Combining count- and length-based z-scores leads to improved predictions in non-invasive prenatal testing.

MOTIVATION: Non-invasive prenatal testing or NIPT is currently among the top researched topic in obstetric care. While the performance of the current state-of-the-art NIPT solutions achieve high sensitivity and specificity, they still struggle with a considerable number of samples that cannot be concluded with certainty. Such uninformative results are often subject to repeated blood sampling and re-analysis, usually after two weeks, and this period may cause a stress to the future mothers as well as increase the overall cost of the test. RESULTS: We propose a supplementary method to traditional z-scores to reduce the number of such uninformative calls. The method is based on a novel analysis of the length profile of circulating cell free DNA which compares the change in such profiles when random-based and length-based elimination of some fragments is performed. The proposed method is not as accurate as the standard z-score; however, our results suggest that combination of these two independent methods correctly resolves a substantial portion of healthy samples with an uninformative result. Additionally, we discuss how the proposed method can be used to identify maternal aberrations, thus reducing the risk of false positive and false negative calls. AVAILABILITY AND IMPLEMENTATION: The open-source code of the proposed methods, together with test data, is freely available for non-commercial users at github web page https://github.com/jbudis/lambda. SUPPLEMENTARY INFORMATION: Supplementary materials are available at Bioinformatics online.

Minimal invasive coronary sinus lead reposition technique for the treatment of phrenic nerve stimulation.

AIMS: Phrenic nerve stimulation (PNS), which is often intolerable for the patient, is a known complication of resynchronization therapy. We describe a new, minimal invasive method for treating PNS. METHODS AND RESULTS: Untreatable PNS was found in nine cardiac resynchronization therapy patients with distal coronary sinus (CS) lead position 6 +/- 6 (0.5-17) months after the implantation. Ablation catheter and Amplatz Left 2 type guiding catheter were introduced into the right atrium via the right femoral vein. Coronary sinus was cannulated with the Amplatz catheter, and on a normal guide wire, a coronary stent was introduced beside the lead into the side branch in seven cases or a bigger stent into the CS in two patients. The ablation catheter was looped around the CS lead in the atrium with bent tip and was drawn backward together with the CS electrode. New lead positions were evaluated with electrophysiological measurements, and the suitable position was stabilized with inflation of the stent. Pericardial effusion was not detected on post-operative echocardiography. After repositioning, suitable pacing parameters were registered (threshold: 1.6 +/- 1.1 V; 0.5 ms, impedance: 565 +/- 62 ohm). Phrenic nerve stimulation was not found with 7.5 V; 1.5 ms pacing. During follow-up (7.7 +/- 4.6 months), stable pacing threshold and impedance values were measured; transient and reprogrammable PNS was present in only one patient. CONCLUSION: Coronary sinus electrode reposition using the femoral approach seems to be a safe and effective procedure, which means smaller burden for the patients compared with the established reposition operation. The technique can be used successfully if the CS lead is in a distal position.

[Successful epicardial ablation of a postinfarction ventricular tachycardia]. / Posztinfarktusos incessant kamrai tachycardia sikeres epicardialis katéterablatiója. Az elso hazai esetismertetés.

Endocardial radiofrequency catheter ablation was performed because of frequent, 150/min monomorphic ventricular tachycardia (VT). In February 2005 it was many times terminated only by ICD shock in a 55-year-old postinfarction patient who received an implantable cardioverter defibrillator (ICD) 5 years ago because of rapid, monomorphic VT. After being asymptomatic for two months, a slower, 120/min, however, incessant ventricular tachycardia was present which was untreatable by a repeated endocardial ablation. Combined antiarrhythmic treatment was not effective either. In June 2005, after another unsuccessful endocardial ablation, epicardial ablation was decided as an "ultimum refugium". After subxyphoidal percutaneous pericardial punction we positioned the ablation catheter in the pericardial space, and ablation at the earliest activation point terminated the permanently ongoing arrhythmia for one and a half month within 5 seconds. After another three ablations we were unable to induce ventricular arrhythmia even with programmed ventricular extrastimulation. During a three-year follow-up, ventricular tachycardia was noticed in only two cases, ICD terminated both arrhythmias with the first antitachycardia pacing. The patient is in NYHA stage II at present. According to our knowledge, our case is the first successful epicardial ablation of incessant ventricular tachycardia in a postinfarction patient in Hungary.

Stabilization of the coronary sinus electrode position with coronary stent implantation to prevent and treat dislocation.

INTRODUCTION: Coronary sinus (CS) leads used for cardiac resynchronization have undergone development in the last years. However, dislocation rate remained high (5-9%). The aim of this study was to investigate the effectiveness and safety of stent implantation in a CS side vein to stabilize the left ventricular lead position after postoperative or intraoperative dislocation of the electrode. METHODS AND RESULTS: Thirty-six patients (age: 64 +/- 9.7 years, 19 primary, 17 ischemic cardiomyopathy, NYHA class III: 30, IV: 6) were treated with stenting. The procedure was performed because of postoperative dislocation in seven patients, while dislocation was observed during the implantation in 29 cases. The electrode was repositioned into the desired position and a bare metal coronary stent was introduced via another guide wire. The stent was deposited at 5- to 15-mm proximal to the tip of the electrode with a pressure of 6 to 14 atmospheres. Control angiography showed no blood flow compromise in any of the side branches or in the coronary sinus. Control echocardiography did not show pericardial effusion due to stenting. During follow-up (11.5 +/- 5.5, 2-23 months), left ventricular pacing threshold increased from 2.2 to 5.6 V in one patient, but dislocation was not found by fluoroscopy. Clinically important pacing threshold increase was not detected in the other cases. Impedance measurements did not suggest lead insulation failure. CONCLUSION: Stent implantation to stabilize the left ventricular lead position seems to be a useful and safe procedure in the treatment of patients with complicated coronary sinus anatomy or lead instability.

[Resynchronization therapy of heart failure]. / Szívelégtelenség reszinkronizációs kezelése.

Heart failure has a high prevalence and it has a poor prognosis despite the advances in pharmacological treatment. Cardiac resynchronization therapy with biventricular pacemaker has a clinically proven efficacy in the treatment of heart failure with intraventricular dyssynchrony. Conventionally the therapy is indicated in severe drug refractory heart failure (NYHA III-IV) with optimal drug treatment, increased QRS duration (> or = 120 ms), echocardiographic parameters (left ventricular ejection fraction at most 35%). Implementation of new methods (tissue doppler echocardiography, CT, MRI, electroanatomical mapping) can help to select potentially responding patients. Individual optimization of therapy can be performed with non-invasive and invasive methods, the efficacy can be improved even in responding patients. Due to the outstanding efficiency widening the indications is a must. Currently, the efficacy is being investigated in mild heart failure and patients with narrow QRS. Several other questions (transvenous or surgical implantation, need of an implantable defibrillator) will be answered in future trials.

Short-term effect of rate control on plasma endothelin levels of patients with tachyarrhythmias.

Radiofrequency catheter ablation or modification of the atrio-ventricular junction is an effective therapy of drug refractory supraventricular tachyarrhythmias (ST). Higher endothelin (ET) levels were observed during nonsustained STs. We aimed to examine the effect of sustained STs and the applied rate-control therapy on plasma ET levels. Twenty-two patients (12 men; mean age, 64.4 +/- 13.2 years; ejection fraction, 41.8 +/- 11.2%; New York Heart Association (NYHA) class I: 3 cases, NYHA II: 11 cases, and NYHA III: 8 cases) suffering of atrial fibrillation (n = 11), atrial flutter (n = 7), atrial paroxysmal tachycardia (n = 3), or sinus tachycardia (n = 1) were studied, having coronary artery disease (n = 8), dilative cardiomyopathy (n = 5), or no underlying diseases (n = 9). All groups went under catheter ablation (same protocol, duration: 35 +/- 10.3 mins; rate before ablation, 100-170/min in every case; after ablation, 70-80/min in Groups I and II and 70-90/min in Group III). A pacemaker (PM) was implanted 2 months before ablation in Group I (n = 9) and during ablation in Group II (n = 7). No PM was implanted in Group III (n = 6). A control group (n = 13; 7 men; mean age, 66.15 +/- 6.7 years) with sinus rhythm got a PM without ST and ablation. Blood samples were collected from the cubital vein immediately before (control), and 5 mins and 24 hrs after ablation. Plasma ET-1 and big ET-1 levels were measured after immunoprecipitation with Western blot analysis. There were no differences between plasma ET-1 levels in the ST groups and the control group (Groups I, II, and III vs. control group: 0.66 +/- 0.04 fmol/ml, 0.93 +/- 0.12 fmol/ml, and 0.68 +/- 0.05 fmol/ml vs. 0.50 +/- 0.05 fmol/ml, respectively; P < 0.05). Comparing the control, 5-min, and 24-hr samples, ET-1 levels decreased significantly after supraventricular tachycardia ablation in Groups I and III (control vs. Group I, 5 mins and 24 hrs: 0.66 +/- 0.04 fmol/ml vs. 0.50 +/- 0.04 fmol/ml and 0.29 +/- 0.05 fmol/ml; control vs. Group III, 24 hrs: 0.68 +/- 0.05 vs. 0.34 +/- 0.05 fmol/ml; P < 0.05). No plasma big ET-1 changes were measured in any of the groups. The rapid decrease of ET levels after catheter ablation suggests that a high ventricular rate can be a trigger of ET production. PM implantation procedure seems to interfere with the ET decrease in ST patients.

Successful management and long term outcome of an accidental subclavian artery injury with a 9 french dilator during pacemaker implantation with collagen-based closure device.

Subclavian artery puncture and dilation with 9 Fr dilator during pacemaker implantation is a rare complication. We present a case, where this complication occurred and the injury was sealed with collagen-based closure device without any complications. Long term follow-up and the control angio-CT revealed no further late vascular complications. Therefore, use of a collagen based closure device for treating accidental iatrogenic subclavian artery injury can be a simple, successful alternative therapy when surgical direct vascular repair is not possible or not available.

The incidence of avascular necrosis of the healthy, contralateral femoral head at the end of the use of Pavlik harness in unilateral hip dysplasia.

We examined the incidence of avascular necrosis (AVN) of the healthy femoral head in unilateral hip dysplasia at the end of the use of the Pavlik harness. The evaluation of AVN was done with the help of standardised roentgenograms. Between 1974 and 1982, 1,064 dysplastic hips (869 children) were treated with the Pavlik harness at the Orthopaedic Department of Semmelweis University. Of these, 674 children who had unilateral hip dysplasia were chosen for this study. In the period of our investigation, ultrasonography was not yet used routinely, so in some cases the hip was mistakenly diagnosed as dysplastic. The average patient age was 3.2 months, and the average length of treatment was 4.9 months. We found no correlation between the appearance of AVN in the healthy hips at the end of treatment with the Pavlik harness and the age of the child at the start of treatment. On the other hand, there was a strong significant correlation between the appearance of AVN and the length of treatment.

Expressed monophasic action potential alternans before the onset of ventricular arrhythmias induced by intracoronary bolus administration of endothelin-1 in dogs.

We showed previously a direct arrhythmogenic effect of the intracoronary infusion of endothelin-1 (ET-1). We aimed to examine the electrophysiological effects of intracoronary bolus administration of ET-1 using monophasic action potential (MAP) recordings. Eight mongrel dogs received boli of ET-1 (1 and 2 nmol) into the left anterior descending coronary artery. These intracoronary ET-1 boli rapidly caused a marked decrease in coronary blood flow (1 nmol, 78+/-7%; 2 nmol, 89+/-7%). Ischaemic changes of MAP morphology, a decrease in upstroke velocity (baseline, 1.78+/-0.2 V/s; 1 nmol, 0.95+/-0.18 V/s; 2 nmol, 0.45+/-0.21 V/s; P<0.01) and a decrease in MAP duration at 90% repolarization (MAPD(90)) [1 nmol, from 191+/-3 to 176+/-5 ms (P<0.05); 2 nmol, from 212+/-4 to 180+/-8 ms (P<0.05)] occurred after ET-1 bolus administration. However, at 7-10 min after the 1 nmol bolus, a significant increase in MAPD(90) was observed (10 min, in the left ventricular anterior epicardial region: from 191+/-3 to 206+/-6 ms; P<0.05). The incidence of ventricular arrhythmias was as follows: after the 1 nmol ET-1 bolus: ventricular tachycardia, 3/8 animals; ventricular fibrillation, 1/8; after the 2 nmol ET-1 bolus: ventricular tachycardia, 5/7; ventricular fibrillation, 5/7. MAP alternans was present in each animal (1 nmol, 18.2+/-5.8%; 2 nmol, 10.8+/-2.5%). Thus electrophysiological and coronary blood flow changes indicate the predominance of an ischaemic arrhythmogenic effect of the bolus administration of ET-1 (shortening of action potential duration; appearance of MAP alternans), whereas the observed delayed prolongation of MAPD(90) suggests a direct arrhythmogenic effect of ET-1. The expressed MAP alternans could have a pathogenic role in the onset of ventricular arrhythmias induced by an intracoronary bolus of ET-1.