Mitochondrial lineage A2ah found in a pre-Hispanic individual from the Andean region.

OBJECTIVES: The aim of this study was to contribute to the knowledge of pre-Hispanic Andean mitochondrial diversity by analyzing an individual from the archaeological site Pukara de La Cueva (North-western Argentina). The date of the discovery context (540 ± 60 BP) corresponds to the Regional Developments II period. METHODS: Two separate DNA extractions were performed from dentin powder of one tooth. HVR I was amplified by PCR from each extract in three overlapping fragments and the haplotype was determined by consensus among all obtained sequences. The procedures were carried out under strict protocols developed for working with ancient DNA. RESULTS: The individual belonged to the A2ah lineage due to the presence of the 16097C and 16098G transitions, which constitute its distinctive motif. This lineage is very rare in Native American populations and was described in four individuals from current groups inhabiting the Bolivian Llanos, two from South-eastern Brazil, and one from the Gran Chaco region. In addition, two other mutations (16260T and 16286T) were shared with one of the individuals from the Bolivian Llanos region. CONCLUSIONS: Considering that the origin of this lineage was postulated for the South American lowlands, the present pre-Hispanic discovery in the Andean area could be taken as a new evidence of gene flow between these regions. Also, it allows the questioning of the geographical origin of this mitochondrial lineage.

Atenolol vs enalapril in young hypertensive patients after successful repair of aortic coarctation.

Late arterial hypertension has been identified as a major predictor for morbidity and mortality in aortic coarctation (AoC) patients. Few data are available about efficacy and tolerability of angiotensin converting enzyme inhibitors vs beta-blockers in young AoC patients. This study aimed to evaluate the tolerability and efficacy on 24-h blood pressure (BP) and left ventricular mass/height(2.7) (LVMI), of atenolol vs enalapril. We enrolled consecutive AoC hypertensive patients with (a) no history of BP treatment or after >48 h of withdrawn, (b) aged 6-20 years, (c) body mass index (BMI) <90th percentile for age and sex, (d) >12 months from a successful AoC repair and (e) no major associated cardiovascular abnormalities. All patient were evaluated with 24-h ambulatory BP monitoring, standard echocardiography, strain-strain rate imaging, at enrolment, 3, 6 and 12 months of treatment. We studied 51 AoC patients (13±3.9 years, BMI: 21.4±4.3 kg m(-2)). Patients were randomly assigned at atenolol treatment (n=26), or enalapril treatment (n=25). The mean follow-up duration was 11±2 months. Both drugs were able to significantly reduce 24-systolic BP (SBP; atenolol: 133±11 mm Hg vs 124±16 mm Hg, P=0.016; enalapril: 135±6 mm Hg vs 127±7 mm Hg, P=0.001). Only enalapril was able to significantly reduce LVMI (47±12 vs 39.6±10 g m(-)(2.7), P=0.016). Only in atenolol group in two cases (7.7%) drug withdrawal was needed because of adverse events. Enalapril and atenolol are similarly effective in reducing SBP. However, only enalapril demonstrated a significant reduction of LVMI. In no case, enalapril was stopped because of adverse events.

Paroxysmal atrial fibrillation in myotonic dystrophy type 1 patients: P wave duration and dispersion analysis.

OBJECTIVE: Myotonic dystrophy type 1 (MD1) is characterized by cardiac involvement, in about 80% of case, that predominantly affects the conduction system. Aim of our study was to evaluate the P-wave duration and dispersion (PD) in MD1 patients underwent pacemaker implantation with conserved systolic and diastolic function. PATIENTS AND METHODS: We enrolled 60 MD1 patients (age 51.3 ± 5 years; 11 females) underwent dual chamber pacemaker implantation for various grade of atrioventricular (AV) block. Sixty sex-and age matched non-MD1 subjects were recruited as controls. P-wave duration and dispersion were carefully measured using 12-lead electrocardiogram. RESULTS: Compared with healthy control group, MD1 patients presented increased maximum P wave duration (106.4 ± 20.9 vs 65.9 ± 8.2 ms, p = 0.03) and PD values (40.1 ± 11 vs 27.1 ± 4.2 ms, p = 0.003). No statistically significant difference was found in minimum P wave duration (69.7 ± 11.8 vs 65.4 ± 8.1 ms, p = 0.4). The MD1 patients with paroxysmal atrial fibrillation, compared with MD1 patients without evidence of atrial fibrillation, presented increased maximum P wave duration (108.1 ± 10.4 vs 78.1 ± 7.9 ms, p = 0.001) and PD values (41.1 ± 8.5 vs 33.2 ± 4.2 ms, p = 0.003). Minimum P wave duration (68.4 ± 8.2 vs 67.1 ± 4.9 ms, p = 0.5) didn't differ between the two groups. CONCLUSIONS: Our data showed a significantly increased P wave duration and dispersion in MD1 patients compared with age and sex-matched healthy controls. We showed a statistically significant increase in PD and P max in MD1 patients subgroup with AF compared to MD1 patients with no arrhythmias.

Physiologic and pathophysiologic changes in the right heart in highly trained athletes.

Exercise causes changes in the heart in response to the hemodynamic demands of increased systemic and pulmonary requirements during exercise. Understanding these adaptations is of great importance, since they may overlap with those caused by pathological conditions. Initial descriptions of athlete's heart focused mainly on chronic adaptation of the left heart to training. In recent years, the substantial structural and functional adaptations of the right heart have been documented, highlighting the complex interplay with left heart. Moreover, there is evolving evidence of acute and chronic cardiac damage, mainly involving the right heart, which may predispose subjects to atrial and ventricular arrhythmias, configuring an exercise-induced cardiomyopathy. The aim of this article is to review the current knowledge on the physiologic and pathophysiologic changes in the right heart in highly trained athletes.

The effect of aortic coarctation surgical repair on QTc and JTc dispersion in severe aortic coarctation newborns: a short-term follow-up study.

Sudden death is a possible occurrence for newborns younger than 1 year with severe aortic coarctation (CoA) before surgical correction. In our previous study, we showed a significant increase of QTc-D and JTc-D in newborns with isolated severe aortic coarctation, electrocardiographic parameters that clinical and experimental studies have suggested could reflect the physiological variability of regional and ventricular repolarization and could provide a substrate for life-threatening ventricular arrhythmias. The aim of the current study was to evaluate the effect of surgical repair of CoA on QTc-d, JTc-d in severe aortic coarctation newborns with no associated congenital cardiac malformations. The study included 30 newborns (18M; 70+/-12 h old) affected by severe congenital aortic coarctation, without associated cardiac malformations. All newborns underwent to classic extended end-to-end repair. Echocardiographic and electrocardiographic measurements were performed in each patient 24 h before and 24 h after the interventional procedure and at the end of the follow-up period, 1 month after the surgical correction. All patients at baseline, 24 h and one month after CoA surgical repair did not significantly differ in terms of heart rate, weight, height, and echocardiographic parameters. There were no statistically significant differences in QTc-D (111.7+/-47.4 vs 111.9+/-63.8 ms vs 108.5+/-55.4 ms; P=0.4) and JTc-D (98.1+/-41.3 vs 111.4+/-47.5 vs 105.1+/-33.4 ms; P=0.3) before, 24 h and 1 month after CoA surgical correction. In conclusions, our study did not show a statistically significant decrease in QTc-D and JTc-D, suggesting the hypothesis that the acute left ventricular afterload reduction, related to successful CoA surgical correction, may not reduce the ventricular electrical instability in the short-term follow-up.

Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

Masked hypertension in young patients after successful aortic coarctation repair: impact on left ventricular geometry and function.

Life expectancy is still reduced in aortic coarctation (AoC) patients despite a successful repair because of late arterial hypertension and atherosclerosis. Masked hypertension (MH) consists of an elevated daytime or awake ambulatory blood pressure (BP) in the presence of a normal BP on conventional measurement at the office. To assess the prevalence of MH among AoC normotensive young patients successfully treated and to evaluate the impact of MH on left ventricular (LV) geometry and function.We studied 76 AoC patients (mean age 14.5±5.7 years, male 64%). According to 24 h ambulatory BP monitoring (ABPM) our sample was divided in real normotensive patients (Group RN, n=40) and MH patients (Group MH, n=36). There was an increased pressure gradient in the aortic arch (15 mm Hg±4 vs 13 mm Hg±4.7, P<0.05), increased LV mass (51 g m(-2.7)±13 vs 46 g m(-2.7)±12, P<0.05), in MH AoC patients. Regional longitudinal deformation properties of the basal septal segment (-15%±2.4 vs -20%±5, P<0.01) and LV twist values (14°±1.6 vs 12°±1.9, P<0.0001) were reduced in the MH group. There is a high prevalence of MH in young patients with repaired AoC, which is associated with abnormal LV structure and function. Clinicians should consider 24 h ABPM measurements in apparently normotensive patients followed up for AoC repair.

Partial atrioventricular septal defect in the fetus: diagnostic features and associations in a multicenter series of 30 cases.

OBJECTIVE: To assess the anatomical features and the associations of partial atrioventricular septal defect (pAVSD) in the fetus. METHODS: This was a retrospective multicenter study of 30 cases of confirmed pAVSD seen since 1996 at two referral centers. The following variables were available for analysis in all cases: indications for fetal echocardiography, diagnostic features, associated cardiac, extracardiac and chromosomal anomalies and fetoneonatal outcome. At fetal echocardiography, the echocardiographic features deemed indicative of pAVSD were: 1) ostium primum atrial septal defect and 2) loss of the normal offset appearance of the atrioventricular valves. RESULTS: Eighteen of the 30 (60%) cases were diagnosed before 24 weeks of gestation and 12 were diagnosed later. Suspicion of congenital heart disease and known aneuploidy (trisomy 21) accounted for 60% of the referral indications. The two anatomical landmarks deemed indicative of pAVSD were detected in all cases at echocardiography. Twelve cases were isolated (one with increased nuchal transluceny at the 12-week scan, one with polyhydramnios, one with fetal growth restriction) including four that were detected on routine ultrasound examination by the authors. Additional cardiac anomalies were present in five (17%) cases, four of which involved aortic coarctation. There were associated chromosomal anomalies in 13 (43%); however, excluding the six cases referred because of known Down syndrome, the adjusted association rate with aneuploidy was 29.2% (7/24). Extracardiac anomalies, including non-chromosomal syndromes, were present in 10 cases (33.3%). Regarding fetoneonatal outcome, there were 13 terminations of pregnancy, one early neonatal death and 16 survivors, including four with mild to severe neurodevelopmental delay due to associated syndromic conditions. CONCLUSIONS: We describe the key echocardiographic features of pAVSD in the fetus. In addition, we have confirmed that the association with trisomy 21 holds also for pAVSD, though to a lesser extent, with a 12.5% association rate in this series. In the fetus, pAVSD seems to be associated with a high rate of chromosomal/non-chromosomal syndromic conditions, including skeletal dysplasias. Inutero, aortic coarctation represents the most frequently associated cardiac lesion (13.3%).

Transposition of the great arteries in the fetus: assessment of the spatial relationships of the arterial trunks by four-dimensional echocardiography.

OBJECTIVE: Coronary arterial abnormalities can be one of the few negative prognostic indicators in transposition of the great arteries (TGA), and their occurrence is related to the type of spatial relationship of the great arteries. The main objective of this study was to assess whether the use of the reconstructed en-face view with color Doppler imaging of the four cardiac valves can demonstrate the different types of spatial relationship of the arterial trunks in fetuses with TGA, in order to derive the risk of coronary abnormalities. A secondary end-point was the evaluation of the type of coronary arterial branching pattern. METHODS: Twenty-three fetuses with a confirmed diagnosis of TGA underwent four-dimensional (4D) echocardiography at 19-33 gestational weeks. The en-face view of the four cardiac valves and color Doppler with high persistence were employed to assess the spatial relationships of the great arteries. In all cases, confirmation of the vessels' arrangement and coronary arterial distribution was obtained at neonatal echocardiography and/or surgery. RESULTS: The spatial relationships of the great vessels was identified correctly in 20/23 (87%) cases. The aorta was found to be located anterior to and to the right of the pulmonary trunk in 13/23 (56.5%) cases and just anterior to the pulmonary artery in 6/23 (26.1%) cases; in the remaining four (17.4%) cases, the two vessels were side by side. With respect to the association between the spatial relationship of the great arteries and the occurrence of an unusual pattern of coronary arterial branching, five of the TGA fetuses had abnormal coronary arterial distribution. CONCLUSIONS: Using 4D echocardiography with color Doppler, it is possible to define the spatial relationships of the great arteries in fetuses with TGA with a high degree of accuracy. This information can be used during counseling to predict the likelihood of abnormal coronary arterial distribution.

Neonatal patent ductus arteriosus recanalization and stenting in critical Ebstein's anomaly.

A critically ill 3-day-old neonate with severe tricuspid valve Ebstein's anomaly, functional pulmonary atresia, and closed ductus arteriosus, unresponsive to prostaglandin infusion, underwent percutaneous ductal recanalization and stenting as an alternative to a surgical shunt. After local prostaglandin infusion through an end-hole catheter, the ductus was passed using a hydrophilic, high-support coronary guidewire. It was then stabilized by coronary stent implantation, after which the arterial oxygen saturation showed a sudden rise. In conclusion, ductus arteriosus recanalization and stenting can be successfully achieved within a few days after spontaneous closure as a cost-effective alternative to a surgical shunt for critical neonatal, duct-dependent Ebstein's anomaly.

Stenting of the arterial duct in newborns with duct-dependent pulmonary circulation.

OBJECTIVE: To evaluate the feasibility and results of stenting of the arterial duct in newborns with duct-dependent pulmonary circulation using low-profile, high-flexibility premounted coronary stents. DESIGN: Prospective interventional and clinical follow-up study. SETTING: Tertiary referral centre. PATIENT POPULATION: Between April 2003 and December 2006, 26 neonates (mean (SD) age 15.2 (19.9) days, mean (SD) weight 3.3 (0.8) kg) underwent attempts at stenting of the arterial duct. MAIN OUTCOME MEASURES: Procedural success and complication rates. Early and mid-term follow-up results. RESULTS: The procedure was successfully completed in 24/26 (92.3%) cases. Minor complications occurred in 2/26 (7.7%) cases. No mortality occurred. After stenting, the ductal diameter increased from 1.2 (1.0) mm to 3.1 (0.4) mm (p<0.001) and the percutaneous O(2) saturation increased from 70 (14)% to 86 (10)% (p<0.001), respectively. Over a mid-term follow-up, 2/24 patients (8.3%) needed a systemic-to-pulmonary artery shunt because of inadequate ductal flow and 4/24 patients (16.7%) underwent stent redilatation after 6.0 (4.4) months, but before corrective surgery. Cardiac catheterisation before corrective surgery in 9 patients showed an increase of the Nakata index from 112 (49) mm/mm(2) to 226 (108) mm/mm(2) (p<0.001), without any left-to-right imbalance of the pulmonary artery size. In the subset of 11 patients who improved without needing an additional source of pulmonary blood supply, the stented arterial duct closed uneventfully in 45.5% of cases after 4.0 (2.2) months. CONCLUSIONS: Stenting of the arterial duct is a feasible, safe and effective palliation in newborns with duct-dependent pulmonary circulation, supporting the spontaneous improvement process or promoting significant and balanced pulmonary artery growth for subsequent corrective surgery.

Long term effects of bosentan treatment in adult patients with pulmonary arterial hypertension related to congenital heart disease (Eisenmenger physiology): safety, tolerability, clinical, and haemodynamic effect.

BACKGROUND: Oral bosentan is an established treatment for pulmonary arterial hypertension (PAH). OBJECTIVE: To evaluate safety, tolerability, and clinical and haemodynamic effects of bosentan in patients with PAH related to congenital heart disease (CHD). PATIENTS: 22 patients with CHD related PAH (8 men, 14 women, mean (SD) age 38 (10) years) were treated with oral bosentan (62.5 mg x 2/day for the first 4 weeks and then 125 mg x 2/day). MAIN OUTCOME MEASURES: Clinical status, liver enzymes, World Health Organisation (WHO) functional class, resting oxygen saturations and 6-min walk test (6MWT) were assessed at baseline and at 1, 3, 6, and 12 months. Haemodynamic evaluation with cardiac catheterisation was performed at baseline and at 12 month follow-up. RESULTS: 12 patients had ventricular septal defect, 5 atrioventricular canal, 4 single ventricle, and 1 atrial septal defect. All patients tolerated bosentan well. No major side effects were seen. After a year of treatment, an improvement was seen in WHO functional class (2.5 (0.7) v 3.1 (0.7); p<0.05), oxygen saturation at rest (87 (6%) v 81 (9); p<0.001), heart rate at rest (81 (10) v 87 (14) bpm; p<0.05), distance travelled in the 6MWT (394 (73) v 320 (108) m; p<0.001), oxygen saturation at the end of the 6MWT (71 (14) v 63 (17%); p<0.05), Borg index (5.3 (1.8) v 6.5 (1.3); p<0.001), pulmonary vascular resistances index (14 (9) v 22 (12) WU m(2); p<0.001), systemic vascular resistances index (23 (11) v 27 (10) WU.m(2); p<0.01), pulmonary vascular resistances index/systemic vascular resistances index (0.6 (0.5) v 0.9 (0.6); p<0.05); pulmonary (4.0 (1.3) v 2.8 (0.9) l/min/m2; p<0.001) and systemic cardiac output (4.2 (1.4) v 3.4 (1.1) l/min/m2; p<0.05). CONCLUSIONS: Bosentan was safe and well tolerated in adults with CHD related PAH during 12 months of treatment. Clinical status, exercise tolerance, and pulmonary haemodynamics improved considerably.

Right superior vena cava draining into the left atrium: prenatal diagnosis and postnatal management.

Right superior vena cava (RSVC) draining into the left atrium, causing hypoxemia, represents a very rare congenital malformation which has not previously been described in the fetus. We describe a case in which fetal echocardiography at 22 weeks' gestation revealed an enlarged superior vena cava connecting abnormally with a mildly enlarged left atrium. Neonatal transthoracic echocardiography confirmed the diagnosis and showed an abnormal connection of the right pulmonary veins to the RSVC. Right-to-left shunt due to anomalous drainage of the RSVC into the left atrium associated with an atrial septal defect and anomalous pulmonary venous return were diagnosed on echocardiography and confirmed by angiography. The newborn was hemodynamically stable at birth and at the 1-year follow-up.

Diagnosis, characterization and outcome of congenitally corrected transposition of the great arteries in the fetus: a multicenter series of 30 cases.

OBJECTIVE: To describe the anatomy, associated anomalies and outcome of 30 cases of congenitally corrected transposition of the great arteries (ccTGA) detected prenatally. METHODS: This was a retrospective observational study of the 30 cases of ccTGA confirmed at autopsy or postnatal echocardiography seen at one of three referral centers from 1994 to 2003. The following data were considered: gestational age at diagnosis, cardiac anatomy, associated cardiac and extracardiac anomalies and fetoneonatal outcome. All fetuses underwent fetal echocardiography and a detailed anomaly scan, with follow-up scans at 3-4-week intervals until delivery. The diagnosis was confirmed at autopsy or after delivery. Follow-up data were retrieved from the clinical files of the patients. RESULTS: The mean gestational age at diagnosis was 25.5 weeks. Intracardiac defects associated with the ccTGA included a ventricular septal defect in 21 cases, pulmonary outflow obstruction in 12 cases, an abnormal tricuspid valve in 10 cases, ventricular hypoplasia in five cases and dextro/mesocardia in five cases. The karyotype was normal in all 24 newborns, and unknown in the cases which resulted in termination of pregnancy (n = 5) or intrauterine death (n = 1). There were associated extracardiac anomalies in four cases only. Three of the four cases of atrioventricular block (AV block) developed in the third trimester, while the fourth appeared after birth. There were nine deaths (five terminations, two perinatal deaths and two infant deaths). The remaining 21 (70%) newborns were alive at a median follow-up time of 32 months, 11 of them after various surgical procedures. CONCLUSIONS: Our data suggest that in fetuses with ccTGA the risk of chromosomal and extracardiac anomalies is low, in accordance with postnatal data. The spectrum of associated cardiac lesions is consistent with that reported in the pediatric literature. These data may be of use during prenatal counseling since no figures regarding survival and/or outcome of ccTGA in the fetus have been reported so far.

Similar cardiac remodelling after transcatheter atrial septal defect closure in children and young adults.

OBJECTIVE: To study the cardiac geometric changes after transcatheter closure of large atrial septal defects (ASDs) according to patient age at the time of the procedure. DESIGN: Prospective echocardiographic follow-up study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTION: 25 asymptomatic patients younger than 16 years (median 8 years; group 1) and 21 asymptomatic adults (median 38 years; group 2) underwent percutaneous closure of large ASD with the Amplatzer septal occluder device (mean 25 (SD 7) mm). MAIN OUTCOME MEASURES: Cardiac remodelling was assessed by M mode and two dimensional echocardiography one and six months after ASD closure. RESULTS: By six months, right atrial volume decreased from 31 (15) to 19 (5) ml/m(2) (p < 0.001) and right ventricular (RV) transverse diameter decreased from 29.8 (8.6) to 23.2 (5.6) mm/m(2) (p < 0.001). Conversely, left atrial volume did not change significantly (from 18 (6) to 20 (6) ml/m(2), NS) and left ventricular (LV) transverse diameter increased from 27.8 (6.4) to 31.8 (7.3) mm/m(2) (p < 0.05). Ventricular remodelling resulted in an RV:LV diameter ratio decrease from 1.1 (0.2) to 0.7 (0.1) (p < 0.001). The magnitude and time course of cardiac remodelling did not differ significantly between the age groups. Indeed, right atrial volume decreased by 33 (26)% versus 37 (23)%, RV diameter decreased by 26 (10)% versus 20 (13)%, LV diameter increased by 17 (15)% versus 15 (10)%, and RV:LV diameter ratio decreased by 36 (8)% versus 27 (15)% in groups 1 and 2, respectively. CONCLUSIONS: Cardiac remodelling after percutaneous ASD closure seems to be independent of the patient's age at the time of the procedure up to early adulthood. Thus, postponing ASD closure for a few years may be a reasonable option for potentially suitable asymptomatic children.