Cardiovascular disease in Down syndrome.

PURPOSE OF REVIEW: In the last 40 years, with a better understanding of cardiac defects, and with the improved results of cardiac surgery, the life expectancy of persons with Down syndrome has significantly increased. This review article reports on advances in knowledge of cardiac defects and cardiovascular system of persons with trisomy 21. RECENT FINDINGS: New insights into the genetics of this syndrome have improved our understanding of the pathogenetic mechanisms of cardiac defects. Recent changes in neonatal prevalence of Down syndrome suggest a growing number of children with cardiac malformations, in particular with simple types of defects. Ethnic and sex differences of the prevalence of specific types of congenital heart disease (CHD) have also been underlined. A recent study confirmed that subclinical morphologic anomalies are present in children with trisomy 21, also in the absence of cardiac defects, representing an internal stigma of Down syndrome. The results of cardiac surgery are significantly improved in terms of immediate and long-term outcomes, but specific treatments are indicated in relation to pulmonary hypertension. Particular aspects of the cardiovascular system have been described, clarifying a reduced sympathetic response to stress but also a 'protection' from atherosclerosis and arterial hypertension in these patients. SUMMARY: Continuing dedication to clinical and basic research studies is essential to further improve survival and the quality of life from childhood to adulthood of patients with trisomy 21.

Outcomes and prognostic factors for postsurgical pulmonary vein stenosis in the current era.

BACKGROUND: The optimal management and prognostic factors of postsurgical pulmonary vein stenosis remain controversial. We sought to determine current postsurgical pulmonary vein stenosis outcomes and prognostic factors in a multicentric study in the current era. METHODS: Seventy-five patients with postsurgical pulmonary vein stenosis who underwent 103 procedures in 14 European/North American centers (2000-2012) were included retrospectively. A specific pulmonary vein stenosis severity score was developed on the basis of the assessment of each pulmonary vein. End points were death, pulmonary vein reintervention, and restenosis. A univariate and multivariate risk analysis was performed. RESULTS: Some 76% of postsurgical pulmonary vein stenosis occurred after repair of a total anomalous pulmonary venous return. Sutureless repair was used in 42 of 103 procedures (41%), patch veinoplasty was used in 28 procedures (27%), and endarterectomy was used in 16 procedures (16%). Overall pulmonary vein restenosis, reintervention, and mortality occurred in 56% (n = 58/103), 49% (n = 50/103), and 27% (n = 20/75), respectively. Sutureless repair was associated with less restenosis (40% vs 67%; P = .007) and less reintervention (31% vs 61%; P = .003). Mortality after sutureless repair (20%; 7/35) tends to be lower than after nonsutureless repair (33%; 13/40) (P = .22). A high postoperative residual pulmonary vein stenosis score at the time of hospital discharge was an independent risk factor for restenosis (hazard ratio [HR], 1.55; P < 10-4), reintervention (HR, 1.33; P < 10-4), and mortality (HR, 1.37; P < 10-4). The sutureless technique was an independent protective factor against restenosis (HR, 0.27; P = .006). CONCLUSIONS: Postsurgical pulmonary vein stenosis still has a guarded prognosis in the current era. The sutureless technique is an independent protective factor against restenosis. The severity of the residual disease evaluated by a new severity score is an independent risk factor for poor outcomes regardless of surgical technique.

Primary Pulmonary Vein Stenosis: Outcomes, Risk Factors, and Severity Score in a Multicentric Study.

BACKGROUND: Primary pulmonary vein stenosis (PPVS) still carries a poor prognosis, and prognostic factors remain controversial. The aim of this study was to determine outcomes and prognostic factors after PPVS repair in the current era. METHODS: Thirty patients with PPVS and a normal pulmonary vein (PV) connection operated on in 10 European/North American centers (2000-2012) were included retrospectively. A specific PVS severity score was developed based on the assessment of each PV. Studied end points were death, PV reoperation, and restenosis. A univariate and multivariate risk analysis was performed. RESULTS: The mean number of affected PVs per patient was 2.7 ± 1.1. Sutureless repair was used in 21 patients (70%), endovenectomy was used in 5 patients, and patch venoplasty was used in 4 patients. Overall PV restenosis, reoperation, and mortality occurred in 50%, 40%, and 30% of patients respectively. Freedom from mortality, reoperation, and restenosis at 8 years of follow-up was 70% ± 8%, 62% ± 8%, and 47% ± 9%, respectively. Restenosis and mortality rates after sutureless repair versus nonsutureless repair were 57% (n = 12 of 21) versus 33% (n = 3 of 9) (p = 0.42) for restenosis and 38% (n = 8 of 21) versus 11% (n = 1 of 9) (p = 0.21) for mortality. Patients selected for a sutureless technique were younger and smaller and had more severe disease before operation. A postoperative high PVS score and pulmonary hypertension 1 month after the operation were independent risk factors for restenosis (hazard ratio [HR], 1.34; p = 0.002 and HR, 6.81; p = 0.02, respectively), reoperation (HR, 1.24; p = 0.01 and HR, 7.60; p = 0.02), and mortality (HR, 1.39; p = 0.01 and HR, 39.5; p = 0.008). CONCLUSIONS: Primary PVS still has a guarded prognosis in the current era despite adoption of the sutureless technique. Postoperative pulmonary hypertension and severity of disease evaluated by a new severity score are independent prognostic factors regardless of surgical technique.

Surgical options after Fontan failure.

OBJECTIVE: The objective of this European multicenter study was to report surgical outcomes of Fontan takedown, Fontan conversion and heart transplantation (HTX) for failing Fontan patients in terms of all-cause mortality and (re-)HTX. METHODS: A retrospective international study was conducted by the European Congenital Heart Surgeons Association among 22 member centres. Outcome of surgery to address failing Fontan was collected in 225 patients among which were patients with Fontan takedown (n=38; 17%), Fontan conversion (n=137; 61%) or HTX (n=50; 22%). RESULTS: The most prevalent indication for failing Fontan surgery was arrhythmia (43.6%), but indications differed across the surgical groups (p<0.001). Fontan takedown was mostly performed in the early postoperative phase after Fontan completion, while Fontan conversion and HTX were mainly treatment options for late failure. Early (30 days) mortality was high for Fontan takedown (ie, 26%). Median follow-up was 5.9 years (range 0-23.7 years). The combined end point mortality/HTX was reached in 44.7% of the Fontan takedown patients, in 26.3% of the Fontan conversion patients and in 34.0% of the HTX patients, respectively (log rank p=0.08). Survival analysis showed no difference between Fontan conversion and HTX (p=0.13), but their ventricular function differed significantly. In patients who underwent Fontan conversion or HTX ventricular systolic dysfunction appeared to be the strongest predictor of mortality or (re-)HTX. Patients with valveless atriopulmonary connection (APC) take more advantage of Fontan conversion than patients with a valve-containing APC (p=0.04). CONCLUSIONS: Takedown surgery for failing Fontan is mostly performed in the early postoperative phase, with a high risk of mortality. There is no difference in survival after Fontan conversion or HTX.

Left ventricular pacing in neonates and infants with isolated congenital complete or advanced atrioventricular block: short- and medium-term outcome.

AIMS: Right ventricular (RV) pacing may induce left ventricular (LV) dysfunction: neonates and infants with isolated congenital complete/advanced atrioventricular block (CCAVB) are at high risk of developing RV pacing-induced LV dyssynchrony, remodelling, and dysfunction. We prospectively investigated whether LV pacing results in normal LV function and good clinical status in the short/medium term. METHODS AND RESULTS: In this single-centre, prospective study, 10 consecutive patients with CCAVB (median age 4 months, range: 0.1-16) underwent pacemaker implantation (4 VVIR, 6 DDD) using epicardial leads (on the LV apex in 8, on the LV free wall in 2). Data were collected at implantation and at 1- and 12-month follow-up. Echocardiographic evaluation included two-dimensional/three-dimensional assessment of LV dimensions, function (ejection fraction, EF), and ventricular synchrony (interventricular and intraventricular dyssynchrony). Prior to pacemaker implantation, EF was normal in six patients, 50% in two, ≤40% in two. All patients showed good clinical status and normal LV dimensions at follow-up. Patients with LV dilatation and impaired EF at implantation showed LV reverse remodelling and enhanced LV function. Normal LV function and synchrony were observed in most patients (one patient with EF 53% and three patients with mild dyssynchrony at 12-month follow-up). Paced QRS complex tended to be wider than native QRS complexes (P = 0.07); QTc duration of paced complexes was within normal limits or only slightly prolonged, without significant differences compared with QTc interval of native complexes. CONCLUSION: At short- and medium-term follow-up, LV pacing results in satisfactory LV electromechanical function and synchrony in neonates and infants with CCAVB.

Favourable mid-term outcome after heart transplantation for late Fontan failure.

OBJECTIVES: Fontan failure (FF) represents a growing and challenging indication for paediatric orthotopic heart transplantation (OHT). The aim of this study was to identify predictors of the best mid-term outcome in OHT after FF. METHODS: Twenty-year multi-institutional retrospective analysis on OHT for FF. RESULTS: Between 1991 and 2011, 61 patients, mean age 15.0 ± 9.7 years, underwent OHT for failing atriopulmonary connection (17 patients = 27.8%) or total cavopulmonary connection (44 patients = 72.2%). Modality of FF included arrhythmia (14.8%), complex obstructions in the Fontan circuit (16.4%), protein-losing enteropathy (PLE) (22.9%), impaired ventricular function (31.1%) or a combination of the above (14.8%). The mean time interval between Fontan completion and OHT was 10.7 ± 6.6 years. Early FF occurred in 18%, requiring OHT 0.8 ± 0.5 years after Fontan. The hospital mortality rate was 18.3%, mainly secondary to infection (36.4%) and graft failure (27.3%). The mean follow-up was 66.8 ± 54.2 months. The overall Kaplan-Meier survival estimate was 81.9 ± 1.8% at 1 year, 73 ± 2.7% at 5 years and 56.8 ± 4.3% at 10 years. The Kaplan-Meier 5-year survival estimate was 82.3 ± 5.9% in late FF and 32.7 ± 15.0% in early FF (P = 0.0007). Late FF with poor ventricular function exhibited a 91.5 ± 5.8% 5-year OHT survival. PLE was cured in 77.7% of hospital survivors, but the 5-year Kaplan-Meier survival estimate in PLE was 46.3 ± 14.4 vs 84.3 ± 5.5% in non-PLE (P = 0.0147). Cox proportional hazards identified early FF (P = 0.0005), complex Fontan pathway obstruction (P = 0.0043) and PLE (P = 0.0033) as independent predictors of 5-year mortality. CONCLUSIONS: OHT is an excellent surgical option for late FF with impaired ventricular function. Protein dispersion improves with OHT, but PLE negatively affects the mid-term OHT outcome, mainly for early infective complications.

Repair of incompetent truncal valves: early and mid-term results.

OBJECTIVES: To analyse the factors associated with in-hospital mortality and mid-term significant neoaortic valve regurgitation (AR) after truncal valve (TV) repair. METHODS: Eleven children underwent TV repair at our institution from July 1999 to March 2012. All children presented significant preoperative TV regurgitation. Valve anatomy was quadricuspid in 7 (64%) patients and tricuspid in 4 (36%). The median age and weight at surgery were 29.6 (range 0.3-173.2) months and 12 (range 2.2-49) kg, respectively. Repair included bicuspidalization through the approximation of two leaflets associated with triangular resection of the opposite one (n = 2, 18%), or either bicuspidalization or tricuspidalization of the TV through excision of one leaflet and related sinus of Valsalva (n = 9, 82%). In 3 patients, repair was associated with coronary detachment before cusp removal, followed by coronary reimplantation. RESULTS: In-hospital death occurred in 2 (18%) patients. Factors associated with hospital mortality were age <1 year (P = 0.05), weight <3 kg (P = 0.02) and longer cross-clamping time (P = 0.008). Follow-up was complete for all patients [median follow-up time: 52.2 (range 132.2-2.5) months]. Mid-term significant AR occurred in 4 patients (45%, moderate in 2 and severe in 2). One with severe AR underwent successful valve replacement 4 months postoperatively, leading to freedom from reintervention of 91%. Freedom from significant AR was 76.2 (33.2-93.5) and 60.9 (20.2-85.6) at 1 and 2 years, respectively. There was a trend towards longer freedom from mid-term significant AR for patients who underwent cusp removal compared with those who did not (P = 0.07). CONCLUSIONS: TV repair in children can be performed safely with fairly good and durable results. Cusp removal might decrease the rate of severe AR on mid-term follow-up.

Cardiac pacing in paediatric patients with congenital heart defects: transvenous or epicardial?

AIMS: Cardiac pacing is a difficult technique in children, particularly in patients with congenital heart defects (CHDs). Few studies to date have addressed this topic. METHODS AND RESULTS: We performed a retrospective analysis of the results of a single centre. Between 1982 and 2008, 287 patients with CHD, median age of 5 years (25-75%, 1-11) underwent cardiac pacing for sinus node dysfunction (SND) and atrioventricular block (AVB); 97% of patients underwent at least one heart surgery. Endocardial systems (Endo) were implanted in 117 patients, epicardial systems (Epi) in 170, with 595 leads (228 Endo, 367 Epi). Endocardial systems showed a significantly older age group with more frequent SND; Epi a younger age group, with more frequent AVB, greater number of surgical interventions. Perioperative complications were mortality 0.6% (Epi), pericardial effusion 0.6% (Epi), and haemothorax 3.4% (Endo). The median follow-up is 5 (2-10) years: the pacing system failed in 29% of patients, 13% Endo, and 40% Epi (P < 0.0001). Multivariate analysis showed a significantly higher risk of failure for Epi, a lower implant age, greater the number of leads implanted. The risk of malfunction of the leads increases significantly for Epi and the younger age when implanted. The steroid-eluting leads have a lower risk of malfunction (P = 0.05), steroid-eluting Endo leads provide significantly better outcomes than Epi. CONCLUSION: Cardiac pacing in paediatric patients with CHD shows satisfactory results in the long term. Endocardial systems show significantly better results than Epi systems. A younger age when implanted is a risk factor for complications at follow-up.

Plastic bronchitis after extracardiac Fontan operation.

BACKGROUND: We discuss 4 cases of plastic bronchitis (PB) after Fontan procedure observed at our Institution, with the aim to identify an effective treatment and possible factors favoring the onset of PB. Plastic bronchitis is an uncommon disease characterized by recurrent formation of large pale bronchial casts obstructing the tracheobronchial tree. The treatment includes inhaled or systemic steroids, aerosolized mucolytics, bronchoscopic lavage, direct bronchoscopic extraction and, in few reports, aerosolized fibrinolytic and pulmonary vasodilators. METHODS: Four cases of PB after Fontan procedure occurred in our center from January 2008 to January 2012. RESULTS: All patients showed preserved ventricle function and underwent embolization of systemic-pulmonary collaterals prior to a Fontan procedure and all had chylothorax in the perioperative period. Two patients died; 1 of massive thrombosis of the superior vena cava and right pulmonary artery and the other of acute asphyxiation and refractory cardiac failure. CONCLUSIONS: The exact causes of PB in Fontan patients remain unknown. An early diagnosis and a multiple therapy with steroids, mucolytics, pulmonary vasodilators, and aerosolized tissue plasminogen activator may be effective.

Surgery for primary cardiac tumors in children: early and late results in a multicenter European Congenital Heart Surgeons Association study.

BACKGROUND: To evaluate indications and results of surgery for primary cardiac tumors in children. METHODS AND RESULTS: Eighty-nine patients aged ≤18 years undergoing surgery for cardiac tumor between 1990 and 2005 from 16 centers were included retrospectively (M/F=41/48; median age 4.3 months, range 1 day to 18 years). Sixty-three patients (68.5%) presented with symptoms. Surgery consisted of complete resection in 62 (69.7%) patients, partial resection in 21 (23.6%), and cardiac transplant in 4 (4.5%). Most frequent histotypes (93.2%) were benign (rhabdomyoma, myxoma, teratoma, fibroma, and hemangioma). Postoperative complications occurred in 29.9%. Early and late mortality were 4.5% each (mean follow-up, 6.3±4.4 years); major adverse events occurred in 28.2% of the patients; 90.7% of patients are in New York Heart Association class I. There were no statistically significant differences in survival, postoperative complications, or adverse events after complete and partial resection in benign tumors other than myxomas. Cardiac transplant was associated significantly with higher mortality rate (P=0.006). Overall mortality was associated to malignancy (P=0.0008), and adverse events during follow-up (P=0.005). CONCLUSIONS: Surgery for primary cardiac tumors in children has good early and long-term outcomes, with low recurrence rate. Rhabdomyomas are the most frequent surgical histotypes. Malignant tumors negatively affect early and late survival. Heart transplant is indicated when conservative surgery is not feasible. Lack of recurrence after partial resection of benign cardiac tumors indicates that a less risky tumor debulking is effective for a subset of histotypes such as rhabdomyomas and fibromas.

Long-term results of the REV (réparation à l'ètage ventriculaire) operation.

OBJECTIVE: Despite its innovative features, the réparation à l'ètage ventriculaire (REV) procedure has not gained large popularity in the treatment of transposition of the great arteries, ventricular septal defect, pulmonary stenosis, and related anomalies, and thus the Rastelli operation remains the preferred type of repair. We try to obviate the alleged lack of long-term results that has been suggested to explain this reluctance to change. METHODS: We reviewed a series of 205 patients who underwent the REV procedure between 1980 and 2003. RESULTS: Hospital mortality was 12% (24 patients). Ten of 181 early survivors residing in distant countries could not be traced for follow-up. There were 13 late deaths (2 of noncardiac causes). Overall survival and freedom from any reoperation at 25 years were 85% and 45%, respectively, as determined by using the Kaplan-Meier method. Reoperation was commonly required because of recurrent right ventricular outflow tract obstruction (36 patients) and rarely by left ventricular outflow tract stenosis (3 patients). By using cumulative method analysis, at the 25-year follow-up interval, the probability of being alive without reoperation was 45%, that of reoperation for right ventricular outflow tract obstruction was 33%, and that of reoperation for left ventricular outflow tract obstruction was 5%. Clinical status is excellent: 137 patients are in New York Heart Association class I (87%), and 131 patients are free of arrhythmias. CONCLUSIONS: These results represent a considerable improvement over those of the Rastelli operation in terms of survival and need for reoperation for right or left ventricular outflow tract obstruction.

Scimitar syndrome: a European Congenital Heart Surgeons Association (ECHSA) multicentric study.

BACKGROUND: Scimitar syndrome is a rare congenital heart disease. To evaluate the surgical results, we embarked on the European Congenital Heart Surgeons Association (ECHSA) multicentric study. METHODS AND RESULTS: From January 1997 to December 2007, we collected data on 68 patients who underwent surgery for scimitar syndrome. Primary outcomes included hospital mortality and the efficacy of repair at follow-up. Median age at surgery was 1.4 years (interquartile range, 0.46 to 7.92 years). Forty-four patients (64%) presented with symptoms. Surgical repair included intraatrial baffle in 38 patients (56%; group 1) and reimplantation of the scimitar vein onto the left atrium in 21 patients (31%; group 2). Eight patients underwent right pneumectomy, and 1 had a right lower lobe lobectomy (group 3). Four patients died in hospital (5.9%; 1 patient in group 1, 2.6%; 3 patients in group 3, 33%). Median follow-up time was 4.5 years. There were 2 late deaths (3.1%) resulting from severe pulmonary arterial hypertension. Freedom from scimitar drainage stenosis at 13 years was 83.8% in group 1 and 85.8% in group 2. Four patients in group 1 were reoperated, and 3 patients (2 in group 1 [6%] and 1 in group 2 [4.8%]) required balloon dilation/stenting for scimitar drainage stenosis. CONCLUSIONS: The surgical treatment of this rare syndrome is safe and effective. The majority of patients were asymptomatic at the follow-up control. There were a relatively high incidence of residual scimitar drainage stenosis that is similar between the 2 reported corrective surgical techniques used.

Surgery for complications of trans-catheter closure of atrial septal defects: a multi-institutional study from the European Congenital Heart Surgeons Association.

OBJECTIVE: This study aims to analyse the collective experience of participating European Congenital Heart Surgeons Association centres in the surgical management of complications resulting from trans-catheter closure of atrial septal defects (ASDs). METHODS: The records of all (n=56) patients, aged 3-70 years (median 18 years), who underwent surgery for complications of trans-catheter ASD closure in 19 participating institutions over a 10-year period (1997-2007) were retrospectively reviewed. Risk factors for surgical complications were sought. Surgical outcomes were compared with those reported for primary surgical ASD closure in the European Association of Cardio-thoracic Surgery Congenital Database. RESULTS: A wide range of ASD sizes (5-34mm) and devices of various types and sizes (range 12-60mm) were involved, including 13 devices less than 20mm. Complications leading to surgery included embolisation (n=29), thrombosis/thrombo-embolism/cerebral ischaemia or stroke (n=12), significant residual shunt (n=12), aortic or atrial perforation or erosion (n=9), haemopericardium with tamponade (n=5), aortic or mitral valve injury (n=2) and endocarditis (n=1). Surgery (39 early emergent and 17 late operations) involved device removal, repair of damaged structures and ASD closure. Late operations were needed 12 days to 8 years (median 3 years) after device implantation. There were three hospital deaths (mortality 5.4%). During the same time period, mortality for all 4453 surgical ASD closures reported in the European Association of Cardio-Thoracic Surgery Congenital Database was 0.36% (p=0.001). CONCLUSIONS: Trans-catheter device closure of ASDs, even in cases when small devices are used, can lead to significant complications requiring surgical intervention. Once a complication leading to surgery occurs, mortality is significantly greater than that of primary surgical ASD closure. Major complications can occur late after device placement. Therefore, lifelong follow-up of patients in whom ASDs have been closed by devices is mandatory.

The scimitar syndrome: an Italian multicenter study.

BACKGROUND: Scimitar syndrome is a rare congenital heart disease. To evaluate the results of managing this malformation surgically, we have embarked on a multicenter Italian study involving seven different centers and reporting the largest published series in the medical literature. METHODS: From January 1997 to December 2007, 26 patients with scimitar syndrome who underwent surgical correction were included. Primary outcomes include hospital mortality and the efficacy of repair at the follow-up. RESULTS: Median age was 11 years (interquartile range, 1.8 to 19.9 years). Nineteen patients (73%) presented with symptoms including upper respiratory tract infections (n = 13), recurrent pneumonia (n = 10), cardiac failure (n = 4), and cyanosis (n = 2). Associated cardiac anomalies were present in 16 patients (63%). Surgical repair included intraatrial baffle repair in 18 patients (69%; group 1), and reimplantation of the "scimitar vein" onto the left atrium in 8 patients (31%; group 2). One patient died in hospital (3.8%; group 1). Postoperative complications were less frequently reported in group 1 (4 of 18 patients, 22%) compared with group 2 (5 of 8 patients, 62%). Median follow-up time was 4 years (interquartile range, 1.8 to 9.7 years). There was 1 late death (1/25 patients, 4%; group 2). Four patients (16%) showed a complete occlusion of the scimitar drainage (2 in group 1, 12%; 2 in group 2, 25%) and 3 patients (12%) required balloon dilation or stenting for scimitar vein stenosis (1 in group 1, 6%; 2 in group 2, 25%). CONCLUSIONS: The intraatrial baffle repair seems to have a lower incidence of postoperative complications and a better patency rate, at last follow-up, than the reimplantation of the scimitar vein onto the left atrium.