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Congenital anomalies of the venous system are a challenge for cardiac catheterization and radiofrequency ablation. This article describes ablation of atrioventricular nodal re-entrant tachycardia performed solely through the azygos continuation in a patient with inferior vena cava interruption.

The significance of atrial fibrillation is increasing, and also the impact of atrial fibrillation (AF) ablation procedures. After any ablation method, the chance to develop other atrial tachyarrhythmias is between 3 and 50 %. In this chapter the different AF ablation techniques, the pathophysiology of the atrial tachycardias, those diagnostic steps, and therapeutic possibilities are reviewed.

Introduction: Transvenous left ventricular (LV) lead positioning via the coronary sinus (CS) sidebranches might be challenging or in some instances impossible, in these cases alternative methods would be preferable. The aim of this study was to investigate the effectiveness and safety of transseptal endocardial left ventricular lead implantation (TELVLI) in severe heart failure patients, and evaluate the long term follow ups of the patients. Objectives: TELVLI was performed in 28 patients (24 men, 61±7 years, NYHA III-IV stage). Methods: Transseptal (TS) puncture was performed via the femoral vein. Intracardiac ulrasound was used to guide the puncture in 21 pts. The site of the puncture was dilated with a 6mm (3 pts), later with an 8 mm balloon (25 pts). After the puncture of the left subclavian vein, an electrophysiological deflectable CS catheter was introduced into the CS sheath. The CS catheter was used to reach the left atrium and the left ventricle through the dilated transseptal puncture hole. In four cases CARTO system was used to find the site of the latest activation, in the other cases right and left ventricular (RV-LV) signals were evaluated and the latest RV-LV delay was determined as latest activation. At the latest LV activation site 65 cm active fixation bipolar lead was screwed into the LV wall. Results: The lead was fixed in the left ventricle in all cases with good pacing threshold values (0,82±0,4 V; 0,4 ms). Puncture complication, pericardial effusion was not observed. Because of intraoperatively started anticoagulation therapy, pocket haematoma was observed postoperatively in three (11%) and needed surgical evacuation in one case (4%). Follow-up is longer than one month in all patients (21±13 months). Significant improvement of the NYHA class was observed in all but one case (96%), on the first month control LV EF was 29±7% vs 36±7%. Early lead dislocation was noticed in three cases (10%), reposition was performed using the original puncture site in two patients, and transvenous implantation was succesfully carried out in the other case. Explantation of the system was necessary because of pocket infection in four cases (14%), in two of these cases TELVLI was carried out succesfully 3 months later. All patients were maintained on anticoagulation therapy either with warfarine or cumarine with INR between 2-3. No thromboembolic complication was noticed during the follow up. Conclusions: TELVLI approach might be an alternative of the surgical epicardial procedure, if transvenous implantation could not be applied, however more evidences and studies are needed to evaluate this method.

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.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.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.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.

Dual ventricular response to a single supraventricular impulse through dual atrioventricular (AV) nodal pathways is an interesting and uncommon phenomenon. Rarely, some patients can exhibit sustained one-to-two conduction producing a non-reentrant AV nodal tachycardia during sinus rhythm [1–6]. We report the case of a patient whose arrhythmia was caused by this mechanism. A 44-years-old male patient who had frequent irregular palpitations was admitted to hospital. He was misdiagnosed with atrial fibrillation and referred to our institute for consideration of pulmonary vein isolation. He did not have any significant disease in his medical history. Echocardiography was normal. The electrocardiogram showed an irregular narrow QRS complex tachycardia. Careful evaluation of the electrocardiograms revealed the presence of two ventricular activations for each atrial beat (Fig. 1). On some occasions, the wide QRS complexes with right bundle branch block (RBBB) morphology not preceded by P waves simulating premature ventricular complexes (PVCs) were observed. Electrophysiological study revealed regular 1:2 AV relationship. Each ventricular signal was preceded by a His deflection with a constant HV interval (46 ms) (Fig. 2a). The AH1 interval between the atrial wave and the first His deflection was 159 ms. The AH2 interval between the atrial wave and the second His deflection was 528 ms. Both AH1 and AH2 intervals were slightly variable. When AH2 interval was shorter than 520 ms, second ventricular responses were conducted by RBBB morphology (Fig. 2a). Because of sustained double responses, we could not perform programmed atrial extra stimulation to identify a jump in AH interval. After detailed electrophysiological examination, radiofrequency (RF) energy was delivered (40 W, 55 C, 66 s) in the posterior aspect of Koch’s triangle, where the typical ‘‘slow pathway potentials’’ were observed. After first RF application, 1:2 response disappeared (Fig. 2b). During post-ablation tests, we did not observe dual AV nodal conduction properties, and we could not induce any arrhythmia. On the 6 month follow-up, the patient was asymptomatic. Non-reentrant AV nodal tachycardia (1:2 tachycardia) is a rare manifestation of dual AV nodal physiology. Persistent simultaneous conduction of P waves over a fast and a slow nodal pathways may lead irregular supraventricular tachycardia. The two major electrophysiological properties of simultaneous anterograde fast and slow conduction during sinus rhythm are: (1) Absence of retrograde ventriculoatrial conduction via fast and slow pathways and (2) Critical conduction delay in slow pathway to allow sequential conduction of impulse from both pathways [1, 2]. Delay has to be longer than the effective refractory period of infranodal conduction system. A recently published review reported just 49 cases between dates of 1950 and 2011 [3]. Nevertheless, the prevalence of AV nodal non-reentrant tachycardia is likely to be underestimated because of difficulties in differential diagnosis. Sustained cycle length alternans is the characteristic for this arrhythmia [4]. However, changes in autonomic tone affecting conduction properties may lead irregular cycle length alternans and rate-dependent aberrancy. For these reasons, it can be erroneously diagnosed as atrial fibrillation, atrial flutter or atrial tachycardia with Wenckebach periodicity [3, 5, 7, 8]. These arrhythmias, E. E. Ozcan G. Szeplaki B. Merkely L. Geller (&) Heart Center, Semmelweis University, Gaal Jozsef street 9, Budapest 1122, Hungary e-mail: laszlo.geller@gmail.com

Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsing-remitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine-1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.

Predicting the prognosis of comatose, post-cardiac-arrest patients is a complex problem in clinical practice. There are several established methods to foretell neurological outcome; however, further prognostic markers are needed. HSP70 (HSPA1A), which increases rapidly in response to severe stress (among others after ischemic or hypoxic events), is a biomarker of cell damage in the ischemic brain and spinal cord. We hypothesized that HSP70 might be a reliable predictor of mortality in post-cardiac-arrest patients. The aim of this study was to analyze the role of extracellular HSP70 in the systemic inflammatory response over time, as well as the predictive value in cardiac arrest patients. Here, we show that the elevation of HSP70 levels in resuscitated patients and their persistence is an independent predictor of 30-day mortality after a cardiac arrest. Forty-six cardiac arrest patients were successfully cooled to 32–34 °C for 24 h, and followed up for 30 days. Twenty-four patients (52.2 %) were alive by the end of follow-up, and 22 patients (47.8 %) died. Forty-six patients with stable cardiovascular disease served as controls. Extracellular HSP70 (measured by ELISA in blood samples) was elevated in all resuscitated patients (1.31 [0.76–2.73] and 1.70 [1.20–2.37] ng/ml for survivors and non-survivors, respectively), compared with the controls (0.59 [0.44–0.83] ng/ml). HSP70 level decreased significantly in survivors, but persisted in non-survivors, and predicted 30-day mortality regardless of age, sex, complications, and the APACHE II score. Extracellular HSP70 could prove useful for estimating prognosis in comatose post-cardiac-arrest patients.

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.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 SECO, 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.Electrode temperatures were lower for Au compared to PtIr in parallel (8 mL/min: 38.1 ± 1.7°C vs 48.0 ± 4.8°C, P0.0001; 15 mL/min: 36.0 ± 1.5°C vs 46.9 ± 5.4°C, P0.0001) and perpendicular position (15 mL/min: 35.5 ± 1.2°C vs 38.4 ± 2.5°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 mm(3) vs 504 ± 212 mm(3) , P = 0.004); however, for 15 mL/min, volumes were comparable (624 ± 269 mm(3) vs 768 ± 466 mm(3) , P = 0.46). No coagulum formation was observed for any of the catheters on the surface and catheter tip.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.

Aim Failure rate to implant left ventricular (LV) lead transvenously is 4-8% in cardiac resynchronization therapy (CRT) patients. Epicardial lead placement is an alternative method and if not applicable case reports and small series showed the feasibility of endocardial LV lead implantation. Electroanatomical mapping might be a useful tool to guide this procedure. Methods and results Four patients had undergone endocardial LV lead implantation after unsuccessful transvenous implantation or epicardial LV lead dysfunction using the transseptal approach. Electroanatomical mapping was used to mark the location of the transseptal puncture. This location point guided the mapping catheter from the subclavian access and facilitated positioning of the LV lead at the adjacent latest activation area of the left ventricle detected by activation mapping. Endocardial active fixation LV leads were successfully implanted in all patients with stable electrical parameters immediately after implantation and over a mean follow-up of 18.3 months (lead impedance 520 ± 177 vs. 439 ± 119 Ω and pacing threshold 0.8 ± 0.2 V, 0.5 ms vs. 0.6 ± 0.1 V, 0.5 ms, respectively). Patients were maintained on anticoagulation therapy with a target international normalized ratio of 3.5-4.5 and did not show any thromboembolic, haemorrhagic events, or infection. Echocardiography showed significant improvement of LV systolic function with marked improvement of the functional status. Conclusions Electroanatomical mapping is a useful technical tool to guide endocardial LV lead implantation. It helps to identify the location of the transseptal puncture and the use of activation mapping might facilitate location of the optimal lead positions during CRT.

A 29-year-old male was admitted to our outpatient clinic because of palpitation and documented narrow QRS arrhythmia. Based on the ECG, supraventricular tachycardia was diagnosed, electrophysiological examination was indicated and ablation therapy was recommended. During positioning of the catheter the patient developed arrhythmia. On the coronary sinus catheter the activation spread from distal to proximal electrodes, suggesting left atrial origin. During atrial entrainment pacing long return cycle was observed and distal coronary sinus pacing resulted in a 15 ms longer cycle length than the arrhythmia. Therefore, the left atrial origin of the arrhythmia was confirmed and double transseptal puncture was performed. Lasso and irrigated tip catheter were introduced into the left atrium and electroanatomical mapping was performed with CARTO3 system. After electroanatomical mapping the origin of tachycardia was located proximally in the left superior pulmonary vein. Ablation was started at the earliest activation point, where acceleration was observed and the arrhythmia stopped after the first ablation. Pulmonary vein isolation was completed, and bidirectional block could be confirmed. After 30 minutes the arrhythmia was not inducible. During follow-up, Holter-examination was negative and the patient remained asymptomatic. The pulmonary vein tachycardia is a supraventricular arrhythmia that can occur at any age, but the diagnosis based on the ECG is not always simple. Detailed electroanatomical mapping is very important in the diagnosis of this type of arrhythmia, although it can be verified with conventional electrophysiological methods as well. Focal ablation may be a therapeutic option; however, total isolation of pulmonary veins can be more effective. Orv. Hetil., 2011, 152, 1374–1378.

In the first part of the review article authors summarize our knowledge on the role of complement in atherogenesis and the development of I/R injury as well as the complement activation products which contribute to these pathological processes. In the second part of the review authors highlight the complement dependent processes which participate at the pathomechanism of cerebrovascular diseases, the development of cerebral infarct in ischemic stroke and the restenosis which may occur a part of the patients who underwent eversion endartectomy operation. Literature data and the recently published data of the authors' group indicate that the complement system is strongly activated at the onset of the ischemic stroke and the extent of this activation is positively correlated with the bad outcome of the disease. This observation may be one of the starting points of the introduction of the complement activation-inhibiting therapy in ischemic stroke.

Summary The possibility of simultaneous measurement of the classical pathway (CP), mannan-binding lectin (MBL)–lectin pathway (LP) and alternative pathway (AP) of complement activation by the recently developed Wielisa method allowed us to investigate the in vivo significance of the C1-inhibitor (C1INH) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0·0001) in patients compared with controls. Depressed LP activity was found in patients compared with controls (P = 0·0008) in homozygous carriers of the normal MBL genotype (A/A), but not in carriers of variant genotypes (A/O, O/O). Activity of CP correlated with LP in patients (Spearman's r = 0·64; P

Objective According to data from animal models, complement activation plays a major role in the brain injury after acute ischemic stroke. Scarce findings are, however, available on the detection of complement activation products in stroke patients. Methods We have measured plasma levels of the five complement activation products (C1rC1sC1inh, C4d, C3a, C5a and SC5b-9) in samples of 26 patients with ischemic stroke upon admission. Twenty-six patients with severe carotid atherosclerosis served as patient controls. Results Levels of two activation products (SC5b-9 and C4d)) were significantly elevated in the plasma of stroke patients, SC5b-9 levels, exhibited significant positive correlation with the clinical severity of stroke, the severity of neurological deficit, as well as with the level of functional disability. Conclusion These findings suggest that complement activation plays an active role in the development of brain infarct. The measurement of complement activation products might help to determine the clinical prognosis after acute ischemic stroke. Furthermore, there is potential usefulness of complement modulating therapy in ischemic stroke.

Objective—Homozygotes for the normal (A) allele of mannose-binding lectin (MBL2) gene have higher risks to develop an early restenosis after eversion carotid endarterectomy (CEA). Activation of the lectin pathway is regulated by C1-inhibitor (C1-INH). The objective of the present study was to determine the predictive value of C1-INH in restenosis after CEA.Methods and Results—C1-INH and MBL-associated serine protease-2 (MASP-2) were determined in samples serially taken from 64 patients with CEA, who were followed-up with carotid duplex scan (CDS) examinations for 14 months.MBL2genotypes were also determined. Patients with >50% restenosis had lower C1-INH levels at 6 weeks (P=0.0052) and at 4 days (P=0.0277) postsurgery. C1-INH levels at 6 weeks correlated inversely with the CDS values at 14 months (r=−0.3415,P=0.0058), but only inMBL2A/A homozygotes (r=−0.5044,P=0.0015). Patients with low C1-INH levels (C1-INH MBL2A/A and low C1-INH levels at 6 weeks postsurgery had 13.97 (95% CI:1.95 to 100.21,P=0.0087) times higher risk to develop an early restenosis. Differences in the MASP-2 concentration were not associated with restenosis.Conclusions—Determining C1-INH levels at 6 weeks postsurgery—together with genotyping ofMBL2—might be a useful marker in the identification of patients with high risk for early carotid restenosis.

Acquired angioedema (AAE) due to the functional deficiency of the C1 inhibitor (C1-INH) is a rare disease characterized by recurrent bouts of edema that involve subcutaneous tissues, the larynx or the gastrointestinal tract. In the present paper, we report the case of a male patient with symptoms of AAE and recurrent deep venous and arterial thrombosis. As a trigger of AAE in the present patient, we revealed primary antiphospholipid syndrome accompanied by antithrombin III deficiency, along with malignancy in the history, and angiotensin-converting enzyme inhibitor therapy. Although anti-C1-INH titers (type I AAE) were normal initially, we observed a sharp increase in anti-C1-INH titers (suggestive of type II AAE) during follow-up. It seems that thrombosis might worsen angioedematous attacks in functional C1-INH deficiency. Thrombophilia should be considered a provoking factor of AAE and should be carefully sought for in these patients, as the key to successful management of AAE is the effective treatment of the underlying disease.

Background Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT. Design We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months. Results RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0–12.8) vs. 19.5 (15.0–23.9) %, p

In order to study if in patients with hereditary angioedema (HAE), copy number of the two genes (C4A and C4A) encoded in the central region of main histocompatibility complex (MHC) influences the diagnostically important C4 serum concentration as well as the clinical course of the disease, we determined copy number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and 246 healthy controls. Distribution of both the C4A and C4B copy numbers significantly (p = 0.0183 and 0.0318, respectively) differed between the two groups, the most marked difference we observed was the lower frequency of the high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of both C4A and C4B genes positively correlated to the longitudinally measured serum C4 concentrations. Moreover, we found an unexpected clinical correlation with the dosage of the C4B gene. The course of the disease was milder in the 9/95 patients carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e. diagnosis was established at significantly (p = 0.0052) older age (36.0 (31.0–39.5)) years versus 20.5 (7.5–31.5 years), biyearly attack rate was significantly (p = 0.0145) lower (1.0 (0.0–11.0)) versus 11.0 (3.5–21.5), and the over-all activity of the classical pathway and the enzyme-inhibitor activity of the C1-inhibitor (C1-INH) was closer to the normal values. These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.

SummaryEarly restenosis following carotid endarterectomy (CEA) is an inflammatory process leading to myointimal hyperplasia of smooth muscle cells. The risk for restenosis is increased in homozygous carriers of the normal (A) allele of mannose-binding lectin (MBL2) gene. Our objective was to study the associ-ations of C3 and as control three non-complement acute-phase reactants (APRs) (C-reactive protein, haptoglobin and α2HS-glycoprotein) with early restenosis following CEA.We also considered, whether MBL2 genotype relates to C3 levels and to the risk of restenosis. Concentrations of the APRs were determined by radial immunodiffusion or immunoturbidimetric methods in 64 patients who underwent eversion CEA and were followed up with carotid duplex scan (CDS) examinations for at least one year. MBL2 genotypes were determined by a PCR-SSP method. C3 levels increased during the follow-up and correlated with the percentage of restenosis detected by CDS at 14 months postsurgery, in MBL2 A/A allele carriers. Patients with high C3 levels had nearly five-fold higher odds for the presence of significant restenosis (>50% reduction in diameter) even after adjusting for MBL2 genotype, age and gender. By contrast, no such associations were detected between the non-complement APRs and early restenosis. C3 is associated with and might have a direct role in the development of an early restenosis following CEA, which is partially related to an intact MBL lectin pathway, thus determining C3 levels might have clinical importance. On the other hand, our results indicate that the regulation of C3 differs from non-complement APRs.

Background C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative. Objective To summarize our experience with hC1-INH concentrate in patients with HAE. Methods Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed. Results Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur. Conclusion The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women. Clinical implications Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.

Deep venous thrombosis associated with acquired angioedema type II in a patient heterozygous for the mutation of factor V Leiden: Effective treatment and follow-up for four years

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 (p0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1-INH-Abs can be used as an activity marker in HAE.

Enhanced release of proinflammatory cytokines may contribute to the pathogenesis of stroke. It was examined whether G to A promoter polymorphism in the tumor necrosis factor-alpha gene at position -308 affects the risk of stroke.We genotyped 336 patients with ischemic stroke and 333 healthy controls for this polymorphism. Patients were divided into different groups based on the Oxfordshire Community Stroke Project (OCSP) or a modified TOAST classification. Distribution of the alleles at -308 GA promoter polymorphism was determined by PCR-RLFP method.Patients with ischemic stroke had a significantly (p0.001) decreased (0.115) frequency of the -308 A (TNF2) allele compared to the healthy controls (0.196). When patients were categorized according to the OCSP classification, it turned out that significant (p=0.002) decrease in TNF2 allele frequency (0.065) was restricted to the patients with lacunar infarct (LACI) whereas the frequency of the TNF2 alleles in patients with the other three subtypes (TACI, PACI, and POCI) did not significantly differ from that in healthy controls. Similar results were obtained when the patients were divided according to the modified TOAST classification: the frequencies of the TNF2 allele were 0.068 and 0.140 (p=0.010) in the patients with small-vessel and non-small vessel (large vessel infarction or ischemic stroke of other origin) infarction, respectively. The age-adjusted odds ratio of the patients carrying the TNF2 allele to develop lacunar infarct was 0.33 (0.16-0.68) (p=0.002) compared to the non-carriers. This difference was also restricted to the male patients.Our results suggest that male carriers of TNF2 allele are less susceptible for the development of lacunar subtype of ischemic stroke than the non-carriers.

O ST E R A B ST R A C T S anatomy. In previous studies, respiratory compensated electroanatomical maps showed better correlation with pre-acquired computed tomography and magnetic resonance images. However, better correlation does not always mean better ablation results and impact of respiratory gating on AF ablation hasn’t been studied yet. Objectives: The aim of this study was to determine the impact of respiratory gating on procedural outcome in patients undergoing catheter ablation of AF. Methods: One-hundred-twenty-eight consecutive patients undergoing pulmonary vein isolation were enrolled to study. All procedures were performed with Carto3 system and image integration. Respiratory gating module (Accuresp algorithm, Carto3, Biosense Webster) was enabled in 42 patients and disabled in 85 patients during procedures. Results: A significant reduction in total procedure times [median 72, interquartile range (IQR) 64-95 min vs median 84 (IQR) 71-104 min, p

Purpose: Previous studies on open irrigation radiofrequency (RF) ablation catheters focused on created lesion volumes, and did not evaluate lesion quality. The aim of this study was to evaluate the effect of different irrigation levels on lesion quality and volume. Methods: A canine thigh model was used. A skin incision was made and a cradle was created and filled with blood (37 °C, 250 ml/min). The ablation catheter was positioned parallel or perpendicular to the muscle surface using a constant force of 10 g. RF lesions were created using a gold tip electrode catheter with 12 irrigation holes and a PtIr catheter with 6 irrigation holes (Biotronik, Berlin, Germany). Both catheters were 7F and had a 3.5 mm electrode tip. RF current was delivered for 60 s at either 50 W (n=18) or 30 W (n=39). Temperature probes were inserted immediately below the surface and at 3.5 and 7 mm depth. Histological examination was performed to evaluate lesion size as well as the homogeneity of the RF lesions. Inhomogeneity was defined as a visual observed multi-band lesion pattern indicating different histological characteristics. Electrode temperature and lesion dimensions were measured. Results: Data of 57 lesions, created in a mongrel dog model, were analyzed. A total number of 47 inhomogeneous and 10 homogeneous lesions were detected. Inhomogeneous lesions were deeper (7.5±1.4 vs. 6.3±2.1 mm, p=0.036), however lesion volume was comparable between the two groups (652±487 vs. 834±396, p=0.249). Lesions with inhomogeneous histological characteristics had lower maximum electrode temperatures during ablation (42.9±6.6 vs. 48.2±8.6 °C, p=0.049). The mean temperatures at 3,5 and 7 mm below the muscle surface were lower for inhomogeneous lesions (41.2±8.1 vs. 50.2±21.4 °C, p=0.035; 38.7±4.0 vs. 45.2±19.0 °C, p=0.034). Inhomogeneity of the lesion was not associated with catheter type (p=0.164), orientation (p=0.185), amount of saline infusion (p=0.305) and power output (p=0.213). Conclusions: Our data suggest that lower catheter tip and tissue temperatures are associated with the development of inhomogeneous acute RF lesion formation. The presence of inhomogeneous RF lesions can theoretically be responsible for the differences between acute and chronic ablation success rates.

Background: Prior studies suggested that right to left ventricular interlead sensed electrical delay (RL-IED) is predictive of echocardiographic response to cardiac resynchronization therapy (CRT). There is limited data on the effect of RL-IED on all-cause mortality in patients receiving a CRT device. Methods: We evaluated patients with RL-IED data available measured during the implantation procedure. Data on all-cause mortality was assessed using follow-up data and the Hungarian National Healthcare Fund Death Registry. Kaplan-Meier survival analyses and multivariate Cox proportional hazards regression models were used to analyze mortality in patients stratified by the median RL-IED (106.5 ms). Results: From 2000 to 2011, 494 patients (44%) of 1122 CRT implantation had RL-IED measurements available. Patients with RL-IED >106.5 ms were younger, had wider QRS complexes, less often atrial fibrillation and more dilated left ventricles. Left ventricular ejection fraction was similar in both groups (RL-IED ≤ 106.5 ms 28.1±7.5% vs. RL-IED > 106.5 ms 27.7±6.8%, p>0.5). During the median follow-up of 28 months, 145 (29%) patients died, 80 patients (16%) with RL-IED > 106.5 ms, and 65 patients (13%) with RL-IED ≤ 106.5 ms. RL-IED > 106.5 ms was associated with a significant, 48% risk reduction in all-cause mortality (HR= 0.52, 95% CI: 0.31-0.88, p= 0.01) after adjustment for clinical covariates (Fig. 1). ![Figure][1] Figure 1 Conclusions: In CRT patients, a longer right to left ventricular interlead electrical delay at the time of device implantation is associated with a significant mortality benefit as compared to those with shorter interlead delay. Right to left ventricular interlead electrical delay is an independent predictor of all-cause mortality in CRT patients. [1]: pending:yes