Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

A pilot histologic comparison of bone-to-implant contact between phosphate-coated and control titanium implants in the canine model.

PURPOSE: This study tested the null hypothesis that phosphate-treated titanium implants would perform no differently on mineral apposition rates (MARs), new bone-to-implant contact (new BIC), and total bone-to-implant contact (total BIC) compared to standard titanium implants. MATERIALS AND METHODS: Forty 3.3×8.0-mm titanium implants, either phosphate-treated or untreated, were placed in the mandibles of five foxhounds following 6 weeks of postextraction healing. The untreated implants (control) had sandblasted, acid-etched (SLA) surfaces, while the treated implants were electrolytically phosphorylated at 50 volts (T50) or 100 volts (T100). Confocal and histologic analyses were performed on all the implants after 4 weeks of healing. RESULTS: The MARs could not be analyzed due to a lack of delineation between the three bone markers. New BIC results for control implants ranged from 6.0% to 56.0% with a mean of 23.92% and standard deviation (SD) of 13.29%; T50 implants ranged from 8.0% to 43.0% with a mean of 22.29% and SD of 10.26%; and T100 implants ranged from 0.0% to 47.0% with a mean of 17.43% and SD of 11.40%. Total BIC results for control implants ranged from 8.0% to 68.0% BIC with a mean of 41.4% and SD of 19.3%; T50 implants ranged from 21.0% to 65.0% with a mean of 43.7% and SD of 15.2%; and T100 implants ranged from 5.0% to 68.0% with a mean of 38.0% and SD of 19.5%. CONCLUSION: Within the limitations of this pilot study, no significant differences in new BIC or total BIC were found between the three implant groups (C, T50, and T100). Given the very large sample size required to show clinically significant differences, phosphated surfaces do not appear to provide additional advantages to SLA surfaces.

Coronary-cameral fistulas in adults (first of two parts).

This is a case series and review of the literature adding 11 new cases. Coronary-cameral fistulas (CCFs) are infrequent anomalies which are in general co-incidentally found during diagnostic coronary angiography (CAG). To delineate the characteristics of congenital and acquired CCFs in adults, we performed a PubMed search for papers dealing with congenital or acquired CCFs in adults. Publications on coronary-vascular fistulas or paediatric subjects were not included. From the world literature, a total of 243 adult patients were identified who had congenital (65%) or acquired (35%) CCFs. In this review, which is part one of a two-part series on CCFs, we describe and discuss the congenital fistulas, give an overview on the published literature and report details of our own series of 11 patients with MMFs and solitary macro CCFs. Of the congenital group, 85% were small or large solitary macro CCFs (cut-off 1.5 mm) and 15% were coronary artery-ventricular multiple micro-fistulas (MMFs). Apical hypertrophic cardiomyopathy was reported in some of the reviewed subjects with MMFs (3/24 = 13%) but not was seen in our own series. Conservative medical management was generally the treatment of choice in congenital MMFs; prophylactic implantable cardioverter defibrillators (ICD) were implanted in 2/24 (8%) of subjects, especially when extensive micro-fistulisations were involved. None of the patients of our own series required an ICD, as the MMFs were of limited size. Congenital or acquired CCFs in adults are infrequent anomalies having a wide spectrum of clinical presentation may varies from asymptomatic to severely devastating states requiring different treatment modalities.

Coronary-cameral fistulas in adults: Acquired types (second of two parts).

Acquired coronary artery fistulas (CCFs) are infrequently detected during conventional coronary angiography. To delineate the characteristics of congenital (first part) and acquired (second part) CCFs in adults, a PubMed search was conducted for papers dealing with congenital or acquired CCFs. None of the publications describing patients with coronary-vascular fistulas were included. Papers dealing with pediatric subjects were excluded. From the world literature, a total of 243 adult patients were selected who had congenital (n = 159/243, 65%) and acquired (n = 84/243, 35%) CCFs. Among the acquired types (n = 72, 85.7%) were traumatic (iatrogenic (n = 65/72, 90%), accidental (n = 7/72, 10%) and (n = 12, 14.3%) spontaneously developing in relation to severe coronary atherosclerosis or myocardial infarction. A high incidence of spontaneous resolution of iatrogenic CCFs resulting from endomyocardial biopsy or following post-septal myectomy was reported. Spontaneous CCFs associated with myocardial ischemia or infarction resolved completely in 8% of the subjects. Early surgical intervention was the treatment of choice in acquired traumatic accidental CCFs. The congenital types are addressed in a previous issue of this journal (first part). In this review (second of two parts, part II), we describe the acquired coronary-cameral fistulas.

Effects of sprayer configuration on efficacy for the control of scab on crabapple using electron beam analysis.

Foliar diseases like apple scab result in significant economic losses to growers each year. Assessment in past studies involved only macroscopic disease ratings. More complete knowledge of the fate and behavior of fungicide has been needed to reduce pesticide use with less off-target contamination. Field studies were conducted in a production nursery for over 4 years. A moderately susceptible cultivar of ornamental crabapple, Malus spp. cv "Candied Apple", was sprayed with a fungicide using two sprayer/nozzle configurations. The fungicide used in this study was Mankocide, combination of Cu(OH)2 and mancozeb that permitted electron beam analysis (EBA) identification based on the presence of Cu, MN and Zn in the molecule and formulation. EBA was conducted using a cold field emission scanning electron microscopy and energy dispersive x-ray microanalyzer. Fresh leaf samples were placed on sticky stubs after each fungicide treatment. The presence or absence of fungal conidia and fungicide residue were measured. EBA permitted direct visualization and identification of the pathogens, morphologically, and chemical characterization of fungicide present. EBA was useful to quantify disease control related to fungicide coverage, sprayer configuration and treatment efficacy.

Delayed paced ventricular activation in the long QT syndrome is associated with ventricular fibrillation.

BACKGROUND: LQTS may cause sudden cardiac death (SCD), but the mechanisms linking gene mutations to ventricular fibrillation (VF) are unclear. OBJECTIVE: To determine whether ventricular activation delays in congenital long QT syndrome (LQTS) are associated with VF and to describe these delays clinically by measuring activation through ventricular myocardium after a premature extrastimulus. METHODS: Forty-six patients with LQTS, including 16 with VF (LQTS VF) were investigated, and the results were compared with those from 24 patients with hypertrophic cardiomyopathy and VF (HCM VF). Electrograms in response to premature stimuli were analyzed for increases in electrogram duration (DeltaED) and the S1S2 coupling intervals at which electrogram latency starts to increase (S1S2(delay)). Two piecewise continuous straight line segments were fitted to the last electrogram deflection as a function of S1S2 interval in the LQTS and HCM VF populations, and the difference in their gradient (alpha) was taken as an index of the abruptness of the onset of this delay. RESULTS: Thirteen LQTS VF and six LQTS non-VF patients had values of DeltaED and S1S2(delay) comparable to those in HCM VF patients, while the remainder (three LQTS VF and 24 LQTS non-VF) had lower values (P<.001). There was only a weak correlation between delay and the corrected QT interval. The HCM and LQTS VF patients could be separated by the value of alpha (P<.01), with the LQTS patients having a more abrupt onset of delay. CONCLUSIONS: Large delays in ventricular activation after an extrastimulus occur in patients with the LQTS, especially those with VF. The change in delay is abrupt in the LQTS, indicating sudden block to activation creating a dynamic substrate for arrhythmogenesis.

Where to draw the mitral isthmus line in catheter ablation of atrial fibrillation: histological analysis.

AIMS: A linear lesion between the left inferior pulmonary vein orifice and mitral annulus, the so-called mitral isthmus, may improve the success of catheter ablation for atrial fibrillation. Gaps in the lesion line, however, may facilitate left atrial flutter. The aim of the study was to determine the optimal location of the lesion line by serial sectioning of the isthmus area. METHODS AND RESULTS: In a post-mortem study of 16 patients with normal left atria, serial sections of the isthmus area from 10 mm superior to and 30 mm inferior to the isthmus were studied by light microscopy. The length of the isthmus was 35+/-7 mm. On average, the muscle sleeve around the coronary sinus ended 10 mm inferior to the isthmus. The prevalence of a ramus circumflexus <5 mm from the endocardial surface, decreased from 60% in the most superior section to 0% in the most inferior section. Atrial arteries were frequently present in all sections. CONCLUSIONS: The thickness of atrial myocardium, the ramus circumflexus sometimes very close to the endocardium, a myocardial sleeve around the coronary sinus, and local cooling by atrial arteries and veins may complicate the creation of conduction block in the mitral isthmus.

ICD: a qualitative study of patient experience the first year after implantation.

BACKGROUND: The experiences of how patients live with an implantable cardioverter defibrillator are still poorly understood. Only a few qualitative studies have investigated this phenomenon. This paper was undertaken as part of a larger project to evaluate quality of life and psychological well-being in those survivors of cardiac arrest who have received an implantable cardioverter defibrillator. AIMS AND OBJECTIVES: The aim of this qualitative study was to explore how implantable cardioverter defibrillator recipients perceive their lives during the first year after implantation of the device. METHODS: A sample of 21 patients who received an implantable cardioverter defibrillator was interviewed during three consecutive periods: one, six and 12 months postdischarge from the hospital. The semi-structured interviews were based on insights gained from a literature review. The transcripts were subjected to content analysis. RESULTS: Analysis of the data revealed seven major categories: physical deterioration, cognitive changes, perceived social support, dependency, contact with the doctor, confrontation with mortality and uncertainty surrounding having a shock. Anxiety, uncertainty, disappointment, frustration, unexpected barriers, acceptance of and dependency on the implantable cardioverter defibrillator played a major role in the lives of implantable cardioverter defibrillator recipients. Well-being improved throughout the year. During the first months after discharge from the hospital the focus was on regaining physical health. During the early postimplantation period both the implantable cardioverter defibrillator recipient and family members had adapted to the situation. Reflection on the impact and consequences of the cardiac arrest was reported more often in the late postimplantation period. CONCLUSIONS: Content analysis is a resourceful approach giving answers to questions that have hardly been addressed within the domain of cardiology. Implantable cardioverter defibrillator recipients face a complex first year, especially the first 6 months. Cognitive deterioration and confrontation with mortality are problems that need to be researched further. RELEVANCE TO CLINICAL PRACTICE: Caregivers are able to explain to future patients what they can expect in the first year after implantation. Caregivers may become more receptive to physical, psychological and social limitations and to emotional and social problems that occur in implantable cardioverter defibrillator recipients, enabling them to act upon them.

A geometric model of mortality and crop protection for insects feeding on discrete toxicant deposits.

Current theory governing the biological effectiveness of toxicants stresses the dose-response relationship and focuses on uniform toxicant distributions in the insect's environment. However, toxicants are seldom uniformly dispersed under field conditions. Toxicant distribution affects bioavailability, but the mechanics of such interactions is not well documented. We present a geometric model of the interactions between insects and heterogeneously distributed toxicants. From the model, we conclude the following: 1) There is an optimal droplet size, and droplets both smaller and larger than this optimum will decrease efficacy. 2) There is an ideal droplet distribution. Droplets should be spaced based on two criteria: calculate the allowable damage, double this quantity, and one lethal deposit should be placed in this area; and define the quantity of leaf the larva could eat before the toxicant decays below the lethal level and place one lethal deposit within this area. 3) Distributions of toxicant where deposits are sublethal will often be ineffective, but the application is wasteful if deposits contain more than a lethal dose. 4) Insect behavior both as individuals and collectively influences the level of crop production provided by an application. This conclusion has implications for both crop protection and natural plant-insect interactions. The effective utilization of new more environmentally sensitive toxicants may depend on how well we understand how heterogeneous toxicant distributions interact with insect behavior to determine the biological outcome.

Comparing greenhouse sprayers: the dose-transfer process.

Three sprayers were evaluated for their affect on retention and efficacy: a carbon dioxide powered high-volume sprayer, a DRAMM coldfogger, and an Electrostatic Spraying Systems (ESS) sprayer with air-assistance. The active ingredients used were spinosad and azadirachtin. The plant canopy was constructed in the greenhouse using potted soybeans (Glycine max (L) Merrill cr Pioneer 9392). Application efficacy with spinosad was assessed using thrips [Western flower thrips, Frankliniella occidentalis (Pergande)] and mite (two-spotted spider mite, Tetranychus urticae Koch) abundance on shoots and leaves. Application efficacy with azadirachtin was assessed using thrips and aphid (soybean aphid, Aphis glycines Matsumura) abundance on shoots and leaves. The atomization characteristics of each sprayer were measured using an Aerometrics phase/Doppler particle analyzer (PDPA) 100-1D. The results of four tests are presented. Two tests used each sprayer according to manufacturer recommendations. These are 'recommended volume' tests that confound differences in toxicant distribution caused by the sprayer with differences caused by changes in application volume. The other two tests were 'constant volume' tests in which all three sprayers were used to deliver the same application volume. Both types of test gave differences between sprayers in retention of toxicant, but only the recommended volume tests showed significant effects of the sprayers on pest abundance. We attribute this difference to the role played by changing application volumes in the dose-transfer process. The constant-volume tests showed that application equipment influences efficacy.

Evaluation of a contraction flow field on hydrodynamic damage to entomopathogenic nematodes-A biological pest control agent.

Mechanized production and delivery of biological pesticides presents challenges because the biological agents must remain viable during these processes. This study evaluates the effect of flow through an abrupt contraction, where flow characteristics similar to that found within bioprocesses and spray equipment are developed, on damage to a benchmark biological pest control agent, entomopathogenic nematodes (EPNs). An opposed-pistons, contraction flow device generated volumetric flow rates ranging between 8.26 cm(3)/s and 41.3 cm(3)/s. Four EPN species were evaluated: Heterorhabditis bacteriophora, Heterorhabditis megidis, Steinernema carpocapsae, and Steinernema glaseri. Damage was quantified by counting living and dead EPNs. Optical and cold field emission scanning electron microscope (CFE-SEM) images provided qualitative information to describe how the damage occurred. The experimental flow field was completely described using FLUENT, a computational fluid dynamics program. Local flow parameters computed in FLUENT were compared to EPN damage. The type and extent of damage varied between EPN species. Damaged Heterorhabditis spp. generally remained whole with an internal rupture located near the center of the body, while Steinernema spp. most often broke into several pieces. The fast-transient stress field generated at the entrance to the contraction caused a momentary tensile loading and then relaxation that damaged the EPNs. At high flow rates, the tensile stresses became large enough to cause failure of the EPN structural membrane. The relative elasticity of the EPN structural membrane may explain the differences in damage observed between the species. It is speculated that the internal rupture of the Heterorhabditis spp. occurred during the processes of stretching and relaxing at the contraction entrance. Appreciable damage was observed at lower average energy dissipation rates for H. bacteriophora (1.23E + 8 W/m(3)), H. megidis (1.72E + 8 W/m(3)), and S. glaseri (2.89E + 8 W/m(3)) compared to S. carpocapsae (3.70E + 8 W/m(3)). Energy dissipation rates within an equipment component should be kept below 1E + 8 W/m(3) to avoid hydrodynamic damage to EPNs. The relationship between average energy dissipation and EPN damage provides important information for future simulation efforts of actual spray equipment components.

Tissue discontinuities affect conduction velocity restitution: a mechanism by which structural barriers may promote wave break.

BACKGROUND: The mechanism by which structural barriers promote wave break and fibrillation is unclear. Conduction velocity (CV) restitution is an important determinant of wave break. Abnormal CV restitution is associated with ventricular fibrillation in patients with heart disease and arises preferentially in fibrotic myocardium. We hypothesize that tissue discontinuities imposed by structural barriers cause abnormal CV restitution. METHODS AND RESULTS: Tissue discontinuities were simulated in cultures of neonatal rat heart cells grown in 8-armed star patterns. Premature stimulation was applied at the extremity of 1 arm (n=12) while extracellular electrograms were recorded at 24 sites throughout the star. Action potentials were recorded at the following 3 sites: in the stimulated arm and at the discontinuity both proximal to and distal from the star center. Extracellular recordings revealed progressive increases in activation delay (indicative for abnormal CV restitution) only at the discontinuity from arms proximal to the star center. The mean increase in delay was 0.81+/-0.41 ms/10 ms for recording sites proximal to and 3.13+/-0.58 ms/10 ms for sites distal from this discontinuity. Depolarizing currents were determined in single cells during premature stimulation and for voltage configurations similar to those arising at the discontinuity. Both voltage-clamp measurements and computer simulations showed that delay at the discontinuity was associated with biphasic, prolonged activation and delayed inactivation of depolarizing current. CONCLUSIONS: Tissue discontinuities cause abnormal CV restitution. Rapid increase in activation after an initial slow activation and delayed inactivation at the discontinuity lengthen the duration of depolarizing current and cause the abnormal restitution.

Sudden death in noncoronary heart disease is associated with delayed paced ventricular activation.

BACKGROUND: Slowed or delayed myocardial activation and dispersed refractoriness predispose to reentrant excitation that may lead to ventricular fibrillation (VF). Increased ventricular electrogram duration (DeltaED) in response to extrastimuli and increased S1S2 coupling intervals at which electrogram duration starts to increase (S1S2delay) are seen both in hypertrophic cardiomyopathy (HCM) in those at risk of VF and in patients with idiopathic VF (IVF). METHODS AND RESULTS: DeltaED and S1S2delay have been measured using paced electrogram fractionation analysis in 266 patients with noncoronary heart disease. Of these, one group of 61 patients had a history of VF and included 21 HCM, 17 IVF, 13 long-QT syndrome (LQTS), 5 dilated cardiomyopathy (DCM), and 5 others. These were compared with 205 patients with similar diseases with no VF history (non-VF group) and a control group (n=12) without heart disease. Results from HCM VF patients (DeltaED, 19+/-3.3 ms; S1S2delay, 350+/-9.7 ms) differed sharply from observations in HCM non-VF patients (DeltaED, 7.3+/-1.35 ms; S1S2delay, 312+/-6.7 ms; P<0.001). DCM VF patients had longer delays (DeltaED, 14.3+/-5.9; S1S2delay, 344+/-11.2) than DCM non-VF patients (DeltaED, 5.8+/-1.87 ms; S1S2delay, 311+/-5.7 ms; P<0.001), with major differences also seen comparing LQTS VF (DeltaED, 12.4+/-5.3 ms; S1S2delay, 343+/-13.8 ms) and LQTS non-VF patients (DeltaED, 11.0+/-2.7 ms; S1S2delay, 320+/-5.4 ms; P<0.001). IVF patients had both severely abnormal and normal areas of myocardium. CONCLUSIONS: Slowed or delayed myocardial activation is a common feature in patients with noncoronary heart disease with a history of VF, and its assessment may allow the prospective prediction of VF risk in these patients.

Radiofrequency catheter ablation of junctional ectopic tachycardia with preservation of atrioventricular conduction.

Junctional ectopic tachycardia is a relatively rare disorder, frequently refractory to drug therapy, and with a poor prognosis in childhood. This report describes a successful radiofrequency catheter ablation of the focus of this arrhythmia in a 9-year-old girl with preservation of normal atrioventricular conduction, using precise catheter navigation with the LocaLisa system and carefully titrated RF delivery.

Pulmonary vein ostium geometry: analysis by magnetic resonance angiography.

BACKGROUND: During a catheter ablation procedure for selective electrical isolation of pulmonary vein (PV) ostia, the size of these ostia is usually estimated using fluoroscopic angiography. This measurement may be misleading, however, because only the projected supero/inferior ostium diameters can be measured. In this study, we analyzed 3-dimensional magnetic resonance angiographic (MRA) images to measure the minimal and maximal cross-sectional diameter of PV ostia in relation to the diameter that would have been projected on fluoroscopic angiograms during a catheter ablation procedure. METHODS AND RESULTS: In 42 patients with idiopathic atrial fibrillation who were scheduled for selective electrical isolation of PV ostia, the minimal and maximal diameters of these ostia were measured from 3-dimensional MRA images. Thereafter, these images were oriented in a 45 degrees right or left anterior oblique direction and the projected diameter of the PV ostia were measured again. The average ratio between maximal and minimal diameter was 1.5+/-0.4 for the left and 1.2+/-0.1 for the right pulmonary vein ostia. Because of the orientation and oval shape of especially the left pulmonary vein ostia, their minimal diameters were significantly smaller than the projected diameters. CONCLUSION: Pulmonary vein ostia, especially those at the left, are oval with the short axis oriented approximately in the antero/posterior direction. Consequently, PV ostia may sometimes be very narrow despite a rather normal appearance on angiographic images obtained during a catheter ablation procedure.