Dysregulation of mannose-6-phosphate-dependent cholesterol homeostasis in acinar cells mediates pancreatitis.

Disordered lysosomal/autophagy pathways initiate and drive pancreatitis, but the underlying mechanisms and links to disease pathology are poorly understood. Here, we show that the mannose-6-phosphate (M6P) pathway of hydrolase delivery to lysosomes critically regulates pancreatic acinar cell cholesterol metabolism. Ablation of the Gnptab gene encoding a key enzyme in the M6P pathway disrupted acinar cell cholesterol turnover, causing accumulation of nonesterified cholesterol in lysosomes/autolysosomes, its depletion in the plasma membrane, and upregulation of cholesterol synthesis and uptake. We found similar dysregulation of acinar cell cholesterol, and a decrease in GNPTAB levels, in both WT experimental pancreatitis and human disease. The mechanisms mediating pancreatic cholesterol dyshomeostasis in Gnptab-/- and experimental models involve a disordered endolysosomal system, resulting in impaired cholesterol transport through lysosomes and blockage of autophagic flux. By contrast, in Gnptab-/- liver the endolysosomal system and cholesterol homeostasis were largely unaffected. Gnptab-/- mice developed spontaneous pancreatitis. Normalization of cholesterol metabolism by pharmacologic means alleviated responses of experimental pancreatitis, particularly trypsinogen activation, the disease hallmark. The results reveal the essential role of the M6P pathway in maintaining exocrine pancreas homeostasis and function, and implicate cholesterol disordering in the pathogenesis of pancreatitis.

A new simplified electrocardiographic score predicts clinical outcome in patients treated with CRT.

Aims: Cardiac Resynchronization Therapy (CRT) reduces morbidity and mortality for patients with heart failure and wide QRS complex, but up to 1/3 of patients are "non-responders" to the therapy. This study examines the ability of a simple standard electrocardiogram (ECG)-based scoring system to predict clinical outcome. Methods and results: Four hundred and ninety-one consecutive patients with CRT-implants (79% males, mean age 71 years, LVEF 24%, 59% with ischemic cardiomyopathy, 83% in NYHA class III) were included from a single large volume centre. All patients met standard indications for CRT, and were followed for 3 years after CRT implantation. Three ECG parameters were measured on the post-implant ECG, and compared to pre-implantation measurements: QRS duration, time to intrinsicoid deflection onset (ID) in V1 lead, amplitude change in V1 lead. Each positive ECG variable was given a numerical value of 1 to create the score (ranging 0-3). Clinical outcome was assessed as a composite of all-cause death, left ventricular assist device implantation, cardiac transplantation and HF hospitalization. Event-free survival was predicted by shortening of QRS duration ≥20 ms (HR 0.66 [95% CI 0.48-0.90] P = 0.009), ≥50% decreased summed R + S amplitude in V1 lead (HR 0.67 [0.49-0.90] P = 0.009) and ≤40 msec ID time in lead V1 during pacing (HR 0.63 [0.46-0.86] P = 0.004). The total score was an independent predictor for both event-free survival (HR 0.65 [0.54-0.77] P < 0.001) and for ≥10% left ventricular ejection fraction improvement (OR 1.7 [1.3-2.3] P < 0.001). Conclusions: Composite data from 12-lead ECG during CRT-treatment can be used in a simple score to predict long-term clinical outcome.

Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal Models.

BACKGROUND & AIMS: Little is known about the signaling pathways that initiate and promote acute pancreatitis (AP). The pathogenesis of AP has been associated with abnormal increases in cytosolic Ca2+, mitochondrial dysfunction, impaired autophagy, and endoplasmic reticulum (ER) stress. We analyzed the mechanisms of these dysfunctions and their relationships, and how these contribute to development of AP in mice and rats. METHODS: Pancreatitis was induced in C57BL/6J mice (control) and mice deficient in peptidylprolyl isomerase D (cyclophilin D, encoded by Ppid) by administration of L-arginine (also in rats), caerulein, bile acid, or an AP-inducing diet. Parameters of pancreatitis, mitochondrial function, autophagy, ER stress, and lipid metabolism were measured in pancreatic tissue, acinar cells, and isolated mitochondria. Some mice with AP were given trehalose to enhance autophagic efficiency. Human pancreatitis tissues were analyzed by immunofluorescence. RESULTS: Mitochondrial dysfunction in pancreas of mice with AP was induced by either mitochondrial Ca2+ overload or through a Ca2+ overload-independent pathway that involved reduced activity of ATP synthase (80% inhibition in pancreatic mitochondria isolated from rats or mice given L-arginine). Both pathways were mediated by cyclophilin D and led to mitochondrial depolarization and fragmentation. Mitochondrial dysfunction caused pancreatic ER stress, impaired autophagy, and deregulation of lipid metabolism. These pathologic responses were abrogated in cyclophilin D-knockout mice. Administration of trehalose largely prevented trypsinogen activation, necrosis, and other parameters of pancreatic injury in mice with L-arginine AP. Tissues from patients with pancreatitis had markers of mitochondrial damage and impaired autophagy, compared with normal pancreas. CONCLUSIONS: In different animal models, we find a central role for mitochondrial dysfunction, and for impaired autophagy as its principal downstream effector, in development of AP. In particular, the pathway involving enhanced interaction of cyclophilin D with ATP synthase mediates L-arginine-induced pancreatitis, a model of severe AP the pathogenesis of which has remained unknown. Strategies to restore mitochondrial and/or autophagic function might be developed for treatment of AP.

Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy.

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 (<4% increase in LVEF) after six months. RESULTS: From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p = 0.01, NT-proBNP: p = 0.13) and by logistic regression (CT-apelin: p = 0.01, NT-proBNP: p = 0.41) analyses. CONCLUSION: Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.

T-wave area as biomarker of clinical response to cardiac resynchronization therapy.

AIMS: There is increasing evidence that left bundle branch block (LBBB) morphology on the electrocardiogram is a positive predictor for response to cardiac resynchronization therapy (CRT). We previously demonstrated that the vectorcardiography (VCG)-derived T-wave area predicts echocardiographic CRT response in LBBB patients. In the present study, we investigate whether the T-wave area also predicts long-term clinical outcome to CRT. METHODS AND RESULTS: This is a retrospective study consisting of 335 CRT recipients. Primary endpoint were the composite of heart failure (HF) hospitalization, heart transplantation, left ventricular assist device implantation or death during a 3-year follow-up period. HF hospitalization and death alone were secondary endpoints. The patient subgroup with a large T-wave area and LBBB 36% reached the primary endpoint, which was considerably less (P < 0.01) than for patients with LBBB and a small T-wave area or non-LBBB patients with a small or large T-wave area (48, 57, and 51%, respectively). Similar differences were observed for the secondary endpoints, HF hospitalization (31 vs. 51, 51, and 38%, respectively, P < 0.01) and death (19 vs. 42, 34, and 42%, respectively, P < 0.01). In multivariate analysis, a large T-wave area and LBBB were the only independent predictors of the combined endpoint besides high creatinine levels and use of diuretics. CONCLUSION: T-wave area may be useful as an additional biomarker to stratify CRT candidates and improve selection of those most likely to benefit from CRT. A large T-wave area may derive its predictive value from reflecting good intrinsic myocardial properties and a substrate for CRT.

Anemia and its association with clinical outcome in heart failure patients undergoing cardiac resynchronization therapy.

PURPOSE: Although a substantial proportion of patients with heart failure (HF) have anemia, there is a paucity of data evaluating the impact of anemia on clinical outcome in CRT patients. Our goal was to examine the ability of baseline hemoglobin (Hb) level and change in Hb level over time to predict clinical 2-year outcome and echocardiographic response to CRT. METHODS: Three hundred consecutive CRT patients (median 72 years [interquartile range (IQR) 16 years], 19% female) with baseline and follow-up hematological profiles available were examined. Baseline anemia was defined as Hb <12 g/dL in women and <13 g/dL in men, and patients were grouped into equal quartiles based on change in Hb. Two-year clinical outcome was determined using a composite endpoint that included HF hospitalization, left ventricular assist device (LVAD) placement, heart transplantation, and all-cause mortality. Echocardiographic reverse remodeling was examined at 6-month follow-up. RESULTS: One hundred fifty-one anemic patients were compared to 149 non-anemic patients. Changes in left ventricular dimensions and ejection fraction were similar for both groups. Univariate predictors of 2-year clinical outcome included baseline creatinine level, diuretic usage, and anemia; in multivariable regression, baseline anemia was an independent predictor for outcome (hazard ratio [HR] 1.79, 95% confidence interval [CI] [1.22-2.63], p = 0.003). The quartile with the most negative change in Hb concentration over time (≤-1.00 g/dL) had poorer event-free 2-year survival (HR 1.84, CI [1.13-3.00], p = 0.014). CONCLUSIONS: Baseline anemia and early postimplantation decline in Hb levels are associated with a worse 2-year prognosis in CRT patients, even though the magnitude of left ventricular reverse remodeling is similar compared to non-anemic patients.

Prognostic implication of baseline PR interval in cardiac resynchronization therapy recipients.

BACKGROUND: Prolongation of the baseline ECG PR interval is frequently encountered among cardiac resynchronization therapy (CRT) recipients. There are conflicting data regarding the association of a prolonged PR interval with long-term clinical outcome in this patient group. OBJECTIVE: The purpose of this study was to compare clinical outcomes and response to CRT in patients with normal (<200 ms) vs prolonged (≥200 ms) baseline PR interval. METHODS: In this study, 283 patients (normal PR interval: n = 158; prolonged PR interval: n = 125) with documented baseline intrinsic PR interval were followed for 3 years after CRT implantation. The study population consisted of 24.7% women (mean age 66 ± 13 years, left ventricular ejection fraction 24% ± 7%). RESULTS: A Cox proportional hazard model identified baseline PR interval as a predictor of the composite end-point (all-cause mortality, heart failure hospitalization, left ventricular assist device implantation, and heart transplantation) in univariate analysis (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17, P = .04) but not in multivariate analysis. It also predicted heart failure hospitalization in univariate (HR 1.6, 95% CI 1.1-2.4, P = .02) and multivariate analysis (HR 1.6, 95% CI 1.0-2.3, P = .03). A prolonged PR interval was associated with lower probability of reverse remodeling defined as ≥10% improvement in ejection fraction (64% vs 77%, P = .057), especially in patients with non-left bundle branch block ECG morphology (41% vs 68%, P = .03). CONCLUSION: Among patients with CRT, a prolonged baseline PR interval is an independent predictor of worse prognosis and lower probability of reverse remodeling, especially for patients with non-left bundle branch block morphology on ECG.

Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy.

Hypothyroidism is associated with an adverse prognosis in cardiac patients in general and in particular in patients with heart failure (HF). The aim of this study was to evaluate the impact of hypothyroidism on patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of level of control of hypothyroidism on risk of adverse events after CRT implantation was also evaluated. We included consecutive patients in whom a CRT device was implanted from April 2004 to April 2010 at our institution with sufficient follow-up data available for analysis; 511 patients were included (age 68.5±12.4 years, women 20.4%); 84 patients with a clinical history of hypothyroidism, on treatment with thyroid hormone repletion or serum thyroid-stimulating hormone level≥5.00 µU/ml, were included in the hypothyroid group. The patients were followed for up to 3 years after implant for a composite end point of hospitalization for HF, left ventricular assist device placement, or heart transplant and cardiac death; 215 composite end point events were noted in this period. In a multivariate model, hypothyroidism (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.027 to 2.085, p=0.035), female gender (HR 0.64, 95% CI 0.428 to 0.963, p=0.032), and creatinine (HR 1.26, 95% CI 1.145 to 1.382, p<0.001) were significantly associated with occurrence of the composite end point; 53.6% of patients with hypothyroidism at baseline developed the composite end point compared with 39.8% of those with euthyroidism (p=0.02). In conclusion, hypothyroidism is associated with a worse prognosis after CRT implantation.

New insights into the methodology of L-arginine-induced acute pancreatitis.

Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5-30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h., In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L-arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5-8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice.

T-wave area predicts response to cardiac resynchronization therapy in patients with left bundle branch block.

INTRODUCTION: Chronic heart failure patients with a left ventricular (LV) conduction delay, mostly due to left bundle branch block (LBBB), generally derive benefit from cardiac resynchronization therapy (CRT). However, 30-50% of patients do not show a clear response to CRT. We investigated whether T-wave analysis of the ECG can improve patient selection. METHODS AND RESULTS: The study population comprised 244 CRT recipients with baseline 12-lead electrocardiogram recordings. Echocardiographic response after 6-month CRT was defined as a ≥5% increase in LV ejection fraction (LVEF). Vectorcardiograms (VCGs) were constructed from the measured 12-lead ECGs using an adapted Kors algorithm on digitized ECGs. Logistic regression models indicated repolarization variables as good predictors of CRT response. The VCG-derived T-wave area predicted CRT response (odds ratio [OR] per 10 µVs increase 1.172 [P < 0.001]) even better than QRS-wave area (OR = 1.116 [P = 0.001]). T-wave area had especially predictive value in the LBBB patient group (OR = 2.77 in LBBB vs. 1.09 in non-LBBB). This predictive value persisted after adjustment of multiple covariates, such as gender, ischemia, age, hypertension, coronary artery bypass graft, and the usage of diuretics and ß-blockers. In LBBB patients, the increase in LVEF was 6.1 ± 9.7% and 11.3 ± 9.1% in patients with T-wave area below and above the median value, respectively (P < 0.01). CONCLUSION: In patients with LBBB morphology of the QRS complex, a larger baseline T-wave area is an important independent predictor of LVEF increase following CRT.

Usefulness of hyponatremia as a predictor for adverse events in patients with heart failure receiving cardiac resynchronization therapy.

Hyponatremia portends a poor prognosis in patients with heart failure (HF). The aim of this study was to evaluate prognostic implication of hyponatremia on adverse events in patients with HF receiving cardiac resynchronization therapy (CRT). Additionally, the impact of improvement of hyponatremia after CRT device implantation was also evaluated. In this retrospective analysis, we included patients in whom a CRT device was implanted between April 2004 and April 2010 at our institution and had a baseline sodium level obtained within 72 hours of implantation. The patients were followed up for 3 years after implantation for subsequent primary composite end points, that is, hospitalization for HF, left ventricular assist device or heart transplant, and all-cause death. Sodium levels were followed up at 3 to 6 months after device implantation. Hyponatremia was defined as a serum sodium level of <135 mmol/L. A total of 402 patients were included (age 68.7 ± 12.3 years, women 20.9%). One hundred seventy-nine adverse events were noted in this period. In a Cox proportional hazards univariate model, hyponatremia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.113 to 2.131, p = 0.009), creatinine (HR 1.267, 95% CI 1.156 to 1.389, p <0.001), and diuretics (HR 2.652, 95% CI 1.401 to 5.019, p = 0.003) were associated with occurrence of the composite end point. A total of 57.9% of patients with hyponatremia at baseline had the composite end point compared with 40.7% of those with normal sodium concentration (p = 0.004). Kaplan-Meier curve showed that hyponatremic patients fared worse. Also, patients in whom hyponatremia resolved after CRT device implantation had lower incidence of the composite end point compared with patients who had normal pre-CRT sodium levels but developed hyponatremia later. In conclusion, baseline hyponatremia is associated with poor prognosis in patients with HF. CRT can resolve hyponatremia in some patients after device implantation. Patients with postimplantation hyponatremia (either newly developed or persistent from baseline) have a poor clinical outcome. Post-CRT improvement of hyponatremia is associated with improved clinical outcomes.

Device-measured physical activity versus six-minute walk test as a predictor of reverse remodeling and outcome after cardiac resynchronization therapy for heart failure.

Implanted devices can provide objective assessment of physical activity over prolonged periods. The purpose of this study was to investigate the prognostic value of device-measured physical activity data compared with a six-minute walk test (6MWT) in predicting clinical response to cardiac resynchronization therapy (CRT). This was a single-center study in which patients who underwent CRT for standard indications were evaluated. Daily physical activity and 6MWT were evaluated postimplant at 1, 3, and 6 months. The primary end point was a composite of heart failure hospitalization, transplant, left ventricular (LV) assist device, and all-cause death at 3 years. Echocardiographic response, defined as a ≥10% improvement in LV ejection fraction (LVEF), at 6 months was the secondary end point. About 164 patients were included: average age was 67.3 ± 12.9 years, 77% were men, baseline LVEF was 25% ± 7%. Kaplan-Meier curves showed superior freedom from the composite end point in the highest tertile of both 6MWT and physical activity compared with the lowest tertile (41 vs 23 cases, respectively, p <0.001) for 6MWT and for activity (22 vs 7 cases, respectively, p = 0.001). In an adjusted multivariate model, independent predictors of improved clinical outcome included 1-month physical activity (hazard ratio 0.546, 95% confidence interval [CI] 0.361 to 0.824, p = 0.004) and 6MWT (hazard ratio 0.581, 95% CI 0.425 to 0.795, p = 0.001). An additional hour of higher activity at 1 month translated to a 1.38 times (95% CI 1.075 to 1.753, p = 0.011) higher likelihood of improved echocardiographic response. In conclusion, device-based measures of physical activity may be useful in predicting echocardiographic reverse remodeling and long-term clinical outcome in patients receiving CRT.

High-volume lesions using a new second-generation open irrigation radiofrequency catheter are associated with the development of inhomogeneous lesions.

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.

Recent advances in the investigation of pancreatic inflammation induced by large doses of basic amino acids in rodents.

It has been known for approximately 30 years that large doses of the semi-essential basic amino acid L-arginine induce severe pancreatic inflammation in rats. Recently, it has been demonstrated that L-arginine can also induce pancreatitis in mice. Moreover, other basic amino acids like L-ornithine and L-lysine can cause exocrine pancreatic damage without affecting the endocrine parenchyma and the ducts in rats. The utilization of these noninvasive severe basic amino acid-induced pancreatitis models is becoming increasingly popular and appreciated as these models nicely reproduce most laboratory and morphological features of human pancreatitis. Consequently, the investigation of basic amino acid-induced pancreatitis may offer us a better understanding of the pathogenesis and possible treatment options of the human disease.

The role of ablation of the atrioventricular junction in patients with heart failure and atrial fibrillation.

Ablation of the atrioventricular junction (AVJ) is a technically easy procedure that is safe and has a high success rate as an intervention for effective ventricular rate control in patients in symptomatic atrial fibrillation. AVJ ablation has been reported to improve quality of life, left ventricular ejection fraction, and exercise duration in these patients and minimize the incidence of inappropriate shocks. Because right ventricular pacing after AVJ ablation may result in decrease in left ventricular function and worsening of heart failure symptoms, there is increasing evidence to support the effectiveness of cardiac resynchronization therapy in atrial fibrillation populations.

Radiofrequency ablation at low irrigation flow rates using a novel 12-hole gold open-irrigation catheter.

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°C vs 48.0 ± 4.8°C, P < 0.0001; 15 mL/min: 36.0 ± 1.5°C vs 46.9 ± 5.4°C, P < 0.0001) 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. 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.

[Electroanatomical mapping and radiofrequency ablation of tachycardia originating in pulmonary vein in an adult patient]. / Fiatalkori vena pulmonalis tachycardia ablatiója elektroanatómiai térképezés segítségével.

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.

Long-term experience with coronary sinus side branch stenting to stabilize left ventricular electrode position.

BACKGROUND: Despite technical advancements, implantation of coronary sinus (CS) leads may be challenging, and dislocation remains a relevant clinical problem. OBJECTIVE: The aim of this study was to investigate the effectiveness, safety, and long-term outcome of stent implantation to anchor the lead to the wall of the CS side branch. METHODS: Stenting of a CS side branch was performed in 312 patients. The procedure was performed because of postoperative lead dislocation in 16 patients and because of an intraoperative unstable lead position or phrenic nerve stimulation in 296 cases. A bare metal coronary stent was introduced over a second guide wire in the same CS sheath. The stent was deposited 5-35 mm proximal to the most proximal electrode. Mechanical damage of the CS side branch or pericardial effusion was not observed owing to stenting. RESULTS: During follow-up (median 28.4, interquartile range 15-37, maximum 70 months), a clinically important increase in the left ventricular pacing threshold was found in four cases and reoperation was necessary in only two patients (0.6%). Phrenic nerve stimulation was observed in 18 instances, and repositioning with an ablation catheter was performed in seven cases. Impedance measurements did not suggest lead insulation failure. Three stented leads were extracted without complication after 3-49 months owing to infection, while four leads were extracted easily during heart transplantation after 7-27 months. CONCLUSION: Stent implantation to stabilize CS lead position seems to be an effective and safe procedure in prevention and treatment of CS lead dislocation in selected cases.