Unexplained syncope: implications of age and gender on patient characteristics and evaluation, the diagnostic yield of an implantable loop recorder, and the subsequent treatment.

BACKGROUND: Syncope is a common clinical problem with a variety of underlying mechanisms, some of which occur more frequently in 1 of the sexes or at a certain age. HYPOTHESIS: There may be clinically significant age- and gender-related differences in patients with unexplained syncope. METHODS: Five hundred seventy patients (54% women) with unexplained syncope received an implantable loop recorder (ILR) and were followed until diagnosis or for at least 1 year. RESULTS: Women were older and more prone to severe trauma during syncope (40.8% vs 29.9%, P = 0.007), and hospitalization was more common at ≥65 years (P = 0.003) without gender difference. Muscle spasms or grand mal seizures were more common in men and at <65 years old. Carotid sinus pressure, exercise testing, coronary angiography and magnetic resonance imaging/computed tomography scans were more commonly performed in men, whereas no test was more common in women. Tilt testing, exercise test, electroencephalography, and neurological or psychiatric evaluation were more common at ≥65 years. There were no age- or gender-related differences in the diagnostic yield of the ILR, whereas patients ≥65 years old more often received specific treatment based on ILR data. CONCLUSIONS: Gender and/or age had relevance for the clinical evaluation, rate of recurrence, and subsequent specific treatment but not for the diagnostic yield of the ILR.

Implantable defibrillators with enhanced detection algorithms: detection performance and safety results from the PainFree SST study.

BACKGROUND: Implantable defibrillators (ICD) are highly effective in reducing arrhythmia-related mortality. ICD shock therapy has been shown to increase psychological distress, health care utilization, and is associated with increased mortality. The Protecta ICDs (Medtronic Inc., Minneapolis, MN, USA) have algorithms designed to reduce unnecessary and inappropriate shock therapy. METHODS AND RESULTS: The PainFree SmartShock™ Technology (PainFree SST) study is a prospective, multicenter, clinical trial with two consecutive phases, a premarket phase safety study and a postmarket phase effectiveness study. We report the results of the PainFree SST safety study. The premarket phase aimed to investigate safety in the first year postimplant, and to determine if the novel algorithms (T-wave discrimination, right ventricular lead noise discrimination and confirmation+) affect appropriate ventricular fibrillation (VF) detection. Patients (total: n = 246 [male 78%, mean age 63 year, primary prevention indication in 76%]) were implanted either with a Protecta XT dual-chamber ICD (n = 114 [46%]) or a defibrillator with cardiac resynchronization therapy (n = 132 [54%]). Appropriate VF detection was measured during VF induction at implantation when the novel algorithms were programmed ON. A two-second delay in VF detection was classified as clinically significant. No delay in VF detection was observed with all algorithms programmed ON. No unanticipated serious adverse device effects occurred during first year postimplant. CONCLUSION: The results of the premarket phase of the PainFree SST trial demonstrate the safety of the Protecta XT defibrillators. Detection of induced VF was not delayed with SmartShock™ algorithms ON.

Managed ventricular pacing compared with conventional dual-chamber pacing for elective replacement in chronically paced patients: results of the Prefer for Elective Replacement Managed Ventricular Pacing randomized study.

BACKGROUND: Several studies have shown that unnecessary right ventricular pacing has detrimental effects. OBJECTIVE: To evaluate whether minimization of ventricular pacing as compared with standard dual-chamber pacing (DDD) improves clinical outcomes in patients referred for pacemaker or implantable cardioverter-defibrillator (ICD) replacement. METHODS: In an international single-blind, multicenter, randomized controlled trial, we compared DDD with managed ventricular pacing (MVP), a pacing mode developed to minimize ventricular pacing by promoting intrinsic atrioventricular conduction. We included patients referred for device replacement with >40% ventricular pacing, no cardiac resynchronization therapy upgrade indication, no permanent atrial fibrillation (AF), and no permanent complete atrioventricular block. Follow-up was for 2 years. The primary end point was cardiovascular hospitalization. The intention-to-treat analysis was performed by using Kaplan-Meier method and the log-rank test. RESULTS: We randomized 605 patients (556 referred for pacemaker and 49 referred for ICD replacement; mean age 75 ± 11 years; 365 [60%] men, at 7.7 ± 3.3 years from first device implantation) to MVP (n = 299) or DDD (n = 306). We found no significant differences in the primary end point cardiovascular hospitalization (MVP: 16.3% vs DDD: 14.5%; P = .72) and the secondary end point persistent AF (MVP: 15.4% vs DDD: 11.2%; P = .08), permanent AF (MVP: 4.1% vs DDD: 3.1%; P = .44), and composite of death and cardiovascular hospitalization (MVP: 23.9% vs DDD: 20.2%; P = .48). MVP reduced right ventricular pacing (median 5% vs 86%; Wilcoxon, P < .0001) as compared with DDD. CONCLUSIONS: In patients referred for pacemaker and ICD replacement with clinically well-tolerated long-term exposure to >40% ventricular pacing in the ventricle, a strategy to minimize ventricular pacing is not superior to standard DDD in reducing incidence of cardiovascular hospitalizations.

Early versus delayed implantation of a loop recorder in patients with unexplained syncope--effects on care pathway and diagnostic yield.

BACKGROUND: This study looked to assess the care pathway and diagnostic yield in patients who received an implantable loop recorder (ILR) after an "initial phase of the diagnostic work-up" (initial work-up) or after a "full evaluation" of unexplained syncope. METHODS AND RESULTS: Physicians classified the timing of an ILR implant in 514 patients as either following an "initial work-up" (n=128; 25%) or "full evaluation" (n=386; 75%). Patients with an "initial work-up" underwent a median (IQ range) of 8 (6-14) tests prior to ILR implant compared to 14 (10-21) tests after "full evaluation" (p<0.0001). Hospitalization and injury before implant were less common in patients with an "initial work-up": 53 vs. 75%, p<0001, and 23% vs. 39%, p<0.001, as were visits to specialists, e.g. neurologist, 32% vs. 50%, p<0.001. At one year after implant, the syncope recurrence rate was 32% in the initial work-up group and 36% in the full evaluation group, and the incidence of recurrences with an ILR-guided diagnosis was 52% and 75% respectively. Diagnoses were cardiac in 90% after "initial work-up" vs. 79% after "full evaluation". CONCLUSIONS: Patients who only underwent an "initial work-up" had fewer investigations and a lower incidence of injury or hospitalization. The diagnostic yield from the ILR was high in both groups. Patients in both groups underwent more investigations than suggested in the ESC guidelines and could have benefitted from limiting the initial evaluation before an ILR is implanted.

Use of an implantable loop recorder to increase the diagnostic yield in unexplained syncope: results from the PICTURE registry.

AIMS: To collect information on the use of the Reveal implantable loop recorder (ILR) in the patient care pathway and to investigate its effectiveness in the diagnosis of unexplained recurrent syncope in everyday clinical practice. METHODS AND RESULTS: Prospective, multicentre, observational study conducted in 2006-2009 in 10 European countries and Israel. Eligible patients had recurrent unexplained syncope or pre-syncope. Subjects received a Reveal Plus, DX or XT. Follow up was until the first recurrence of a syncopal event leading to a diagnosis or for ≥1 year. In the course of the study, patients were evaluated by an average of three different specialists for management of their syncope and underwent a median of 13 tests (range 9-20). Significant physical trauma had been experienced in association with a syncopal episode by 36% of patients. Average follow-up time after ILR implant was 10±6 months. Follow-up visit data were available for 570 subjects. The percentages of patients with recurrence of syncope were 19, 26, and 36% after 3, 6, and 12 months, respectively. Of 218 events within the study, ILR-guided diagnosis was obtained in 170 cases (78%), of which 128 (75%) were cardiac. CONCLUSION: A large number of diagnostic tests were undertaken in patients with unexplained syncope without providing conclusive data. In contrast, the ILR revealed or contributed to establishing the mechanism of syncope in the vast majority of patients. The findings support the recommendation in current guidelines that an ILR should be implanted early rather than late in the evaluation of unexplained syncope.

MolLoc: a web tool for the local structural alignment of molecular surfaces.

MolLoc stands for Molecular Local surface comparison, and is a web server for the structural comparison of molecular surfaces. Given two structures in PDB format, the user can compare their binding sites, cavities or any arbitrary residue selection. Moreover, the web server allows the comparison of a query structure with a list of structures. Each comparison produces a structural alignment that maximizes the extension of the superimposition of the surfaces, and returns the pairs of atoms with similar physicochemical properties that are close in space after the superimposition. Based on this subset of atoms sharing similar physicochemical properties a new rototranslation is derived that best superimposes them. MolLoc approach is both local and surface-oriented, and therefore it can be particularly useful when testing if molecules with different sequences and folds share any local surface similarity. The MolLoc web server is available at http://bcb.dei.unipd.it/MolLoc.

Effective labeling of molecular surface points for cavity detection and location of putative binding sites.

We present a method for detecting and comparing cavities on protein surfaces that is useful for protein binding site recognition. The method is based on a representation of the protein structures by a collection of spin-images and their associated spin-image profiles. Results of the cavity detection procedure are presented for a large set of non-redundant proteins and compared with SURFNET-ConSurf. Our comparison method is used to find a surface region in one cavity of a protein that is geometrically similar to a surface region in the cavity of another protein. Such a finding would be an indication that the two regions likely bind to the same ligand. Our overall approach for cavity detection and comparison is benchmarked on several pairs of known complexes, obtaining a good coverage of the atoms of the binding sites.

Discovery of similar regions on protein surfaces.

Discovery of a similar region on two protein surfaces can lead to important inference about the functional role or molecular interaction of this region for one of the proteins if such information is available for the other. We propose a new characterization of protein surfaces based on a spin-image representation of the surfaces that facilitates the simultaneous search of the entire surface of each of two proteins for a matching region. For a surface point, we introduce spin-image profiles that are related to the degree of exposure of the point to identify structurally equivalent surface regions in two proteins. Unlike some related methods, we do not assume that a known fixed region of one of the protein surfaces is to be matched on the other protein surface. Rather, we search for the largest similar regions on each of the two surfaces. In spite of the fact that this approach is entirely geometric and no use is made of physicochemical properties of the protein surfaces or fold information, it is effective in identifying similar regions on both surfaces even when the region corresponds to a binding site on one of the proteins. The discovery of similar regions on two or more proteins also has implications for drug design and pharmacophore identification. We present experimental results from datasets of more than 50 protein surfaces.