Rare case of Kawasaki disease with cardiac tamponade and giant coronary artery aneurysms.

Kawasaki disease is an acute systemic vascular disease, generally self-limited and typically affecting children <5 years old, which leads to coronary artery aneurysms in about 25% of untreated cases. Cardiovascular involvement is characterised by transient pancarditis, in acute phase, while coronary illness, ranging from mild dilation to giant CAAs occurs late, rarely before the 10th day since fever onset. Here, we describe a peculiar case of KD, which occurred in a 4-month-old infant and presented with exudate cardiac tamponade and early giant aneurism of both the proximal right coronary artery) and the left circumflex coronary artery, in acute phase of the disease.

Transcatheter Closure of Arterial Duct in Infants < 6 kg: Amplatzer Duct Occluder Type I vs Amplatzer Duct Occluder II Additional Sizes.

Transcatheter closure of arterial duct (AD) remains challenging in low-weight patients and using Amplatzer Duct Occluder devices is still considered off-label in infants < 6 kg. This study aimed to report a large, single-center experience of percutaneous AD closure in infants < 6 kg as well as to compare the most frequently used devices, Amplatzer Duct Occluder type I (ADO I) and Amplatzer Duct Occluder type II Additional Sizes devices (ADO II-AS) (St. Jude Medical Corp, St. Paul, MN, USA). From March 2000 to March 2017, among the 762 patients submitted to percutaneous closure of AD at our Institution, 33 were infants < 6 kg (age 4.8 ± 2.1 months; weight 5.0 ± 0.9 kg). Fourteen patients (45%) underwent ADO I (Group I) and 19 patients ADO II-AS (Group II) device implantation. AD diameter was 2.6 ± 0.8 (range 1.5-4.0) mm resulting in QP/QS of 2.6 ± 0.0.9 (range 1.1-4.5). Successful device deployment was achieved in all patients without procedural morbidity or mortality. Procedural and fluoroscopy times were not significantly different between the groups. However, total X-ray absorbed dose was significantly higher in Group I (121 ± 69 vs 29 ± 16 mGy/cm2, p < 0.01). Immediate, 24 h, and mid-term (46 ± 37 months, median 39) complete occlusion were recorded in 72.7, 90.9, and 97% of patients, respectively without significant difference between the groups. In conclusion, transcatheter closure of AD with Amplatzer Duct Occluder devices is feasible, safe, and effective also in infants less than 6 kg, without significant difference between the most commonly used devices, namely, ADO I and ADO II-AS.

Fate of Duct-Dependent, Discontinuous Pulmonary Arteries After Arterial Duct Stenting.

Significant and balanced PA growth following arterial duct (AD) stenting has already been consistently reported in literature. However, to date, no data are available about the role of this approach as palliation of congenital heart disease with a duct-dependent discontinuous pulmonary artery (dPA). The aim of this study was to evaluate the fate of a dPA of ductal origin following trans-catheter AD stabilization. Angiographic PA evaluation was performed in seven patients submitted to neonatal AD stenting as palliative recruitment of dPA. Five patients showed discontinuity of one PA, while two patients had both PAs served by bilateral ducts. PA growth was evaluated as per the Nakata index, McGoon ratio as well as dPA (n = 9) versus heart-dependent PA (hPA; n = 5) size and z-score changes. AD stabilization was performed using coronary stents dilated to 3.2 ± 0.3 mm (median 3.4), with significant increase of O2 saturation (from 83 ± 11 to 95 ± 5%, p < 0.02). Control angiography was performed 5.1 ± 2.8 months (median 6 months) after duct stenting, showing significant growth of the dPA (from 3.7 ± 1.0 to 7.6 ± 2.7 mm, p < 0.001; z-score from -0.7 ± 1.4 to 1.7 ± 2.2, p < 0.01). A trend toward better growth of the dPA as compared with the hPA was found (117 ± 87 vs. 54 ± 34%, p = NS). The final vessel size was still significantly different between the groups (dPA 7.6 ± 2.7 vs. hPA 11.9 ± 3.4 mm, p = 0.02), although the final z-score value did not significantly differ (dPA 1.7 ± 2.2 vs. hPA 3.8 ± 0.9 mm, p = NS). In conclusion, percutaneous AD stenting is effective in promoting a significant catch-up growth of duct-dependent dPA, being, therefore, advisable as a reliable alternative to surgical palliation.

Pulmonary artery growth after arterial duct stenting in completely duct-dependent pulmonary circulation.

OBJECTIVE: Significant and balanced pulmonary artery (PA) growth following arterial duct (AD) stenting has already been reported in literature. However, no data are so far available about the role of this percutaneous approach in promoting PA growth in the case of congenital heart disease (CHD) with completely duct-dependent pulmonary blood flow (CDD-PBF). Aim of this study was to evaluate the effect of AD stenting in this pathophysiological setting. METHODS: PA growth was evaluated as Nakata index and McGoon ratio as well as individual PA z-score changes in 49 patients submitted to neonatal AD stenting according to their pathophysiology (CDD-PBF (n=15) versus multiple PBF sources (n=34)). RESULTS: Control angiography was performed 7.2±6.4 months (range 1-8, median 6) after AD stenting. In the whole population, significant and balanced PA growth was recorded (Nakata index+122±117%; left pulmonary artery (LPA) z-score +84±52%; right pulmonary artery (RPA) z-score +92±53% versus preprocedure, p<0.0001 for all comparisons). Percentage increase of global and branch vessel size was not significantly different in patients with CDD-PBF compared with those with multiple PBF sources (Nakata index 89±90% vs 144±124%; LPA z-score 63±40% vs 89±58%; RPA z-score 74±35% vs 100±57%, p=NS for all comparisons) as was final absolute PA size (Nakata index 237±90 vs 289±80 mm(2)/m(2), p=NS). CONCLUSIONS: Percutaneous AD stenting was associated with significant and balanced PA growth in CHD with completely duct-dependent pulmonary circulation over a short-term follow-up. Thus, it may be considered as an alternative to surgical palliation in this subset of patients.

Fate of Hypoplastic Pulmonary Arteries After Arterial Duct Stenting in Congenital Heart Disease With Duct-Dependent Pulmonary Circulation.

OBJECTIVES: This study sought to evaluate the impact of arterial duct (AD) stenting in promoting catch-up growth of hypoplastic pulmonary artery (PA) tree in congenital heart disease with duct-dependent pulmonary circulation (CHD-DPC). BACKGROUND: Significant and balanced PA growth following AD stenting has already been consistently reported in the literature. However, no data are so far available about the role of this approach in severe PA hypoplasia, which significantly impacts the risk of surgical repair. METHODS: Pre-surgical angiographic PA evaluation was performed in 45 patients with confluent PAs submitted to neonatal AD stenting as palliation of CHD-DPC. PA growth was evaluated as Nakata Index and McGoon ratio as well as individual PA z-score changes, both in the whole population and according to the original vessel size (Nakata Index <100 mm(2)/m(2), Group I [n = 15] vs. Nakata Index >100 mm(2)/m(2), Group II [n = 30]). RESULTS: Control angiography was performed 7.5 ± 6.5 months (median 6 months) after duct stenting, showing significant and balanced PA growth. The Nakata Index increased from 143 ± 73 mm(2)/m(2) to 270 ± 88 mm(2)/m(2) (124 ± 118%, p < 0.0001); left PA z-score from -0.7 ± 1.7 to 1.0 ± 1.4; right PA z-score from -0.6 ± 1.3 to 1.2 ± 1.3 (p < 0.0001 for both comparisons). Group I showed a greater increase of global PA growth (Nakata Index increase 227 ± 141% vs. 72 ± 57%, p < 0.001) as compared with Group II. Final PA size did not significantly differ between the groups (246 ± 105 mm(2)/m(2) vs. 282 ± 78 mm(2)/m(2), p = NS). CONCLUSIONS: Percutaneous AD stenting is highly effective in promoting a significant and balanced catch-up growth of diminutive PAs, being therefore advisable in this subset of patients as a reliable alternative to surgical palliation.

Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical complications.

During fetal life, patent arterial duct diverts placental oxygenated blood from the pulmonary artery into the aorta by-passing lungs. After birth, decrease of prostacyclins and prostaglandins concentration usually causes arterial duct closure. This process may be delayed, or may even completely fail in preterm infants with arterial duct still remaining patent. If that happens, blood flow by-pass of the systemic circulation through the arterial duct results in pulmonary overflow and systemic hypoperfusion. When pulmonary flow is 50% higher than systemic flow, a hemodynamic "paradox" results, with an increase of left ventricular output without a subsequent increase of systemic output. Cardiac overload support neuro-humoral effects (activation of sympathetic nervous system and renin-angiotensin system) that finally promote heart failure. Moreover, increased pulmonary blood flow can cause vascular congestion and pulmonary edema. However, the most dangerous effect is cerebral under-perfusion due to diastolic reverse-flow and resulting in cerebral hypoxia. At last, blood flow decreases through the abdominal aorta, reducing perfusion of liver, gut and kidneys and may cause hepatic failure, renal insufficiency and necrotizing enterocolitis. Conclusions Large patent arterial duct may cause life-threatening multi-organ effects. In pre-term infant early diagnosis and timely effective treatment are cornerstones in the prevention of cerebral damage and long-term multi-organ failure.

Lipoprotein(a) concentration does not differ between sexes in healthy offspring of patients with premature myocardial infarction.

AIMS: Although a family history of coronary artery disease (CAD) is an established factor influencing lipoprotein(a) [Lp(a)] levels, the effect of sex on Lp(a) concentration remains unclear. A potential cause of the conflicting findings regarding the effect of sex on this novel CAD risk factor is the limited ability of the studies, to date, to adequately control for the potential confounding effect of CAD familial predisposition. Our purpose was to evaluate the influence of sex on Lp(a) concentration in healthy young individuals by controlling for family history of CAD. In order to achieve our goal, we compared Lp(a) levels in pairs of brothers and sisters with a positive parental history of premature myocardial infarction (PHPMI). METHODS: We measured Lp(a) concentration in 77 healthy brother-sister pairs with PHPMI (mean age: brothers: 18.4 ± 6.2 years and sisters: 18.1 ± 5.8 years). Total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (Apo) A-I and B were also measured. RESULTS: Lp(a) levels did not differ between siblings of different sex (male vs. female sex: 0.994 ± 1.29 vs. 0.860 ± 0.82 µmol/l, P = 0.940); moreover, the prevalence of elevated (>1.071 µmol/l) Lp(a) concentrations between sexes was the same (29.9%). As expected, compared to female sex, male sex showed higher total/HDL-cholesterol ratio (3.642 ± 0.99 vs. 3.329 ± 0.89, P = 0.017) and lower HDL-cholesterol (1.221 ± 0.24 vs. 1.343 ± 0.28 mmol/l, P = 0.001), Apo A-I (1.390 ± 0.20 vs. 1.474 ± 0.23 g/l, P = 0.003) concentrations and Apo A-I/Apo B ratio (1.632 ± 0.49 vs. 1.830 ± 0.66, P = 0.016). CONCLUSION: Our results show that healthy young men with PHPMI have a similar Lp(a) levels but worse lipid profile than women.

Arterial duct stenting: Do we still need surgical shunt in congenital heart malformations with duct-dependent pulmonary circulation?

BACKGROUND: Despite current trends toward primary repair, surgical systemic-to-pulmonary shunt is still an invaluable palliative option in some patients with congenital heart defects and duct-dependent pulmonary circulation. However, arterial duct stabilization with a high-flexibility coronary stent could be an effective alternative in high-risk surgical candidates or whenever short-term pulmonary blood flow support is anticipated. METHODS AND RESULTS: On the basis of ductal origin and morphology, the stenting procedure can be performed from an arterial or venous route. Following arterial duct angiographic imaging, the stabilizing stent is chosen to completely cover the entire ductal length and dilated slightly less than the proposed surgical shunt. Procedural failure depends mainly on ductal tortuosity and ranges around 10% of cases. Morbidity and mortality are 8-11% and less than 1%, respectively. Mid-term fate of the stented duct is spontaneous, slow and progressive closure within a few months. Compared with a Blalock-Taussig shunt, stented ducts result in similar but more uniform pulmonary artery growth over a mid-term follow-up. CONCLUSION: Arterial duct stenting is a technically feasible, well tolerated and effective palliation in congenital heart disease with duct-dependent pulmonary circulation. It is advisable either in high-risk neonates or whenever a short-term pulmonary blood flow support is anticipated. The stented duct appears less durable than a conventional surgical shunt although it is highly effective in promoting a global and uniform pulmonary artery growth.

Pulmonary artery growth after palliation of congenital heart disease with duct-dependent pulmonary circulation: arterial duct stenting versus surgical shunt.

OBJECTIVES: The aim of this study was to compare the pulmonary artery (PA) growth after arterial duct (AD) stenting versus modified Blalock-Taussig shunt (MBTS) in neonates with congenital heart disease with duct-dependent pulmonary circulation (CHD-DPC). BACKGROUND: Arterial duct stenting is increasingly deemed a reliable alternative to surgical shunt in CHD-DPC. A stented duct might better adapt to the PA anatomy than a surgical conduit, thereby promoting a more uniform PA development. METHODS: This study enrolled 27 patients with CHD-DPC submitted to AD stenting (n = 13, Group I) or MBTS (n = 14, Group II) at our institution. The PA growth was angiographically assessed with the Nakata and McGoon indexes as well as the individual PA z-scores. The right-to-left PA diameter ratio was considered as index of uniform growth. RESULTS: After 10 +/- 5 months, both options had promoted a significant increase of the Nakata index (from 136 +/- 72 mm/m(2) to 294 +/- 99 mm/m(2), p < 0.0001, Group I; from 151 +/- 74 mm/m(2) to 295 +/- 177 mm/m(2), p < 0.003, Group II) and McGoon ratio (from 1.5 +/- 0.3 to 2.1 +/- 0.3, p < 0.0001, Group I; from 1.6 +/- 0.3 to 2.0 +/- 0.5, p < 0.01, Group II). However, the surgical shunt had caused a worsening of the left-to-right PA diameter ratio compared with AD stenting (0.9 +/- 0.1 Group I vs. 1.6 +/- 0.9 Group II, p < 0.01), due to preferential growth of the PA contralateral to the shunt. CONCLUSIONS: Percutaneous AD stenting is as effective as MBTS in promoting a global PA growth in CHD-DPC. In addition, it ensures an even distribution of the pulmonary blood flow, thereby promoting a more balanced pulmonary vascular development than MBTS.

Pulmonary artery growth following arterial duct stenting in congenital heart disease with duct-dependent pulmonary circulation.

OBJECTIVES: The aim of this study was to assess the pulmonary artery (PA) growth following arterial duct (AD) stenting in neonates with congenital heart disease (CHD) with duct-dependent pulmonary circulation. BACKGROUND: AD stenting is increasingly deemed as a reliable alternative to surgical shunt in CHD with duct-dependent pulmonary circulation. Allowing the stent to conform to the PA anatomy might avoid any unbalance of lung perfusion and promote a uniform growth of the main PAs. METHODS: Of the 47 neonates and infants submitted to AD stenting as palliation of CHD with duct-dependent pulmonary circulation at our Institution, 15 underwent angiographic evaluation of the PA development before surgical repair due to progressive decrease of the systemic oxygen saturation. The Nakata and McGoon indexes as well as the left-to-right PA diameter ratio were considered as being indicative of global and balanced growth. RESULTS: Ductal stabilization was achieved with coronary stents dilated to 3.3 + or - 0.4 mm (range 2.5-4). The control angiography was performed 7 + or - 3 months (range 3-13) after the stenting procedure. At that time, the Nakata and McGoon indexes had significantly increased from 132 + or - 67 to 287 + or - 94 mm/m(2) and from 1.6 + or - 0.3 to 2.1 + or - 0.2 mm/m(2), respectively (P < 0.0001 for both comparisons), due to uniform vascular growth (left PA z-score from -0.7 + or - 1.6 to 1.4 + or - 1.2; right PA from -0.8 + or - 1.4 to 1.4 + or - 1.2, P < 0.0001 for both comparisons; final left-to-right PA ratio 0.9 + or - 0.1). CONCLUSIONS: Percutaneous AD stabilization with highly flexible coronary stents is effective in promoting a significant and balanced growth of the PAs in CHD with duct-dependent pulmonary circulation.

Age-related differences in factors associated with cigarette smoking among Italian high school students.

INTRODUCTION: Adolescents' cigarette smoking is related to several factors. The aim of this study among high school students was to test the hypothesis that factors related to smoking behavior could differ in early (14-16-year-old students, younger age group) vs. late (17-21-year-old students, older age group) adolescence. METHODS: The smoking behavior of 910 students was evaluated by a questionnaire. Students were categorized on the basis of their lifetime smoking behavior as never, former, occasional and regular smoker. Data were analyzed using Student's t-test, chi-square test and multinomial logistic regression analysis. RESULTS: In multinomial logistic regression analysis, variables related to adolescents' smoking behavior for both age groups were: positive attitude toward smoking (P < 0.001), illicit drug use (younger age group, P < 0.001; older age group, P = 0.003), smoking at home with parents (younger age group, P = 0.038; older age group, P < 0.001) and get drunk at least once (younger age group, P = 0.002; older age group, P = 0.026). In the younger age group, a significant association was also found between students' smoking behavior and having smoked a cigar at least once (P = 0.006) and smoking behavior of the best friend of the same sex (P = 0.001), whereas the relationship with the hours spent with friends of the opposite sex was of borderline significance (P = 0.058). In the older age group, other factors related to adolescent's smoking behavior were minimizing health consequences of smoking (P = 0.002) and the hours spent with friends of the same sex (P = 0.026). CONCLUSION: Our study demonstrates that, as adolescence advances, factors related to smoking behavior can vary.

Congenital heart disease in live-born children: incidence, distribution, and yearly changes in the Campania Region.

OBJECTIVES: Congenital heart disease (CHD), the most common cardiac malformation in the fetal and neonatal period, represents a heterogeneous group of defects with little known cause. The aim of this study was to investigate the incidence rate (IR) of CHD without spontaneous resolution in the first year of life, the age at diagnosis, the most common type of CHD, and the IR changes in severe and nonsevere CHD during the study period. METHODS: From January 1997 to December 2002, 4559 live births with CHD (diagnosed until December 2004) were enrolled in the Campania Region. Number of live-born children by month was derived from national registries. RESULTS: About 70% of CHD patients were diagnosed within the first year of life. The overall mean regional IR of CHD was 11.1 (confidence interval 10.8-11.4) patients per 1000 live-born children. The overall mean IR of CHD was significantly different in the five provinces of the Campania Region, but the annual IR remained stable in each of them throughout the study period. The relative risk in live-born children and residents in the areas with an elevated IR of CHD was higher for nonsevere CHD, but of low significance for severe CHD. At least one-third of CHD patients had atrial septal defects. CONCLUSIONS: We described the highest IR of CHD from one of the largest samples used up to now for this purpose (410 181 live-born children), but we think that this value could be higher (poor surveillance in some areas). Moreover, this study increases the awareness that CHD patients with a few symptoms are frequently underdiagnosed in areas with inadequate health services and that by an improved availability of pediatric echocardiographic assesments seem warranted. Eight years of surveillance and an increasing attention of both pediatricians and cardiologists to mild CHD in some provinces allowed us to demonstrate that, despite previous reports, the most common CHD in our region was atrial septal defect.

Lipoprotein(a) levels are increased in healthy young subjects with parental history of premature myocardial infarction.

BACKGROUND AND AIM: Most but not all studies in children, adolescents and young adults with a family history of coronary artery disease have reported an increase in lipoprotein(a) (Lp(a)) concentrations. The aim of this study was to assess if healthy children, adolescents and young adults with a parental history of premature myocardial infarction (PHPMI) have increased Lp(a) levels and are at higher risk of elevated (>30 mg/dl) Lp(a) concentrations. METHODS AND RESULTS: One hundred fifty healthy children, adolescents and young adults with PHPMI (55% males; age 18+/-6.7 years) and 150 age- (+/-1 year) and gender-matched control subjects participated in the study. Concentrations of total plasma cholesterol, low-density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, apolipoprotein (Apo) A-I and B, triglycerides and Lp(a) were determined after fasting for 14 h. Participants with PHPMI had higher concentrations of LDL-cholesterol (107.9+/-31.1 vs. 99.2+/-28.7 mg/dl, p=0.01), Apo B (89.6+/-26.4 vs. 82.8+/-20.2 mg/dl, p=0.011) and Lp(a) (26.7+/-34.0 vs. 19.2+/-23.2 mg/dl, p=0.012) and lower HDL-cholesterol concentrations (47.9+/-11.3 vs. 50.7+/-13.9 mg/dl, p=0.038) than participants without PHPMI. Thirty percent of PHPMI positive subjects had elevated Lp(a) concentrations vs. 16.7% of PHPMI negative subjects (p=0.009; relative risk 2.14; 95% CI 1.23-3.73). In a conditional logistic regression analysis, Lp(a) concentration was significantly and independently associated with PHPMI. CONCLUSIONS: Healthy young subjects with PHPMI have increased Lp(a) levels, a higher risk for elevated Lp(a) concentrations within an unfavourable lipid profile.

Prognostic value of intra-left ventricular electromechanical asynchrony in patients with hypertrophic cardiomyopathy.

AIMS: We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM). The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function. METHODS AND RESULTS: The study population included 123 HCM patients (39.4+/-5.9 years) and 123 age- and sex-matched healthy subjects, followed up for 48.4+/-8.8 months. By use of pulsed DMI, the following regional parameters were evaluated in six different basal myocardial segments: myocardial peak velocities and systolic time-intervals; myocardial intraventricular (intra-V-Del) and interventricular (inter-V-Del) systolic delays. DMI analysis in HCM showed lower myocardial systolic and early-diastolic peak velocities of all the segments. As for time intervals, HCM showed significant inter- and intra-V delays (P<0.0001), whereas homogeneous systolic activation of the ventricular walls was assessed in controls. During the follow-up, 16 cardiac deaths (12 sudden deaths) were observed in HCM patients. InHCM, DMI intra-V-Del was the most powerful independent predictor of sudden cardiac death (P<0.0001). In particular, an intra-V-Del>45 ms is identified with high sensitivity and specificity in HCM patients at higher risk of ventricular tachycardia and sudden cardiac death (test accuracy: 88.8%). CONCLUSION: In HCM patients, DMI indexes of intra-V-Del may provide additional information for selecting subgroups of HCM patients at increased risk of ventricular arrhythmias and sudden cardiac death at follow-up. Accordingly, such patients may be more actively identified for early intensive treatment and survey.

Congenital heart disease in a population of dizygotic twins: an echocardiographic study.

BACKGROUND: Congenital heart disease (CHD) is the most common malformation in the fetal and neonatal period but little is known about its cause. The distribution analysis of CHD in dizygotic twins could provide a useful tool to evaluate the role of genetic and environmental factors in the development of CHD. Dizygotic twins are siblings with different genes, growing together in the same womb. AIM OF STUDY: To investigate the occurrence of CHD in a large sample of dizygotic twins of nonconsanguineous healthy parents, comparing the data from non-twin patients. METHODS: From January 1999 to December 2002, we enrolled 1743 CHD patients with, at least 1 sibling, and 66 pairs of dizygotic twins, referred to our tertiary center. The diagnosis of CHD was based on clinical and echocardiographic evaluation. RESULTS: Considering only the sibling nearest in age for each non-twin patient the recurrence was 67/1743 (3.8%). Among these 67 patients, 35 (52.2%) had a sibling with the same or similar CHD. Conversely, considering all 1886 siblings, recurrence of CHD in the non-twin group was 70/1743 (4%). Of the 70 patients, 36 (36/70, 51.4%) had a sibling with the same suspected pathogenic mechanism of CHD. In 9/66 pairs of twins (13.6%), both siblings had a CHD. In the nine pairs of twins in whom both siblings had a CHD, the percentage of concordance (based on the suspected pathogenic mechanism) for CHD was 100% (p<0.05). CONCLUSIONS: Our findings suggest that the higher recurrence and concordance of CHD found in dizygotic twins could depend on some poorly identified environmental risk during the pregnancy.

Familial recurrence of congenital heart disease in patients with ostium secundum atrial septal defect.

AIMS: Ostium secundum atrial septal defect (osASD) is one of the most common cardiac malformations. Few data are available on the familial recurrence of congenital heart disease (CHD), in particular, in a large group of patients with isolated osASD. The aim is to investigate the familial recurrence of CHD in up to third-degree relatives from a large sample of consecutively enrolled patients with osASD, taking into account the influence of degree of relatedness (as number of relatives). METHODS AND RESULTS: From January 1998 to December 2002, we enrolled 583 patients with osASD and 408 healthy subjects, referred to our tertiary centre. We hypothesized that a positive family history required at least one relative with CHD to constitute a risk factor. In this model of analysis, the null hypothesis is a similar familial history between cases and controls. Among 583 patients with osASD, 109 (19%) had at least one relative with CHD. Among the 408 healthy subjects studied, only 23 (6%) had a family history of CHD. A familial recurrence of CHD was demonstrated in 72 of 312 (23%) patients with isolated osASD and in 37 of 271 (13.6%) patients with non-isolated osASD. Familial recurrence of isolated osASD was demonstrated in 22 of 312 patients (7%) with an isolated osASD and only in six of 271 patients (2.2%) with non-isolated osASD. The familial recurrence risk of isolated osASD in patients with isolated osASD was higher in sibs, especially in sisters (33.3%). CONCLUSION: This study underscores the role of genetic factors in the determination of CHD, particularly osASD. Our results could represent the basis for further studies to calculate a 'value of family history' to adapt the familial recurrence to the real size of each family group. In this way, we could select families with a 'tendency' to develop CHD, particularly osASD. In these families, we could analyse the genetic pattern to establish abnormalities and the bases of CHD.