A Pilot Trial to Compare the Long-Term Efficacy of Pulmonary Vein Isolation with High-Power Short-Duration Radiofrequency Versus Laser Energy with Rapid Ablation Mode.

BACKGROUND: Pulmonary vein (PV) reconnection is the major cause of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). The probability of reconnection is higher if the primary lesion is not sufficiently effective, which can be unmasked with an adenosine provocation test (APT). High-power short-duration radiofrequency energy (HPSD) guided with ablation index (AI) and the third generation of the visually guided laser balloon (VGLB) are new methods for PVI. METHODS: A total of 70 participants (35 in each group) who underwent a PVI with either AI-guided HPSD (50 W; AI 500 for the anterior and 400 for the posterior wall, respectively) or VGLB ablation were included in this observational pilot trial. Twenty minutes after each PVI, an APT was performed. The primary endpoint was the event-free survival from AF after three years. RESULTS: A total of 137 (100%) PVs in the HPSD arm and 131 PVs (98.5%) in the VGLB arm were initially successfully isolated (p = 0.24). The overall procedure duration was similar in both arms (155 ± 39 in HPSD vs. 175 ± 58 min in VGLB, p = 0.191). Fluoroscopy time, left atrial dwelling time and duration from the first to the last ablation were longer in the VGLB arm (23 ± 8 vs. 12 ± 3 min, p < 0.001; 157 (111-185) vs. 134 (104-154) min, p = 0.049; 92(59-108) vs. 72 (43-85) min, p = 0.010). A total of 127 (93%) in the HPSD arm and 126 (95%) PVs in the VGLB arm remained isolated after APT (p = 0.34). The primary endpoint was met 1107 ± 68 days after ablation in 71% vs. 66% in the VGLB and HPSD arms, respectively (p = 0.65). CONCLUSIONS: HPSD and VGLB did not differ with respect to long-term outcome of PVI. A large, randomized study should be conducted to compare clinical outcomes with respect to these new ablation techniques.

Ventricular arrhythmia burden in patients with implantable cardioverter defibrillator and remote patient monitoring during different time intervals of the COVID-19 pandemic.

PURPOSE: The current study investigated whether the changes in patient care in times of the COVID-19 pandemic, especially the reduction of in-person visits, would result in a deterioration of the arrhythmic and clinical condition of patients with an implantable cardioverter defibrillator (ICD) and remote patient monitoring. METHODS: Data were obtained from a local ICD registry. 140 patients who received ICD implantation at our department and had remote patient monitoring were included. The number of patients with ventricular arrhythmias, appropriate ICD therapy, the number of visits to our outpatient clinic and hospitalization due to acute coronary syndrome, stroke or heart failure were compared during three time intervals of the COVID-19 pandemic (first (LD1) and second (LD2) national lockdown in Germany and the time after the first lockdown (postLD1)) and a time interval 1 year before the pandemic began (preCOV). Each time interval was 49 days long. RESULTS: Patients had significantly fewer visits to our outpatient clinic during LD1 (n = 13), postLD1 (n = 22) and LD2 (n = 23) compared to the time interval before the pandemic (n = 43, each p ≤ 0.05). The number of patients with sustained ventricular arrhythmias, appropriate ICD therapy and clinical events showed no significant difference during the time intervals of the COVID-19 pandemic and the time interval 1 year prior. CONCLUSIONS: The lockdown measures necessary to reduce the risk of infection during the COVID-19 pandemic, led to a reduction of in-person patient visits, but did not result in a deterioration of the arrhythmic and clinical condition of ICD patients with remote patient monitoring.

Effects of Adaptive Servo-Ventilation on Nocturnal Ventricular Arrhythmia in Heart Failure Patients With Reduced Ejection Fraction and Central Sleep Apnea-An Analysis From the SERVE-HF Major Substudy.

Background: The SERVE-HF trial investigated the effect of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with heart failure with reduced ejection fraction (HFrEF). Objective: The aim of the present ancillary analysis of the SERVE-HF major substudy (NCT01164592) was to assess the effects of ASV on the burden of nocturnal ventricular arrhythmias as one possible mechanism for sudden cardiac death in ASV-treated patients with HFrEF and CSA. Methods: Three hundred twelve patients were randomized in the SERVE-HF major substudy [no treatment of CSA (control) vs. ASV]. Polysomnography including nocturnal ECG fulfilling technical requirements was performed at baseline, and at 3 and 12 months. Premature ventricular complexes (events/h of total recording time) and non-sustained ventricular tachycardia were assessed. Linear mixed models and generalized linear mixed models were used to analyse differences between the control and ASV groups, and changes over time. Results: From baseline to 3- and 12-month follow-up, respectively, the number of premature ventricular complexes (control: median 19.7, 19.0 and 19.0; ASV: 29.1, 29.0 and 26.0 events/h; p = 0.800) and the occurrence of ≥1 non-sustained ventricular tachycardia/night (control: 18, 25, and 18% of patients; ASV: 24, 16, and 24% of patients; p = 0.095) were similar in the control and ASV groups. Conclusion: Addition of ASV to guideline-based medical management had no significant effect on nocturnal ventricular ectopy or tachyarrhythmia over a period of 12 months in alive patients with HFrEF and CSA. Findings do not further support the hypothesis that ASV may lead to sudden cardiac death by triggering ventricular tachyarrhythmia.

Heart failure with recovered ejection fraction (HFrecEF): A new entity with improved cardiac outcome.

BACKGROUND: Aim of the study was a better characterization of heart failure (HF) with recovered ejection fraction (HFrecEF) and undulating EF (HFuEF) with regard to re-hospitalization due to congestive HF (CHF), adequate electric therapies (AETs) and mortality compared to HF with reduced EF (HFrEF), mid-range EF (HFmrEF) and preserved EF (pEF). METHODS: Retrospective study of 342 participants with an implantable cardioverter defibrillator (ICD) for primary or secondary prevention. Type of HF was classified according to left ventricular EF with 4.7 ± 3.1 investigations for each patient. RESULTS: Re-hospitalization due to CHF was similar in HFrecEF (7 (9.5%)), HFmrEF (2(9.0%)) and pEF (8(12.9%); p = n.s.) and significantly higher in HFrEF (62(38.0%)) and HFuEF (6(28.6%); p < .001 compared to HFrecEF and HFrEF). AETs were significantly lower in HFrecEF (13(17.6%)) compared to HFrEF (57(35.0%)), HFmrEF (7(31.8%)), pEF (18(29.0%)) and HFuEF (6(28.6%); each p < .01 compared to HFrecEF). Mortality was similar in HFrecEF (6(8.1%)) compared to HFuEF (0(0%)), pEF (4(6.5%)) and HFmrEF (2(9.0%), p = n.s.) and significantly lower compared to HFrEF (52(31.9%), p < .001). HFrEF was the strongest predictor for mortality besides age and chronic renal insufficiency according to Cox Regression (each p < .05) opposite to arterial hypertension, diabetes, type of cardiomyopathy and secondary prevention ICD indication (each p = n.s.). CONCLUSIONS: HFrecEF indicates as a new entity of HF with similar prognosis as pEF and HFmrEF with regard to re-hospitalization due to CHF and mortality and even better prognosis with regard to AETs. HFuEF showed similar rates of re-hospitalization due to CHF and AETs compared to HFrEF, but lower rates of mortality.

Ventricular arrhythmia in heart failure patients with reduced ejection fraction and central sleep apnoea.

Cheyne-Stokes respiration (CSR) may trigger ventricular arrhythmia in patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). This study determined the prevalence and predictors of a high nocturnal ventricular arrhythmia burden in patients with HFrEF and CSA (with and without CSR) and to evaluate the temporal association between CSR and the ventricular arrhythmia burden. This cross-sectional ancillary analysis included 239 participants from the SERVE-HF major sub-study who had HFrEF and CSA, and nocturnal ECG from polysomnography. CSR was stratified in ≥20% and <20% of total recording time (TRT). High burden of ventricular arrhythmia was defined as >30 premature ventricular complexes (PVCs) per hour of TRT. A sub-analysis was performed to evaluate the temporal association between CSR and ventricular arrhythmias in sleep stage N2. High ventricular arrhythmia burden was observed in 44% of patients. In multivariate logistic regression analysis, male sex, lower systolic blood pressure, non-use of antiarrhythmic medication and CSR ≥20% were significantly associated with PVCs >30·h-1 (OR 5.49, 95% CI 1.51-19.91, p=0.010; OR 0.98, 95% CI 0.97-1.00, p=0.017; OR 5.02, 95% CI 1.51-19.91, p=0.001; and OR 2.22, 95% CI 1.22-4.05, p=0.009; respectively). PVCs occurred more frequently during sleep phases with versus without CSR (median (interquartile range): 64.6 (24.8-145.7) versus 34.6 (4.8-75.2)·h-1 N2 sleep; p=0.006). Further mechanistic studies and arrhythmia analysis of major randomised trials evaluating the effect of treating CSR on ventricular arrhythmia burden and arrhythmia-related outcomes are warranted to understand how these data match with the results of the parent SERVE-HF study.

Novel Implantable Cardioverter Defibrillator Programming With High Rate Cut-Off, Long Detection Intervals and Multiple Anti-Tachycardia Pacing Reduces Mortality.

BACKGROUND: Implantable cardioverter defibrillator (ICD) therapies, even when appropriate, are associated with increased risk. Therapy-reducing strategies have been shown to reduce the mortality rate.Methods and Results:In total, 895 patients with ICD and cardiac resynchronization therapy with defibrillation function (CRT-D) were included in the study; of these, 506 (57%) patients undergoing secondary prevention were included. Devices implanted before May 2014 were programmed according to conventional programming (CP), the others according to our novel programming (NP) with high rate cut-off, longer detection intervals and 4-6 anti-tachycardia pacing (ATP) trains in the ventricular tachycardia (VT) zone. Time-to-first-event for mortality, appropriate and inappropriate therapies were analyzed. Follow-up time was 24.0 months (IQR 13.0-24.0 months). There was a significant reduction in mortality rate (11.4% vs. 25.4%, P<0.001) and in the rate of appropriate (18.8% vs. 42.2%, P<0.001) and inappropriate therapies (5.2% vs. 18.0%, P<0.001) with NP according to Kaplan-Meier analyses. In multivariate analysis, NP (hazard ratio [HR]=0.35; P<0.001), chronic kidney disease (HR=1.55), reduced ejection fraction (EF) (HR=1.35), secondary ICD indication (HR=2.35) and age at implantation (HR=1.02) were associated with mortality reduction. NP was also associated with significant reduction in the rate of appropriate and inappropriate therapies. These results were consistent after stratification for primary and secondary prevention. CONCLUSIONS: Novel ICD programming reduced mortality and morbidity due to appropriate or inappropriate ICD therapies in secondary as well as in primary ICD indication.

The low acute effectiveness of a high-power short duration radiofrequency current application technique in pulmonary vein isolation for atrial fibrillation.

BACKGROUND: Application of high power radiofrequency (RF) energy for a short duration (HPSD) to isolate pulmonary vein (PV) is an emerging technique. But power and duration settings are very different across different centers. Moreover, despite encouraging preclinical and clinical data, studies measuring acute effectiveness of various HPSD settings are limited. METHODS: Twenty-five consecutive patients with symptomatic atrial fibrillation (AF) were treated with pulmonary vein isolation (PVI) using HPSD. PVI was performed with a contact force catheter (Thermocool SF Smart-Touch) and Carto 3 System. The following parameters were used: energy output 50 W, target temperature 43°C, irrigation 15 mL/min, targeted contact force of > 10 g. RF energy was applied for 6-10 s. Required minimal interlesion distance was 4 mm. Twenty minutes after each successful PVI adenosine provocation test (APT) was performed by administrating 18 mg adenosine to unmask dormant PV conduction. RESULTS: All PVs (100 PVs) were successfully isolated. RF lesions needed per patient were 131 ± 41, the average duration for each RF application was 8.1 ± 1.7 s. Procedure time was 138 ± 21 min and average of total RF energy duration was 16.3 ± 5.2 min and average amount of RF energy was 48209 ± 12808 W. APT application time after PVI was 31.1 ± 8.3 min for the left sided PVs and 22.2 ± 4.6 min (p = 0.005) for the right sided PVs. APT was transiently positive in 18 PVs (18%) in 8 (32%) patients. CONCLUSIONS: Pulmonary vein isolation with high power for 6-10 s is feasible and shortens the procedure and ablation duration. However, acute effectiveness of the HPSD seems to be lower than expected. Further studies combining other ablation parameters are needed to improve this promising technique.

High Predictive Value of Adenosine Provocation in Predicting Atrial Fibrillation Recurrence After Pulmonary Vein Isolation With Visually Guided Laser Balloon Compared With Radiofrequency Ablation.

BACKGROUND: We recently demonstrated that the acute reconnection rate detected with adenosine provocation test (APT) was significantly lower after pulmonary vein isolation (PVI) with visually guided laser balloon ablation (VGLB) than with RF ablation (RF). We evaluated the recurrence rate of atrial arrhythmias at 12 months after VGLB vs. RF and the significance of APT results for the outcome.Methods and Results:Fifty patients with paroxysmal AF were randomized to either RF or VGLB ablation in a 1 : 1 fashion. After PVI each PV underwent an APT. All patients underwent a 3-day Holter and clinical follow-up every 3 months. Significantly less PVs reconnected during APT in the VGLB-arm (10 PV (10.8%) vs. 29 PV (30.9%); P=0.001). Significantly less patients had a recurrence of atrial arrhythmia in the VGLB-arm (3 vs. 9; P=0.047). In the VGLB-arm no recurrence was seen in those patients with a negative APT (negative predictive value (NPV)=100%). Only 3 of the 8 patients with a positive APT in the VGLB-arm had a recurrence (positive PV (PPV)=37%). Recurrences in the RF-arm were seen in 3 patients with positive APT as well as in 6 patients with negative APT (PPV=18% and NPV=33%). CONCLUSIONS: There was significantly less recurrence of atrial arrhythmias at 12 months after PVI with VGLB. A negative APT after PVI with VGBL predicted freedom from AF with a very high NPV meaning that the high acute efficiency of the VGLB persisted long term.

Long-term outcomes and predictors of recurrence after pulmonary vein isolation with multielectrode ablation catheter in patients with atrial fibrillation.

PURPOSE: Despite various techniques used in atrial fibrillation ablation, recurrence of atrial arrhythmias still constitutes a clinical problem. The aim of this study was to document the long-term outcomes of pulmonary vein isolation with a ring-shaped ablation catheter (PVAC). METHODS: All consecutive patients presenting with paroxysmal or persistent atrial fibrillation (pxAF or perAF, respectively) treated with PVAC (first generation) were enrolled. After standard follow-up during the first year, all patients were contacted for long-term follow-up. In addition to the patient's medical history, 3-day Holter monitoring was performed. Endpoints were atrial fibrillation-related symptoms, ECG documentation of atrial fibrillation or other left atrial arrhythmias and reablation. RESULTS: In total, 125 patients (78% with pxAF) were enrolled. All but two pulmonary veins (0.4% of 485 pulmonary veins) could be successfully isolated. At 12 months, 83% of patients in the pxAF group and 53% of patients in the perAF group were free from symptoms. The mean long-term follow-up was 51 ±â€Š14 months. Regarding long-term efficacy, 56% of patients in the pxAF group and 28% of patients in the perAF group were free from any recurrence at 72 months. Independent predictors of event-free survival were perAF (hazard ratio 2.76, P = 0.001) and the existence of mild valvular disease (hazard ratio 2.69, P = 0.001). No significant complication due to PVAC occurred, especially no ischemic stroke. CONCLUSION: Long-term follow-up indicated for the first time in such a considerable cohort that pulmonary vein isolation with PVAC is a safe and very efficient method for treating pxAF - despite known microembolism issues. Patients with perAF receive less benefit from PVAC and ablation therapy should be reserved to pxAF. Significantly, even mild valvular disease was an independent predictor of atrial fibrillation recurrence.

A RAndomized Trial to compare the acute reconnection after pulmonary vein ISolation with Laser-BalloON versus radiofrequency Ablation: RATISBONA trial.

INTRODUCTION: Dormant conduction and acute reconnection in the pulmonary veins (PV) during a PV isolation can be detected by performing an adenosine provocation test (APT). Visually guided laser balloon ablation (VGLB) creates deep transmural lesions, thus causing less acute reconnection. This study compared the acute PV reconnection rate after isolation with VGLB or with RF using an APT. METHODS AND RESULTS: Patients with paroxysmal AF were randomized to PVI with the VGLB or RF ablation. Each PV underwent an APT at least 20 minutes after successful isolation with injection of 18 mg adenosine. Primary endpoint was the difference between the two ablation methods regarding acute PV reconnection rate detected with APT. A total of 50 patients were randomized into the study (25 VGLB). The basic characteristics and mean procedure time were not different between the two groups. Note that 96% of the 97 targeted PVs in the VGLB group and 98% of the 96 targeted PVs in the RF group could be isolated (P  =  0.41). APT was performed at similar times (after 28 minutes in VGLB-arm vs. after 31.5 minutes in RF-arm; P  =  0.12). Significantly less PVs were reconnected during APT in the VGLB group than in the RF group (10 PV [10.8%] vs. 29 PV [30.9%]; P  =  0.001). CONCLUSION: The acute PV reconnection rate is significantly less after PVI with VGBL than with RF. The clinical significance of this apparently better procedural efficiency of the VGBL ablation should be assessed with new randomized studies looking at AF recurrence.

Clinical Impact of the Microembolic Signal Burden During Catheter Ablation for Atrial Fibrillation: Just a Lot of Noise?

OBJECTIVES: Microembolic signal detection by transcranial Doppler ultrasonography may be considered a surrogate for cerebral events during invasive cardiac procedures. However, the impact of the microembolic signal count during pulmonary vein isolation on the clinical outcome is not well evaluated. We investigated the effect of the microembolic signal count on the occurrence of new silent cerebral embolism measured by diffusion-weighted imaging (DWI)-magnetic resonance imaging (MRI), changes in neuropsychological testing, and the occurrence of clinical events during long-term follow-up after pulmonary vein isolation. METHODS: Pulmonary vein isolation was performed in 41 patients. The total microembolic signal burden (classified into "solid," "gaseous," and "equivocal") and sustained thromboembolic showers of greater than 30 seconds were recorded. Diffusion-weighted imaging-MRI and neuropsychological testing were performed before and after pulmonary vein isolation to assess for silent cerebral embolism and neuropsychological sequelae. Long-term follow-up was performed by telephone to assess for stroke/transient ischemic attack. RESULTS: A total of 68,729 microembolic signals (14,893 solid, 11,909 gaseous, and 41,927 equivocal) with an average of 1676 signals per patient and 42 thromboembolic showers were recorded. No correlation between the microembolic signal/thromboembolic shower count and the occurrence of new DWI lesions or neuropsychological capability was found. After a mean follow-up ± SD of 49 ± 4 months, 1 patient had an overt transient ischemic event, which was not associated with a high microembolic signal count. CONCLUSIONS: In this multicenter study, we found no impact of the intraprocedural microembolic symbol/thromboembolic shower count on the occurrence of new DWI lesions, neuropsychological capability, or overt neurologic deficits after pulmonary vein isolation. Thus, not only the microembolic signal count but also procedural/individual factors may contribute to commensurable clinical damage, which may challenge this method as a valid biomarker during pulmonary vein isolation.

Online Measurement of Microembolic Signal Burden by Transcranial Doppler during Catheter Ablation for Atrial Fibrillation-Results of a Multicenter Trial.

INTRODUCTION: Left atrial pulmonary vein isolation (PVI) is an accepted treatment option for patients with symptomatic atrial fibrillation (AF). This procedure can be complicated by stroke or silent cerebral embolism. Online measurement of microembolic signals (MESs) by transcranial Doppler (TCD) may be useful for characterizing thromboembolic burden during PVI. In this prospective multicenter trial, we investigated the burden, characteristics, and composition of MES during left atrial catheter ablation using a variety of catheter technologies. MATERIALS AND METHODS: PVI was performed in a total of 42 patients using the circular-shaped multielectrode pulmonary vein ablation catheter (PVAC) technology in 23, an irrigated radiofrequency (IRF) in 14, and the cryoballoon (CB) technology in 5 patients. TCD was used to detect the total MES burden and sustained thromboembolic showers (TESs) of >30 s. During TES, the site of ablation within the left atrium was registered. MES composition was classified manually into "solid," "gaseous," or "equivocal" by off-line expert assessment. RESULTS: The total MES burden was higher when using IRF compared to CB (2,336 ± 1,654 vs. 593 ± 231; p = 0.007) and showed a tendency toward a higher burden when using IRF compared to PVAC (2,336 ± 1,654 vs. 1,685 ± 2,255; p = 0.08). TES occurred more often when using PVAC compared to IRF (1.5 ± 2 vs. 0.4 ± 1.3; p = 0.04) and most frequently when ablation was performed close to the left superior pulmonary vein (LSPV). Of the MES, 17.004 (23%) were characterized as definitely solid, 13.204 (18%) as clearly gaseous, and 44.366 (59%) as equivocal. DISCUSSION: We investigated the burden and characteristics of MES during left atrial catheter ablation for AF. All ablation techniques applied in this study generated a relevant number of MES. There was a significant difference in total MES burden using IRF compared to CB and a tendency toward a higher burden using IRF compared to PVAC. The highest TES burden was found in the PVAC group, particularly during ablation close to the LSPV. The composition of thromboembolic particles was balanced. The impact of MES, TES, and composition of thromboembolic particles on neurological outcome needs to be evaluated further. (Clinical Trial Registration: Deutsches Register Klinischer Studien, https://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003465. DRKS00003465.).

Silent cerebral events as a result of left atrial catheter ablation do not cause neuropsychological sequelae--a MRI-controlled multicenter study.

PURPOSE: Recently, diffusion-weighted magnetic resonance imaging (DW-MRI) revealed silent cerebral events (SCEs) as an acute complication of pulmonary vein isolation (PVI). We investigated whether SCEs following PVI are associated with neuropsychological deficits observed during patients' follow-up examinations. METHODS: After PVI, 52 patients were eligible for follow-up. PVI was performed using a variety of ablation technologies (duty-cycled phased radiofrequency (RF) multipolar ablation with the Pulmonary Vein Ablation Catheter® (PVAC) in 24 patients, cooled-tip RF ablation in 23 patients, and cryoballoon ablation in five patients). Fluid-attenuated inversion recovery (FLAIR)- and DW-MRI studies were performed 1 day before PVI and 1 day and 1 month afterward to detect pre-existing cerebral lesions or post-ablation SCEs. At the same times, eight neuropsychological tests were administered. We evaluated changes in patients' neuropsychological capabilities and compared changes in patients with SCEs to those without SCEs. RESULTS: FLAIR-MRI revealed pre-existing cerebral lesions in 42 patients (81 %), and DW-MRI demonstrated new SCEs in 25 patients (48 %) (17 treated with phased RF (PVAC) (71 %), six treated with irrigated RF (26 %), and two treated with cryoablation (40 %)). Neuropsychological test results showed no significant impairment (in median z scores) 1 day and 1 month after the ablation procedure. There was no difference in neuropsychological capabilities between patients with SCEs and those without SCEs except in one subtest (part of the verbal working memory test). CONCLUSIONS: The incidence of pre-existing cerebral lesions and post-ablation SCEs was high. The frequency of SCEs depends on the ablation technology used. Neither PVI nor post-ablation SCEs have any effect on neuropsychological capabilities.

Unmasking the dormant pulmonary vein conduction with adenosine administration after pulmonary vein isolation with laser energy.

AIMS: The isolation of the pulmonary veins (PVs) is the mainstay of atrial fibrillation (AF) ablation, which with current ablation techniques can be achieved in almost all cases. Reconnection of PVs constitutes the most frequent cause of AF recurrence. Visually guided laser balloon ablation (VGLA) is a novel system with very high rate of persistence of pulmonary vein isolation (PVI) three months after the first procedure shown in preclinical and clinical studies. We aimed to determine the acute efficiency of the laser energy during PVI with the help of adenosine provocation. METHODS AND RESULTS: Twenty-six patients (19 male; mean age 64 ± 9 years) with symptomatic paroxysmal AF were included in the study. Pulmonary vein isolation was performed using the VGLA system. After successful PVI, we studied the effects of intravenous adenosine (18 mg) on activation of each PV at least 20 min after PVI. A total of 104 PVs were targeted. The balloon catheter could not be placed in two PVs. Of the remaining 102 PVs 99 (97% of the ablated PVs) could be successfully isolated. Adenosine was administered for each isolated PV in 25 patients. Only six PVs (6.7%) in five patients (20%) showed a PV reconnection during adenosine provocation. CONCLUSION: Pulmonary vein isolation with VGLA is a feasible technique for PVI with a very effective acute lesion formation. The clinical significance of this low reconnection rate has to be determined.

A unique access for the ablation catheter to treat electrical storm in a patient with extracorporeal life support.

AIMS: Extracorporeal membrane oxygenation (ECMO) is a very effective bridging therapy in patients with cardiogenic shock. To perform coronary angiography in these patients our group developed an unique system to get urgent vascular access with minimal additional vascular complication risk. The 6 Fr coronary catheters are introduced through a standard Y-connector, which is inserted into the arterial cannula of the ECMO-line close to the patient, the blind end of which is then equipped with a haemostatic valve (Check-Flo Performer accessory adapter, Cook Medical, USA). To the best of our knowledge, we here present the first patient, in whom this system had been used to insert an 8 Fr radiofrequency ablation catheter to treat incessant ventricular fibrillation. METHODS AND RESULTS: A 66-year-old patient had been transferred with electrical storm 5 days after an acute MI. After failed interventional and medical therapies an ECMO system had been inserted (right femoral artery cannula 15 Fr, left femoral vein cannula 21 Fr) and an electrophysiological study had been performed because of incessant ventricular fibrillation episodes, which always were induced by the same ventricular premature beat (VPB). During this first EP study over the left femoral artery the VPB could be targeted and successfully ablated. Unfortunately the VPB recovered again after some days so a second EP study had to be performed. This time the left femoral artery could not be used because of a postinterventional complication so we used the arterial cannula of the ECMO system as the access for the ablation catheter using a Y-connector. Using this way again a successful ablation procedure could be performed, after getting familiar with manipulation the ablation catheter over the ECMO cannula and with the help of different curved ablation catheters. The issue of compromising of the effective lumen of the arterial cannula by the ablation catheter`s cross sectional area could be overcome with increasing the rotational speed of the V-A ECMO. CONCLUSION: Ablation of ventricular arrhythmias using a Y-connector to insert the ablation catheter into the arterial cannula is feasible in patients with a V-A ECMO system avoiding additional arterial puncture with potentially major vascular complications in critically ill patients. Manipulation of the catheter is not as easy as using a standard sheath but can well be performed after a short habituation.

Lone atrial fibrillation as a positive predictor of left atrial volume reduction following ablation of atrial fibrillation.

AIMS: We investigated predictors of left atrial volume reduction (LAVR) in patients with atrial fibrillation (AF) undergoing AF ablation. METHODS AND RESULTS: Sixty patients with AF underwent pulmonary vein isolation (PVI) using a pulmonary vein ablation catheter (PVAC). All patients underwent cardiac imaging by computed tomography or magnetic resonance imaging to determine LAV 1 day before and 140 ± 9.5 days after PVI. Clinical follow-up and 72 h electrocardiogram Holter monitoring were performed 1, 3, and 6 months after ablation, and every 6 months thereafter. Significant LAVR (n = 60, 89.3 ± 3.9 vs. 79.5 ± 3.6 mL, P < 0.0001) was shown for the study group as a whole, caused particularly by the subgroup of patients with ablation success (n = 45, 85.2 ± 4.6 vs. 72.5 ± 3.7 mL, P < 0.0001). In addition, significant LAVR was shown for patients with lone AF (n = 25, 88.8 ± 6.8 vs. 72.7 ± 5.3 mL, P < 0.0001), but not for patients with AF and concomitant arterial hypertension (n = 32, 89 ± 4.8 vs. 86.7 ± 5 mL, P = 0.3), coronary artery disease (n = 12, 91.6 ± 7.8 vs. 89.1 ± 7.8 mL, P = 0.26), or left ventricular hypertrophy (n = 10, 86.3 ± 5.5 vs. 83.1 ± 5.3 mL, P = 0.27). Multivariate analysis revealed absence of arterial hypertension, lone AF, ablation success, and initial LA enlargement as independent predictors for significant LAVR following ablation (each P < 0.05). CONCLUSION: Based on the subgroup of patients with lone AF, PVI leads to a significant LAVR 4 months after the procedure, especially in patients with clinical success in terms of AF freedom. Comorbidities such as arterial hypertension may prevent this reverse atrial remodelling, despite AF freedom. Clinical implications need to be further elucidated.

Increased myocardial SERCA expression in early type 2 diabetes mellitus is insulin dependent: In vivo and in vitro data.

BACKGROUND: Calcium (Ca2+) handling proteins are known to play a pivotal role in the pathophysiology of cardiomyopathy. However little is known about early changes in the diabetic heart and the impact of insulin treatment (Ins). METHODS: Zucker Diabetic Fatty rats treated with or without insulin (ZDF ± Ins, n = 13) and lean littermates (controls, n = 7) were sacrificed at the age of 19 weeks. ZDF + Ins (n = 6) were treated with insulin for the last 6 weeks of life. Gene expression of Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a, further abbreviated as SERCA) and phospholamban (PLB) were determined by northern blotting. Ca2+ transport of the sarcoplasmatic reticulum (SR) was assessed by oxalate-facilitated 45Ca-uptake in left ventricular homogenates. In addition, isolated neonatal cardiomyocytes were stimulated in cell culture with insulin, glucose or triiodthyronine (T3, positive control). mRNA expression of SERCA and PLB were measured by Taqman PCR. Furthermore, effects of insulin treatment on force of contraction and relaxation were evaluated by cardiomyocytes grown in a three-dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5 days by insulin. By western blot phosphorylations status of Akt was determed and the influence of wortmannin. RESULTS: SERCA levels increased in both ZDF and ZDF + Ins compared to control (control 100 ± 6.2 vs. ZDF 152 ± 26.6* vs. ZDF + Ins 212 ± 18.5*# % of control, *p < 0.05 vs. control, #p < 0.05 vs. ZDF) whereas PLB was significantly decreased in ZDF and ZDF + Ins (control 100 ± 2.8 vs. ZDF 76.3 ± 13.5* vs. ZDF + Ins 79.4 ± 12.9* % of control, *p < 0.05 vs control). The increase in the SERCA/PLB ratio in ZDF and ZDF ± Ins was accompanied by enhanced Ca2+ uptake to the SR (control 1.58 ± 0.1 vs. ZDF 1.85 ± 0.06* vs. ZDF + Ins 2.03 ± 0.1* µg/mg/min, *p < 0.05 vs. control). Interestingly, there was a significant correlation between Ca2+ uptake and SERCA2a expression. As shown by in-vitro experiments, the effect of insulin on SERCA2a mRNA expression seemed to have a direct effect on cardiomyocytes. Furthermore, long-term treatment of engineered heart tissue with insulin increased the SERCA/PLB ratio and accelerated relaxation time. Akt was significantly phosphorylated by insulin. This effect could be abolished by wortmannin. CONCLUSION: The current data demonstrate that early type 2 diabetes is associated with an increase in the SERCA/PLB ratio and that insulin directly stimulates SERCA expression and relaxation velocity. These results underline the important role of insulin and calcium handling proteins in the cardiac adaptation process of type 2 diabetes mellitus contributing to cardiac remodeling and show the important role of PI3-kinase-Akt-SERCA2a signaling cascade.

Differential expression of potassium channels and abnormal conduction in experimental tachycardia-induced heart failure.

Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1.5, and KvLQT1 were measured by real time PCR. Experimental heart failure was characterized by left ventricular dilatation (13 ± 1 mm vs. 9 ± 1, p < .001), depressed fractional shortening (25 ± 5% vs. 40 ± 4, p < .001), and left atrial remodeling with increased diameter (16 mm ± 2 vs. 12 ± 1, p = .002) and weight (1.3 g ± 0.2 vs. 0.5 ± 0.1, p = .01). A prolongation of P-wave (44 ± 5 ms vs. 40 ± 4, p = .001) and PQ-interval (73 ± 10 ms vs. 66 ± 9, p = .009) occurred. In heart failure, BNP mRNA levels showed a significant upregulation in the left ventricle and atrium (1.83 AU ±1.31 vs. 0.67 ± 0.65, p < .05 and 7.16 AU ±1.76 vs. 0.77 ± 0.48, p < .05). Left ventricular Kv1.5 mRNA was reduced by 50% (p < .001) and KvLQT1 was reduced by 70% (p < .001). rERG and Kv4.3 mRNA were unchanged (n = ns). In contrast, left atrial Kv4.3 and KvLQT1 were reduced by 70% (p < .001), whereas rERG and Kv1.5 were unchanged (p = ns). Significant correlations were present between BNP and K+-channel expressions. Heart failure is characterized by significant changes in the gene expression of repolarizing K+-currents with a differential atrial and ventricular pattern. These molecular changes occur together with changes in cardiac function, geometry, conduction, and BNP expression and provide a functional basis for electrical vulnerability in heart failure.

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report.

BACKGROUND: Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. METHODS: After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. RESULTS: Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content. CONCLUSION: Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling.