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Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.
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Plasma-derived polyclonal antibody therapeutics, such as intravenous immunoglobulin, have multiple drawbacks, including low potency, impurities, insufficient supply and batch-to-batch variation. Here we describe a microfluidics and molecular genomics strategy for capturing diverse mammalian antibody repertoires to create recombinant multivalent hyperimmune globulins. Our method generates of diverse mixtures of thousands of recombinant antibodies, enriched for specificity and activity against therapeutic targets. Each hyperimmune globulin product comprised thousands to tens of thousands of antibodies derived from convalescent or vaccinated human donors or from immunized mice. Using this approach, we generated hyperimmune globulins with potent neutralizing activity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in under 3 months, Fc-engineered hyperimmune globulins specific for Zika virus that lacked antibody-dependent enhancement of disease, and hyperimmune globulins specific for lung pathogens present in patients with primary immune deficiency. To address the limitations of rabbit-derived anti-thymocyte globulin, we generated a recombinant human version and demonstrated its efficacy in mice against graft-versus-host disease.
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Linfocitos B/inmunología , COVID-19/terapia , Globulinas/biosíntesis , SARS-CoV-2/inmunología , Animales , Anticuerpos Antivirales/inmunología , Células CHO , Cricetulus , Ensayo de Inmunoadsorción Enzimática , Globulinas/inmunología , Humanos , Inmunización Pasiva , Ratones , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/inmunología , Virus Zika/inmunología , Sueroterapia para COVID-19RESUMEN
IL-10 is a potent anti-inflammatory cytokine capable of suppressing a number of proinflammatory signals associated with intestinal inflammatory diseases, such as ulcerative colitis and Crohn's disease. Clinical use of human IL-10 (hIL-10) has been limited by anemia and thrombocytopenia following systemic injection, side effects that might be eliminated by a gut-restricted distribution. We have identified a transcytosis pathway used by cholix, an exotoxin secreted by nonpandemic forms of the intestinal pathogen Vibrio cholerae A nontoxic fragment of the first 386 aa of cholix was genetically fused to hIL-10 to produce recombinant AMT-101. In vitro and in vivo characterization of AMT-101 showed it to efficiently cross healthy human intestinal epithelium (SMI-100) by a vesicular transcytosis process, activate hIL-10 receptors in an engineered U2OS osteosarcoma cell line, and increase cellular phospho-STAT3 levels in J774.2 mouse macrophage cells. AMT-101 was taken up by inflamed intestinal mucosa and activated pSTAT3 in the lamina propria with limited systemic distribution. AMT-101 administered to healthy mice by oral gavage or to cynomolgus monkeys (nonhuman primates) by colonic spray increased circulating levels of IL-1R antagonist (IL-1Ra). Oral gavage of AMT-101 in two mouse models of induced colitis prevented associated pathological events and plasma cytokine changes. Overall, these studies suggest that AMT-101 can efficiently overcome the epithelial barrier to focus biologically active IL-10 to the intestinal lamina propria.
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Colitis/metabolismo , Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Animales , Células Cultivadas , Colon/metabolismo , Enfermedad de Crohn/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Inflamación/metabolismo , Macaca fascicularis , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones SCID , Membrana Mucosa/metabolismo , Ratas , Ratas Wistar , Transcitosis/fisiologíaRESUMEN
Electrocardiographic Decision Support - Myocardial Ischaemia (EDS-MI) is a graphical decision support for detection and localization of acute transmural ischaemia. A recent study indicated that EDS-MI performs well for detection of acute transmural ischaemia. However, its performance has not been tested in patients with non-ischaemic ST-deviation. We aimed to optimize the diagnostic accuracy of EDS-MI in patients with verified acute coronary occlusion as well as patients with non-ischaemic ST deviation and compare its performance with STEMI criteria. We studied 135 patients with non-ischaemic ST deviation (perimyocarditis, left ventricular hypertrophy, takotsubo cardiomyopathy and early repolarization) and 117 patients with acute coronary occlusion. In 63 ischaemic patients, the extent and location of the ischaemic area (myocardium at risk) was assessed by both cardiovascular magnetic resonance imaging and EDS-MI. Sensitivity and specificity of ST elevation myocardial infarction criteria were 85% (95% confidence interval (CI) 77, 90) and 44% (95% CI 36, 53) respectively. Using EDS-MI, sensitivity and specificity increased to 92% (95% CI 85, 95) and 81% (95% CI 74, 87) respectively (p=0.035 and p<0.001). Agreement was strong (83%) between cardiovascular magnetic resonance imaging and EDS-MI in localization of ischaemia. Mean myocardium at risk was 32% (± 10) by cardiovascular magnetic resonance imaging and 33% (± 11) by EDS-MI when the estimated infarcted area according to Selvester QRS scoring was included in myocardium at risk estimation. In conclusion, EDS-MI increases diagnostic accuracy and may serve as an automatic decision support in the early management of patients with suspected acute coronary syndrome. The added clinical benefit in a non-selected clinical chest pain population needs to be assessed.
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Oclusión Coronaria/diagnóstico , Sistemas de Apoyo a Decisiones Clínicas , Electrocardiografía , Isquemia Miocárdica/diagnóstico , Adulto , Anciano , Algoritmos , Estudios de Casos y Controles , Angiografía Coronaria , Oclusión Coronaria/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Pericarditis/diagnóstico , Pericarditis/fisiopatología , Estudios Retrospectivos , Sensibilidad y Especificidad , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/fisiopatologíaRESUMEN
An automated ECG-based method may provide diagnostic support in the management of patients with acute coronary syndrome. The Olson method has previously proved to accurately identify the culprit artery in patients with acute coronary occlusion. METHODS: The Olson method was applied to 360 patients without acute myocardial ischemia and 52 patients with acute coronary occlusion. RESULTS: This study establishes the normal variation of the Olson wall scores in patients without acute myocardial ischemia, which provides the basis for implementation of the Olson method for triage of patients with acute coronary syndrome. All patients with acute occlusion had Olson wall scores above the upper limit of normal. CONCLUSION: The Olson method can be used for ischemia detection with very high sensitivity. Future studies are needed to explore specificity in patients with non-ischemic ST elevation.
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Algoritmos , Oclusión Coronaria/complicaciones , Oclusión Coronaria/diagnóstico , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiología , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND AND PURPOSE: Culprit coronary artery assessment in the triage ECG of patients with suspected acute coronary syndrome (ACS) is relevant a priori knowledge preceding percutaneous coronary intervention (PCI). We compared a model-based automated method (Olson method) with an expert-rule based method for the culprit artery assessment. METHODS: In each of the 53 patients who were admitted with the working diagnosis of suspected ACS, scheduled for emergent angiography with a view on revascularization as initial treatment and subsequently found to have an angiographically documented completely occluded culprit artery, culprit artery location was assessed in the preceding ECG by both the model-based Olson method and the expert-rule based method that considered either visual or computer-measured J-point amplitudes. ECG culprit artery estimations were compared with the angiographic culprit lesion locations. Proportions of correct classifications were compared by a Z test at the 5% significance level. RESULTS: The Olson method performed slightly, but not significantly, better, when the expert-rule based method used visual assessment of J-point amplitudes (88.7% versus 81.1% correct; P=0.28). However, the Olson method performed significantly better when the expert-rule based method used computer-measured J-point amplitudes (88.7% versus 71.7% correct; P<0.05). CONCLUSION: The automated model-based Olson method performed at least at the level of expert cardiologists using a manual rule-based method.
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Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/fisiopatología , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Sistemas Especialistas , Modelos Cardiovasculares , Síndrome Coronario Agudo/etiología , Algoritmos , Simulación por Computador , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: The purpose of this study is to present a new and improved method for translating the electrocardiographic changes of acute myocardial ischemia into a display which reflects the location and extent of the ischemic area and the associated culprit coronary artery. This method could be automated to present a graphic image of the ischemic area in a manner understandable by all levels of caregivers; from emergency transport personnel to the consulting cardiologist. BACKGROUND: Current methods for the ECG diagnosis of ST elevated myocardial infarction (STEMI) are criteria driven, and complex, and beyond the interpretive capability of many caregivers. New methods are needed to accurately diagnose the presence of acute transmural myocardial ischemia in order to accelerate a patient's clinical "door to balloon time." The proposed new method could potentially provide the information needed to accomplish this objective. METHODS: The new method improves the precision of diagnosis and quantification of ischemia by normalizing the ST segment inputs from the standard 12 lead ECG, transforming these into a three dimensional vector representation of the ischemia at the electrical center of the heart. The myocardial areas likely to be involved in this ischemia are separately analyzed to assess the probability that they contributed to this event. The source of the ischemia is revealed as a specific region of the heart, and the likely location of the associated culprit coronary artery. Seventy 12 lead ECGs from subjects with known single artery occlusion in one of the three main coronary arteries were selected to test this new method. Graphic plots of the distribution of ischemia as indicated by the method are consistent with the known occlusion. The analysis of the distribution of ischemic areas in the myocardium reveals that the relationships between leads with either ST elevation or ST depression, provide critical information improving the current method.
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Algoritmos , Enfermedad de la Arteria Coronaria/diagnóstico , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Isquemia Miocárdica/diagnóstico , Reconocimiento de Normas Patrones Automatizadas/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Humanos , Isquemia Miocárdica/etiología , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The myocardial area at risk (MaR) has been estimated in patients with acute myocardial infarction (AMI) by using ST segment based ECG methods. However, as the process from ischemia to infarction progresses, the ST segment deviation is typically replaced by QRS abnormalities, causing a falsely low estimation of the total MaR if determined by using ST segment based methods. A previous study showed the value of the consideration of the abnormalities in the QRS complex, in addition to those in the ST segment estimating the total MaR for patients with anterior AMI. The purpose of this study was to investigate the same method for patients with inferior AMI. METHODS: Thirty-two patients with acute inferior ST elevation myocardial infarction received (99m)Tc-Sestamibi before percutaneous coronary intervention. SPECT was performed within 2 hours after treatment and was used as a gold standard for the estimation of the total MaR. The ECG recorded at admission in the hospital was used for the ECG estimates of the total MaR. This included a ST segment estimation of the ischemic component of the total MaR (Aldrich score) and an estimation of the infarcted component of the total MaR in the acute phase of AMI by QRS abnormalities (Selvester score). These scores were added for the combined ECG score. RESULTS: The ischemic component of the total MaR estimated by the Aldrich score alone no statistically significant correlation with SPECT (r=0.17, p=0.36). The infarcted component of the total MaR estimated by the Selvester score showed a significant correlation with SPECT (r=0.55, p=0.001). When the Aldrich and Selvester scores were combined, the correlation with SPECT improved (r=0.58, p<0.001). Both the Aldrich and Selvester score alone underestimated the mean MaR measured by SPECT (respectively p=0.007 and p<0.0001). There was no statistically significant difference between the mean MaR estimated by the sum of Aldrich and Selvester and the MaR measured by SPECT (p=0.636). CONCLUSION: The estimation of the total MaR was more accurate by taking both ST deviation and QRS abnormalities in account than by using either method alone. A new ECG method to determine the total MaR during acute coronary occlusion should consider both its ischemic and infarcted components.
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Algoritmos , Diagnóstico por Computador/métodos , Electrocardiografía/métodos , Infarto del Miocardio/diagnóstico , Reconocimiento de Normas Patrones Automatizadas/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Vectorcardiographic QRS loops illustrate the electrical activation of the left ventricle (LV) in 3-dimensional space; however, the individual variability in these loops is not well understood. The left bundle-branch fan distributes the initial activation to the LV and has been shown to distribute its fascicles between the LV papillary muscles. Computer models of LV activation using papillary muscle as the initial electrical activation points accurately predict QRS duration and frontal plane axis. METHODS: Twelve healthy adults received standard 12-lead electrocardiograms and 1.5-T cardiac magnetic resonance imaging. A software developed by ECG-TECH Corp (Huntington Station, NY) generated 3-dimensional QRS vector loops for each subject. Short- and long-axis papillary muscle positions were measured for each subject using cardiac magnetic resonance images. A theoretical plane equidistant from the endocardial origins of each papillary muscle was constructed. Vectors perpendicular to the QRS vector loop and the theoretical plane termed the plane identifier were used for comparison. Spearman rank correlation was used to compare the azimuth and elevation of the plane identifiers of the QRS vector loop and the theoretical plane. RESULTS: No correlation was found between the azimuth or elevation of the theoretical plane and the QRS vector loops with Spearman rank correlation coefficients of ρ = 0.11 (P = .71) and ρ = 0.22 (P = .49), respectively. Subgroup analysis by QRS vector loop morphology (planar vs nonplanar, narrow vs wide) also demonstrated no correlation. CONCLUSIONS: Modeling the activation of the LV based on papillary muscle position alone may be overly simplistic. Better understanding of what other factors contribute to individual variation in LV activation will help develop a more useful theoretical model.
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Sistema de Conducción Cardíaco/fisiología , Músculos Papilares/fisiología , Vectorcardiografía/métodos , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Valor Predictivo de las Pruebas , Programas Informáticos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: The myocardial area at risk (MaR) has been estimated in patients with acute myocardial infarction (AMI) by using ST segment-based electrocardiographic (ECG) methods. As the process from ischemia to infarction progresses, the ST-segment deviation is typically replaced by QRS abnormalities causing a falsely low estimated total MaR if determined by using ST segment-based methods. The purpose of this study was to investigate if consideration of the abnormalities in the QRS complex, in addition to those in the ST segment, provides a more accurate estimated total MaR during anterior AMI than by considering the ST segment alone. METHODS: Twenty-five patients with acute anterior ST elevation myocardial infarction (STEMI) received technetium Tc 99m-sestamibi before percutaneous coronary intervention. Single photon emission computed tomography (SPECT) was performed within 2 hours after treatment and was used as a criterion standard for the estimated total MaR. The ECG recorded at admission in the hospital was used for the ECG estimated total MaR. This included an ST-segment estimated ischemic component of the total MaR (Aldrich score) and an estimated infarcted component of the total MaR in the acute phase of AMI by QRS abnormalities (Selvester score). These scores were added for the combined ECG score. RESULTS: The ischemic component of the total MaR estimated by the Aldrich score alone had no statistically significant correlation with SPECT (r = 0.21, P = .32). The infarcted component of the total MaR estimated by the Selvester score showed a significant correlation with SPECT (r = 0.49, P = .01). Each score gave a significant underestimated total MaR measured by SPECT (P < .01). When the Aldrich and Selvester scores were combined, the correlation with SPECT was r = 0.47, P = .02. The combined score still underestimated the total MaR by SPECT (P < .01), though the difference was smaller in comparison to either method alone (P < .01). CONCLUSION: The ECG estimated total MaR was more accurate by taking both ST deviation and QRS abnormalities into account than by using either method alone. A new ECG method to determine the total MaR during acute coronary occlusion should consider both its ischemic and infarcted components.
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Electrocardiografía/métodos , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Medición de Riesgo , Procesamiento de Señales Asistido por Computador , Tecnecio Tc 99m SestamibiRESUMEN
BACKGROUND: Knowledge of the location and size of ischemic myocardium at risk for infarction could impact prehospital patient triage and reperfusion therapy. The 12-lead electrocardiogram (ECG) can roughly estimate ischemia size; however, individual precordial ECG leads are at different distances from the left ventricle (LV) and certain LV walls have greater effects on the ECG. Vectorcardiographic corrected orthogonal lead systems can display the magnitude and direction of the ST-segment "injury current" vector in 3-dimensional space. We assessed whether the vectorcardiographic ST-vector direction and magnitude derived from the ECG by the inverse-Dower method can estimate the location and size of ischemia. METHODS AND RESULTS: Thirty-two patients underwent elective coronary angioplasty with control and 5-minute balloon-occlusion ECG and sestamibi injection followed by single photon emission computed tomography (SPECT). The ST-vector direction derived from the inverse-Dower method was projected to an LV model with normal coronary artery anatomy. The graphical display of ST-vector location could discriminate among occlusions of the different coronaries. The ST-vector located ischemia within the SPECT defect in 75% (24/32) of all patients and 96% (24/25) of patients with ischemia in more than 12% of the LV. ST-vector magnitude had a Spearman correlation of r = 0.68 (P < .0001) with SPECT ischemia size. CONCLUSIONS: The 3-dimensional ST vector derived from the ECG can be graphically projected onto an LV model to localize ischemia, and ST-vector magnitude correlates with ischemia size. Further study is warranted to assess the ability of vectorcardiographic imaging to risk-stratify and provide decision-support for patients with acute myocardial infarction.
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Algoritmos , Gráficos por Computador , Diagnóstico por Computador/métodos , Imagenología Tridimensional/métodos , Isquemia Miocárdica/diagnóstico , Interfaz Usuario-Computador , Vectorcardiografía/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Simulation of the electrical activation of the heart and its comparison with real in vivo activation is a promising method in testing potential determinants of excitation. Simulation of the electrical activity of the human heart is now emerging as a step forward for understanding and predicting electrophysiologic patterns in humans. Initial points of excitation and the manner in which the activation spreads from these points are important variables determining QRS complex characteristics. It has been suggested that in humans, the initial excitation of the left ventricle is a primary determinant of QRS complex characteristics, and that excitation begins at the papillary muscles and septum, where the fascicles of the left bundle branch insert. The aim of this study is to test the hypothesis that QRS duration and direction of QRS axis in the frontal plane have excellent agreement between real QRS and simulated QRS using papillary muscle position to indicate the border of the origin of early ventricular activation. METHODS: Fourteen healthy adult volunteers were included in the study. Magnetic resonance imaging data were obtained to assess the papillary muscle positions. Twelve-lead electrocardiographic (ECG) recordings were used to obtain real ECG data for assessment of QRS duration and QRS axis in each subject. Simulation software developed by ECG-TECH Corp (Huntington, NY) was used to simulate the ECG of each subject to determine simulated QRS duration and QRS frontal plane axis. QRS duration and QRS axis data were compared between simulated and real ECG and agreement between these variables was calculated. RESULTS: Seventy-nine percent of subjects had a difference of the QRS duration between real and simulated ECG of less than 10 milliseconds. The calculated strength of agreement between simulated and real QRS duration was 71% and considered as "good" (kappa statistics). In 70% of subjects, the difference in the QRS axis was less than 10 degrees . The calculated strength of agreement between simulated and real QRS axis was 80% and considered as "excellent" (kappa statistics). CONCLUSIONS: The results of this study suggest that the sites of the initiation of electrical activity in the left ventricle, as assessed by the positions of papillary muscles, may be considered as primary determinants of the QRS duration and QRS axis in humans. This knowledge may help in predicting normal QRS characteristic on a patient-specific basis. In this study, simulation of the QRS complex was based on papillary muscles from human hearts.
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Mapeo del Potencial de Superficie Corporal/métodos , Electrocardiografía/métodos , Sistema de Conducción Cardíaco/fisiología , Modelos Cardiovasculares , Contracción Miocárdica/fisiología , Músculos Papilares/anatomía & histología , Músculos Papilares/fisiología , Adulto , Simulación por Computador , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: QRS complex characteristics are considered to be one of the most significant diagnostic and prognostic determinants for assessment of several cardiac conditions. However, there is a large variability of the QRS complex even among "normal" individuals. This study was based on 2 assumptions: (1) that the portion of the left ventricular endocardium activated earliest is directly supplied by the "fanlike" distribution of the anterior, middle, and posterior fascicles of the left bundle branch, and (2) that the anterior and posterior fascicles course toward their respective mitral papillary muscles. These structures could therefore serve as anatomical landmarks to indicate the borders of this fanlike distribution of primary "start points" of left ventricular activation. AIMS: The primary aim of this study is to test the hypothesis that location of both papillary muscles closer to the septum correlates with longer QRS duration. The secondary aim of the study is to test the hypothesis that the balance of the distances of the anterior and posterior papillary muscles from the septum is related to the direction of the frontal plane QRS axis. METHODS: The study population consisted of 16 healthy adult volunteers with a mean age of 26 +/- 9 years, mean height of 170 +/- 12 cm, and mean weight of 68 +/- 10 kg. Measurements were done on the magnetic resonance images from all study subjects. Positions of papillary muscles were assessed as a predictive variable of QRS duration. RESULTS: A significant correlation was found between the closer position of both papillary muscles to the septum and longer QRS duration (R = 0.7, P = .02). Subjects with higher ratio of anterior papillary muscle vs posterior papillary muscle free wall angle correlates with inferior rotation of the average axis of QRS complex in the frontal plane (R = 0.5, P = .04). CONCLUSIONS: The positions of the papillary muscles in relation to the free wall and septum wall can be predictive of both QRS duration and the direction of the QRS complex of the heart. These results might provide a new basis for prediction of QRS complex characteristics of an individual and, thus, differentiate between real QRS complex abnormalities and variants of normal.
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Electrocardiografía , Sistema de Conducción Cardíaco/anatomía & histología , Sistema de Conducción Cardíaco/fisiología , Imagen por Resonancia Magnética , Válvula Mitral/anatomía & histología , Válvula Mitral/fisiología , Músculos Papilares/anatomía & histología , Músculos Papilares/fisiología , Adulto , Femenino , Humanos , Masculino , Estadística como AsuntoRESUMEN
This new training method is based on developing a sound understanding of the sequence in which electrical excitation spreads through both the normal and the infarcted myocardium. The student is made aware of the cardiac electrical performance through a series of 3-dimensional pictures during the excitation process. The electrocardiogram 3D Heart 3-dimensional program contains a variety of different activation simulations. Currently, this program enables the user to view the activation simulation for all of the following pathology examples: normal activation; large, medium, and small anterior myocardial infarction (MI); large, medium, and small posterolateral MI; large, medium, and small inferior MI. Simulations relating to other cardiac abnormalities, such as bundle branch block and left ventricular hypertrophy fasicular block, are being developed as part of a National Institute of Health (NIH) Phase 1 Small Business Innovation Research (SBIR) program.