. The follow-up was 98% (230/234 patients)., Results: With 19.5%, the hospital mortality was significantly increased in group I compared with 6.7% in group II (P = 0.002; overall, 10.7%). Mitral valve repair or replacement had no influence on early outcome, although mitral valve repair was performed more often in group I (37 versus 19%). The survival (valve-related event-free survival) after discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and 53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II, respectively. The long-term functional capacity was equally good in both groups (New York Heart Association mean, 1.86 versus 1.72)., Conclusions: Patients with ischemic MVD are in a worse cardiac condition with significantly higher hospital mortality than patients with non-ischemic MVD and coronary artery bypass grafting. Once discharged from hospital, both groups have comparable long-term outcomes, with the best results in patients with degenerative MVD.

We present a case of two missiles in the heart causing coronary artery disease with first onset 44 years after the injury. The missiles were close to the right coronary artery and the left anterior descending coronary artery. The missiles initiated local arteriosclerosis in these vessels, with an extremely stretched time frame from injury to the onset of symptoms for coronary artery disease.