Ultra-High to Ultra-Low Drug-Loaded Micelles: Probing Host-Guest Interactions by Fluorescence Spectroscopy.

Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.

Critical analysis of ineffective post implantation implantable cardioverter-defibrillator-testing.

AIM: To test of the implantable-cardioverter-defibrillator is done at the time of implantation. We investigate if any testing should be performed. METHODS: All consecutive patients between January 2006 and December 2008 undergoing implantable cardioverter-defibrillator (ICD) implantation/replacement (a total of 634 patients) were included in the retrospective study. RESULTS: Sixteen patients (2.5%) were not tested (9 with LA/LV-thrombus, 7 due to operator's decision). Analyzed were 618 patients [76% men, 66.4 + 11 years, 24% secondary prevention (SP), 46% with left ventricular ejection fraction (LVEF) < 20%, 56% had coronary artery disease (CAD)] undergoing defibrillation safety testing (SMT) with an energy of 21 + 2.3 J. In 22/618 patients (3.6%) induced ventricular fibrillation (VF) could not be terminated with maximum energy of the ICD. Six of those (27%) had successful SMT after system modification or shock lead repositioning, 14 patients (64%) received a subcutaneous electrode array. Younger age (P = 0.0003), non-CAD (P = 0.007) and VF as index event for SP (P = 0.05) were associated with a higher incidence of ineffective SMT. LVEF < 20% and incomplete revascularisation in patients with CAD had no impact on SMT. CONCLUSION: Defibrillation testing is well-tolerated. An ineffective SMT occurred in 4% and two third of those needed implantation of a subcutaneous electrode array to pass a SMT > 10 J.

Impact of surround flow catheter tip irrigation in contact force ablation on the incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation: a prospective comparative study.

AIMS: Aim of this study was to evaluate the impact of a recently introduced contact force ablation catheter with modified irrigation technology compared with a conventionally irrigated ablation catheter on the incidence of endoscopically detected oesophageal lesions (EDEL). METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent atrial fibrillation (AF) who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter with conventional irrigation (Group 1; n = 50) or with a recently introduced intensified 'surround flow' irrigation technology (Group 2; n = 50). Assessment of EDEL was performed by oesophagogastroduodenoscopy in all patients after ablation. A total of 100 patients (mean age 63.6 ± 12.1 years; men 58%) with paroxysmal (n = 41; 41%) or persistent AF were included. Groups 1 and 2 patients were comparable in regard to baseline characteristics and procedural parameters, especially ablation time at posterior left atrial wall. Overall, 13 patients (13%) developed EDEL after AF ablation (8 oesophageal ulcerations, 5 erythema). The incidence of EDEL including oesophageal ulcerations was higher in Group 2 compared with Group 1 patients without statistical significance (18 vs. 8%, P = 0.23). One pericardial tamponade and one access site bleeding occurred in Group 2. No further adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of an improved ablation catheter irrigation technology (surround flow) in conjunction with contact force measurement was associated with a higher but not statistically significant probability of oesophageal thermal lesions. Further studies including larger patient cohorts are needed.

Incidence of asymptomatic oesophageal lesions after atrial fibrillation ablation using an oesophageal temperature probe with insulated thermocouples: a comparative controlled study.

AIMS: Oesophageal probes to monitor luminal oesophageal temperature (LET) during atrial fibrillation (AF) catheter ablation have been proposed, but their effects remain unclear. Aim of this study is to evaluate the effects of an oesophageal temperature probe with insulated thermocouples. METHODS AND RESULTS: Patients with symptomatic, drug-refractory paroxysmal or persistent AF who underwent left atrial radiofrequency (RF) catheter ablation were prospectively enrolled. Patients were ablated using a single-tip RF contact force ablation catheter. An intraluminal oesophageal temperature probe was used in Group 1. In Group 2, patients were ablated without LET monitoring. Assessment of asymptomatic endoscopically detected oesophageal lesions (EDEL) was performed by oesophagogastroduodenoscopy (EGD) in all patients. Eighty patients (mean age 63.7 ± 10.7 years; men 56%) with symptomatic, drug-refractory paroxysmal (n = 28; 35%) or persistent AF were included. Group 1 and Group 2 patients (n = 40 in each group) were comparable in regard to baseline characteristics, but RF duration on the posterior wall was significantly shorter in Group 1 patients. Overall, seven patients (8.8%) developed EDEL (four ulcerations, three erythema). The incidence of EDEL in Group 1 and Group 2 patients was comparable (7.5 vs. 10%, P = 1.0). No major adverse events were reported in both groups. CONCLUSION: According to these preliminary results, the use of oesophageal temperature probes with insulated thermocouples seems to be feasible in patients undergoing AF RF catheter ablation. The incidence of post-procedural EDEL when using a cut-off of 39°C is comparable to the incidence of EDEL without using a temperature probe.

Impact of periprocedural anticoagulation strategy on the incidence of new-onset silent cerebral events after radiofrequency catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCEs) have been observed on diffusion-weighted cerebral magnetic resonance imaging (MRI) in a substantial number of asymptomatic patients after atrial fibrillation (AF) ablation procedures. The purpose of this study was to investigate if periprocedural oral anticoagulation (OAC) management affects the incidence of new-onset SCE after radiofrequency catheter ablation (RFCA) of AF. METHODS AND RESULTS: One hundred ninety-two consecutive patients (64 ± 10.1 years, 38.5 % women) with symptomatic paroxysmal (n = 80, 41.7 %) or persistent AF undergoing RFCA of AF were prospectively enrolled. Periprocedural anticoagulation strategies were defined as uninterrupted use of novel oral anticoagulants (NOACs) (group I, n = 64), interrupted use of NOACs (group II, n = 42), continuation of vitamin K antagonist (VKA) with an international normalized ratio (INR) between 2.0 and 3.0 (group III, n = 43), and VKA discontinuation bridged with low molecular weight heparin (group IV, n = 43). Cerebral MRI was performed 1 to 2 days after RFCA for detection of new SCE. Overall, new SCEs were detected in 41 patients (21.4 %) after AF ablation. New SCEs were detected in 12.5 % in group I, 35.7 % in group II, 18.6 % in group III, and 23.3 % in group IV (p < 0.05). Multivariable logistic regression analysis revealed persistent AF and discontinuation of periprocedural OAC (group II and IV) to be independent predictors for the development of SCE. No relevant complications were identified. CONCLUSIONS: Periprocedural continuation of NOAC as well as continuation of VKA seems to be safe and significantly reduce the occurrence of SCE after AF ablation.

Multiple breath washout analysis in infants: quality assessment and recommendations for improvement.

Infant multiple breath washout (MBW) testing serves as a primary outcome in clinical studies. However, it is still unknown whether current software algorithms allow between-centre comparisons. In this study of healthy infants, we quantified MBW measurement errors and tried to improve data quality by simply changing software settings. We analyzed best quality MBW measurements performed with an ultrasonic flowmeter in 24 infants from two centres in Switzerland with the current software settings. To challenge the robustness of these settings, we also used alternative analysis approaches. Using the current analysis software, the coefficient of variation (CV) for functional residual capacity (FRC) differed significantly between centres (mean ± SD (%): 9.8 ± 5.6 and 5.8 ± 2.9, respectively, p = 0.039). In addition, FRC values calculated during the washout differed between -25 and +30% from those of the washin of the same tracing. Results were mainly influenced by analysis settings and temperature recordings. Changing few algorithms resulted in significantly more robust analysis. Non-systematic inter-centre differences can be reduced by using correctly recorded environmental data and simple changes in the software algorithms. We provide implications that greatly improve infant MBW outcomes' quality and can be applied when multicentre trials are conducted.

Spatial Relationship of Focal Impulses, Rotors and Low Voltage Zones in Patients With Persistent Atrial Fibrillation.

INTRODUCTION: Focal impulses (FI) and rotors are sources associated with the initiation and maintenance of atrial fibrillation (AF). Their ablation results in a lower recurrence rate. The aim of this study was to characterize for the first time the spatial relationship between such sources and atrial low voltage zones (LVZ) representing fibrosis. METHODS: Twenty-five consecutive patients undergoing their first ablation for persistent AF were included. Voltage mapping of both atria was done during AF. Endocardial mapping of FI and rotors (sources) was performed using a basket catheter and displayed using RhythmView(TM) (Topera Inc.) before ablation. Spatial relationship of LVZ and sources was analyzed. RESULTS: LVZs covered 13 ± 12% of right atrial (RA) endocardial surface and 33 ± 25% of left atrial (LA) endocardial surface. The median number of sources was 1 [1-3] in RA and 3 [1-4] in LA. Of LA sources, 18 (30%) were definitely not associated with LVZs or pulmonary vein (PV) antra. Of RA sources, 32 (84%) were remote from LVZ. During ablation of such sources substantial cycle length (CL) prolongation or AF conversion occurred in 11/23 patients (48%). Altogether, 8/11 (73%) of these pertinent sources were located remotely from LVZ and PV antra. CONCLUSIONS: There is a wide discrepancy in distribution of LVZ areas and sites of identified rotors. Site and incidence of FIRM sources appear to be unpredictable with atrial substrate mapping. Further prospective, randomized studies are necessary to elucidate the impact of additional ablation of such sources in patients with persistent or longstanding persistent AF.

Effect of Different Ablation Settings on Acute Complications Using the Novel Irrigated Multipolar Radiofrequency Ablation Catheter (nMARQ).

BACKGROUND: Single-shot ablation devices for pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF) have been increasingly used in clinical practice. OBJECTIVE: A novel mapping-system integrated irrigated multipolar circular ablation catheter (nMARQ) has been introduced for PVI but data on larger patient cohorts on acute safety and efficacy are lacking. METHODS: A total of 145 consecutive patients undergoing AF ablation treated with the nMARQ underwent endoscopic evaluation of esophageal thermal damage (EDEL) and brain MRI for detection of silent cerebral events (SCE). During the course of our experience different modifications of the ablation strategy, including energy delivery at the left atrial posterior wall, were evaluated. RESULTS: Effective PVI was achieved in 99% of all PVs during a mean procedure-duration of 115 (±36) minutes and ablation-duration of 18 (±8) minutes. Acute major complications occurred in 3 patients (2.1%) and asymptomatic complications like SCE in 26% and EDEL in 21%. There was a significant reduction in EDEL when not using a thermal esophageal probe (0% vs. 28%, P < 0.0001). Ablation under oral anticoagulation led to lower SCE incidences compared to interrupted anticoagulation regimen (15% vs. 31%, P = 0.7). Out of 65 patients with completed 12-month follow-up, 43 (66%) were in stable sinus rhythm. CONCLUSIONS: PVI using the nMARQ is safe and effective in patients with symptomatic AF. Not using an esophageal temperature probe during ablation has relevantly reduced the incidence of EDEL. Ablations under continued oral anticoagulation have reduced incidence of SCE. Further studies on long-term efficacy are needed.

Association between left atrial low-voltage area, serum apoptosis, and fibrosis biomarkers and incidence of silent cerebral events after catheter ablation of atrial fibrillation.

BACKGROUND: Silent cerebral events (SCE) have been identified on cerebral diffusion-weighted cerebral magnetic resonance imaging (DE-MRI) after catheter ablation (CA) of atrial fibrillation (AF). The purpose of this study was to investigate the impact of atrial remodeling on the incidence of SCE after AF CA. METHODS: Forty patients (67.8 ± 10 years, 47.5 % women) with symptomatic paroxysmal (n = 11, 27.5 %) or persistent AF undergoing AF CA were prospectively enrolled. LA fibrosis was estimated by intraprocedural bipolar voltage mapping in sinus rhythm. Apoptosis-stimulating fragment (Fas-Ligand) and amino terminal peptide from collagen III (PIIINP) concentrations were analyzed of LA and femoral vein blood. Cerebral DE-MRI was performed 1 to 2 days after CA of AF for detection of SCE. In nine patients (22.5 %), new SCE were detected on DE-MRI after AF CA. RESULTS: Patients with SCE had higher CHA2DS2-VASc score, larger left atrial diameter (LADmax), and higher surface area of left atrial low-voltage (24 ± 11.2 vs 3.5 ± 4.2 %, p < 0.0001). Concentrations of peripheral PIIINP (103.7 ± 25.9 vs 81.8 ± 16.7 pg/ml, p < 0.01) and Fas-Ligand (124.1 ± 22.4 vs 87.6 ± 19.4 pg/ml, p < 0.01) were significantly higher in patients with SCE and correlated to low-voltage surface area (p < 0.01). Multivariable logistic regression analysis revealed peripheral Fas-Ligand, LADmax, CHA2DS2-Vasc score, and LA low-voltage area proportion to be independent predictors for the development of SCE. CONCLUSIONS: LA remodeling, estimated by LADmax and LA low-voltage area, has significant relationship with the risk of SCE after AF ablation. Moreover, Fas-Ligand may act as an independent predictor for SCE in the context of AF CA.

Higher incidence of esophageal lesions after ablation of atrial fibrillation related to the use of esophageal temperature probes.

BACKGROUND: Endoscopically detected esophageal lesions (EDELs) have been identified in apparently asymptomatic patients after catheter ablation of atrial fibrillation (AF). The use of esophageal probes to monitor luminal esophageal temperature (LET) during catheter ablation to protect esophageal damage is currently controversial. OBJECTIVE: The purpose of this study was to investigate the impact of the use of esophageal temperature probes during AF catheter ablation on the incidence of EDELs. METHODS: Eighty consecutive patients (mean age 63.8 ± 11.36 years; 68.8% men) with symptomatic, drug-refractory paroxysmal (n = 52, 65%) or persistent AF who underwent left atrial radiofrequency catheter ablation were prospectively enrolled. Posterior wall ablation was power limited (≤25 W). In the first 40 patients, LET was monitored continuously (group A), whereas no esophageal temperature probe was used in group B (n = 40 patients). Assessment of EDEL was performed by endoscopy within 2 days after radiofrequency catheter ablation. RESULTS: Overall, 13 patients (16%) developed EDELs after AF ablation. The incidence of EDELs was significantly higher in group A than group B (30% vs 2.5%, P < .01). Within group A, patients who developed EDEL had higher maximal LET during AF ablation than patients without EDEL (40.97 ± 0.92°C vs 40.14 ± 1.1°C, P = .02). Multivariable logistic regression analysis revealed the use of an esophageal temperature probe as the only independent predictor for the development of EDEL (odds ratio 16.7, P < .01). CONCLUSION: The use of esophageal temperature probes in the setting of AF catheter ablation per se appears to be a risk factor for the development of EDEL.

Silent cerebral events/lesions related to atrial fibrillation ablation: a clinical review.

Brain magnetic resonance imaging (MRI) has identified a high incidence of cerebral ischemia in asymptomatic patients after atrial fibrillation (AF) ablation (silent). Detection of cerebral ischemic events on MRI is based on acute hyperintense lesions on diffusion-weighted imaging. In the literature, the incidence is related to specifications of MRI and depends on the definition applied. In comparative studies, silent cerebral events (SCE, diffusion-weighted MRI [DWI] positive only) appear to be approximately 3 times more common compared to using a definition of silent cerebral lesions (SCL; without fluid attenuated inverse recovery sequence [FLAIR] positivity). Whereas the FLAIR sequence may turn positive within days after the ischemic event, SCE definition is highly sensitive for early phases of ischemic brain damage. SCE/SCL appear to represent cerebral ischemic infarcts and determine the "embolic fingerprint" of a specific ablation technology and strategy used. The optimum time point for detecting SCE is early after AF ablation (24-72 hours), whereas detection of SCL can only be performed within the first 2-7 days (due to delay of FLAIR positivity). Different technology-, procedure-, and patient-related parameters have been identified to play a role in the multifactorial genesis of SCE/SCL. In recent years, evidence has been gathered that there may be differences of SCE/SCL rates depending upon the ablation technology used, but small patient numbers and a large number of potential confounders hamper all studies. As major findings of recent studies, mode of periprocedural and intraprocedural anticoagulation has been identified as a major predictor for incidences of SCE/SCL. Whereas procedural characteristics related to higher SCE/SCL-rates may be modified, unchangeable patient-related factors should be taken into account for future individualized risk assessment. Novel ablation devices introduced into the market should be tested for their potential embolic fingerprint and refinements of ablation procedures to reduce their embolic potential should be prompted. The knowledge of "best practice" in terms of low SCE/SCL rates has prompted changes in work-flow, which have been implemented into ablation procedures using novel ablation devices. So far, no study has linked SCE/SCL to neuropsychological decline and the low number of AF-ablation-associated events needs to be weighted against the multitude of preexisting asymptomatic MRI-detected brain lesions related to the course of AF itself. Future studies are needed to evaluate if more white matter hyperintensities due to AF may be prevented by AF ablation (producing only a small number of SCE/SCL).

Stand-alone mapping using different transluminal mapping catheters--an accurate and safe way to isolate all pulmonary veins with the cryoballoon?

PURPOSE: Cryoballoon isolation of the pulmonary veins (PVI) is an effective and safe method in the treatment of patients with paroxysmal atrial fibrillation (PAF). The circular mapping catheter Achieve® (Medtronic Inc., Minneapolis, USA) can be introduced into the pulmonary vein (PV) through the inner lumen of the balloon catheter, allowing online mapping of the PV electrograms during ablation. We prospectively compared the accuracy of this catheter in both available sizes to a standard circular mapping catheter (SCMC) in order to determine bidirectional PV block. METHODS: Patients with symptomatic PAF underwent cryoballoon ablation using either the Achieve® 15-mm catheter (group 1, 15 patients) or the Achieve® 20 mm (group 2, 15 patients). PV potentials were recorded using Achieve® before, during, and after ablation, and exit block was obtained by pacing from inside the PV. Accuracy of PV potential detection was controlled by a SCMC before and after ablation. RESULTS: Rate of PV which could be isolated exclusively using the Achieve® as guidewire was 98 % (59/60) in group 1 and 93 % (57/60) in group 2. Online signal recording during ablation was possible in 40 and 60 % of PV (p = 0.037), respectively. Final Achieve® diagnosis was accurate in 55/60 (92 %) of the PVs and 12/15 (80 %) of patients in group 1 and 60/60 (100 %) of PV and 15/15 (100 %) of patients in group 2. CONCLUSION: Stand-alone mapping using Achieve® 15 mm resulted in a significant lack of diagnostic accuracy. Achieve® 20 mm provided excellent diagnostic accuracy comparable to a SCMC and should be preferentially used.

Residual conduction after pulmonary vein isolation with a circular multielectrode radiofrequency ablation catheter: the role of adenosine and orciprenalin during a prolonged observation time.

INTRODUCTION: Recurrences after pulmonary vein isolation (PVI) in patients (pts) with paroxysmal atrial fibrillation (AF) are mostly due to PV reconnection. The effect of adenosine, orciprenalin and their combination on left atrial PV conduction after PVI with a phased radiofrequency (RF) circular multielectrode ablation catheter (Pulmonary Vein Ablation Catheter, PVAC) was prospectively evaluated during a prolonged waiting time. In addition, it was assessed whether pharmacological reconnection characterizes veins requiring use of an irrigated catheter. METHODS AND RESULTS: In 116 consecutive pts [age 62 (IQR:52,68) years, 46% female], PVI was achieved with the PVAC alone in 114/116 (98%) pts and 461/464 (99%) veins after a median of 26 (IQR:22,32) applications delivering 1782 s (IQR:1518,2197) of RF. Mostly transient PV reconnections were observed in 40/116 (34%) pts and 57/464 (12%) PVs, a median of 44 (IQR:30,58) min after initial isolation. Adenosine, alone (43/57, 75%) or during orciprenalin infusion (7/57, 12%), unmasked residual conduction in the majority of veins (50/57, 88%). Additional PVAC applications less frequently achieved permanent isolation in veins showing reconnection compared to those that didn't (52/57, 91% vs. 404/407, 99%; P < .001). All PVs that could not be isolated with the PVAC were successfully treated with a standard irrigated catheter. CONCLUSIONS: After apparent PVI with the PVAC, drug-challenge after prolonged observation unmasked residual PV conduction in a significant number of pts, and adenosine was the most effective strategy. Drug-induced PV reconnection was difficult to treat with the PVAC. Whether this strategy improves clinical outcome of PVI with phased RF needs to be investigated.

Multiple-breath washout measurements can be significantly shortened in children.

Multiple-breath washout (MBW)-derived lung clearance index (LCI) is a sensitive measure of ventilation inhomogeneity in patients with cystic fibrosis (CF), but LCI measurement is time consuming. We systematically assessed ways to shorten LCI measurements. In 68 school-aged children (44 with mild CF lung disease) three standard nitrogen (N2) MBWs were applied. We assessed repeatability and diagnostic performance of (1) LCI measured earlier from three MBW runs and (2) LCI measured at complete MBW (1/40th of starting N2 concentration) from two runs only. Compared with the standard LCI from three complete MBW runs, the new LCI based on three N2MBW runs until 1/20th, or two complete runs until 1/40th, provided similar or better repeatability as well as sensitivity and specificity for CF lung disease. Alternative ways to measure LCI reduced test duration in children with CF by 30% and 41%, respectively. LCI measurements can be reliably shortened in children. These new MBW protocols may advance the transition of LCI from research into clinical settings.

The importance of class-I antiarrhythmic drug test in the evaluation of patients with syncope: unmasking Brugada syndrome.

INTRODUCTION: The Brugada syndrome (BrS) can first present with syncope. Class-I antiarrhythmic drug (AAD) test is used to unmask the diagnostic coved-type ECG pattern in case it is not spontaneously present. The aim of the study was to analyze patients with BrS presenting with syncope as first manifestation and compare patients with syncope and a spontaneous coved-type ECG to patients with syncope in whom a class-I AAD test unmasked the disease. METHODS AND RESULTS: Fifty-eight of 157 probands (36.9%) had syncope as first manifestation of the disease. Twenty-six patients (44.8%, group A) showed a spontaneous coved-type ECG diagnostic for BrS at first presentation. In 32 patients (55.2%, group B) without spontaneous coved-type ECG pattern at first presentation (36% normal ECGs and 19% type-II ECG pattern), a class-I AAD test unmasked the disease. Twenty-one patients of group A and 29 patients of group B underwent implantable cardioverter defibrillator (ICD) implantation. The mean follow up as 9.7 ± 55.7 month. Four patients in group A (15.4%) and 3 patients (9.3%) in group B had appropriate ICD shock delivery due to ventricular fibrillation or ventricular tachycardia (P = NS). CONCLUSION: One of 3 patients with BrS presents first with syncope. More than one-third of these patients have a normal ECG at investigation for syncope and the correct diagnosis would have been missed without a class-I AAD test. Patients presenting with syncope are at similar risk irrespective of the presence of a spontaneous coved-type ECG.

A critical analysis of the scientific evidence behind international guidelines related to cardiac arrhythmias.

BACKGROUND: Guidelines have become very important in assisting with decision making in clinical practice. However, few studies have analyzed the level of evidence (LOE) underlying guidelines critically. This study aims to assess the accuracy of the referenced literature that has led to recommendations with a level of evidence A (LOE-A) rating. METHODS AND RESULTS: The latest updates of the practice guidelines related to arrhythmia posted on the European Society of Cardiology (ESC) web site were analyzed. The referenced literature for LOE-A recommendation was analyzed to reassess the proposed grading scheme for LOE-A. Furthermore, the clearly defined positive (Class I) and negative (Class III) recommendations with correctly referenced LOE-A were assessed. A median of 5.4% of all recommendations per guideline (interquartile range 4.9% to 9.7%) were categorized as LOE-A, but only 3.7% (IQR 3.4% to 4.9%) were accurately referenced as LOE-A. In total, 27 of 698 recommendations (median 1.2% per guideline [IQR 0.95% to 3.7%]) were correctly referenced as Class I or III LOE-A recommendations implying definite evidence-based positive or negative conclusion. CONCLUSIONS: Our findings raise the question of the accuracy of LOE-A in medical guidelines in general and highlight the importance of a critical use of all recommendations. Moreover, they underline the need for improving the guideline-writing process. Further randomized double-blinded and/or crossover-designed studies should focus on areas with a gap in the evidence, such as existing but not yet convincing (LOE-B) or conflicting (Class II) evidence.

Detection and hemodynamic significance of cardiac pacemaker-induced phrenic nerve stimulation.

The authors investigated acoustic cardiography, the digital analysis of electrocardiogram (ECG) and heart sounds, to detect phrenic nerve stimulation (PNS) and assess its hemodynamic significance. They studied 42 patients and induced 46 instances of PNS induced through cardiac pacing at various locations in the heart. These 46 instances of PNS were either independently documented using fluoroscopy or were symptomatic. The authors collected acoustic cardiography data including the electromechanical activation time (interval from Q onset to the first heart sound [S1]) as a percentage of the RR interval (%EMAT) to assess systolic function. Acoustic cardiography provided evidence of PNS when it occurred. They also found significant %EMAT prolongation when right ventricular pacing was associated with PNS (Delta%EMAT=2.7, P=.012), but none beyond the normal range with right ventricular pacing in the absence of PNS. Documented PNS occurred in 33 episodes (60%) in patients with noticeable symptoms. Stimulation amplitudes could be found that generated asymptomatic PNS for all of the five participants explicitly tested for it. PNS can be asymptomatic. PNS due to right ventricular pacing is associated with impaired left ventricular systolic function. Acoustic cardiography is an effective method of detecting and assessing the hemodynamic significance of pacemaker-related PNS.

Feasibility, safety, and outcome of a challenging transseptal puncture facilitated by radiofrequency energy delivery: a prospective single-centre study.

AIMS: Although it has been shown that a transseptal (TS) puncture in the electrophysiology laboratory is associated with a high success and a low complication rate, this procedure remains challenging particularly in difficult septum anatomies (aneurismal septum and thick septum) and during repeat TS catheterization. Radiofrequency (RF) electrocautery current delivery through the TS needle has been shown to facilitate the TS puncture. The aim of this study was to verify prospectively the feasibility, safety, and outcome of RF energy delivery associated with the standard TS technique in patients undergoing a challenging TS puncture. METHODS AND RESULTS: Over a 14-month period, 162 consecutive patients underwent left atrial (LA) arrhythmia ablation in our centre. Among them, we enrolled 18 patients who failed LA access after two TS puncture attempts. In these patients, an RF delivery through TS (RF-TS) needle approach was used to reach the LA. All 18 patients had a successful RF-TS at the first attempt. A transoesophageal echocardiography (TEE) guidance and fluoroscopy views were used in all patients. No acute complications were reported. There have been no clinical sequelae after 10 +/- 4 months of follow-up following the RF-TS approach. Challenging TS punctures were more frequent in repeat LA catheterization when compared with the first LA catheterization, respectively, in 35% (13 of 37) and 4% (5 of 125) of the patients. CONCLUSION: Radiofrequency electrocautery delivery associated with the standard TS approach is a safe and reproducible technique to reach the left atrium, using the TEE guidance. This technique is helpful during repeat TS catheterization and in the presence of anatomical atrial septum abnormalities.

Ivabradine to treat inappropriate sinus tachycardia after the fast pathway ablation in a patient with severe pectus excavatum.

We present the case of a 49-year-old woman with atrioventricular nodal re-entrant tachycardia and a severe pectus excavatum. The patient underwent an electrophysiological study and fast pathway ablation. Fast pathway ablation was not done on purpose but accidentally, likely due to the abnormal position of the heart in the chest cavity in this patient suffering from severe pectus excavatum. Some hours after the ablation, the patient developed inappropriate sinus tachycardia (IST), complaining of dyspnea and fatigue. IST has been described as a complication of fast pathway ablation in 10% of the cases. In our case it was not possible to treat IST with beta-blockers due to an important lowering of the blood pressure. Digitalis, given as second choice, was not successful. Ivabradine-the specific sinus node If current inhibitors-was used to successfully lower the heart rate with immediate relief of symptoms. A 24-hour Holter, 10 days later, showed a complete control of the heart rate without any episode of IST. The patient was completely symptom free and able to undertake her normal daily activities without any discomfort. Our case confirms the potential use of ivabradine for indications other than coronary artery disease.

Transseptal puncture for atrial fibrillation ablation in a patient with previous Tirone David intervention: the role of real-time 3D transesophageal echocardiography guidance.

In this case report we describe the important role of real-time three-dimensional transesophageal echocardiography guidance in performing double transseptal puncture for atrial fibrillation ablation in a patient who underwent a previous Tirone David intervention.