Jan Marek

Resynchronization pacing is a useful adjunct to the management of acute heart failure after surgery for congenital heart defects

The acute hemodynamic effect of atrioventricular (AV) and inter/intraventricular (IV) resynchronization accomplished by temporary pacing using multiple epicardial pacing wires was evaluated in 20 children (aged 3.4 months to 14.0 years) after surgery for congenital heart defects fulfilling the following criteria: (1) presence of AV and/or IV conduction delay, and (2) need for inotropic support. AV resynchronization (n = 13) was achieved by AV delay optimization during atrial synchronous right ventricular outflow tract pacing. IV resynchronization (n = 14) was accomplished by atrial synchronous pacing from the right ventricular lateral wall in 7 patients with right bundle branch block and normal AV conduction and by atrial synchronous multisite ventricular pacing in another 7 patients with previously performed AV resynchronization. Compared with baseline values, AV resynchronization resulted in an increase in arterial systolic, mean, and pulse pressures by 7.2 +/- 8.3% (p <0.01), 8.6 +/- 8.1% (p <0.005), and 6.9 +/- 13.5% (p = NS), respectively. IV resynchronization used either alone or added to previously performed AV resynchronization led to a pressure increase of 7.0 +/- 4.7%, 5.9 +/- 4.7%, and 9.4 +/- 7.8%, respectively (p <0.001 for all). The combined effect of AV and IV resynchronization resulted in a systolic, mean, and pulse pressure increase of 10.2 +/- 5.0% (range 4.0 to 19.1), 8.6 +/- 5.4% (range 0.8 to 14.8), and 15.2 +/- 8.5% (range 6.1 to 33.3), respectively (p <0.001 for all). The increase in systolic arterial pressure after IV resynchronization was positively correlated with the initial QRS duration (r = 0.62, p <0.05) and extent of QRS shortening (r = 0.66, p <0.05). In conclusion, resynchronization pacing led to a significant increase in arterial blood pressure and was a useful adjunct to the treatment of acute postoperative heart failure in patients with AV and/or IV conduction delay.

Prenatal ultrasound screening of congenital heart disease in an unselected national population: a 21-year experience

Objective To determine the prevalence and spectrum of congenital heart disease (CHD) and the impact of a national prenatal ultrasound screening programme on outcome in a well-characterised population. Design and setting A comprehensive registry was created of all paediatric and fetal patients with CHD over a 21-year period (1986–2006) in the Czech Republic. The centralised healthcare system enabled confirmation of prenatal and postnatal findings clinically and by post mortem. Patients and results In the entire cohort of 9475 fetuses referred for detailed cardiac evaluation, 1604 (16.9%) had CHD, of which 501 (31.2%) had additional extracardiac anomalies. In the pregnancies which continued, 59 (8.6%) of 685 fetuses died in utero, and 626 (91.4%) babies were born alive. Prenatal detection rate was highest in double outlet right ventricle (77.3%) and hypoplastic left heart (50.6%). Detection rate increased significantly (p<0.001) for 12/17 lesions comparing 1986–1999 and 2000–2006. In recent years, detection of hypoplastic left heart reached 95.8% while transposition of the great arteries was diagnosed antenatally in only 25.6%. Conclusion The nationwide prenatal ultrasound screening programme enabled detection of major cardiac abnormalities in 1/3 of patients born with any CHD and 80% of those with critical forms. Nevertheless, owing to the severity of lesions and associated extracardiac anomalies, the overall mortality of antenatally diagnosed CHD remains high. These findings are important for the understanding natural history of CHD for the establishing of screening programmes in Europe.

Long term ventricular performance after intra-atrial correction of transposition: left ventricular filling is the major limitation

Objective To establish the incidence of systolic and diastolic dysfunction of the right and left ventricle in a large cohort of patients after Mustard or Senning operations and to assess changes in the incidence on long term follow up. Design Postoperative case-control study using radionuclide ventriculography. Ejection fractions, peak filling rates, rapid filling periods and fractions, slow filling periods and fractions, and atrial contraction periods and fractions were studied. Setting Tertiary care centre, ambulatory and hospital inpatient care. Patients A convenience sample of 153 patients studied at median age of 6.9 years (median 4.4 years after surgery). In 99 cases another study was available at a median age of 15.3 years (median 13 years after surgery and 8.8 years after the first study). Results Respective incidences of dysfunction in the first and the second study were as follows: ejection fraction–right ventricle 7.8% and 8.1%, left ventricle 7.2% and 10.1%; peak filling rate–right ventricle 0% and 4.2%, left ventricle 14.3% and 29.5% (p < 0.05); rapid filling period– right ventricle 18.3% and 11.6%, left ventricle 30.2% and 30.5%; slow filling period—right ventricle 4.8% and 3.2%; left ventricle 11.9% and 23.2%;atrial contraction period–right ventricle 0.8% and 4.2%, left ventricle 15.1% and 26.3%; rapid filling fraction–right ventricle both 0%, left ventricle 82.5% and 79.0%; slow filling fraction–right ventricle 0.8% and 4.2%, left ventricle 37.3% and 30.5%; atrial contraction fraction–right ventricle both 0%, left ventricle 79.4% and 71.6%. Conclusions The incidence of systolic ventricular dysfunction is 8% (right ventricle) and 10% (left ventricle) 13 years after surgery, without a significant increase over the eight year follow up. Diastolic filling is abnormal in up to 80% of patients and left ventricular peak filling rate deteriorates with time.

Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease

All approved drugs for Alzheimer disease (AD) in clinical practice ameliorate the symptoms of the disease. Among them, acetylcholinesterase inhibitors (AChEIs) are used to increase the cholinergic activity. Among new AChEI, tacrine compounds were found to be more toxic compared to 7-MEOTA (9-amino-7-methoxy-1,2,3,4-tetrahydroacridine). In this Letter, series of 7-MEOTA analogues (N-alkyl-7-methoxytacrine) were synthesized. Their inhibitory ability was evaluated on recombinant human acetylcholinesterase (AChE) and plasmatic human butyrylcholinesterase (BChE). Three novel compounds showed promising results towards hAChE better to THA or 7-MEOTA. Three compounds resulted as potent inhibitors of hBChE. The SAR findings highlighted the C(6)-C(7)N-alkyl chains for cholinesterase inhibition.

Recommendations for the practice of fetal cardiology in Europe.

F ETAL CARDlOLOGY IS CURRENTLY PRACTISED IN of rhythm. An early accurate diagnosis will make most European countries, blit even within possible parental choice, as well as providing the countries there is a great variation in the service opportunity to plan the delivery and postnatal provided. The recommendations provided in this management so as to optimize the outcome, document are intended to be guide for all paediatric Support can also be provided to specialists in fetal cardiologists undertaking fetal echocardiography with medicine, and to obstetricians, in the management the view of providing a service in fetal cardiology. It is of fetuses with functional disturbances, as in tWinclear that the health and legal systems vary from counto-tWin transfusion syndrome try to country, so that not all aspects of these recomb. To provide appropriate counselling and support mendations Can be implemented in all countries, The for parents and families following prenatal recommendations, nonetheless, provide a framework diagnosis l that can be adapted to fit in with local situations, c, To communicate results to the referring obstetri-

Seven-Year Experience of Noninvasive Preoperative Diagnostics in Children with Congenital Heart Defects: Comprehensive Analysis of 2,788 Consecutive Patients

The spectrum of patients operated on without preoperative catheterization and angiography, the accuracy of echocardiographic diagnosis and its impact on the results of surgical treatment were prospectively assessed in 2,788 children consecutively operated for congenital heart defects (CHD) between 1986 and 1992. The overall percentage of surgery based solely on noninvasive preoperative examination increased from 63% in 1986 to 81% in 1990 and decreased to 72% in 1992. There were no differences in the preoperative diagnostic approach between groups of newborn, infants and children. A high percentage of patients with patent ductus arteriosus (96.5%), atrial septal defect (94%), incomplete atrioventricular septal defect (88.6%), ventricular septal defect (86.3%), coarctation of the aorta (80.2%) and total anomalous pulmonary venous connection (79.3%) was referred for surgery without prior invasive examination, while a lower percentage was found in univentricular heart (48.4%), pulmonary atresia (34.6%) and double outlet right ventricle (27.7%). More patients with pulmonary and tricuspid atresia were catheterized before complete repair compared to those who underwent palliative surgery (p < 0.01 and p < 0.0001, respectively). The echocardiographic diagnosis was correct in 96% of patients. Two patients of those with incomplete preoperative diagnosis died early postoperatively, both with missed apical ventricular septal defect. One with tetralogy of Fallot died after reoperation, the other with persistent truncus arteriosus due to sepsis. When the echocardiographic findings are in full agreement with the clinical status, physical examination, ECG and chest X-ray, we recommend cardiac surgery without prior catheterization in many patients with CHD.

Results of primary and two-stage repair of interrupted aortic arch

OBJECTIVE Early results of primary and two-stage repair of interrupted aortic arch have improved. Experience with different surgical approaches should be analysed and compared. METHODS Forty neonates and infants with interrupted aortic arch underwent primary repair (19 patients) or palliative operation (21 patients). Twenty (50%) patients were followed-up for 5.1+/-4.3 years. All patients were regularly examined with the aim of determining clinical development, presence of residual lesions or complications and need for re-intervention. Aortic arch and the left ventricular outflow tract growth were assessed by echocardiographic examination. Data from hospital and outpatient department records were analysed. RESULTS The early mortality was 61.9% after palliative operations and 36.8% after the primary repair. Presence of complications (P < 0.001), earlier year of surgery (P < 0.01), bad clinical condition and acidosis (P < 0.05) represented statistically significant risk factors for death in the whole series. In seven (87.5%) out of eight early survivors, after the initial palliative operation, closure of ventricular septal defect and debanding were done, and in three (37.5%) patients, re-operation for aortic arch obstruction was also required. Out of 12 patients, after the primary repair, one required early re-operation for persistent left ventricular outflow tract obstruction and two needed late re-intervention for left bronchus obstruction. In three (25%) patients, after the primary repair, left ventricular outflow tract obstruction with a maximal systolic pressure gradient higher than 30 mmHg developed. At present, all 20 early survivors are alive. Five patients, after palliative operation, are in NYHA class 1, but in three patients, who are in class III or IV, the outcome is influenced by severe complications. All patients after the primary repair are in class I or II. CONCLUSIONS Our experience confirmed better results after the primary repair of interrupted aortic arch, which was associated with lower mortality, prevalence of severe complications and need for re-intervention. Higher prevalence of subaortic stenosis after primary repair could be explained by patient selection early in our experience. We recommend the primary repair of interrupted aortic arch and associated heart lesions in neonates, however, in unfavourable conditions an individualised surgical approach with initial palliative surgery should be considered.

Physicochemical Properties and Supernucleophilicity of Oxime-Functionalized Surfactants: Hydrolytic Catalysts toward Dephosphorylation of Di- and Triphosphate Esters

Aggregation and kinetic studies have been performed to understand the hydrolytic potencies of the series of oxime-functionalized surfactants, viz., 3- hydroxyiminomethyl-1-alkylpyridinium bromide (alkyl = CnH2n+1, n = 10, 12, 14, 16, 18) in the cleavage of phosphate esters, p-nitrophenyl diphenyl phosphate (PNPDPP) and bis(2,4-dinitrophenyl) phosphate (BNDPP), in mixed micelles with cetylpyridinium bromide (CPB). Micellization and surface properties of mixed micelles functional surfactants with CPB were studied by conductivity and surface tension measurements. Acid dissociation constants (pKa) were determined, the effect of functional surfactant alkyl chain length and pH on the observed rate constant (kobs) for phosphate ester cleavage has been discussed, and the effect of substrate on the supernucleophilicities of the studied oximes was monitored. Functionalized oxime-based surfactants were proved to be supernucleophiles to attack on the P═O center of tri- and diphosphate esters. Oximes with hexadecyl alkyl chain length (3-C16) showed maximum micellar effect on the rate constants toward PNPDPP. Micellar effects were analyzed in terms of the pseudophase model.

Congenital absence of aortic and pulmonary valve in a fetus with severe heart failure.

A case of congenital absence of both aortic and pulmonary valves with severe heart failure detected prenatally by cross-sectional and pulsed and colour Doppler echocardiography is reported in small for gestational age male fetus in 17th week of gestation. Additional double outlet right ventricle, hypoplastic left ventricle, and ventricular septal defect, as well as multiple extracardiac anomalies, were found by prenatal echocardiographic investigation and confirmed by necropsy examination. Retrograde diastolic Doppler waveforms retrieved from pulmonary artery, aorta, and umbilical arteries revealed massive insufficiency throughout both the great arteries, which eliminated diastolic placental perfusion, documented by absent anterograde diastolic flow in the umbilical vein. These prenatal echocardiographic findings may contribute to an understanding of the mechanism of rapid and progressive heart failure and growth retardation in the fetus. Severe cardiac failure may explain why congenital aplasia of both the aortic and the pulmonary valves has not been described postnatally, and only two fetal cases revealed by necropsy have been published.

Preparation of the Pyridinium Salts Differing in the Length of the N-Alkyl Substituent

Quaternary pyridinium salts with chains ranging from C8 to C20 belong in the large group of cationic surfactants. In this paper, the preparation of such cationic surface active agents based on the pyridinium moiety and differing in the length of the N-alkyl chain is described. Additionally, HPLC technique was established to distinguish each prepared pyridinium analogue. This study represents universal method for preparation and identification of quaternary pyridinium detergents.