Atrial proarrhythmic effect of lead as one of the PM10 metal components of air pollution. An in-silico study.

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.

The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study.

Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.

Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders.

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl-9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single-nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean-dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.

Importancia del mapeo óptico de cultivos de cardiomiocitos HL-1 en estudios electrofisiológicos / Importance of the optical mapping of HL-1 cardiomyocyte cultures in electrophysiological studies

Introducción: El desarrollo de herramientas para investigar la actividad electrofisiológica cardiaca ha permitido profundizar en el conocimiento sobre los mecanismos subyacentes a las arritmias cardiacas. Los sistemas de mapeo óptico constituyen una tecnología que responde a la necesidad de superar varios obstáculos en la experimentación. Objetivo: Proporcionar una visión general de la importancia del mapeo óptico en cultivos celulares HL-1, en las investigaciones en electrofisiología cardiaca. Métodos: Se realizó una revisión sobre los estudios electrofisiológicos que involucran la línea celular HL-1 utilizando la técnica de mapeo óptico. Conclusiones: Los trabajos se caracterizan por la implementación de la técnica respecto a la tecnología de los equipos de mapeo, a la utilización de diferentes colorantes y al objetivo de la investigación. Están enfocados en el estudio de mecanismos arritmogénicos, procesos de estiramiento mecánico o remodelación del tejido y en el análisis de nuevos biomateriales. Lo anterior, sustenta la relevancia del mapeo óptico en la investigación cardiaca(AU)

Introduction: The development of tools to study cardiac electrophysiological activity has made it possible to broaden knowledge about the mechanisms underlying cardiac arrhythmias. Optical mapping systems constitute a technology that responds to the need to overcome several hurdles in experimentation. Objective: Provide an overview of the importance of optical mapping in HL-1 cell cultures in cardiac electrophysiology research. Methods: A review was conducted of electrophysiological studies involving the HL-1 cell line using the optical mapping technique. Conclusions: The studies are characterized by implementation of the technique with respect to the technology of mapping equipment, the use of different colorants and the purpose of the research. They focus on the study of arrhythmogenic mechanisms, mechanical stretch processes or tissue remodeling as well as the analysis of new biomaterials. The above substantiates the relevance of optical mapping in cardiac research(AU)

Individual variations and sex differences in hemodynamics with percutaneous arterial oxygen saturation (SpO2) in young Andean highlanders in Bolivia.

BACKGROUND: Many studies have reported specific adaptations to high altitude, but few studies have focused on physiological variations in high-altitude adaptation in Andean highlanders. This study aimed to investigate the relationships between SpO2 and related factors, including individual variations and sex differences, in Andean highlanders. METHODS: The participants were community-dwelling people in La Paz, Bolivia, aged 20 years and over (age range 20-34 years). A total of 50 men and 50 women participated in this study. Height, weight, SpO2, hemoglobin concentration, finger temperature, heart rate, and blood pressure were measured. Information about lifestyle was also obtained by interview. RESULTS: There were individual variations of SpO2 both in men (mean 89.9%, range 84.0-95.0%) and women (mean 91.0%, range 84.0-96.0%). On Student's t test, men had significantly lower heart rate (p = 0.046) and SpO2 (p = 0.030) than women. On the other hand, men had significantly higher SBP (p < 0.001), hemoglobin (p < 0.001), and finger temperature (p = 0.004). In men, multiple stepwise regression analysis showed that a higher SpO2 was correlated with a lower heart rate (ß = - 0.089, p = 0.007) and a higher finger temperature (ß = 0.308, p = 0.030) (r2 for model = 0.18). In women, a higher SpO2 was significantly correlated with a higher finger temperature (ß = 0.391, p = 0.015) (r2 for model = 0.12). A higher SpO2 was related to a higher finger temperature (ß = 0.286, p = 0.014) and a lower heart rate (ß = - 0.052, p = 0.029) in all participants (r2 for model = 0.21). Residual analysis showed that individual SpO2 values were randomly plotted. CONCLUSION: Random plots of SpO2 on residual analysis indicated that these variations were random error, such as biological variation. A higher SpO2 was related to a lower heart rate and finger temperature in men, but a higher SpO2 was related to finger temperature in women. These results suggest that there are individual variations and sex differences in the hemodynamic responses of high-altitude adaptation in Andean highlanders.

Electroanatomical mapping based on discrimination of electrograms clusters for localization of critical sites in atrial fibrillation.

Locating critical sites on the atrial surface during AF to guide the ablation procedures is an open problem. Electrogram-guided approaches have been proposed. However, electrograms (EGM) are complex and not well-described type of signals and anatomically-based pulmonary vein isolation remains been recommended as the cornerstone procedure. We introduce a method that builds an electroanatomical map to visualize the distribution of different morphological patterns of the EGM signals over the atrial surface. The proposed scheme uses EGM signals recorded with a commercial cardiac mapping. Likewise, two morphological and two non-linear features are computed from each single EGM. Patterns are discriminated using a semi-supervised clustering approach that does not need a priory definition of EGM morphologies or classes. The method was tested under two scenarios: a set of EGM signals recorded in AF patients and a set of signals obtained from 2D simulations of atrial conduction sustained by rotors. Our method was able to locate the clusters in a map of the atrial surface of each patient. These locations allow the specialist to study the distribution of critical AF sites. The method was able to locate the pivot point of the rotors in the 2D models. Our results suggest that the proposed method is a potential assisting tool for guided ablation procedures. Further clinical studies are needed to establish the relationship between clusters and arrhythmogenic substrates in AF, and to validate the usefulness of the method to locate critical conduction sites in patients.

Entropy Mapping Approach for Functional Reentry Detection in Atrial Fibrillation: An In-Silico Study.

Catheter ablation of critical electrical propagation sites is a promising tool for reducing the recurrence of atrial fibrillation (AF). The spatial identification of the arrhythmogenic mechanisms sustaining AF requires the evaluation of electrograms (EGMs) recorded over the atrial surface. This work aims to characterize functional reentries using measures of entropy to track and detect a reentry core. To this end, different AF episodes are simulated using a 2D model of atrial tissue. Modified Courtemanche human action potential and Fenton-Karma models are implemented. Action potential propagation is modeled by a fractional diffusion equation, and virtual unipolar EGM are calculated. Episodes with stable and meandering rotors, figure-of-eight reentry, and disorganized propagation with multiple reentries are generated. Shannon entropy ( S h E n ), approximate entropy ( A p E n ), and sample entropy ( S a m p E n ) are computed from the virtual EGM, and entropy maps are built. Phase singularity maps are implemented as references. The results show that A p E n and S a m p E n maps are able to detect and track the reentry core of rotors and figure-of-eight reentry, while the S h E n results are not satisfactory. Moreover, A p E n and S a m p E n consistently highlight a reentry core by high entropy values for all of the studied cases, while the ability of S h E n to characterize the reentry core depends on the propagation dynamics. Such features make the A p E n and S a m p E n maps attractive tools for the study of AF reentries that persist for a period of time that is similar to the length of the observation window, and reentries could be interpreted as AF-sustaining mechanisms. Further research is needed to determine and fully understand the relation of these entropy measures with fibrillation mechanisms other than reentries.

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion.

The mechanisms of atrial fibrillation (AF) are a challenging research topic. The rotor hypothesis states that the AF is sustained by a reentrant wave that propagates around an unexcited core. Cardiac tissue heterogeneities, both structural and cellular, play an important role during fibrillatory dynamics, so that the ionic characteristics of the currents, their spatial distribution and their structural heterogeneity determine the meandering of the rotor. Several studies about rotor dynamics implement the standard diffusion equation. However, this mathematical scheme carries some limitations. It assumes the myocardium as a continuous medium, ignoring, therefore, its discrete and heterogeneous aspects. A computational model integrating both, electrical and structural properties could complement experimental and clinical results. A new mathematical model of the action potential propagation, based on complex fractional order derivatives is presented. The complex derivative order appears of considering the myocardium as discrete-scale invariant fractal. The main aim is to study the role of a myocardial, with fractal characteristics, on atrial fibrillatory dynamics. For this purpose, the degree of structural heterogeneity is described through derivatives of complex order γ = α + jß. A set of variations for γ is tested. The real part α takes values ranging from 1.1 to 2 and the imaginary part ß from 0 to 0.28. Under this scheme, the standard diffusion is recovered when α = 2 and ß = 0. The effect of γ on the action potential propagation over an atrial strand is investigated. Rotors are generated in a 2D model of atrial tissue under electrical remodeling due to chronic AF. The results show that the degree of structural heterogeneity, given by γ, modulates the electrophysiological properties and the dynamics of rotor-type reentrant mechanisms. The spatial stability of the rotor and the area of its unexcited core are modulated. As the real part decreases and the imaginary part increases, simulating a higher structural heterogeneity, the vulnerable window to reentrant is increased, as the total meandering of the rotor tip. This in silico study suggests that structural heterogeneity, described by means of complex order derivatives, modulates the stability of rotors and that a wide range of rotor dynamics can be generated.

Enterobacterias productoras de carbapenemasas en pacientes del Servicio de Clínica Médica del Hospital Nacional de Itauguá

Introducción: las bacterias con enzimas carbapenemasas (KPC) tienen una gran capacidad de diseminación, son causantes de brotes nosocomiales y se asocian a mayor mortalidad y estancia hospitalaria. Objetivos: determinar la frecuencia de KPC en el Servicio de Clínica Médica del Hospital Nacional y determinar los factores de riesgo asociados. Materiales y método: estudio observacional, descriptivo, prospectivo, de corte transversal, que se realizó mediante hisopado rectal a 63 pacientes internados en el Servicio de Clínica Médica del Hospital Nacional entre octubre y noviembre del 2014. Resultados: la edad media de la muestra fue 51±15 años, el 50% de sexo masculino. En 13% de los pacientes se obtuvo un resultado positivo para KPC, el tiempo promedio de internación de éstos fue de 30±33 días vs 27±26 días de los pacientes KPC negativo. El único factor de riesgo significativo fue la cohabitación con otros pacientes con KPC. Conclusiones: la frecuencia de KPC en el Servicio de Clínica Médica del Hospital Nacional de Itauguá fue 13%. El principal factor de riesgo para adquirir KPC es la cohabitación con un paciente colonizado por el mismo germen.

Introduction: Carbapenemase producing bacteria (KPC) have great capacity of spreading, are causative agents of nosocomial outbreaks and are associated to higher mortality and longer hospital stay. Objectives: To determine the frequency of KPC in the Medical Clinic Service of the National Hospital and associated risk factors. Materials and method: This was a prospective descriptive cross-sectional study that performed rectal swab to 63 patients admitted into the Medical Clinic Service of the National Hospital between October and November, 2014. Results: Mean age of the sample was 51±15 years, and 50% was men. In 13% of the patients, a positive result for KPC was found and the mean time of hospitalization of these patients was 30±33 days vs 27±26 days of KPC negative patients. The only significant risk factor was daily contact with other KPC patients. Conclusions: The frequency of KPC in the Medical Clinic Service of the National Hospital of Itauguá was 13%. The main risk factor to acquire KPC was daily contact with a patient colonized by the same germ.

Effect of the electrograms density in detecting and ablating the tip of the rotor during chronic atrial fibrillation: an in silico study.

AIMS: Identification in situ of arrhythmogenic mechanisms could improve the rate of ablation success in atrial fibrillation (AF). Our research group reported that rotors could be located through dynamic approximate entropy (DApEn) maps. However, it is unknown how much the spatial resolution of catheter electrodes could affect substrates localization. The present work looked for assessing the electrograms (EGMs) spatial resolution needed to locate the rotor tip using DApEn maps. METHODS AND RESULTS: A stable rotor in a two-dimensional computational model of human atrial tissue was simulated using the Courtemanche electrophysiological model and implementing chronic AF features. The spatial resolution is 0.4 mm (150 × 150 EGM). Six different lower resolution arrays were obtained from the initial mesh. For each array, DApEn maps were constructed using the inverse distance weighting (IDW) algorithm. Three simple ablation patterns were applied. The full DApEn map detected the rotor tip and was able to follow the small meander of the tip through the shape of the area containing the tip. Inverse distance weighting was able to reconstruct DApEn maps after applying different spatial resolutions. These results show that spatial resolutions from 0.4 to 4 mm accurately detect the rotor tip position. An ablation line terminates the rotor only if it crosses the tip and ends at a tissue boundary. CONCLUSION: A previous work has shown that DApEn maps successfully detected simulated rotor tips using a high spatial resolution. In this work, it was evinced that DApEn maps could be applied using a spatial resolution similar to that available in commercial catheters, by adding an interpolation stage. This is the first step to translate this tool into medical practice with a view to the detection of ablation targets.

Dynamic approximate entropy electroanatomic maps detect rotors in a simulated atrial fibrillation model.

There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.

IDENTIFICACIÓN DE ZONAS SUSCEPTIBLES DE ABLACIÓN EN FIBRILACIÓN AURICULAR PERMANENTE IMPLEMENTANDO ENTROPÍA APROXIMADA EN UN MODELO 2D / IDENTIFICATION OF TARGET SITES FOR ABLATION DURING PERMANENT ATRIAL FIBRILLATION IMPLEMENTING APPROXIMATE ENTROPY IN A 2D MODEL / IDENTIFICAÇÃO DE ÁREAS SUSCETÍVEIS DE ABLAÇÃO PERMANENTE DE FIBRILAÇÃO ATRIAL NA IMPLEMENTAÇÃO ENTROPY APROXIMADO UM MODELO 2D

La fibrilación auricular (FA) es la arritmia cardiaca más común. La ablación con catéter se ha convertido en la principal estrategia terapéutica para el tratamiento de la FA paroxística, sin embargo, los resultados en FA permanente no son completamente satisfactorios. Se propone la ablación de los electrogramas auriculares complejos fragmentados (CFAE) para la terminación de un rotor como mecanismo de mantenimiento de FA permanente. El objetivo de este trabajo es caracterizar los CFAE mediante la implementación de entropía aproximada (ApEn) y correlacionarlos con el tip de un rotor simulado. Para esto, se desarrolló un modelo 2D de tejido de aurícula humana bajo condiciones de FA permanente; se registraron electrogramas unipolares durante la actividad del rotor y se desarrolló un algoritmo para la medida de ApEn. La ApEn permitió localizar los CFAE con una alta precisión y relacionarlos con el tip del rotor. Por lo que este índice podría ser muy eficaz en la identificación de zonas susceptibles de ablación.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Catheter ablation has become the main therapeutic strategy for the treatment of paroxysmal AF, however, results in permanent AF are not completely satisfactory. Ablation of complex fractionated atrial electrograms (CFAE) is proposed for the termination of a rotor as mechanism of permanent AF maintenance. The aim of this work is to characterize the CFAE by implementing approximate entropy (ApEn) and to correlate with the tip of a simulated rotor. For this, a 2D model of human atrial tissue under permanent FA conditions was developed. Unipolar electrograms were recorded during the rotor activity and an algorithm to measure ApEn was developed. The ApEn allowed locate the CFAE with high precision and relate them to the tip of the rotor. So this index could be very effective in identifying target sites for ablation.

A fibrilação atrial (FA) é a arritmia cardíaca mais comum. A ablação por cateter tornou-se a principal estratégia terapêutica para o tratamento da fibrilação atrial paroxística, no entanto, resulta em FA permanente não são completamente satisfatórios. Ablação de fones de ouvido eletrocardiogramas complexos fragmentada (CFAE) para a conclusão de um rotor como um mecanismo de manutenção da FA permanente, é proposto. O objetivo deste trabalho é caracterizar o CFAE através da implementação de entropia aproximada (ApEn) e correlacioná-los com a ponta de um rotor simulado. Para isso, um modelo em 2D do tecido atrial humano sob condições de FA permanente desenvolvido; unipolares electrogramas foram registados durante a actividade do rotor e um algoritmo para medir ApEn desenvolvido. O ApEn permitido CFAE localizar com precisão elevada e relacioná-los com a ponta do rotor. Portanto, esta taxa pode ser muito eficaz na identificação de áreas suscetíveis a ablação.

Características de los pacientes con supervivencia mayor de 20 años tras un trasplante cardiaco / Characteristics of patients with survival longer than 20 years following heart transplantation

Introducción y objetivos. Los receptores de trasplante cardiaco que sobreviven más de 20 años están aumentando. Poco se conoce de su seguimiento, sus comorbilidades y su mortalidad. Identificar predictores de larga supervivencia puede guiar la selección de candidatos para los donantes disponibles. Métodos. Se revisó la información sobre la clase funcional, las comorbilidades y la mortalidad de pacientes trasplantados antes de 1992. Para identificar los predictores de supervivencia > 20 años, se construyó un modelo de regresión logística utilizando las variables asociadas a supervivencia en el análisis univariable. Resultados. Se comparó a 39 supervivientes con seguimiento > 20 años (el 26% del total) con 90 pacientes que sobrevivieron entre 1 y 20 años. Las principales complicaciones fueron hipertensión, disfunción renal, infecciones y neoplasias. Tras 30 meses de seguimiento, 6 murieron, lo que implica una mortalidad del 6%/año (frente a un 2,5-3% en los años 1 a 19). Las principales causas de muerte fueron infección (50%), cáncer (33%) y vasculopatía del injerto (17%). Los supervivientes eran más jóvenes y delgados, y tenían cardiopatía no isquémica y menos isquemia en cirugía. La regresión logística identificó la edad del receptor < 45 años (odds ratio = 3,9; intervalo de confianza del 95%, 1,6-9,7; p = 0,002) y la miocardiopatía idiopática (odds ratio = 3; intervalo de confianza del 95%, 1,4-7,8; p = 0,012) como predictores independientes de supervivencia > 20 años. Conclusiones. En nuestra serie, más del 25% sobrevive más de 20 años con el mismo injerto y lleva vida independiente a pesar de las comorbilidades. La edad del receptor < 45 años y la miocardiopatía idiopática se asociaron a larga supervivencia. Estos datos pueden ayudar a la asignación de donantes (AU)

Introduction and objectives. The number of heart-transplant recipients exceeding 20 years of follow-up is steadily increasing. However, little is known about their functional status, comorbidities, and mortality. Identifying the predictors of prolonged survival could guide the selection of candidates for the low number of available donors. Methods. Functional status, morbidities, and mortality of heart-transplant patients between 1984 and 1992 were analyzed. To identify predictors of 20-year survival, a logistic regression model was constructed using the covariates associated with survival in the univariate analysis. Results. A total of 39 patients who survived 20 years (26% of patients transplanted before 1992) were compared to 90 recipients from the same period who died between 1 and 20 years post-transplantation. Major complications were hypertension, renal dysfunction, infections, and cancer. After a mean follow-up of 30 months, 6 survivors had died, yielding a mortality rate of 6% per year (vs 2.5%-3% in years 1-19). Causes of mortality were infection (50%), malignancy (33%), and allograft vasculopathy (17%). Long-term survivors were younger and leaner, and had nonischemic cardiomyopathy and lower ischemic time. Logistic regression identified recipient age <45 years (odds ratio=3.9; 95% confidence interval, 1.6-9.7; P=.002) and idiopathic cardiomyopathy (odds ratio=3; 95% confidence interval, 1.4-7.8; P=.012) as independent predictors for 20-year survival. Conclusions. One fourth of all heart-transplant patients in our series survived >20 years with the same graft, and most enjoy independent lives despite significant comorbidities. Recipient age <45 years and idiopathic cardiomyopathy were associated with survival beyond 2 decades. These data may help decide donor allocation (AU)

Characteristics of patients with survival longer than 20 years following heart transplantation.

INTRODUCTION AND OBJECTIVES: The number of heart-transplant recipients exceeding 20 years of follow-up is steadily increasing. However, little is known about their functional status, comorbidities, and mortality. Identifying the predictors of prolonged survival could guide the selection of candidates for the low number of available donors. METHODS: Functional status, morbidities, and mortality of heart-transplant patients between 1984 and 1992 were analyzed. To identify predictors of 20-year survival, a logistic regression model was constructed using the covariates associated with survival in the univariate analysis. RESULTS: A total of 39 patients who survived 20 years (26% of patients transplanted before 1992) were compared to 90 recipients from the same period who died between 1 and 20 years post-transplantation. Major complications were hypertension, renal dysfunction, infections, and cancer. After a mean follow-up of 30 months, 6 survivors had died, yielding a mortality rate of 6% per year (vs 2.5%-3% in years 1-19). Causes of mortality were infection (50%), malignancy (33%), and allograft vasculopathy (17%). Long-term survivors were younger and leaner, and had nonischemic cardiomyopathy and lower ischemic time. Logistic regression identified recipient age <45 years (odds ratio=3.9; 95% confidence interval, 1.6-9.7; P=.002) and idiopathic cardiomyopathy (odds ratio=3; 95% confidence interval, 1.4-7.8; P=.012) as independent predictors for 20-year survival. CONCLUSIONS: One fourth of all heart-transplant patients in our series survived >20 years with the same graft, and most enjoy independent lives despite significant comorbidities. Recipient age <45 years and idiopathic cardiomyopathy were associated with survival beyond 2 decades. These data may help decide donor allocation.

RADIAL: a novel primary graft failure risk score in heart transplantation.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early mortality after heart transplantation (HT). Our aim is to propose a working definition of PGF and to develop a predictive risk score. METHODS: PGF was defined by four criteria reflecting significant myocardial dysfunction, severe hemodynamic impairment, early onset after HT, and absence of secondary causes of graft dysfunction. We identified independent risk factors for PGF in a derivation series of 621 HTs and constructed a predictive model. After proving its internal consistency we tested the model in a prospective validation series. RESULTS: The incidence and lethality of PGF in our series were 9% and 80%, respectively. We identified 6 multivariate risk factors for PGF (Right atrial pressure ≥ 10 mm Hg, recipient Age ≥ 60 years, Diabetes mellitus, Inotrope dependence, donor Age ≥ 30 years, Length of ischemic time ≥ 240 minutes--i.e., RADIAL). Analysis of isolated right ventricular failure showed similar predictors. The RADIAL score was obtained by adding 1 point for each of these factors present in a given HT. PGF incidence increased significantly as the RADIAL score increased (p < 0.001 for trend). Rates of actual and predicted PGF incidence for RADIAL subgroups showed a good correlation (C-statistic = 0.74). In a prospective validation cohort, RADIAL score kept its predictive ability. CONCLUSIONS: PGF as defined by these criteria showed a high impact on early post-HT mortality in our series. The RADIAL score showed good ability to predict the development of PGF, and could be useful in the prevention and early treatment of this complication.

Failure of percutaneous closure of prosthetic, aortic paravalvular leak.

We report the progression of aortic insufficiency after percutaneous closure of an aortic prosthesis paravalvular leak with the Amplatzer vascular plug (AGA Inc, Golden Valley, MN). Removal of the device and replacement of the aortic prosthesis was successfully performed. Based on operative findings, we hypothesize that shape mismatch between the occluder system and the leak might promote tearing at the end of slanted defects further enhancing the regurgitant area.

Self-perceived oral health status and influencing factors of the elderly residents of a peri-urban area of La Paz, Bolivia.

AIM: To assess the self-perceived oral health status of the elderly in Bolivia and explore the relationship between the socio-demographic and subjective factors that influence such perception. DESIGN: A cross sectional study. SETTING: Pampahasi, peri-urban area of La Paz, Bolivia. PARTICIPANTS: A 22.5% (300) sample was selected randomly from the total population (1,336) of 60 years and above. Of the participants, 293 agreed to participate in the survey. METHODS: Information was collected by interviews at home. RESULTS: The mean age was 70 years (SD = 7.7), with more females (57%) than males. Sixty per cent of subjects categorised their oral health as poor. Logistic regression analysis showed that poor self-perceived oral health was associated significantly with not going to school, no/ fair satisfaction with economic status, poor chewing ability, perception of need for dental treatment, and poor self-perceived general health status. CONCLUSIONS: Socio-economic factors seem to contribute to poor oral health among the elderly in Bolivia. Considering that these factors are associated with bad oral health behaviour and few visits to dental clinics, there is a need to design dental education programmes and enhance accessibility to dental clinics for elderly people living in the peri-urban areas of La Paz, Bolivia.

Influence of hypothermia on right atrial cardiomyocyte apoptosis in patients undergoing aortic valve replacement.

BACKGROUND: There is increasing evidence that programmed cell death can be triggered during cardiopulmonary bypass (CPB) and may be involved in postoperative complications. The purpose of this study was to investigate whether apoptosis occurs during aortic valve surgery and whether modifying temperature during CPB has any influence on cardiomyocyte apoptotic death rate. METHODS: 20 patients undergoing elective aortic valve replacement for aortic stenosis were randomly assigned to either moderate hypothermic (ModHT group, n = 10, 28 degrees C) or mild hypothermic (MiHT group, n = 10, 34 degrees C) CPB. Myocardial samples were obtained from the right atrium before and after weaning from CPB. Specimens were examined for apoptosis by flow cytometry analysis of annexin V-propidium iodide (PI) and Fas death receptor staining. RESULTS: In the ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative) decreased after CPB, while early apoptotic (annexin positive, PI negative) and late apoptotic or necrotic (PI positive) cells increased. In contrast, no change in the different cell populations was observed over time in the MiHT group. Fas expression rose after reperfusion in the ModHT group but not in MiHT patients, in which there was even a trend for a lower Fas staining after CPB (p = 0.08). In ModHT patients, a prolonged ischemic time tended to induce a higher increase of Fas (p = 0.061). CONCLUSION: Our data suggest that apoptosis signal cascade is activated at early stages during aortic valve replacement under ModHT CPB. This apoptosis induction can effectively be attenuated by a more normothermic procedure.

[Valve repair for chronic mitral regurgitation]. / Reparación valvular en la insuficiencia mitral crónica.

Valve repair is the best surgical treatment for mitral regurgitation. In the present article we describe the results of mitral valve repair in patients with chronic mitral regurgitation treated at our center during the last eight years. The degree of correction of valve insufficiency, functional benefit, in-hospital morbidity and mortality, postoperative outcome of ventricular function, and middle-term overall and reoperation-free survival are analyzed.