Cryoablation for atrial fibrillation and antiarrhythmic drug pretreatment: a single referral center experience.

OBJECTIVE: Pulmonary vein isolation (PVI) ablation has emerged as the gold standard of ablative strategies to treat medically refractory paroxysmal and persistent atrial fibrillation (AF). Regardless of the superiority of catheter ablation based on PVI over antiarrhythmic drug therapy, recurrence rates of AF remain higher than desired. PVI via cryoablation has rapidly become a mainstream treatment for AF, due to its effectiveness and fast learning curve. Our objective was to assess the safety and efficacy of cryoablation in a single referral center. PATIENTS AND METHODS: This is a retrospective analysis of results after cryoablation treatment of AF over three years. 146 patients with AF underwent a cryoablation procedure in our clinical center and were followed-up for three years after the procedure. All patients received cryoablation of the pulmonary veins, although concomitant procedures were performed in 6 patients (re-ablation), including radiofrequency and cryoablation. RESULTS: Cryoablation was clinically successful in 90.83% of the patients with paroxysmal AF and 60% of those with persistent AF. The clinical success of cryoablation was correlated with pretreatment with amiodarone and in the case of re-ablation. Concerning postoperative complications, major bleeding was correlated with female gender, treatment with rivaroxaban and amiodarone. CONCLUSIONS: Among large trials, freedom from recurrent AF is about 65% with follow-up limited to 1 to 2 years. PVI via balloon cryoablation is a safe and efficient guideline-based treatment for AF, producing a durable event-free result in most patients out to 3 years with better outcomes than previously reported.

Clinical implementation of cardiac resynchronization therapy-regional disparities across selected ESC member countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Level of patient and operator dose in the largest cardiac centre in Greece.

The objective of this study was to investigate the patient and staff doses in the most frequent interventional cardiology (IC) procedures performed in Onassio, the largest Cardiac Centre in Greece. Data were collected from three digital X-ray systems for 212 coronary angiographies, 203 percutaneous transluminal coronary angioplasties (PTCA) and 134 various electrophysiological studies. Patient skin dose was measured using suitably calibrated slow radiotherapy films and cardiologist dose using suitably calibrated thermoluminescent dosemeters placed on left arm, hand and foot. Patient median dose area product (DAP) (all examinations) ranged between 6.7 and 83.5 Gy cm2. Patient median skin dose in PTCA was 799 mGy (320-1660 mGy) and in RF ablation 160 mGy (35-1920 mGy). Median arm, hand and foot dose to the cardiologist were 12.6, 27 and 13 microSv, respectively, per procedure. The great range of radiation doses received by both patients and operators confirms the need for continuous monitoring of all IC techniques.

Prolonged asystole during head-up tilt testing with clomipramine infusion.

This case report describes a patient with a history of neurocardiogenic syncope, who had had a negative head-up tilt test with isoprenaline, but he experienced a prolonged asystole during a head-up tilt test with clomipramine (serotonin reuptake inhibitor) 24 h later. This patient was successfully treated with fluoxetine.

Head-up tilt test with clomipramine challenge in vasovagal syndrome--a new tilt testing protocol.

PURPOSE: The aim of the study was to randomly compare clomipramine, used as a challenge-agent during head-up tilt test, with isoproterenol, used in the conventional test, in patients with vasovagal syndrome. SUBJECTS AND METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5mg in 5min) at the start of head-up tilt test (Clom-HUT) in 126 patients (mean age 41+/-16 years) with positive history of recurrent neurocardiogenic syncope, and in 54 healthy control subjects (mean age 46+/-15 years). All subjects had also been tested with a conventional 60 degrees head-up tilt test (Con-HUT) for 30 min and, if negative, isoproterenol infusion was performed at the end of the test. The two tests were performed in a random order with a 24-h interval between them. RESULTS: Fifty-two of the 126 patients (41%) and two of the 54 controls had a positive response to Con-HUT. In the Clom-HUT the proportion of patients who experienced a positive response increased to 83% (105 subjects), while this happened only to four control subjects. The predictive accuracy of Clom-HUT increased compared to Con-HUT from 58 to 86%, respectively. CONCLUSION: The results indicate an increased responsiveness of central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion during tilt test seems to improve considerably its diagnostic value.

Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome.

OBJECTIVES: We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND: Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS: The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsivity. All subjects had been previously tested with a basic 60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS: Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS: The results indicate an increased responsivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.

Pulmonary vein flow analysis by transoesophageal echocardiogr phy in patients with chronic atrial fibrillation; 1 year follow-up after cardioversion.

AIMS: Left and right upper pulmonary vein flow can be adequately recorded by transoesophageal Doppler echocardiography. The aim of this study was to investigate whether analysis of the pulmonary venous flow velocity pattern can predict the long-term maintenance of sinus rhythm after successful cardioversion of chronic atrial fibrillation. METHODS AND RESULTS: Thirty-six consecutive patients, aged 53+/-9 years, with chronic atrial fibrillation of 5.33+/-2 months duration, were subjected to transoesophageal Doppler echocardiography to record left and right upper pulmonary venous flow, 24 h and 3 months following successful cardioversion. One year following cardioversion, 12 patients (33.3%) were in sinus rhythm (sinus rhythm group) while the remaining 24 patients were in atrial fibrillation (atrial fibrillation group). At 24 h following cardioversion, biphasic systolic forward flow in the left and/or right upper pulmonary venous flow velocity was detected in 10 patients of the sinus rhythm group and in four patients of the atrial fibrillation group (P<0001). The systolic fraction was significantly higher in the sinus rhythm group, 0.48+/-0.04 and 0.39+/-0.06, P<0.001 for the left upper pulmonary venous flow, and 0.52+/-0.05 and 0.41+/-0.04, P<0.001 for the right upper pulmonary venous flow, respectively. In patients who displayed a biphasic systolic forward flow and in whom the right upper pulmonary venous flow systolic fraction was higher than 0.50 at 24 h post-cardioversion, the probability of maintenance of sinus rhythm at 1 year exceeded 95%. CONCLUSION: The detection of a biphasic systolic forward flow in the pulmonary venous flow velocity, and of a right upper pulmonary vein systolic fraction higher than 0.50 as early as 24 h following cardioversion of chronic atrial fibrillation, identifies patients who will remain in sinus rhythm 1 year after cardioversion.

Central serotonergic responsiveness in neurocardiogenic syncope: a clomipramine test challenge.

BACKGROUND: Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine. METHODS AND RESULTS: Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results. CONCLUSIONS: Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.

Prospective randomized trial of external versus internal transcatheter cardioversion in patients with chronic atrial fibrillation.

To evaluate the safety and long-term efficacy of internal transcatheter cardioversion, forty patients with chronic, lone atrial fibrillation were studied. The patients were randomised to internal transcatheter cardioversion or to conventional external cardioversion. In cases where the procedure was unsuccessful, cross-over to the alternate method was performed. Oral anticoagulation therapy was started three weeks prior to the procedure and was maintained for another three weeks following successful cardioversion. Sinus rhythm was restored in 16/18 patients (88%) in the internal cardioversion group, versus 9/22 patients (40%) in the external cardioversion group (p < 0.01). In addition, 8/13 (61%) patients who were crossed-over to internal cardioversion were successfully cardioverted to sinus rhythm. In contrast, both patients who were crossed-over to external cardioversion remained in atrial fibrillation. During a mean follow-up period of 23 months, 13 (39.3%) patients maintained sinus rhythm. Using the intention to treat principle, the recurrence rate was not statistically different between the two methods. It is concluded that internal cardioversion is more effective in acutely restoring sinus rhythm compared to external cardioversion. However, both methods have similar long-term recurrence rates.

Cardiac denervation after radiofrequency ablation of supraventricular tachycardias.

Inappropriate sinus tachycardia and atrial arrhythmias have been reported after radiofrequency ablation. Previous studies have suggested that cardiac denervation is a possible explanation for these rhythm disturbances. The aim of this study was to investigate possible alterations in autonomic innervation of the heart after ablation using the techniques of heart rate variability (HRV) analysis and metaiodobenzylguanidine (I-123 MIBG) scintigraphy. The subjects of this study were 30 consecutive patients aged 25 to 40 years, without structural heart disease, who underwent radiofrequency ablation of atrioventricular nodal slow pathways, and posteroseptal and left lateral accessory pathways because of symptomatic recurrent reentrant tachycardias. Time and frequency domain analysis of HRV after ablation revealed a significant reduction in the indexes of the mean of all 5-minute standard deviation of RR intervals (p = 0.042), low frequency (p = 0.0005), and total frequency (p = 0.008) compared with preablation values in the group of patients who underwent atrioventricular nodal slow pathway ablation. Patients who underwent ablation of a posteroseptal accessory pathway also had significant attenuation of the indexes of standard deviation about the mean RR interval (p = 0.03), standard deviation of 5-minute mean RR intervals (p = 0.006), and low-frequency (p <0.0001), and high-frequency (p <0.0001) components. Significant I-123 MIBG map defects, indicating efferent cardiac sympathetic denervation, were also found in the same groups of patients: atrioventricular nodal group (p = 0.0024), posteroseptal accessory pathway group (p = 0.0007). None of the above changes in HRV and 123-I MIBG scintigraphy were seen in patients who underwent ablation of left lateral accessory pathways. We conclude that radiofrequency ablation in the anterior, mid-, and posterior regions of the low intraatrial septum may disrupt sympathetic fibers located in these regions, causing cardiac sympathetic denervation. The density of these fibers appear to be less along the left atrioventricular groove.

CGMP levels following ANP challenge are markers of subsequent successful reversion of lone atrial fibrillation to sinus rhythm.

The aim of the present study was to assess whether cGMP release to ANP stimulation can be a biochemical marker of subsequent successful electrical cardioversion of lone atrial fibrillation to sinus rhythm. For this purpose, we studied 13 patients with chronic, lone atrial fibrillation of less than one year's duration who presented to our laboratory for electrical therapy of their arrhythmia. Prior to electrical cardioversion, peripheral venous cGMP levels were assessed at baseline and following an intravenous challenge of 50 Ug human ANP. Venous blood samples for cGMP assessment were taken a) at baseline, b) 5 and 10 mins after the end of ANP infusion. ANOVA of repeated measures was used for statistical analysis. Eight of the study patients were successfully cardioverted to sinus rhythm, while the remaining 5 were not. Although no difference was noted between the two groups regarding the mean time of arrhythmia duration as well as left atrial and ventricular dimensions, ANP stimulation provoked significantly greater cGMP release in patients whose arrhythmia reverted to sinus rhythm, when compared with that of patients whose arrhythmia persisted (p < 0.001). Therefore, cGMP levels following ANP challenge might discriminate between patients with chronic AF who are going to be successfully cardioverted and those who are not. These findings imply that the underlying atrial disease might be different in extent/nature between patients with lone AF responsive to cardioversion and those with resistant arrhythmia.

Hormonal responses during tilt-table test in neurally mediated syncope.

The hormonal profile during tilt testing was examined in syncopal patients. An increase in the growth hormones cortisol and prolactin was found during syncope, suggesting an implication of central serotonergic activation.

Left atrial function and atrial natriuretic factor/cyclic guanosine monophosphate changes in DDD and VVI pacing modes.

Left atrial systolic function and the plasma of atrial natriuretic factor (ANF) and cyclic guanosine monophosphate (cGMP) were investigated as possible markers for the development of pacemaker syndrome during VVI pacing. Patients who developed pacemaker syndrome during VVI pacing had a significant decrease in left atrial emptying fraction and a substantial increase in ANF and cGMP plasma levels.