Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC).

OBJECTIVE: Ebstein's anomaly is a rare congenital cardiac condition and data regarding pregnancy outcomes in this patient group are scarce. We evaluated the maternal and perinatal risks of pregnancy in 81 women with Ebstein's anomaly. METHODS: The Registry of Pregnancy and Cardiac disease is a prospective global registry of pregnancies in women with structural cardiac disease. Pregnancy outcomes in women with Ebstein's anomaly were examined. The primary outcome was the occurrence of a major adverse cardiac event (MACE) defined as maternal mortality, heart failure, arrhythmia, thromboembolic event or endocarditis. Secondary endpoints were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation as well as right atrial and ventricular dimensions. RESULTS: In the 81 women with Ebstein's anomaly (mean age 29.7±6.1 years, 46.9% nulliparous), MACE occurred in 8 (9.9%) pregnancies, mostly heart failure (n=6). There were no maternal deaths. Prepregnancy signs of heart failure were predictive for MACE. Almost half of the women were delivered by caesarean section (45.7%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and 4.9% of the infants had congenital heart disease. In the subgroup in which prepregnancy and postpregnancy data were available, there was no difference in tricuspid valve regurgitation grade or right atrial and ventricular dimensions before and after pregnancy. CONCLUSIONS: Most women with Ebstein's anomaly tolerate pregnancy well, but women with prepregnancy signs of heart failure are at higher risk for MACE during pregnancy and should be counselled accordingly.

Atypical microdeletion 22q11.2 in a patient with tetralogy of Fallot.

The 22q11.2 microdeletion syndrome (22q11.2 DGS) is characterized by an extreme intrafamilial and interfamilial variability. The main clinical features are congenital heart defects, palatal abnormalities, learning disability, facial dysmorphisms and immune deficiency. In 85-90% of cases, the 22q11.2 DGS is caused by a heterozygous ~3-Mb deletion, including the TBX1 gene, considered one of the major genes responsible for heart defects. Individuals with atypical deletions with at least one breakpoint outside low copy repeats have been reported. Our patient is a child presenting tetralogy of Fallot (TOF) with an atypical 22q11.2 deletion proximal to the critical DiGeorge region. The rearrangement was inherited from the healthy mother and spanned ~642-970 kb, encompassing DGCR6 and PRODH, two novel possible candidate genes for conotruncal heart defects.

Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation.

OBJECTIVES: To evaluate the effects of endothelin inhibitors (ERAs) on hemodynamic and functional parameters in patients post-Fontan procedure with high pulmonary vascular resistance (PVR). METHODS: Among our cohort of patients with Fontan circulation, 8 children, 8 adolescents, and 8 adults had PVR ≥2 WU*m2. These patients were treated with ERAs (minors with bosentan, adults with macitentan) and reevaluated after 6 months. Pre- and posttreatment hemodynamic variables were assessed by cardiac catheterization. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). Our primary endpoint was to obtain a reduction of PVR; the secondary endpoint was to obtain an improvement of functional capacity. RESULTS: Under treatment, New York Heart Association class improved for adolescents and adults. PVR decreased (P = .01) in all groups: in children from the median value 2.3 (interquartile range 2.0-3.1) to 1.9 (1.4-2.3) WU*m2, in adolescents from 2.3 (2.1-2.4) to 1.7 (1.4-1.8) WU*m2, and in adults from 2.8 (2.0-4.7) to 2.1 (1.8-2.8)WU*m2. In 71% of patients, PVR fell to less than 2 WU*m2. Cardiac index increased in adolescents from 2.6 (2.4-3.3) to 3.6 (3.4-4.3) L/min/m2, P = .04, and in adults from 2.1 (2.0-2.3) to 2.8 (2.3-4.7) L/min/m2, P = .03. CPET showed that only adolescents displayed a significant functional improvement. Anaerobic threshold improved from 17 (13-19) to 18 (13-20) mL/kg/min, P = .03; oxygen consumption and VO2 max increased from 1.3 (1.0-1.6) to 1.7 (1.1-1.9) L/min, P = .02 and from 25 (21-28) to 28 (26-31) L/min, P = .02, respectively. Oxygen pulse increased from 7.9 (5.7-10.4) to 11.2 (8.2-13.0) L/beat, P = .01. CONCLUSIONS: This is the first study that assesses by cardiac catheterization and CPET the effects of ERA in patients with Fontan circulation with increased PVR. These results suggest that ERAs might provide most pronounced hemodynamic and functional improvement in adults and adolescents.

[Preliminary results and future perspectives of the Piedmont Adult Congenital Heart Disease Registry]. / Risultati iniziali e prospettive future del Registro Piemontese delle Cardiopatie Congenite dell'Adulto.

BACKGROUND: Adults with congenital heart disease are a relatively new population that progressively increases in size and complexity. In Italy, there are no accurate data concerning the distribution of congenital defects and the long-term outcome relating to both congenital heart disease per se and comorbidities, due to the aging process. METHODS: The Piedmont Adult Congenital Heart Disease Registry has been designed to investigate these aspects and to support a high quality healthcare development for grown-up congenital heart patients. Within 2 years, 459 consecutive patients routinely followed in 10 divisions of cardiology in Piedmont were included in the project. Electronic dedicated software has supported data collection. RESULTS: Mean age of patients is 35 ± 16 years. Septal defects are the most common type of congenital heart disease (35.3%). At baseline evaluation, 71.7% of patients reported a previous surgical and/or percutaneous treatment and 6.3% an electrophysiological procedure. Freedom from intervention is 44%, 81% and 56% at the age of 18, 30 and 45 years, respectively. Patients who had a treatment during infancy show a better intervention-free survival (p=0.038) compared with patients treated during adulthood. Despite the majority of the population had an almost preserved functional status, 27.5% had ≥1 long-term sequelae (arrhythmias 27.5%; pulmonary hypertension 5.2%; neurological problems 4.1%; cyanosis 4.8%; liver dysfunction 2.4%; enteropathy 2.4%; lung disease 2.2%). During 2 years of follow-up, the estimated mortality rate is 0.88%. CONCLUSIONS: Adults with congenital heart disease are a heterogeneous population of relatively young patients with relevant clinical and social problems. The late sequelae related to both the underlying heart disease and the advancing age require continuous monitoring and lifelong specialized care.

Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy?

BACKGROUND: In patients with Fontan circulation, the liver is profoundly affected by chronic venous stasis. Little is known about early hepatic changes in this population. METHODS: We performed echocardiography, abdominal ultrasound, liver elastography, cardiac catheterization, esophago-gastro-duodenoscopy and calculated MELD-XI score in 64 Fontan patients (69% minors), at an interval of 1-15years since Fontan. RESULTS: Cardiac output remained stable in the first 5years after Fontan, then significantly decreased (r=-0.45, p(r=0)=0.003). NYHA class significantly increased after Fontan. Patients in NYHA class II/III (n=21, 14 minors) had significantly higher hepatic pressures, but normal ventricular function and pulmonary vascular resistances (PVR). Patients with pulmonary arterial pressure (PAP) ≥15mmHg (n=12, 6 minors) and those with PVR≥2WU*m(2) (n=27, 25 minors), had higher hepatic pressures (p<0.0001), a higher incidence of liver collaterals and/or esophageal varices (p<0.0001) and splenomegaly (p<0.02). Liver stiffness (LS) was elevated in most patients (median, 25th-75th percentile:17.3KPa, 14.1-21.4). It rapidly increased during the first 5-years after Fontan, compared to the following 5-years (from 12.2KPa, 9.8-14.1 to 17.5KPa, 14.3-24.5, p=0.007), then remained stable (19.1KPa, 16.9-22.6, p=0.60). MELD-XI score increased linearly with the time interval since Fontan (r=0.31, p(r=0)=0.01). For patients above 12years we found a linear correlation between LS and MELD-XI score in the 6-15years period after Fontan (r=0.40. p(r=0)=0.04). The overall incidence of established liver cirrhosis was 22%. CONCLUSIONS: This is the largest study showing that Fontan circulation prompts early, progressive and eventually irreversible liver damage. Precautions should be taken immediately after Fontan, to protect this fragile population.

Interventional catheterization after total cavopulmonary connection: experience in 68 patients.

BACKGROUND: Total cavopulmonary connection (TCPC) is performed in patients having a single ventricle to allow the passive flow of systemic venous blood to the lungs. Interventional catheterization is needed to treat residual defects or complications. AIMS: We discuss our results concerning 68 patients who had had TCPC from January 1995 to December 2010. METHODS: Initial and follow-up catheterization data were reviewed retrospectively. Mid-term results were evaluated by means of angiography and/or CT scan. RESULTS: Mean age at TCPC was 5 years (2.5-18); mean interval between TCPC and catheterization was 5.6 years (1.5-15). Sixty-nine catheterizations were performed in 53 patients. Eleven patients (21%) had low venous pressure, did not display a right-to-left shunt, and did not need any intervention. Fifteen patients (28%) had low venous pressure and only needed the closure of the fenestration. The remaining 27 patients (51%) needed the following interventions: embolization of venous vessels prompting right-to-left shunt (n = 15), stenting or reconnection of pulmonary arteries (n = 5), stenting or recanalization of systemic veins (n = 11), other procedures (n = 5). In 3 patients the fenestration could not be closed due to high venous pressure. After the interventions oxygen saturation increased from 90.5%± 4.8% to 94.7% ± 3.6% (P = 0.002). CONCLUSIONS: Our data show that 49% of patients with TCPC are in good condition late after surgery. However, half of these patients continue to need interventions generally aimed at suppressing stenoses at various levels of TCPC or at occluding vessels prompting right-to-left shunt. This population should enter a multicenter program aimed at identifying patients at risk.

Interventional catheterisation of stenotic or occluded systemic veins in children with or without congenital heart diseases: early results and intermediate follow-up.

AIMS: Limited data exists on midterm results concerning paediatric interventions on stenotic or occluded systemic veins following indwelling lines, cardiac surgery, or catheterisations. The purpose of this study was to report our acute and intermediate results concerning patients with (Group A) and without (Group B) congenital heart diseases (CHD) over a 10-year period. METHODS AND RESULTS: From January 2000 to December 2010, 32 patients (23 in Group A and nine in Group B, respectively) underwent 39 interventional catheterisations aimed to dilate or recanalise occluded iliofemoral veins, inferior or superior venae cavae. Initial and follow-up catheterisation data were reviewed retrospectively. Midterm results were evaluated by means of echography, angiography, and CT scan in all 15 and 17 patients, respectively. Median age and weight of all patients at catheterisation were five years (range 0.1-18) and 15 kg (range 2-60), respectively. Fifty-two stents were implanted in 29 patients (32 vessels). In 25 patients 28 vessels were occluded and required recanalisation. There were no major complications. In all but three patients it was possible to treat the lesion. There were two procedural complications (5.1%): one acute stent occlusion and one local dissection. At a median follow-up of 2.5 years (range 1-10) we observed six complications of stenting (11.5%): two fractures, two occlusions and two restenoses. CONCLUSIONS: Interventional catheterisation of stenotic or occluded systemic veins grants good immediate results at a low rate of complication. Stent dilatation or recanalisation may open the vessel for use during future procedures. However, long-term results are yet to be established.

Spinal cord stimulation and 30-minute heart rate variability in refractory angina patients.

BACKGROUND: Spinal cord stimulation (SCS) has proven antianginal and antiischemic effects in severe coronary artery disease patients, minimizing frequency, intensity, and duration of pain. The mechanism explaining these effects has been detected in a sympathicolytic effect of the SCS. We monitored 30-minute-long recordings of the heart rate variability (HRV) and its spectral power parameters to evaluate the influence of SCS on the sympathetic/parasympathetic balance. METHODS AND RESULTS: Eight patients underwent HRV recordings in controlled environmental conditions. The patients were seated in a relaxed position and isolated from external contacts. During three consecutive 30-minute periods, the SCS was programmed, in a randomized fashion, to stimulate at a level generating paresthesias (ON), at a subliminal level (SUB, amplitude 80% of ON), or switched off (OFF). The low-frequency/high-frequency ratio during stimulation (ON) was significantly lower compared to that found while the SCS was turned OFF (0.54, 0.35-1.04 vs 1.21, 0.80-2.48; P = 0.036). The stimulation resulted in a median 52% (33-65%) reduction of the sympathetic activity compared to basal (ON vs OFF, P = 0.049). CONCLUSION: No difference emerged instead comparing OFF versus SUB (P = 0.575). The stimulation effect was not influenced by the randomized sequence. Thirty-minute SCS significantly influenced the sympathetic/parasympathetic balance reducing sympathetic modulation.