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.

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.

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.

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).

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.

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.

Malignant ventricular arrhythmia in a case of adult onset of spinal muscular atrophy (Kugelberg-Welander disease).

We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg-Welander disease [KWD]) and malignant ventricular arrhythmias.

Improved cardiac performance through pacing-induced diaphragmatic stimulation: a novel electrophysiological approach in heart failure management?

AIMS: Pharmacological conditioning of the phrenic nerve can positively influence systolic performance, and diaphragm activation improves ventilatory function. Here we investigate whether pacing-induced diaphragmatic stimulation (PIDS) may improve left ventricular (LV) systolic function. METHODS AND RESULTS: We studied a total of 35 patients (4 females, mean age 67 +/- 9 years, ejection fraction 61 +/- 14%) within 7 days following open heart surgery. The haemodynamic impact of different PIDS and ventricular pacing configurations and coupling intervals was tested in 132 episodes. Success of PIDS was assessed using fluoroscopy and palpation. Left ventricular systolic performance was recorded using the electromechanical activation time (EMAT) obtained through acoustic cardiography. Eighteen subjects were tested in the catheter laboratory and 17 in the intensive care unit. For both groups, EMAT significantly improved when the diaphragm was stimulated 20 ms after the onset of ventricular pacing. In all instances, PIDS could be induced with or without causing patient symptoms, and LV systolic performance improvement was comparable in symptomatic and asymptomatic modes. No desensitization of the diaphragm was observed following PIDS delivery 4-6 and 24 h following open heart surgery. CONCLUSION: Pacing-induced diaphragmatic stimulation, if synchronized to the onset of ventricular contraction with a fixed, non-zero coupling delay, can improve LV systolic function reproducibly for at least 1 h without causing patient symptoms. The absence of diaphragm desensitization further underscores the potential of PIDS as a practical therapeutic approach in device-based heart failure management.

Early recovery of pulmonary vein conduction after cryoballoon ablation for paroxysmal atrial fibrillation: a prospective study.

AIMS: To assess the incidence of early pulmonary vein (PV) reconnection, characterize the anatomic features of the reconducting veins, and analyse the time course of their recovery in a series of consecutive patients with paroxysmal atrial fibrillation (AF) undergoing ablation with the Arctic Front Cryoballoon. METHODS AND RESULTS: We prospectively enrolled 26 patients (20 males; age 55.4 +/- 4.1) for circumferential PV cryoballoon isolation for highly symptomatic paroxysmal AF. Following isolation of all veins, we analysed PV potentials in each vein after 30 and 60 min with a circular mapping catheter. After successful electrical isolation of all 104 PV's, recurrence was observed only in three veins (2.8%) after 30 min. Two further cryoballoon applications in each of these veins lead to their isolation. These veins were still electrically disconnected at 60 min. No PV reconnection was observed in any of the other 101 veins (97.1%) at 30 and 60 min. CONCLUSION: Cryoballoon ablation of the PV's ostia is a very effective technique to achieve electrical isolation, with a very low rate of early reconnection.

Novel trans-septal approach using a Safe Sept J-shaped guidewire in difficult left atrial access during atrial fibrillation ablation.

Nowadays, trans-septal (TS) puncture is a relatively safe and straightforward procedure in experienced hands. However, in the presence of a thick, aneurysmatic or extremely elastic fossa ovalis crossing the septum might be challenging. We here describe the use of a novel guidewire that permits easy and safe 'over the wire' TS access during atrial fibrillation ablation.

Noninvasive detection of left ventricular systolic dysfunction by acoustic cardiography in cardiac failure patients.

BACKGROUND: Despite its shortcomings, ejection fraction (EF) is widely used to detect left ventricular systolic dysfunction (LVSD) as has prolonged QRS duration as indirect evidence of LVSD. However, acoustic cardiography provides other parameters for detecting LVSD without these limitations. One parameter, the electromechanical activation time (EMAT), is prolonged in LVSD. We compared the abilities of acoustic cardiography, EF, and QRS duration to detect LVSD. METHODS AND RESULTS: We studied a sample of 108 patients who underwent elective diagnostic cardiac catheterization. The diagnostic findings included left ventricular filling pressures, angiographic EF, and maximum left ventricular dP/dt. We defined LVSD as a maximum left ventricular dP/dt of <1600 mm Hg/s. At thresholds of 35% and 50% to detect LVSD, the sensitivities of angiographic EF were 39% and 74%; specificities were 89% and 70%, respectively. At QRS duration thresholds of 100 and 120 ms, sensitivities were 63% and 35%; specificities, 63% and 89%, respectively. At thresholds of 100 and 110 ms, EMAT had sensitivities of 53% and 42%, and specificities of 90% and 100%, respectively. EMAT performed better than LV EF or QRS duration in hemodynamic subgroups. CONCLUSIONS: Acoustic cardiography is a convenient, automated diagnostic method whose performance for detecting LVSD exceeds both angiographic EF and QRS duration alone.

Recorded heart sounds for identification of ventricular tachycardia.

BACKGROUND: The ECG discrimination of ventricular tachycardia (VT) vs. supraventricular tachycardia (SVT) is both important and often difficult. In this study, we tested the hypothesis that recorded digital cardiac acoustical data reflect hemodynamic changes that can be used for VT detection. METHODS: We studied 57 subjects (42 males, mean age 57, range 24-83 years) who had undergone electrophysiological testing for known and suspected cardiac arrhythmias. Acoustic cardiography (Audicor, Inovise Medical, Inc.) was performed during each subject's electrophysiological study. We evaluated the ability of S1 intensity and S1 variability to discriminate between VT and supraventricular rhythm. RESULTS: The 57 subjects had 17 episodes of VT and 76 episodes of supraventricular rhythm--including 22 episodes of SVT. VT had a lower S1 intensity and higher S1 variability than supraventricular rhythm (2.63+/-1.78 mV vs. 4.70+/-5.03 mV and 0.45+/-0.24 vs. 0.21+/-0.11, respectively). Conversely, left bundle branch block, right bundle branch block or SVT did not affect either S1 intensity or its variability. Ventricular pacing increased S1 variability but did not affect S1 intensity. The sensitivity of S1 variability for detecting VT was 50% at 100% specificity. CONCLUSION: VT is associated with both decreased S1 intensity and increased beat-to-beat S1 variability. The electronic recording and digital processing of digital heart sound data is useful for identifying VT and may facilitate the differential diagnosis of clinically important tachyarrhythmias, particularly in emergency situations where advanced techniques such as electrophysiology studies are not available.

Comparison of different approaches for optimization of atrioventricular and interventricular delay in biventricular pacing.

AIMS: It has been shown that optimizing atrioventricular (AV) and interventricular (VV) delay improves cardiac performance in patients with biventricular pacemakers. However, there is no standard method for optimization available yet. The aim of this study was to compare echocardiographic parameters-displacement imaging, A wave duration, and aortic velocity time integral (VTI)-and acoustic cardiography derived electromechanical activation time (EMAT) using different approaches of AV and VV delay optimization. We tested whether the initial optimization of the AV interval followed by VV optimization at that optimal AV interval or initial optimization of the VV interval followed by AV optimization at the determined optimal VV interval was accurate and consistent, and how this compared to testing every conceivable combination of AV and VV intervals available. METHODS AND RESULTS: A group of 20 patients with biventricular pacemakers was included. Displacement imaging, A wave duration, and aortic VTI were determined at different combinations of AV (100, 150, 200, 250 ms) and VV (RV40, 0, LV40 ms) intervals. If AV duration was determined first, displacement imaging identified the best setting in 8/20, aortic VTI in 10/20, A duration in 13/20, and EMAT in 18/20 patients. With VV duration determined first, the best setting was more difficult to identify regardless of the method used. There was a poor agreement in optimal AV and VV delays of the different methods, and there was no single patient in whom all four methods yielded the same delay combination. CONCLUSION: It is advisable to measure a full grid of AV and VV delays to identify optimal settings rather than optimizing one of the two delays first. Different techniques for delay optimization resulted in different optimal delay combinations.

First experience with real-time three-dimensional transoesophageal echocardiography-guided transseptal in patients undergoing atrial fibrillation ablation.

AIMS: Transseptal (TS) puncture during atrial fibrillation (AF) ablation is a relatively safe procedure in experienced hands. However, major and minor complications cannot be completely ruled out. Real-time three-dimensional transeosophageal echocardiography (RT 3D TEE) is a novel imaging technology that permits direct visualization of the fossa ovalis in a 3D perspective, thereby sensibly lowering the likelihood of potential adverse effects during TS. In our study, we describe the technique and assess the feasibility, advantages, and safety of this novel imaging method in guiding TS puncture in a series of consecutive patients undergoing AF ablation. METHODS AND RESULTS: We performed TS puncture guided by RT 3D TEE under general anaesthesia in 24 consecutive patients (16 male, 55.4 +/- 8.1 years) undergoing ablation for drug refractory AF. The fossa ovalis could clearly be seen and easily be distinguished from surrounding anatomical structures in all 24 patients. All punctures required a single attempt to access left atrium. Mean orientation of the needle hub when puncturing was 4.30 o'clock (ranging from 3 o'clock to 6.30 o'clock), and mean distances from the needle tip to the aortic and to the posterior wall were, respectively, 13.5 +/- 7 and 35 +/- 7.3 mm. Total fluoroscopic time was 120.6 +/- 34 s. No major or minor complications were experienced. CONCLUSION: Real-time three-dimensional transeosophageal is a very useful tool in guiding TS puncture in patients undergoing AF ablation with the invaluable advantage of the 3D direct visualization of the fossa ovalis. This permits fast and safe transatrial access with a single puncture attempt.

Improved response to cardiac resynchronization therapy through optimization of atrioventricular and interventricular delays using acoustic cardiography: a pilot study.

BACKGROUND: The purpose of this pilot study was to determine the utility of acoustic cardiography for the optimization of atrioventricular (AV) and interventricular (VV) delays in cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We evaluated 14 patients (86% male, mean age 64 +/- 9 years, mean time since implant 15 +/- 18 months). Subjects were enrolled >10 weeks after CRT implant. Spiroergometry and 2-dimensional/3-dimensional echocardiography were used to assess cardiac performance for "out-of-the-box" settings (baseline settings: AV 120 ms, VV 0 ms) versus optimal settings (determined by acoustic cardiography). Cardiac performance measurements were performed 6 weeks after settings were modified. Optimal AV/VV settings were determined based on the lowest electromechanical activation time (EMAT, the time from the onset of QRS to the mitral valve component of the first heart sound). Statistical analysis was performed using a paired 2-tailed Student's t-test. In comparison to "out-of-the-box" settings, AV/VV delay optimization with acoustic cardiography improved cardiac performance as indicated by significant changes in work capacity, maximum oxygen uptake, oxygen pulse, ejection fraction, end-systolic volume, and velocity-time integral in left ventricular outflow tract. CONCLUSIONS: AV and VV optimization by acoustic cardiography produces significant improvements in objective clinical and hemodynamic parameters in comparison to typical "out-of-the-box" settings.

How much is too much? Oligosymptomatic presentation after 11.5 g of diphenhydramine.

We report the case of a 47-year-old male obese Caucasian patient presenting 2 hours after ingestion of 11.5 g of diphenhydramine. Despite this excessive overdose, he showed only a few hours of impaired consciousness and no further symptoms. A diphenhydramine plasma concentration of 15,352 nmol/L was measured 8 hours after the overdose ingestion. A heterogeneous CYP2D6 extensive metabolizer genotype excludes a pharmacokinetic explanation for this unusually oligosymptomatic presentation. However, the patient suffered from longstanding, refractory depression despite numerous treatment attempts with various drugs, pointing to the possibility of decreased pharmacodynamic responsiveness for therapeutic and toxic effects.