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

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

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

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

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

Cardiac MRI Based Left Ventricular Global Function Index: Association with Disease Severity in Patients with ICD for Secondary Prevention

Left ventricular (LV) ejection fraction (LVEF) is the most widely used prognostic marker in cardiovascular diseases. LV global function index (LVGFI) is a novel marker which incorporates the total LV structure in the assessment of LV cardiac performance. We evaluated the prognostic significance of LVGFI, measured by cardiovascular magnetic resonance (CMR), in predicting mortality and ICD therapies in a real-world (ICD) population with secondary ICD prevention indication, to detect a high-risk group among these patients. In total, 105 patients with cardiac MRI prior to the ICD implantation were included (mean age 56 ± 16 years old; 76% male). Using the MRI data for each patient LVGFI was determined and a cut-off for the LVGFI value was calculated. Patients were followed up every four to six months in our or clinics in proximity. Data on the occurrence of heart failure symptoms and or mortality, as well as device therapies and other vital parameters, were collected. Follow up duration was 37 months in median. The mean LVGFI was 24.5%, the cut off value for LVGFI 13.5%. According to the LVGFI Index patient were divided into 2 groups, 86 patients in the group with the higher LVGFI und 19 patients in the lower group. The LVGFI correlates significantly with the LVEF (r = 0.642, p I, the initial device or a medication (each p = n.s.). Further, in Kaplan–Meier analysis no association was evident between the LVGFI and adequate ICD therapy (p = n.s.). In secondary prevention ICD patients reduced LVGFI was shown as an independent predictor for mortality and rehospitalization, but not for ICD therapies. We were able to identify a high-risk collective among these patients, but further investigation is needed to evaluate LVGFI compared to ejection fraction, especially in patients with an elevated risk for adverse cardiac events

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* mug/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- kt-SERCA2a signaling cascade

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 degrees 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