Increase of serum interleukin 6 and interferon γ is associated with the number of impulses in patients with supraventricular arrhythmias treated with radiofrequency catheter ablation.

BACKGROUND: Activation of the immune system plays a pathogenic role in the process of myocardial remodeling in patients with supraventricular arrhythmias. The intensity of this process is associated with the effectiveness of electrical cardioversion and radiofrequency catheter ablation (RFA). The aim of this study was to test the ability of the biochip microarray to detect immune parameters in patients with supraventricular arrhythmias undergoing RFA treatment. METHODS: We used a biochip-based microarray system to determine multiple immune parameters in a group of 35 patients who had undergone RFA for atrioventricular nodal reentry tachycardia (AVNRT), atrial flutter (AFL) and atrial fibrillation (AF). RESULTS: Before the procedure, serum IL-6 and VEGF levels were significantly increased in patients with atrial fibrillation compared to patients with AVNRT (IL-6: 6.4±6.3 ng/L vs. 1.5±0.7 ng/L, P < 0.01; VEGF: 132.4±74 ng/L vs. 88.5±56.4 ng/L, P < 0.01). After the procedure, serum IL-6, VEGF, IFN-γ and MCP-1 levels significantly increased compared to baseline (IL-6: 5.2±4.8 ng/L vs. 2.9±2.1 ng/L, P < 0.01; VEGF: 195.8±160 ng/L vs. 119.8± 110 ng/L, P < 0.05; IFN-γ: 3.1±1.2 ng/L vs. 2.3±0.6 ng/L, P < 0.05; MCP-1: 104.1±84.5 ng/L vs. 54.5±50 ng/L, P < 0.05). Serum IL-6 and IFN-γ were associated with the number of RFA applications (IL-6: r = 0.56, n 33; IFN-γ: r = 0.47, n 33). CONCLUSIONS: This study showed that biochip-based microarray can be useful in the detection of immune activation in patients with arrhythmias and can detect myocardial injury after RF procedures.

Prevalence, kinetic changes and possible reasons of elevated cardiac troponin T in patients with AV nodal re-entrant tachycardia.

BACKGROUND: Elevated cardiac troponin (cTn) has been reported to occur with AVNRT. Little is known about prevalence, kinetic changes, and possible reasons of increased cTn. METHODS: We evaluated 139 consecutive patients presenting with AVNRT to the emergency department between 2006 and 2010. Cardiac troponin T (cTnT) was measured serially at baseline, after three and six hours. Patients were evaluated for the presence of structural heart disease or CAD. Troponin was defined as elevated if a value exceeded the lower limit of detection (10 ng/l) using the fourth generation cTnT, or if the value > 99 th percentile (14 ng/l) using the new highly sensitive cTn assay. RESULTS: A cTnT > LLD (n = 29) or > 99 th percentile (n = 16) was found in 45 patients (32.4%) within the initial six hours after hospitalization. All patients were symptomatic with palpitations, chest discomfort or dyspnea. A complete cardiac evaluation was carried out, including coronary angiography in 32 patients demonstrating an underlying structural heart disease or CAD in 18 cases (56%). Significant CAD was detected in 16 cases. 8 cases required PCI during hospitalization. Elevated cTnT was seen in patients with and without structural heart disease. CONCLUSIONS: AVNRT is a possible reason for elevated cTnT, even in the absence of relevant structural heart disease or CAD.

Markers of myocardial damage, tissue healing, and inflammation after radiofrequency catheter ablation of atrial tachyarrhythmias.

INTRODUCTION: Radiofrequency ablation produces a localized endomyocardial necrosis that may result in release of biochemical markers reflecting myocardial cell damage, inflammation, and tissue reparation. The aim of this study was to determine the extent of rise and time course of markers of inflammation and tissue reparation in patients undergoing radiofrequency catheter ablation. METHODS AND RESULTS: Serial blood samples were taken from patients with AV nodal reentrant tachycardia (n = 5), Wolff-Parkinson-White syndrome (n = 3), and atrial flutter (n = 5) undergoing radiofrequency ablation. Blood was taken before ablation (day 0, baseline) and at day 1 and day 120 after ablation. The proinflammatory marker interleukin-6 (IL-6), troponin I (TNI), and myoglobin, as well as matrix metalloproteinase-9 (MMP-9), a marker for myocardial healing, were measured by enzyme-linked immunosorbent assay. Levels of IL-6, TNI, myoglobin, and MMP-9 were significantly elevated on day 1 after ablation compared to baseline levels. Seven of the 13 patients had troponin levels greater than the threshold of significant myocardial damage (>0.1 ng/mL) on day 1. Plasma levels of MMP-9 were still elevated on day 120 compared to values before ablation (P = 0.021). CONCLUSION: Markers of inflammation, wound healing, and myocardial damage are increased in patients who undergo radiofrequency ablation. Levels of MMP-9, a marker for myocardial healing and repair, are still elevated 120 days after the procedure, suggesting that radiofrequency ablation induces tissue damage leading to a long-term process of reparation.

Endothelial damage and activation of the hemostatic system during radiofrequency catheter isolation of pulmonary veins.

AIMS: To determine the systemic thrombogenic effect of radiofrequency catheter isolation of the pulmonary veins (PVI) in the treatment of atrial fibrillation. METHODS AND RESULTS: We studied endothelial damage marker (von Willebrand factor [vWf]), fibrinolysis markers (tissue plasminogen activator [t-PA], plasminogen activator inhibitor-1 [PAI-1]) and coagulation activation markers (D-dimer [DD]) in 30 patients (pts) undergoing PVI. Heparin was administered continuously after double transseptal puncture in all pts. Concentrations of vWf and t-PA were significantly increased after accomplishing PVI compared to the baseline values, and elevated levels persisted 24 hours later ( p < 0.01). PAI-1 levels decreased following PVI compared to the baseline levels ( p = 0.02). PAI-1 levels normalized 24 hours after the procedure. DD increased continuously during the procedure with the peak following PVI ( p < 0.01). Higher DD concentrations persisted 24 hours later ( p = 0.02). In a multivariate analysis, total procedure time correlated significantly with the peak vWf and DD concentrations, while total RF energy dose correlated only with peak vWf ( r = 0.82). Time to heparin administration correlated with DD levels prior to the first RF pulse ( r = 0.83, p < 0.01) as well as after PVI ( r = 0.75, p < 0.01). A group of patients heparinized within the first hour of the PVI procedure had normal preablation DD levels and significantly mitigated DD levels following PVI compared to the group of patients heparinized later ( p < 0.01). CONCLUSIONS: Pulmonary vein ablations cause an increased systemic procoagulant state as reflected by fibrin turnover, fibrinolysis activation and endothelial perturbation. The activation of the coagulation cascade could be decreased by early heparin administration.

Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways.

Baroreflex gain and coronary sinus norepinephrine and epinephrine levels were measured before and immediately after radiofrequency ablation in the posteroseptal region in 9 patients with atrioventricular nodal reentrant tachycardia or posteroseptal accessory pathways. Arterial baroreflex gain was significantly reduced after radiofrequency ablation (p = 0.046), whereas coronary sinus epinephrine and norepinephrine levels did not change significantly compared with preablation levels.

Does radiofrequency ablation increase creatine kinase and troponin-T?

Radiofrequency ablation produces a focal area of myocardial necrosis. Creatine kinase (total & MB fraction) and troponin-T were analysed in 54 patients who underwent electrophysiological study and radiofrequency ablation for atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia and idiopathic ventricular tachycardia. The age of the patients was 36 +/- 12 years; 17 patients underwent slow pathway modification for atrioventricular nodal reentrant tachycardia, 26 patients underwent accessory pathway ablation and 11 patients underwent ablation for idiopathic ventricular tachycardia. There was no significant rise in creatine kinase, creatine kinase total & MB fraction and troponin-T in the patients who underwent slow pathway ablation for atrioventricular nodal reentrant tachycardia. In patients with atrioventricular reentrant tachycardia, there was no significant rise in creatine kinase and creatine kinase total & MB fraction levels, while troponin-T levels rose from 0.13 +/- 0.06 to 0.29 +/- 0.16 eta g/ml (p < 0.05). There was an increase in creatine kinase, creatine kinase total & MB fraction and troponin-T levels after idiopathic ventricular tachycardia ablation from 68.4 +/- 44.9 to 138.0 +/- 81.7 IU (p < 0.05), 2.77 +/- 3.34 to 25.2 +/- 19.8 IU (p < 0.05) and 0.09 +/- 0.04 to 0.34 +/- 0.08 eta g/ml (p < 0.001) respectively. Radiofrequency ablation of atrioventricular nodal reentrant tachycardia does not cause any significant myocardial damage to raise any cardiac enzymes. Ablation of atrioventricular reentrant tachycardia results in only minor injury causing rise in only troponin-T levels. However, ventricular tachycardia ablation results in significant myocardial injury raising all the cardiac enzymes.

The activation of platelet function, coagulation, and fibrinolysis during radiofrequency catheter ablation in heparinized patients.

INTRODUCTION: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients. METHODS AND RESULTS: We studied the activation of coagulation (prothrombin fragment 1+2 [PF1+2]), platelets (beta-thromboglobulin [beta-TG])) and fibrinolysis (plasmin-antiplasmin complexes [PAP] and D-dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously after the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PF1+2 (r = 0.83, P < 0.001) and (b) the increase of PF1+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PF1+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16), or (c) RF current duration (range 46 to 687 sec). Plasma beta-TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D-dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01, respectively). All parameters were normal the next morning. CONCLUSION: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.

Neurohumoral and hemodynamic mechanisms of diuresis during atrioventricular nodal reentrant tachycardia.

Thirty-two consecutive patients with paroxysmal supraventricular tachycardias, with previously defined mechanisms of the tachycardias, were interviewed by noninvestigators about whether they experienced symptoms of diuresis during or at the termination of the tachycardias, to test the hypothesis that patients with AV nodal reentrant tachycardia would have a feeling of diuresis, polyuria, or both during or at the termination of the tachycardia. Twelve of the 13 patients with AV nodal reentrant tachycardia (92%), two of the 15 patients with AV reentrant tachycardia (13%), and one of the 4 patients with atrial flutter associated with 2:1 AV conduction (25%) felt diuresis during or at the termination of the tachycardias (AV nodal reentrant tachycardia vs other forms of tachycardia; P < 0.001). In 14 of the 32 patients, the right atrial pressure and plasma atrial natriuretic peptide (ANP) concentration were measured during both the tachycardias and sinus rhythm. The mean right atrial pressure during AV nodal reentrant tachycardia was significantly elevated compared to that during other forms of tachycardia (P < 0.01). The plasma ANP concentration during AV nodal reentrant tachycardia was also elevated significantly compared to that during other forms of tachycardias (P < 0.001). There were no significant differences in the cycle lengths of the tachycardias, age, left atrial dimensions, or the left ventricular ejection fraction between the AV nodal reentrant tachycardia and the other forms of tachycardia. We concluded that the feeling of diuresis during or at the termination of tachycardia was a more common symptom in patients with AV nodal reentrant tachycardia. The higher secretion of plasma ANP from the right atrium might be involved in the mechanism of this symptom.

Temperature and impedance monitoring during slow pathway ablation in patients with AV nodal reentrant tachycardia.

INTRODUCTION: Successful radiofrequency ablation of an accessory pathway has been demonstrated to be associated with an electrode-tissue interface temperature of approximately 60 degrees C or an impedance change of -5 to -10 omega. However, the temperature and impedance changes associated with ablation of AV nodal reentrant tachycardia (AVNRT) using the slow pathway approach have not been reported. Therefore, the purpose of this study was to define the temperature and impedance changes achieved during ablation of AVNRT: METHODS AND RESULTS: The study included 35 consecutive patients with AVNRT undergoing radiofrequency ablation of the slow pathway with a fixed power output of 32 W, and using a catheter with a thermistor bead embedded in the distal 4-mm electrode. The procedure was successful in each patient. The steady-state electrode-tissue interface temperature during successful applications of energy was 48.5 +/- 3.3 degrees C (range 42 degrees to 56 degrees C), and the steady-state temperature during ineffective applications was 46.8 degrees +/- 5.5 degrees C (P = 0.03). The mean impedance change during all applications of energy was -1.4 +/- 2.8 omega, and did not differ significantly during effective and ineffective applications. Coagulum formation resulted during five applications (2.7%) in two patients (5.7%). There were no recurrences during 114 +/- 21 days of follow-up. CONCLUSIONS: Successful ablation of AVNRT using fixed power output is achieved at an electrode-tissue interface temperature of approximately 48 degrees C and is associated with a drop in impedance of 1 to 2 omega. These findings suggest that slow pathway ablation requires less heating at the electrode-tissue interface than does accessory pathway or AV junction ablation.

Endogenous adenosine is an antiarrhythmic agent.

BACKGROUND: Adenosine administered intravenously terminates supraventricular tachycardias (SVT) involving the AV node as part of the reentrant circuit. Dipyridamole increases interstitial myocardial levels of this nucleoside. This study was designed to determine whether intravenous dipyridamole increases coronary sinus plasma adenosine concentrations ([Ado]cs) in humans to levels sufficient to alter electrophysiological parameters and terminate SVT. METHODS AND RESULTS: A custom-designed catheter and syringe for sampling blood for measurement of [Ado]cs was placed in the coronary sinuses of 7 patients. [Ado]cs and refractory periods and conduction characteristics of the atrium and AV node were determined after autonomic blockade and dipyridamole infusion (5 micrograms.kg-1.min-1 after a loading dose of 0.56 mg/kg). The atrial effective and functional refractory periods remained unchanged after dipyridamole infusion. In contrast, the AV nodal functional refractory period increased from 350 +/- 32 to 381 +/- 41 milliseconds (P = .03); the Wenckebach cycle length also increased from 309 +/- 47 to 350 +/- 57 milliseconds (P < .0001). Coincident with these changes, [ADO]cs increased from 0.18 +/- 0.11 to 0.31 +/- 0.12 mumol/L (P = .02). In another 10 patients with AV or AV nodal reentrant tachycardia, SVT was induced, and coronary sinus blood samples were drawn. Dipyridamole was infused, and coronary sinus blood samples were obtained after 15 minutes or coincident with termination of SVT. Mean [ADO]cs increased from 0.17 +/- 0.06 mumol/L during SVT to 0.38 +/- 0.21 mumol/L after dipyridamole (P = .02). Mean tachycardia cycle length increased from 334 +/- 132 to 375 +/- 139 milliseconds (P = .02); this effect was confined to the AV node, as demonstrated by an increase in AH interval from 171 +/- 144 to 214 +/- 140 milliseconds (P = .003). SVT terminated with the infusion of dipyridamole in 4 of the 10 patients. CONCLUSIONS: Administration of dipyridamole is associated with elevation of [ADO]cs, with coincident prolongation of the mean Wenckebach cycle length and AV nodal functional refractory period. During SVT, dipyridamole leads to prolongation of the AH interval and tachycardia cycle length and to an increase in [ADO]cs, with termination of SVT in four patients. These results support the hypothesis that adenosine may function as an endogenous antiarrhythmic metabolite.

Clinical experience with propafenone for cardiac arrhythmias in the young.

Seventy-two children were treated with propafenone between 1980 and 1990. The mean age was 34 months (range 0-192). Arrhythmias included atrioventricular re-entry tachycardia in 32 patients (44%), atrial flutter in 16 (22%), atrial or junctional ectopic tachycardia in 10 (14%), atrial re-entry tachycardias in three (4%) and ventricular arrhythmias in 11 patients (16%). The efficacy of oral treatment was good in patients with atrio-ventricular re-entry tachycardia (80%), atrial flutter (71%) and atrial ectopic tachycardia (83%); it was poor in ventricular arrhythmias (40%). The mean oral dose was 13.5 mg.kg-1. day-1. Dosage and serum levels of propafenone did not differ whether the patients were treated successfully or not. No correlation between dosage and serum level was observed. Intravenous propafenone administration was only partially successful in suppressing supraventricular tachycardias (6 of 11 patients). The presence of a congenital heart defect and the time of onset of the arrhythmias had a significant influence on the efficacy of propafenone. Better results were observed in patients with normal hearts and in whom onset of arrhythmia was pre-natal (success 80%) as well as in patients with arrhythmias seen early after surgery for congenital heart defects (success 87%). Success (65%) was also observed in patients without congenital heart defects and postnatal onset of supraventricular arrhythmias. Patients with ventricular or supraventricular arrhythmias late after corrective surgery showed the poorest response (31%).

Plasma concentration of atrial natriuretic peptide in spontaneous atrioventricular re-entrant tachycardias of childhood.

Plasma atrial natriuretic peptide was measured in 13 children between the ages of 1 week and 2 years 9 months during atrioventricular re-entrant tachycardia and 15 minutes after the restoration of sinus rhythm. There was a significant decline in atrial natriuretic peptide during sinus rhythm. Plasma concentrations of the peptide were significantly higher during tachycardia in seven infants under 1 year than in the six older children. The heart rates and the duration of tachycardia were not significantly different in the two age groups. Cardiac failure was present in five of seven children under 18 weeks of age during tachycardia but in none of the older children. The plasma concentration of atrial natriuretic peptide did not significantly correlate with duration of tachycardia or heart rate. If tachycardia occurs in young infants the low functional reserve capacity of the developing heart leads to cardiac failure more frequently and it is likely that this was the cause of the significantly higher plasma concentration of atrial natriuretic peptide in the younger children.

Prospective evaluation of parenteral magnesium sulfate in the treatment of patients with reentrant AV supraventricular tachycardia.

This study prospectively assessed the electrophysiologic effects of parenteral magnesium sulfate administration on paroxysmal atrioventricular (AV) reentrant supraventricular tachycardia and the efficacy of magnesium to terminate these arrhythmias. Eleven normomagnesemic patients, seven with orthodromic reentrant supraventricular tachycardia that used an accessory AV pathway, and four with typical AV nodal reentry were examined. All patients had a history of sustained supraventricular tachycardia requiring pharmacologic therapy or electrical cardioversion for termination of tachycardia. After baseline electrophysiologic study, including documentation of sustained supraventricular tachycardia that was reproducibly induced, parenteral magnesium sulfate (a bolus of 0.3 mEq/kg of elemental magnesium infused over a 10-minute period followed by a maintenance infusion of 0.2 mEq/kg/hr) was administered during sustained supraventricular tachycardia. The serum magnesium concentration increased from (mean +/- standard deviation) 1.9 +/- 0.2 mg/dl to 4.0 +/- 0.6 mg/dl (p = 0.0001). Except for flushing and mild diaphoresis during infusion of the magnesium sulfate bolus, and dry heaves in one patient, there were no untoward effects or significant changes in systolic blood pressure. During administration of magnesium, the tachycardia cycle length increased from 319 +/- 39 msec to 348 +/- 43 msec (p = 0.0001). Slowing of the tachycardia occurred predominantly in the antegrade limb of the circuit at the level of the AV node with the AH interval increasing from 171 +/- 66 msec to 197 +/- 68 msec (p = 0.0001), whereas there was no significant change in the HV interval (43 +/- 3 msec to 43 +/- 4 msec, p = NS) or the VA interval (106 +/- 43 msec to 110 +/- 47 msec, p = NS) during tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic and clinical effects of flecainide for recurrent paroxysmal supraventricular tachycardia.

The antiarrhythmic effects of flecainide acetate were evaluated in 9 patients with paroxysmal atrioventricular (AV) nodal tachycardia and 17 patients with AV tachycardia. An electrophysiologic study was performed before and after intravenous flecainide acetate, 2 mg/kg body weight, was infused over 15 minutes and was followed by a maintenance infusion of 1.6 mg/kg given over 1 hour to 26 patients and during oral treatment to 15. Treatment with oral flecainide acetate was continued for 14 +/- 5 months. Intravenous flecainide acetate terminated AV nodal tachycardia by blocking the retrograde fast pathway conduction in 7 of 7 patients and AV tachycardia by blocking retrograde conduction in the extranodal pathway in 10 of 10 patients. AV nodal tachycardia and AV tachycardia were noninducible in 8 of 9 patients (90%, p less than 0.001) and 11 of 17 patients (65%, p less than 0.001), respectively. Long-term treatment with oral flecainide acetate suppressed AV nodal tachycardia and AV tachycardia in 8 of 9 patients (90%, p less than 0.001) and 11 of 17 patients (65%, p less than 0.001), respectively. A favorable outcome was associated with block in the accessory pathway after intravenous flecainide acetate and noninducibility during oral treatment. Recurrences preferentially occurred in the younger patients. Flecainide acetate is effective in the acute and long-term management of paroxysmal supraventricular reentry tachycardia by suppressing conduction through the retrograde fast limb of the tachycardia circuit. The clinical effect can be predicted by electrophysiologic testing.