Reliability of the first-trimester cardiac scan by ultrasound-trained obstetricians with high-frequency transabdominal probes in fetuses with increased nuchal translucency.

OBJECTIVE: To examine prospectively the reliability of ultrasound-trained obstetricians performing a first-trimester fetal cardiac scan with high-frequency transabdominal probes, by confirming normal or abnormal heart anatomy, in pregnancies referred for increased nuchal translucency thickness (NT). METHODS: Trained obstetric operators assessed the fetal heart in 133 fetuses with increased NT (> 95th centile) at 11-14 weeks of gestation. A high-frequency transabdominal probe was used to confirm or refute normal cardiac anatomy rather than to establish a specific diagnosis. Following this preliminary screening by the ultrasound-trained obstetrician, specialized fetal echocardiographers rescanned the fetal heart in order to confirm the accuracy of the obstetric operators' findings and to establish a diagnosis in abnormal cases. Fetal cardiologists repeated the examinations at 20 and 32 weeks of pregnancy. Postnatal follow-up lasted 2 years. Twelve fetuses with normal karyotype and normal anatomy were lost to follow-up. RESULTS: A total of 121 fetuses with increased NT between 11 and 14 weeks' gestation were studied. Congenital heart disease (CHD) was detected in 20/121 (16.5%) fetuses. In addition, there were three with mild ventricular disproportion, the right ventricle being larger than the left, considered as a minor non-specific cardiac abnormality. CHD was associated with chromosomal anomalies in 12/20 (60%) cases. Among the 121 fetuses, there was agreement between ultrasound-trained obstetricians and fetal cardiologists in 116 (95.9%) of the cases, and the ultrasound-trained obstetricians correctly identified 18 cases with major cardiac defects. However, there was disagreement in five cases: two with small ventricular septal defects and three with ventricular disproportion. CONCLUSIONS: Our results provide evidence that obstetricians, trained to study the heart in the second trimester, can also differentiate reliably between normal and abnormal heart findings in the first trimester, when using a high-frequency transabdominal ultrasound probe.

Spatial velocity profile changes along the cord in normal human fetuses: can these affect Doppler measurements of venous umbilical blood flow?

OBJECTIVE: Several studies have assumed a parabolic velocity profile through the umbilical vein (UV) to derive the mean spatial velocity that is indispensable for flow rate calculations. However, the structure and arrangement of the umbilical cord suggest that velocity profiles may vary. The aim of this study was to evaluate UV spatial flow velocity profiles at different sites along the umbilical cord. METHODS: Ten singleton pregnancies with a gestational age between 26 and 34 weeks were included in the study. Ultrasound equipment with an inbuilt function for analysis of the spatial velocity profile along a line located in a fixed plane was used to obtain UV velocity profiles. Velocity profiles were obtained at the placental insertion and in a free intra-amniotic loop of the cord. Two-dimensional (2D) velocity distribution coefficients were evaluated as ratios between mean and maximum velocities along the investigated lines. RESULTS: 2D velocity distribution coefficients at the placental insertion (0.85 +/- 0.03) were significantly higher (P < 0.00001) than those obtained from a free loop of cord (0.76 +/- 0.03). Values indicated that velocity profiles are approximately flat at the placental insertion and become more parabolic moving downstream. Moreover, profiles become skewed in association with cord curvature and show peculiar biphasic shapes immediately downstream from the placenta. CONCLUSIONS: Flow velocity profiles in the UV are not perfectly parabolic and modify along the cord. These characteristics may affect the evaluation of UV blood flow rate.

Controlled fetal blood-letting of the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome: preliminary results.

OBJECTIVE: To investigate the feasibility of withdrawal of blood from the recipient twin as a new method for the treatment of severe twin-twin transfusion syndrome. METHODS: Seven consecutive monozygotic monochorionic twin pregnancies affected by severe twin-twin transfusion syndrome were treated. Fetal blood was withdrawn from the recipient twin using cordocentesis. The volume of blood to be removed was determined using the formula for intrauterine blood transfusion of anemic fetuses. Fetal outcome was evaluated in relation to changes in the amniotic fluid and in growth curves (comparing the differences between the centiles of the estimated fetal weight before the procedure and the centiles of weight at birth), fetal mortality, gestational age at delivery, neonatal weight and neurological damage. RESULTS: Overall, seven of the 14 (50%) fetuses survived; at least one fetus survived in five (71%) pregnancies, both fetuses survived in two (29%) pregnancies, while in two (29%) pregnancies there were no survivors. No maternal complications were observed. At follow-up, one (14%) baby had minor neurological damage. CONCLUSIONS: Withdrawal of blood from the recipient twin in the treatment of severe twin-twin transfusion syndrome was associated with survival similar to that of the alternative techniques of serial amniodrainage and fetoscopic laser surgery, with some possible advantages such as reduced neurological damage compared with serial amniodrainage. It is also less invasive compared with fetoscopic laser surgery.

Color-Doppler velocimetry of uterine arteries in pregnant and nonpregnant patients during multiovulation induction for IVF.

OBJECTIVES: To evaluate uterine artery resistance during multiovulation induction in relation to the implantation rate in patients attending in vitro fertilization (IVF) cycles. PATIENTS: Multiovulation induction for IVF was monitored by daily determination of the pulsatility index (PI) of the uterine arteries, obtained by a transvaginal probe (6.5 MHz) implemented with color-flow imaging. Doppler data were obtained from 5 days before hCG administration to the day of follicular aspiration. One IVF cycle was monitored in 70 patients. In 17 patients, 41 IVF cycles were monitored until a successful attempt occurred. RESULTS: In the 70 patients studied during one IVF attempt, the PI of the uterine arteries significantly varied (P < 0.001) in the different phases of the cycle. In the 24 patients who conceived, a significantly lower PI (P < 0.03) was found throughout the cycle. This result was mainly due to a highly significant difference of PI values observed the day after hCG administration (P < 0.005). In the 17 patients who conceived after 1 to 4 negative in vitro fertilizations, no significant difference in PI was observed in the uterine artery resistance in cycles in which implantation was or was not successful. CONCLUSIONS: Uterine artery resistance varies significantly during phases of the induction therapy. Uterine artery resistance is lower throughout the course of multiovulation induction in patients with higher pregnancy rates. The PI on the day after hCG administration was the best index of pregnancy rate. Low uterine artery resistance was present even in negative attempts in patients who eventually achieved a successful implantation. PI values < or = 3 can be considered a favorable prognostic factor for future IVF cycles.

[Experience in primary prevention of cardiovascular risk factors in children]. / Esperienze di prevenzione primaria sui fattori di rischio cardio-vascolare nei bambini.

Pathologic studies have shown that atherosclerosis may already be present in childhood as reversible fatty streaks in the aortic intima. These findings are directly related to total serum cholesterol and inversely related to serum HDL cholesterol. This study was aimed at screening children and young adolescents of Novara for cardiovascular risk factors and achieving a specific health educational program. We screened a sample of 2560 children and young adolescents aged 10 to 16 years (mean 12) for known family history of cardiovascular diseases and hyperlipidemia, blood pressure values, serum cholesterol fractions and triglycerides. Of the 2560 children, 786 were considered at risk according to pre-defined cutoff points for systolic BP (> 120 mmHg) 10.6%, diastolic BP (> 80 mmHg) 3.4%, total serum cholesterol (= > 160 mg/dl) 18.7%, serum HDL cholesterol (< 40 mg/dl) 49.5%, total serum cholesterol/HDL ratio (> 4) 28.0%, and triglycerides (> 150 mg/dl) 3.7%. Parents were invited to change family lifestyle according to a specific health educational program, which included advice about diet and physical activity. All children at risk were re-examined 1 year later. Mean values of total serum cholesterol (129 +/- 26 vs 143 +/- 30, p < 0.001), triglycerides (86 +/- 28 vs 91 +/- 32, p < 0.01) and total serum cholesterol/HDL ratio (3.7 vs 3.8, p NS) were found to be lower than at index evaluation. The distribution of total cholesterol curve shifted to the left, and the high risk cases (total serum cholesterol > 200 mg/dl) lowered from 56 to 24 at the follow-up evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

[The functional and hemodynamic benefits of automatic atrioventricular interval delay in permanent atrial synchronized pacing]. / Benefici funzionali ed emodinamici dell'accorciamento automatico dell'intervallo atrio-ventricolare nella stimolazione cardiaca permanente di tipo atrio-sincronizzato.

OBJECTIVES: In order to assess possible functional and hemodynamic benefits of different programming of atrioventricular (AV) delay--156 ms fixed vs 156 to 63 adaptive--two maximal exercise tests (cyclette) were performed in 8 patients (6 males, 2 females; 69 +/- 6 years) implanted with Chorus 6003 (Ela Medical, France) DDD pacemakers for complete AV block with normal sinus node function. METHODS: The measured parameters were: pacing rate, cardiac output (thermodilution method), oxygen consumption (2001 gas-exchange analyser), arterial-venous difference (derived from pulmonary oxygen saturation, through an optical-fibers Swan-Ganz catheter coupled to an Oximetric3-Abbott oximeter), human atrial natriuretic factor and lactate plasmatic levels, anaerobic threshold. RESULTS: A better cardiac output (11.4 +/- 1.7 vs 10.1 +/- 1.8 l/min) and oxygen consumption (1521 +/- 425 vs 1408 +/- 465 ml/min) were observed at maximal exercise with adaptive rather than with fixed AV delay programming (p < 0.05); moreover anaerobic threshold point was reached later during exercise test with adaptive AV delay (242 +/- 92 vs 216 +/- 109 sec, p = 0.05). On the contrary, with adaptive and fixed AV delay, there were not statistically different values of maximal heart rate (139 +/- 9 vs 139 +/- 9), levels at maximal exercise of arterial-venous difference (12.5 +/- 2 vs 12.8 +/- 1.4 Vol%O2), human atrial natriuretic factor (63 +/- 17 vs 78 +/- 48 pg/ml), lactate (29 +/- 15 vs 29 +/- 18 mg/dl), and oxygen consumption at anaerobic threshold point (772 +/- 164 vs 786 +/- 229 ml/min). CONCLUSIONS: In DDD pacing adaptive AV delay causes aerobic and hemodynamic benefits.

Construction of a library of bovine genomic fragments enriched in CpG islands.

A procedure is described to isolate DNA probes from the bovine genome that are enriched in sites for the so-called rare cutter restriction endonucleases. A collection of SacII (CvCGCGG)-Hin-dIII fragments from bovine sperm was established in the plasmid Bluescript. 180 clones were picked at random and analysed for the presence of inserts with sites for the following rare cutters: EagI, BsshII, NarI, MluI, NruI, NaeI: 70% of the clones contained at least 1 site and 5% contained four different such sites. 22.8% had multiple sites for one or more of the rare cutters tested. Sequence analysis for 16 clones confirmed the cloning of DNA with a G+C content and a proportion of CpG vs GpCs indicative of CpG islands.

A new approach to the prevention of endless loop tachycardia in DDD and VVD pacing.

Endless loop tachycardia (ELT) is a possible complication in dual chamber pacing; it is usually prevented by programming the atrial refractory period (PVARP) longer than the retrograde ventriculoatrial (VA) conduction interval; this in some patients limits the upper rate. In 15 patients with a DDD (nine patients) or a single-pass lead VDD pacemaker (six patients) and retrograde atrial activation, telemetric recording documented a significant difference in amplitude of antegrade, and retrograde atrial potentials (VDD 1.21 +/- 0.32 mV vs 0.56 +/- 0.23 mV, P = 0.008; DDD 2.7 +/- 1 vs 1.8 +/- 1 mV, P = 0.038; Student's t-test for paired data). In 3/15 patients ELT stopped after programming of atrial sensitivity to a value greater than the retrograde P wave amplitude; in 11/15 patients this occurred at a sensing value lower than or equal to retrograde P wave amplitude with a high pass band filter operating. One patient required PVARP lengthening. Holter monitoring showed no more ELTs. In most patients with a DDD or single-pass lead VDD pacemaker with widely programmable sensing amplitude and Hi/Low bandpass filters, individual programming of atrial channel sensitivity prevents ELT without affecting the PVARP and, consequently, upper rate limit.

[Termination of ventricular tachycardia by noninvasive methods]. / Interruzione di una tachicardia ventricolare con metodiche non invasive.

Present paper reports on a patient referred for sustained, hemodynamically well tolerated, ventricular tachycardia, terminated by noninvasive temporary pacing. The tachycardia was refractory to chest tump and intravenous standard drugs (lidocaine and propafenone). Demonstration of spontaneous atrioventricular dissociation and ventricular capture during transesophageal atrial pacing allowed rapid and correct diagnosis. Overdrive with external noninvasive ventricular pacing proved effective in terminating ventricular tachycardia and converting it to sinus rhythm. These observations suggest that noninvasive approach to hemodynamically stable ventricular tachycardia can provide a safe and effective alternative to more aggressive medical management.

Lack of influence of atrioventricular delay on stroke volume at rest in patients with complete atrioventricular block and dual chamber pacing.

Dual chamber pacing (DDD) maintains atrioventricular (AV) sequence; AV delay programmability modifies the relationship between atrial and ventricular contraction. To evaluate the hemodynamic effects of such a modification, ten patients with a DDD unit for complete AV block were studied by time-motion (M-mode) and Doppler echocardiography during inhibited ventricular pacing (VVI), atrial-triggered ventricular pacing (VDD) and atrioventricular sequential pacing (DVI) at different AV delay (90, 140, 190, 240 msec). A significant improvement in stroke volume (SV) (15%-20%, P less than 0.05) was seen during DDD versus VVI pacing; no changes, however, were observed in the same patient with different AV delay or during DVI versus VDD pacing. These data suggest that programming of AV delay does not affect systolic performance at rest; longer diastolic filling times recorded during DDD pacing with "short" AV delay (90-140 msec) do not seem to be a hemodynamically relevant epi-phenomenon of PM programming.

Restriction fragment length polymorphism analysis of the kappa-casein locus in cattle.

The two common genetic variants (A and B) of bovine kappa-casein originate from two point mutations in the codons for the aminoacids in position 136 and 148. These mutations give rise to polymorphic sites for the restriction endonucleases Hin dIII, AluI, HinfI, Mbo II and TaqI. We have examined DNAs of several Italian Friesian cows and bulls of known and unknown genotype by Southern analyses using kappa-casein cDNA probes. Restriction fragment length polymorphisms (RFLPs) specific for the A and B alleles were identified for each of the above enzymes, except for AluI, which has a non-polymorphic site 12bp away from the polymorphic one. We have also found two new polymorphic sites for MboII and TaqI in the non-coding regions. These sites differentiate the A allele into two new variants, named A1 and A2. The RFLP analysis permits the characterization of kappa-casein alleles even in the absence of their expression. This should facilitate selective breeding programmes aimed at increasing the frequency of the kappa-casein B allele whose product improves the cheesemaking properties of milk.

Respiratory-dependent atrial pacing, management of sinus node disease.

The effectiveness of respiratory-dependent atrial pacing (AAI-RD) was assessed in 23 patients (11 male, 12 female; 68 +/- 10 years) with symptomatic isolated sinus node disease (SND). Follow-up was performed at 3 month intervals and included history taking, physical examination, ECG recording and 24-hour Holter monitoring. An incremental treadmill exercise test was performed in 21/23 patients before pacemaker implantation, in 23/23 patients after implantation (at least two tests with different programmed settings of respiratory rate/paced rate ratio); 21/23 patients underwent treadmill tests during both fixed rate 70 bpm and AAI-RD pacing. Physiological sensitivity of AAI-RD pacing was found excellent in 34 tests (85%) and fair in six (15%). Spontaneous heart rate was significantly higher after pacemaker implantation (bpm 115 +/- 20 vs 98 +/- 24, P less than 0.001). In 10/21 patients paced rate was significantly higher during AAI-RD vs AAI pacing (131 +/- 9 vs 106 +/- 16, P less than 0.001) with better total work time (min 9.9 +/- 4 AAI-RD vs 6.8 +/- 2.6 AAI, P less than or equal to 0.002), higher oxygen consumption at anaerobic threshold (ml/min 1137 +/- 406 AAI-RD vs 882 +/- 268 AAI-RD vs 5.5 +/- 2.6 AAI, P = 0.001). No significant difference was found in 7/21 patients (overlap between spontaneous and paced rate during both AAI-RD and AAI programming); 4/21 patients did not reach anaerobic threshold owing to osteomuscular limitations. AV block was detected in 1/23 patients, Biorate circuital failure in 1/23, sporadic undersensing in 5/23, short and symptom-free myopotential inhibitions in 10/23.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiological sensitivity of respiratory-dependent cardiac pacing: four-year follow-up.

Clinical and physiological data on long-term follow-up of 143 patients with respiratory-dependent pacemakers (RDP3) are reported; 121 patients received ventricular (VVI-RD) and 22 patients atrial (AAI-RD) respiratory-dependent stimulation. Functional evaluation was based on the exercise testing (130 pts) with oxygen uptake VO2, ventilation, ECG and arterial pressure monitoring and the dynamic Holter electrocardiogram (95 pts). In each patient, the stimulation rate curve selected was that which produced the best work tolerance and moved the anaerobic threshold to the right. Respiratory levels were assessed by telemetry verifying proper sensing of tidal volume variations and absence of interference and artefacts. In patients with VVIR or AAIR stimulation, exercise tolerance, oxygen uptake and anaerobic threshold increased significantly in comparison with VVI or AAI pacing respectively. The physiological sensitivity of the stimulation system (i.e., a linear relationship of the pacing rate with metabolic requirements) was excellent (up to exhaustion) in 70%, very good (up to anaerobic threshold) in 20% and erratic (no relationship between pacing rate and VE/VO2) in 10% of patients. In dynamic electrocardiographic monitoring, the automatic pacing rate was always predominant during the night and during rest periods; the pacing rate increased properly with daily activity; myopotential inhibition (none longer than 3,500 ms) was observed in 38 patients, but without subjective complaints. The incidence of the RDP3 malfunction was less than 8%; it may have stemmed from the pacing system itself, or from other clinical conditions. Oversensing of impedance system pulses has not been recorded in the last 3 years. Partial respiration undersensing results from incorrect accessory lead position, pulmonary emphysema, marked obesity or other causes. Respiratory sensing becomes erratic at the anaerobic threshold point in such patients, but functions well at submaximum exercise levels. In patients with left ventricular failure, exercise tolerance was improved by setting a lower ratio between the pacing rate and respiration, which prevented the occurrence of excessive pacing rates.

Sustained beneficial hemodynamic effects of low transdermal nitroglycerin doses compared with placebo in patients with congestive heart failure.

In an attempt to resolve some of the controversies concerning the dose requirements and duration of effects of transdermal nitroglycerin (NTG) in patients with heart failure (CHF), the short-term hemodynamic responses to transdermal NTG, in a 20 cm2 self-adhesive patch (10 mg/24 h), were evaluated in 10 patients with severe chronic CHF using a randomized, within-patient, double-blind, placebo-controlled cross-over trial. Serial hemodynamic measurements over 24 h revealed sustained effects that began 1 h after the application of nitroglycerin patch and fully persisted throughout the study. The peak effect occurred at 4 h with the pulmonary capillary wedge pressure decreasing from 33.7 +/- 8.4 to 21.4 +/- 9 mmHg (mean +/- SD) (p less than 0.05) and the cardiac index increasing from 2.5 +/- 0.6 to 3 +/- 0.6 l/min/m2 (p less than 0.01). Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures (from 43.5 +/- 9.5 to 31 +/- 11.4 and from 7.4 +/- 6.6 to 3.8 +/- 4.7 at peak effect, respectively) as well as pulmonary and systemic vascular resistances (from 10.7 +/- 6.6 to 6.5 +/- 3.2 and from 26.2 +/- 5.1 to 22.5 +/- 5.7, respectively). There was no change in heart rate or systemic arterial pressure. These beneficial hemodynamic responses persisted for 24 h. No rebound deterioration occurred upon withdrawal of the nitroglycerin. No significant hemodynamic changes occurred during placebo treatment period. Thus, low doses (10 mg/24 h) of transdermal nitroglycerin induce significant hemodynamic benefit that is sustained for 24 h in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Physiologic limitations of dual chamber stimulators during physical activity]. / Limitazioni fisiologiche degli stimolatori bicamerali durante l'attività fisica.

Dual chamber DDD pacing is fully physiologic when chronotropic response of sinus node to exercise is normal and when retrograde ventriculo-atrial conduction is absent. Comparison of results from exercise test with increasing work load showed that atrial-triggered ventricular pacing provides a significant functional benefit (delta VO2 15%) P less than 0.01, if compared with fixed rate ventricular pacing. The benefit is closely related with the amount of sinus rate increase during exercise. In patients with sinus node syndrome the atrial triggered ventricular pacing rate did not show significant increase during exercise and exercise capability was similar to that observed with fixed ventricular pacing. Retrograde ventriculo-atrial conduction was observed in 56% of patients with sick sinus syndrome and 28% of patients with complete AV block and was the reason for endless loop tachycardias (ELTs). ELTs can be eliminated by lengthening atrial refractory period (ARP). In patients with ARP greater than or equal to 250 ms (47%), mild (8:7, 4:3) or important (2:1) AV block appeared during exercise test, with sudden drop of pacing rate and cardiac output at highest work load. Among other "physiologic" pacing modes, respiration traced ventricular stimulation showed high physiologic sensitivity (90%) and haemodynamic benefit comparable to that obtained during dual chamber pacing and without the related disadvantages.

[Arrhythmia in patients with a DDD bicameral pacemaker]. / Aritmie in pazienti portatori di pacemaker bicamerale DDD.

Dual chamber pacemakers, with coordinate atrial and ventricular sensing and stimulation (DDD), even if allowing "physiological" pacing, exhibited new and complicated arrhythmic manifestations, whose real frequency is still unascertained. In 65 patients (mean age 68 +/- 12 years), implanted with a DDD multiprogrammable device (15 pts. Medtronic Versatrax 7000 A, 50 pts. Pacesetter AFP 283), we carried out a 24 hours Holter monitoring while pacemaker was programmed with standard parameters. In a subset of 15 patients Holter monitoring was performed before and after pacemaker implantation. We evidenced: a) atrial sensing and/or pacing malfunction in 3 patients (4.5%); b) pacer-unrelated arrhythmias in 49 patients (75%): atrial extra beats 35 patients (54%), ventricular extra beats 23 patients (35%), non-sustained ventricular tachycardias 10 patients (15%), atrial tachyarrhythmias 8 patients (12%); c) supraventricular arrhythmias with PM-mediated high rate ventricular pacing in 12 patients (18%); d) PM induced and sustained endless loop tachycardias in 31 patients (47%); e) arrhythmias depending on over-sensing in 11 patients (17%): myopotential interferences 9 patients (14%), cross-talk ventricular pacing inhibition 2 patients (3%). The prevalence of ventricular arrhythmias was not different before and after the pacemaker implantation. The prevalence of atrial extrasystoles (53% versus 40%) and atrial tachyarrhythmias (26% versus 6%) decreased after the pacemaker implantation. Aimed reprogramming with progressive extension of atrial refractory period (from 250 to 400 msec and DDX) achieved disappearance of PM-endless loop tachycardias in 95%. Use of multi-programmability lowered the incidence and symptoms of most PM-related arrhythmias. Drug therapy was of choice in clinical arrhythmias unrelated to pacer.