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BACKGROUND: Despite significant improvements in cardiac output and functional capacity with cardiac resynchronization therapy (CRT), incidence of sudden cardiac death still remains high. Reversal of physiological myocardial activation sequence during epicardial pacing increases the transmural dispersion of repolarization (TDR). The aim of this study was to compare the effects of endocardial and epicardial biventricular pacing on repolarization parameters in the same patient group. METHODS: Seven patients who had transseptal endocardial left ventricle (LV) lead placement, in whom epicardial CRT had failed due to coronary sinus (CS) lead dislodgement after successful implantation, were admitted to the study. LV endocardial leads were implanted through the inter-atrial septum in a lateral position. ECGs were scanned before and after successful epicardial and endocardial biventricular pacing and analyzed using digital callipers. ECG markers of TDR (TpTe and TpTe/QT ratio) were measured and compared. RESULTS: Baseline QRS durations (161.7+/-15.9 vs 162.2+/-17.8 ms, p = 0.95), TpTe values (107.1+/-20.5 vs 108.5+/-17.6 ms, p = 0.89) and TpTe/QT ratios (0.24+/-0.05 vs 0.24+/-0.03, p = 0.88) were similar before epicardial and endocardial CRT. QRS interval reduction was similar (-28.3+/-11.6 vs -29.1+/-11.4 ms, p = 0.89) in both groups. Compared to transseptal endocardial CRT, epicardial CRT was associated with a significant increase in TpTe (17.1+/-19.5 vs -12.6+/-18.9 ms, p = 0.01) and TpTe/QT ratio (0.03+/-0.04 vs -0.02+/-0.03, p = 0.04). CONCLUSION: Transseptal LV endocardial pacing is associated with significant reduction in TDR characteristics compared to epicardial pacing in CRT. Further studies are warranted to determine whether these effects may contribute to reduction of arrhythmias in patients with CRT. This article is protected by copyright. All rights reserved.

Aims Data on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro–B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline. Methods and results Heart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23–0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23–1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28–36%; P

Aims The low lymphocyte counts and high neutrophil leucocyte fractions have been associated with poor prognosis in chronic heart failure. We hypothesized that the baseline ratio of the neutrophil leucocytes to the lymphocytes (NL ratio) would predict the outcome of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). Methods and results The qualitative blood counts and the serum levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) of 122 chronic heart failure patients and 122 healthy controls were analysed prospectively in this observational study. The 2-year mortality was considered as primary endpoint and the 6-month reverse remodelling (≥15% decrease in the end-systolic volume) as secondary endpoint. Multivariable regression analyses were applied and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. The NL ratio was elevated in chronic heart failure patients when compared with the healthy controls [2.93 (2.12–4.05) vs. 2.21 (1.64–2.81), P < 0.0001]. The baseline NL ratio exceeding 2.95 predicted the lack of the 6-month reverse remodelling [n = 63, odds ratio = 0.38 (0.17–0.85), P = 0.01; NRI = 0.49 (0.14–0.83), P = 0.005; IDI = 0.04 (0.00–0.07), P = 0.02] and the 2-year mortality [n = 29, hazard ratio = 2.44 (1.04–5.71), P = 0.03; NRI = 0.63 (0.24–1.01), P = 0.001; IDI = 0.04 (0.00–0.08), P = 0.02] independently of the NT-proBNP levels or other factors. Conclusion The NL ratio is elevated in chronic heart failure and predicts outcome after CRT. According to the reclassification analysis, 4% of the patients would have been better categorized in the prediction models by combining the NT-proBNP with the NL ratio. Thus, a single blood count measurement could facilitate the optimal patient selection for the CRT.

The authors present the history of a 62-year-old man on continuous rivaroxaban therapy who was scheduled for pulmonary vein isolation due to persistent atrial fibrillation. Preoperative transesophageal echocardiography detected the presence of left atrial appendage thrombus. Thrombophilia tests showed that the patient was heterozygous carrier of the methylene-tetrahydrofolate reductase gene mutation. The authors hypothesized that a direct thrombin inhibitor might exert a more appropriate effect against thrombosis in this case and, therefore, a switch to dabigatran was performed. After two months of anticoagulation with the direct thrombin inhibitor and folic acid supplementation the thrombus resolved. The authors underline that thrombus formation may develop in atrial fibrillation even if the patient is adequately treated with rivaroxaban. This case suggests, that methylene-tetrahydrofolate reductase gene mutation may modulate the efficacy of direct Xa factor inhibitors. According to this case history, dabigatran may be an effective therapeutic option in resolving established thrombus. Orv. Hetil., 2016, 157(4), 154–156.

Background Patients with atrial fibrillation (AF) frequently have atrial scarring characterised by discrete regions of low voltage. Pre-existing left atrial scarring is an independent predictor of pulmonary vein isolation (PVI) failure. Novel mapping algorithms have also been developed to assess the degree of atrial fibrosis. This may be expressed as a percentage of the total left atrial (LA) volume mapped. In addition to the electrical remodelling seen, structural remodelling occurs, with dilatation and reduced function. The most accurate determinant of LA function is debated, but the most frequently used method is transmitral A Wave velocity on pulsed-wave Doppler. The relationship between LA function and electrical changes seen in AF has not been defined. Methods This was a single centre observational study. Left atrial voltage maps were created in patients undergoing PVI for the first time in the Mater Private Hospital between August 2016 and April 2017. LA voltage maps were initially created with a Lasso catheter with some further points taken with a Smarttouch ablation catheter (both Biosense Webster, Diamond Bar, California). Voltage greater than 0.5 mV was accepted as normal tissue and voltages Results Out of 96 patients who had undergone PVI, only 24 were found to have had sinus rhythm on pre-procedural echo. The mean age was 63.5 (standard deviation or SD 10.6) years. 66% of the group were men. 58% had paroxysmal AF. The mean amplitude of the A-wave in the study was 0.61 (SD 0.16) ms-1. An average of 1269.7 (SD 857.0) mapping points were taken. The mean LA percentage scar was 25.1 (SD 20.3) %. Using linear regression, adjusted for age at time of procedure, there was a significant negative association between a wave (in ms-1) and % LA scar (Beta coefficient -72.44, 95% CI -122.99 to -21.88, p=0.007). Using pairwise correlation, the correlation coefficient between LA scar and A wave was -0.38, p=0.06. Conclusion Our study found an inverse correlation between transmitral A wave and degree of left atrial scarring when LA function was adjusted for patient age, indicating that LA electrical remodelling as measure by percentage scar is associated with decreased LA function in patients with AF. However, there were only 24 patients in this study and ongoing research with more patients is warranted to further substantiate this.

Lead dislocations of pacemaker systems are reported in all and even in high-volume centers. Repeated procedures necessitated by lead dislocations are associated with an increased risk of complications. We investigated a minimal invasive method for right atrial and ventricular lead repositioning. The minimal invasive method was applied only when passive fixation leads were implanted. During the minimal invasive procedure, a steerable catheter was advanced through the femoral vein to move the distal end of the lead to the appropriate position. Retrospective data collection was conducted in all patients with minimal invasive and with conventional method, at a single center between September 2006 and December 2012. Forty-five minimal invasive lead repositionings were performed, of which eight were acutely unsuccessful and nine electrodes re-dislocated after the procedure. One hundred two leads were repositioned with opening of the pocket during the same time, including the ones with unsuccessful minimal invasive repositionings. One procedure was acutely unsuccessful in this group and four re-dislocations happened. A significant difference of success rates was noted (66.6% vs. 95.1%, p = 0.001). One complication was observed during the minimal invasive lead repositionings (left ventricular lead microdislodgement). Open-pocket procedures showed different types of complications (pneumothorax, subclavian artery puncture, pericardial effusion, hematoma, fever, device-associated infection which necessitated explantation, atrial lead dislodgement while repositioning the ventricular one, deterioration of renal function). The minimal invasive method as a first alternative is safe and feasible. In those cases when it cannot be carried out successfully, the conventional method is applicable.

Cardiac arrest causes generalized ischemia/hypoxia, and subsequent resuscitation inflicts reperfusion injury, the pathology of which is not fully understood. Moreover, predicting the prognosis of comatose, post-cardiac-arrest patients is a complex clinical challenge. We hypothesized that the extent of complement activation might be a reliable predictor of mortality in this population. Forty-six comatose cardiac arrest patients were enrolled into our prospective cohort study, conducted in a tertiary care university clinic. All subjects were cooled to 32-34 degrees C body temperature for 24 hours and then, allowed to rewarm to normothermia. All patients underwent diagnostic coronary angiography. On admission, at 6 and at 24 hrs, blood samples were taken from the arterial catheter. In these, complement products (C3a, C3, C4d, C4, SC5b9, and Bb) were measured by ELISA in blood samples. Patients were followed-up for 30 days; 22 patients (47.8%) died by the end of this period. We observed that complement activation (determined as the C3a to C3 ratio) was higher in non-survivors than in survivors at each time point. In the multivariate Cox regression analysis, the C3a/C3 ratio determined 24 hours after the initiation of therapeutic hypothermia predicted 30-day mortality regardless of age, sex, and the APACHE II score. Complement activation occurs in post-cardiac arrest patients, and its extent correlates with 30-day survival. The C3a/C3 ratio might prove useful for estimating the prognosis of comatose post-cardiac-arrest patients. This article is protected by copyright. All rights reserved.

Background After catheter ablation there is often a discrepancy between acute and chronic success rates. We aimed to evaluate major determinants for lesion quality and understand different manifestations of lesion structures. Methods In a canine thigh muscle model radiofrequency (RF) current was delivered for 60 seconds at 30 W (n = 39) or 50 W (n = 18) with 15-g contact force. A second-generation 12-hole gold open irrigation catheter (SGIT) and a first-generation six-hole platinum-iridium catheter (FGIT; Biotronik, Berlin, Germany) were used. Electrode and tissue temperatures (at the surface and 3.5-mm and 7-mm depth) were recorded and lesion dimensions were measured. Lesions with steam pops were excluded. Histological examination was performed to evaluate homogeneity of the lesions. Inhomogeneity was defined as a visual multiband lesion pattern indicating different histological characteristics. Results In total 57 lesions were created. Seventeen lesions were excluded (steam pops) and 40 lesions were analyzed. A total number of 11 homogeneous and 29 inhomogeneous lesions were identified. Using the SGIT catheter 16.7% of the lesions was homogeneous and 83.3% inhomogeneous; for FGIT it was 43.8% and 56.2% (P = 0.065), respectively. Homogeneous lesions had lower volumes as compared to inhomogeneous lesions (514.0 ± 198.8 vs 914.8 ± 399.1 mm, P = 0.003). Multiple logistic regression analysis indicated that the SGIT catheter is a significant predictor for inhomogeneous lesions (odds ratio 6.5, 95% confidence interval 1.1–38.8; P = 0.040) independent from power setting and flow rate. Conclusions The development of inhomogeneous lesions after acute RF ablation is associated with higher lesion volumes and the use of the second-generation irrigation gold-tip catheter.

Persistent left superior vena cava is a rarely seen anomaly but it may be an arrhythmogenic source for paroxysmal atrial fibrillation. Furthermore, the complex anatomicregion between the left superior vena cava and the pulmonary veins may leads to misinterpretation of the pulmonary vein recordings during atrial fibrillation ablation. Approaches that might be helpful to overcome these problems are discussed in this case report.

A case of a 38-year-old male patient is reported. Left ventricular assist device was implanted because of end stage heart failure. In the early postoperative period, electrical storm with rapid ventricular tachycardia (VTs) occurred that was refractory to medical therapy. Emergency VT ablation was performed successfully. VT frequently occurs after LVAD implantation and radiofrequency ablation can be an effective therapeutic option. We report a case of a 38-year-old male patient, who suffered an extensive anterior ST-segment elevation myocardial infarction in 2002 treated with thrombolysis. LAD PCI (2005), amiodarone-induced hyperthyreosis (2007) and primary prophylactic ICD implantation (2008) are the most relevant findings in his past medical history. Since then he required several hospitalizations for worsening heart failure symptoms. In May 2013, he was admitted due to rapid VT causing hemodynamic instability requiring two appropriate ICD shocks. Heart transplantation was considered as an option but it was contraindicated because of high pulmonary vascular resistance refractory to vasodilator therapy. Left ventricular assist device (LVAD, HeartMate II) implantation was performed as ‘‘destination therapy’’. In the early postoperative period (5 days after implantation) electrical storm occurred requiring multiple ICD shocks. Shock therapy of ICD was deactivated and multiple external electric cardioversions were needed despite the intravenous administration of high dose antiarrhythmic drugs (amiodarone, procainamide and beta blocker). Due to drug refractory electrical storm radiofrequency ablation of the incessant VT was decided in the early postoperative period. Procedure was performed under uninterrupted anticoagulation, respecting the high thromboembolic risk of the assist device. We decided to use transaortic retrograde approach only. During the electrophysiological study sustained monomorphic VT was inducible (cycle length: 330 ms, superior axis, right bundle branch block morphology). During ongoing arrhythmia, rapid electroanatomic mapping (CARTO3, Biosense Webster) was performed which found that the site of earliest activation is at the inferoseptal region of the left ventricle, in the intrinsic myocardial scar near to the junction of the inflow cannula. The exit point was also identified at the same site with entrainment mapping. Then 5 radiofrequency ablations were applied (total ablation time 790 s, energy 40 W, temperature 43 C) using 3.5 mm irrigated tip catheter (Thermocool, D curve, Biosense Webster). We would like to highlight that the ablation site was near to the inflow cannula but we kept some distance from the device to avoid damaging of the surgical sutures. The VT stopped immediately and was no longer inducible even with 2 ventricular extrastimuli at 330 ms drive. No complications were observed during or in relation to the ablation procedure (total procedure time: 45 min, fluoroscopy time: 8 min). After the procedure, patient was free of sustained VT episodes during the 12-month follow-up period. VT is frequently observed in patients after LVAD implantation, but very limited data are available regarding VT ablation in the early postoperative period. Until now publications usually dealt with VTs originating near the cannula, but there are scarce data about VTs arising from the intrinsic scar [1–5]. Managing VT in these difficult N. Szegedi G. Szeplaki B. Merkely L. Geller (&) Heart and Vascular Center, Semmelweis University, Varosmajor street 68, Budapest 1122, Hungary e-mail: laszlo.geller@gmail.com

Early recognition of ventricular tachycardias (VTs) with epicardial circuits is crucial. Surface electrocardiogram (ECG) suggesting an epicardial origin could guide ablation procedures and increase success rates. A 35-year-old female patient with VT treated by combined epicardial and endocardial ablation approach is presented in this report, and the role of surface electrocardiogram and timing of epicardial access is discussed.

Untwisting contributes to left ventricular filling through suction generation. We sought to investigate diastolic function and untwisting dynamics in different forms of left ventricular hypertrophy: in athlete's heart and hypertrophic cardiomyopathy. Elite athletes in kayaking, canoeing and rowing (n=28), patients with hypertrophic cardiomyopathy (HCM, n=15) and healthy sedentary volunteers (n=13) were compared. Left ventricular volumes, wall thickness-to-volume ratio were assessed by cardiac MRI. Following conventional and tissue Doppler measurements, untwist and untwist rate were determined by speckle tracking echocardiography. Wall thickness-to-volume ratio describing remodelling was significantly higher in HCM, but similar in athletes and controls (athlete vs. HCM vs. control: 0.107±0.019 vs. 0.271±0.091 vs. 0.104±0.012 mm×m²/ml, mean±SD, p

BACKGROUND: High irrigation rates during radiofrequency (RF) ablation may cause fluid overload and limit lesion size. This in vivo animal study assessed the safety and efficacy of RF ablation at low irrigation rates using a novel 12-hole gold catheter. METHODS: A total of 103 lesions, created on the thigh of five mongrel dogs, were analyzed. Lesions were created using a 12-hole irrigated gold-tip (Au) and a six-hole irrigated platinum-iridium (PtIr) catheter (both 7F/3.5-mm electrode; BIOTRONIK SE & CO, KG, Berlin, Germany) in parallel and perpendicular orientation. RF current was delivered for 60 seconds at 30 W using 8 mL/min and 15 mL/min irrigation. Electrode temperature, steam pops, lesion dimensions, and coagulum formation were recorded. RESULTS: Electrode temperatures were lower for Au compared to PtIr in parallel (8 mL/min: 38.1 +/- 1.7 degrees C vs 48.0 +/- 4.8 degrees C, P < 0.0001; 15 mL/min: 36.0 +/- 1.5 degrees C vs 46.9 +/- 5.4 degrees C, P < 0.0001) and perpendicular position (15 mL/min: 35.5 +/- 1.2 degrees C vs 38.4 +/- 2.5 degrees C, P = 0.003). The number of steam pops between Au and PtIr was comparable for parallel (8 mL/min: 14% vs 27%, P = 0.65; 15 mL/min: 14% vs 43%, P = 0.21) and perpendicular orientation (8 mL/min: 25% vs 17%, P = 1.00; 15 mL/min: 18% vs 0%, P = 0.48). Au created larger volumes than PtIr at 8 mL/min irrigation (861 +/- 251 mm3 vs 504 +/- 212 mm3 , P = 0.004); however, for 15 mL/min, volumes were comparable (624 +/- 269 mm3 vs 768 +/- 466 mm3 , P = 0.46). No coagulum formation was observed for any of the catheters on the surface and catheter tip. CONCLUSION: RF ablation at low flow rate using a novel 12-hole irrigation Au catheter is safe and results in larger lesions than with a PtIr electrode.

Background. In-stent restenosis (ISR) is the gradual narrowing of the vessel lumen after coronary stent implantation due to the increase in vascular smooth muscle cell proliferation. Vascular endothelial growth factor (VEGF) protein plays an important role in this process. Our aim was to analyze the association of single nucleotide polymorphisms of the VEGF gene (rs2010963 and rs6999447) with the occurrence of ISR after coronary artery bare metal stent (BMS) implantation. Methods. 205 patients with a history of BMS implantation and a repeated coronarography were prospectively enrolled. Patients were assigned to diffuse restenosis group (n=105) and control group (n=100) and VEGF genotypes were determined. Results. Diffuse ISR was significantly more frequently observed in patients with homozygous normal genotype of rs2010963 polymorphism, and this polymorphism was independently associated with diffuse ISR. Conclusions. RS2010963 is associated with higher incidence of development of diffuse coronary ISR in patients treated with BMS implantation.

Context: Assessment of response to cardiac resynchronization therapy (CRT) is essential.Objective: To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT.Methods: Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (

Background In-stent restenosis occurs in 10–30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. Methods In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. Results Average follow-up time was 1.0 (+ − 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ − 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. Conclusions MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism.

The chronic inflammation plays an important role in heart failure and complement components might be useful markers of the prognosis. We set out to evaluate their predictive value in the clinical outcomes of patients with cardiac resynchronization therapy (CRT).We determined the complement levels C3, C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide (NT-proBNP) of 126 heart failure patients in a prospective, single-center observational study before and 6 months after CRT implantation.CRT reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p 0.0001] and the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0) ng/mL, p = 0.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L, p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a 165 ng/mL hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and other factors. After reclassification, we observed a significant net reclassification improvement [NRI = 0.71 (0.43-0.98), p 0.0001] and integrated discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002].In patients with CRT, elevated C3a levels increase the risk of mortality independent of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by reducing the complement activation.

The authors present the history of a 62-year-old man on continuous rivaroxaban therapy who was scheduled for pulmonary vein isolation due to persistent atrial fibrillation. Preoperative transesophageal echocardiography detected the presence of left atrial appendage thrombus. Thrombophilia tests showed that the patient was heterozygous carrier of the methylene-tetrahydrofolate reductase gene mutation. The authors hypothesized that a direct thrombin inhibitor might exert a more appropriate effect against thrombosis in this case and, therefore, a switch to dabigatran was performed. After two months of anticoagulation with the direct thrombin inhibitor and folic acid supplementation the thrombus resolved. The authors underline that thrombus formation may develop in atrial fibrillation even if the patient is adequately treated with rivaroxaban. This case suggests, that methylene-tetrahydrofolate reductase gene mutation may modulate the efficacy of direct Xa factor inhibitors. According to this case history, dabigatran may be an effective therapeutic option in resolving established thrombus.

Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction.Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed.Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n=57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86);p=0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51);p=0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model.Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT.

Eur J Clin Invest 2011; 41 (2): 176–182 Abstract Background Fetuin-A is a glycoprotein that inhibits extraosseous and vascular calcification. Its serum level is lower in patients with atherosclerosis compared with healthy controls, but its role is unknown in aneurysmal diseases. The aim of our study was to investigate the association of serum fetuin-A levels with aortic aneurysms of different aetiology: Marfan syndrome and atherosclerosis. Material and methods In a single centre cross-sectional observational study, 105 patients (30 with atherosclerotic aortic aneurysm, 15 with Marfan syndrome, 30 with peripheral arterial disease and 30 healthy controls) were examined; sera were analysed for fetuin-A, standard markers of possible inflammation, lipid profile, kidney and hepatic disease and diabetes. Systemic atherosclerosis was assessed by carotid intima-media thickness (IMT) measurement and arterial calcification score of cardiac valves, carotids, aorta and femoral arteries determined by ultrasound. Results Serum fetuin-A levels (median and IQR) were significantly lower in the atherosclerotic aneurysm cohort than in patients with Marfan syndrome: 708 μg mL−1 (612–780) and 756 μg mL−1 (708–816), respectively, (P = 0·0428). Fetuin-A levels were 754 μg mL−1 (713–777) in the control group and 654 μg mL−1 (600–756) in patients with peripheral arterial disease. Mean and maximum IMT, ACS values and homocysteine levels were significantly higher in patients with atherosclerosis: P

There is remarkable interest on identifying factors predicting outcome after VT ablation. Our aim was to determine predictors of long-term all-cause mortality in patients undergoing VT ablation. Between 1st of January 2009 and 31st of December 2015 VT ablation was performed in 151 patients with

The diagnosis of hereditary angioedema (HAE) is based on complement tests. We studied for the first time the possible association between complement parameters measured at the time of diagnosis and disease severity in 115 patients with HAE. Serum levels of functional C1-inhibitor (C1-INH f ), antigenic C1-inhibitor (C1-INH a ), C4 and hemolytic activity of the classical pathway (CH50) were determined at the time of diagnosis. We found a significant correlation between severity scores and baseline C1-INH f levels, as determined by ELISA assay ( p = 0.0003). On the other hand, there was no correlation between severity scores and other complement parameters (C1-INH a , C4, and CH50). We consider the correlation between severity scores and baseline C1-INH f levels an important pathophysiological observation. Our findings underlie the potential significance of monitoring functional C1-INH levels in relation to clinical disease course.

Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients.Characteristic parameters of liver function (including bilirubin, GOT, GPT, gammaGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively.From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study.Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

Complement activation plays an important role in ischemia/reperfusion (I/R) injury. The objective of the present study was to detect the presence and mechanism of complement activation in patients who underwent carotid endarterectomy (CEA).Complement activation products C1rsC1-inhibitor, C4d, C3a and SC5b-9 and concentrations of C-reactive protein (CRP) were measured in samples serially taken from 16 patients with eversion CEA and 10 with carotid artery stenting (CAS) in the first 24h post-surgery/intervention. MBL2 genotypes were also determined.In patients with CEA an intense increase in C3a levels were observed immediately after surgery (p0.001), accompanied by a slight elevation in SC5b-9 levels (p0.05). C3a levels remained elevated until 4h post-surgery, compared with the baseline values and with CAS patients. Peak C3a levels correlated with the time of carotid clamping (r=0.5921, p=0.02). No significant changes were detected in C1rsC1-inhibitor or C4d levels following CEA, and we found no association between the generation of C3a and MBL2 genotypes or CRP levels. Complement activation was not present in patients with CAS.Early complement activation follows CEA and correlates with the time of I/R injury. The lack of C4d generation suggests the role of the alternative and not the lectin pathway in the process.

Hereditary angioedema (HAE) is characterized by episodic edematous attacks due to the deficiency of the C1-inhibitor (C1-INH). Recently, we have described that the long-term use of danazol affects lipid metabolism, resulting in decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL) cholesterol levels, which might lead to accelerated, early atherosclerosis. Our aim in the present study was to investigate the impact of danazol treatment on the risk of atherosclerosis in HAE patients.The prevalence of vascular disease, as well as carotid intima-media thickness (IMT)--an objective marker of atherosclerosis--was determined in 32 HAE patients undergoing danazol prophylaxis, and compared to 25 HAE patients without danazol treatment, as well as to 20 healthy controls. Distinct atherosclerosis risk profiles were determined in addition.HAE patients with danazol prophylaxis had higher body mass index (p=0.0055 and 0.0020), creatinine (p=0.0001 and 0.0130), alanine aminotransferase (p=0.0298 and 0.0457), LDL (p=0.0060 and0.0001) and decreased HDL (p0.0001 and0.0001) levels compared to both control groups. The prevalence of vascular diseases did not differ in the two patient groups. No significant differences were observed in mean (0.43 (0.37-0.50)mm vs. 0.40 (0.35-0.49)mm, p=0.5465) carotid IMT values, when comparing patients with or without long-term danazol prophylaxis.Thickening of IMT due to danazol use was not observed in HAE patients. We hypothesize that the functional deficiency of C1-INH might confer protection against atherosclerosis in these patients.

Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) and characterized by recurrent bouts of angioedema. Autoimmune disorders frequently occur in HAE. Previously we found, that danazol has an adverse effect on serum lipid profile: reduced high-density lipoprotein (HDL) and elevated low-density lipoprotein (LDL) cholesterol levels are associated with long-term prophylactic use, whereas total cholesterol levels are unchanged. Our aim was to study the anti-cholesterol antibody (ACHA) production in HAE patients and compare it with those of healthy blood donors, and to investigate the possible associations between ACHA levels and serum lipid profile alterations caused by danazol. Anti-cholesterol IgG levels were measured by ELISA and their correlation with serum concentrations of total cholesterol, HDL, LDL, triglycerides was determined in HAE patients receiving/not receiving danazol. Serum ACHA levels were significantly higher in HAE patients, compared to healthy blood donors (P < 0.0001). Longterm danazol prophylaxis had no effect on serum ACHA levels in HAE patients. However, we found a significant, negative correlation between ACHA levels and serum total cholesterol (r =−0.4033, P = 0.0200), LDL (r =−0.4565, P = 0.0076) and triglyceride (r =−0.4230, P = 0.0121) levels only in danazol-treated patients, but not in HAE patients who did not receive long-term prophylaxis. Patients with HAE have higher baseline ACHA levels compared to healthy subjects, and this might reflect polyclonal B-cell activation. The latter would be a potential explanation for the lack of an increased incidence of infectious diseases in HAE patients, but might lead to increased autoimmunity.

Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood.

Background Ischemic stroke is a multifactorial disorder with genetic and environmental components. The aim of our study was to investigate whether two polymorphisms of the estrogen receptor α (ESR1) gene (ESR1 c.454-397T>C and c.454-351A>G) are associated with ischemic stroke in a Caucasian population from Hungary. Methods One hundred and ninety-eight patients with ischemic stroke and 180 control subjects were enrolled in this case–control study. Ischemic stroke subtypes were categorized according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as large-artery atherosclerosis, small-artery occlusion, cardioembolism or stroke of other determined etiology. The ESR1 Pvu II and Xba I genotypes were determined using the PCR-RFLP method. Results There were no significant differences in the genotype, allele and haplotype frequencies of Pvu II and Xba I polymorphisms between the group of patients with ischemic stroke and the control group. Furthermore, ESR1 Pvu II and Xba I genotypes, alleles and haplotypes were not associated with any subtype of ischemic stroke. Conclusions We did not observe an association between ESR1 Pvu II and Xba I gene polymorphisms and ischemic stroke or any subtype of ischemic stroke. However, further studies are needed to explore the complex interaction between environmental factors and ESR1 gene polymorphisms in the risk of ischemic stroke, particularly in ethnically different populations.

The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p

Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) . Patients experience recurrent bouts of edema, which can occur in almost any region of the body. As regards the treatment of the disease, danazol (an attenuated androgen) is used, among other agents, for long-term prophylaxis.The aim of this study was to investigate the possible adverse effects of danazol on serum lipid profile, as well as to ascertain whether danazol treatment is associated with an increased risk of atherosclerosis.Serum concentrations of total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, apolipoprotein A-I, apolipoprotein B-100, and lipoprotein(a) were compared between danazol-treated patients with HAE and 2 control groups (ie, patients who did not receive long-term danazol prophylaxis and untreated healthy subjects).Serum concentrations of HDL ( P = .0002 and P.0001) and apolipoprotein A-I ( P = .0015 and P.0001) were significantly lower, whereas LDL ( P = .0129 and P = .0127) and apolipoprotein B-100 ( P = .0456 and P = .0013) were higher in the danazol-treated patients compared with the 2 control groups, respectively. No significant difference was found in total cholesterol, triglyceride, or lipoprotein(a) levels. Patients who received danazol had an 11.6 (95% CI, 2.7-49.7) times higher risk for abnormally low HDL levels and a 4.4 (95% CI, 1.2-16.0) times lower risk for high LDL concentrations.Our findings indicate that the long-term use of danazol is associated with an increased risk for early atherosclerosis in patients with HAE. Consequently, monitoring of HDL and LDL levels at regular intervals is recommended during follow-up.

Atherosclerosis is an inflammatory disease. The complement system plays an important role in the atherosclerotic process. However, lesser data is available on the possible role of C3 as a risk factor for atherosclerosis. Therefore, in a follow up study we determined C3 levels in 266 patients with pre-existing severe coronary artery disease (CAD) and compared their serum C3 concentrations with the cause of the disease. We investigated whether C3 levels predict the major complications of severe CAD during a 5-year long follow up period in patients, who have received an aorto-coronary bypass graft surgery. C3 concentrations were elevated in the patients with severe CAD compared to 182 healthy controls, and women had higher C3 concentrations than men. Pathological C3 levels (C3> or =1.8 g/L) were able to predict major complications of atherosclerosis (death by cardiac events, new acute myocardial infarction, stroke, carotid surgery and peripheral arterial disease) that developed during the follow up period only in women (OR: 4.1, 95% C.I. 1.23-13.61, p = 0.0249) independent of other risk factors for atherosclerosis. Our data supports the assumption that high C3 indicates the progression of atherosclerosis as a special marker of chronic inflammation.

Background: There are previous studies about the prognostic significance of quality of life (QoL) in CRT-implanted patients measured with complex heart failure questionnaires. However, there is no data with the EuroQol-5 Dimensions (EQ-5D) questionnaire, which provides a simple descriptive profile

Radiofrequency (RF) catheter ablation guided by electroanatomic mapping systems is an effective therapy for atrial fibrillation. However, it may be affected by respiration movements. The aim of this study was to determine the impact of respiratory gating on procedural parameters in patients undergoing catheter ablation of atrial fibrillation (AF).One-hundred forty consecutive patients undergoing pulmonary vein isolation were admitted to study. Respiratory gating module (AccuResp algorithm, Carto3, Biosense Webster) was enabled in 70 patients and disabled in 70 patients during procedures. Successful pulmonary vein isolation and sinus rhythm were obtained in all patients. A significant reduction in total procedure times [median 77, interquartile range (IQR 66-95) min vs median 82 (IQR 72-104) min, p0.05] and fluoroscopy times [median 14 (IQR 9-17) min vs median 16 (IQR 12-22) min, p0.05] were observed in the respiratory gated group. Although ablation times (duration between the first and last ablation) were significantly shorter in respiratory gated group [median 37 (IQR 32-53) min vs median 48 (IQR 39-65) min, p0.05], total RF application durations were not different between two groups [median 1,554 (IQR 1,213-2,196) s vs median 1,802 (IQR 1,344-2,448) s, p = 0.11]. Difference in electroanatomical map reconstruction times was not significant [median 14 (IQR 12-16) min in gated group vs median 13 (IQR 10-18) min in nongated group, p = 0.19].Respiratory gating significantly improves fluoroscopy and ablation times during electroanatomic mapping guided AF ablation. Respiratory gated maps may provide uninterrupted continuous ablation applications. Furthermore, using automatic respiratory gating module does not prolong mapping times.

Brugada syndrome is associated with a high risk of sudden cardiac death. Currently, the cornerstone of therapy is implantation of an implantable cardioverter defibrillator (ICD). Recently, a novel approach to preventively ablate the substrate located in the anterior epicardial region of the right ventricular outflow tract showed promising results by reducing the number of ventricular fibrillation episodes in patients with ICD. Here we report on a patient with Brugada syndrome who refused ICD therapy in whom a successful epicardial right ventricular outflow tract substrate ablation was performed. In some special cases, ablation therapy might be considered as the sole therapeutic option for these patients.

Pace-mapping is an important tool during the ablation of premature ventricular complexes (PVCs) or ventricular tachycardia. The automated pace mapping system software (PaSo module, CARTO XP v9, Biosense/Webster) allows direct comparisons between paced ECGs and the acquired PVC ECG during ablation in a reasonable time. We report our experience with the automated pace mapping system during the ablation of PVCs in the left ventricular outflow tract (LVOT). A 67-year-old male patient was referred to our Department because of recurrent resting atypical chest pain. A 12 lead ECG showed frequent PVCs with LVOT morphology and a 24-hour Holter ECG revealed, that 31% of the total beats were monomorphic PVCs. We decided to perform a radiofrequency catheter ablation. After recording an electroanatomic and an activation map during PVCs, pace-mapping was performed with the PaSo module of the CARTO system. The best percent match area (89.0%) was found in the LVOT, where we performed multiple ablations and PVCs disappeared. According to our initial experience, automated pace-mapping systems might be useful during ablation of PVCs or ventricular tachycardias. Appropriate use of the software allows more objective and faster comparisons compared with conventional manual techniques.

A 47-year-old woman underwent bilateral lung transplantation for pulmonary fibrosis in June of 2013. The early postoperative period was complicated by continuous atrial arrhythmias that proved unresponsive to antiarrhythmic agents (propafenon and bisoprolol). Therefore, in February 2014, we performed an electrophysiological study after adequate antibiotic and antimycotic prophylaxis. During the procedure, the clinical tachycardia was easily inducible with burst atrial pacing and programmed atrial extrastimuli. Tachycardia cycle length varied between 380 ms and 420 ms, and A-A-V response after ventricular burst pacing suggested atrial tachycardia. Entrainment mapping from the area of early activation failed to demonstrate reentry as the underlying mechanism of the tachycardia, thus ectopic atrial tachycardia was diagnosed. Electroanatomical mapping was performed with ENSITE NavX system (Endocardial Solutions Inc.) during ongoing arrhythmia (Figure ​(Figure1).1). Activation map showed that earliest activation was in the right atrium, corresponding to a scar of the extracorporeal membrane oxigenator (ECMO) cannula during lung transplantation. To avoid paralysis of the diaphragm, we paced the high right atrial region with high energy to demonstrate and mark the location of right phrenic nerve. Subsequently, we performed RF ablation with 3.5 mm irrigated tip catheter (AlCath Flux Blue G eXtra) using 40 W energy and 43°C temperature limit. After the application of one RF ablation at the site of earliest activation (ablation time 46 seconds), the arrhythmia stopped immediately and was no longer inducible even after administration of isoproterenol. The total procedure time was 75 minutes with a fluoroscopy time of 2.3 minutes. No procedural complications occurred. Outpatient visits and 24-hour Holter electrocardiogram monitoring were scheduled every 3 months. The patient was free of symptoms and arrhythmia episodes without any antiarrhythmic medication during the 9-month follow-up period. FIGURE 1 Left side: 12 lead surface electrocardiogram (paper speed 100 mm/sec) and intracardiac electrocardiogram (ablation catheter and coronary sinus catheter) during ongoing arrhythmia. Cycle length is changing from beat to beat. The local activation recorded ... Atrial tachyarrhythmias are frequent after lung transplantation but the incidence of right atrial tachycardia is very low. Most commonly atrial fibrillation is observed in the early postoperative period and left atrial tachycardia occurs later in time.1-4 Right atrial tachycardia might also be associated to the operation, during which an ECMO is implanted with cannulation of the right atrium and aorta. Damaging the anterior part of the high right atrium during this step might be the ground of arrhythmia substrate formation. To the best of our knowledge, our case represents the first successful ablation of right atrial tachycardia after lung transplantation due to scarring of a passagere cannula of ECMO. Ablation of typical right atrial flutter and left atrial tachycardias originating from the donor pulmonary veins has been reported previously.1-4 Atrial ablation in lung transplant recipients is rarely performed, in contrast to heart transplant recipients, where ablation of atrial arrhythmias has repeatedly been reported and arrhythmias are dominantly originating from the right atrium.5