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Research paper thumbnail of Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PloS one, 2017

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart fai... more Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventric...

Research paper thumbnail of T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure

Journal of the American Heart Association, Jan 19, 2017

Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dis... more Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was sig...

Research paper thumbnail of Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols

Progress in Biophysics and Molecular Biology, 2016

Models of ion channel dynamics are usually built by fitting isolated cell experimental values of ... more Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived * Corresponding author identification of major ionic conductance contributors to steady-state AP markers, including AP D 90 , AP D 75 , AP D 50 , AP D 25 , T riangulation and maximal and minimal values of V and dV /dt during the AP (V max , V min , dV /dt max , dV /dt min ).

Research paper thumbnail of Automatic SVM classification of Sudden Cardiac Death and Pump Failure Death from Autonomic and Repolarization ECG Markers

Journal of Electrocardiology, 2015

Considering the rates of sudden cardiac death (SCD) and pump failure death (PFD) in chronic heart... more Considering the rates of sudden cardiac death (SCD) and pump failure death (PFD) in chronic heart failure (CHF) patients and the cost-effectiveness of their preventing treatments, identification of CHF patients at risk is an important challenge. In this work, we studied the prognostic performance of the combination of an index potentially related to dispersion of repolarization restitution (Δα), an index quantifying T-wave alternans (IAA) and the slope of heart rate turbulence (TS) for classification of SCD and PFD. Holter ECG recordings of 597 CHF patients with sinus rhythm enrolled in the MUSIC study were analyzed and Δα, IAA and TS were obtained. A strategy was implemented using support vector machines (SVM) to classify patients in three groups: SCD victims, PFD victims and other patients (the latter including survivors and victims of non-cardiac causes). Cross-validation was used to evaluate the performance of the implemented classifier. Δα and IAA, dichotomized at 0.035 (dimensionless) and 3.73μV, respectively, were the ECG markers most strongly associated with SCD, while TS, dichotomized at 2.5ms/RR, was the index most strongly related to PFD. When separating SCD victims from the rest of patients, the individual marker with best performance was Δα≥0.035, which, for a fixed specificity (Sp) of 90%, showed a sensitivity (Se) value of 10%, while the combination of Δα and IAA increased Se to 18%. For separation of PFD victims from the rest of patients, the best individual marker was TS≤2.5ms/RR, which, for Sp=90%, showed a Se of 26%, this value being lower than Se=34%, produced by the combination of Δα and TS. Furthermore, when performing SVM classification into the three reported groups, the optimal combination of risk markers led to a maximum Sp of 79% (Se=18%) for SCD and Sp of 81% (Se=14%) for PFD. The results shown in this work suggest that it is possible to efficiently discriminate SCD and PFD in a population of CHF patients using ECG-derived risk markers like Δα, TS and IAA.

Research paper thumbnail of T-wave alternans predicts ICD discharge in MADIT II patients with elevated resting heart rate

In this work we measure T-wave alternans (TWA) using the multilead Laplacian likelihood ratio met... more In this work we measure T-wave alternans (TWA) using the multilead Laplacian likelihood ratio method (mLLR) in MADIT II patients, and we evaluate its ability to predict ventricular tachycardia or ventricular fibrillation events requiring an ICD shock and to predict sudden cardiac death (SCD). Our results indicate that the average TWA measured between 80 and 90 beats/min in resting ECGs is associated with future ICD therapy in MADIT II patients with elevated resting heart rate.

Research paper thumbnail of Comparison of source separation techniques for multilead T-wave alternans detection in the ECG

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2010

T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden c... more T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden cardiac death. In this work, we evaluate different source separation techniques for multilead detection of TWA in the electrocardiogram (ECG). Two periodicity-based techniques - periodic component analysis (πCA) and the newly proposed spectral ratio maximization (SRM) - are compared to two independence-based techniques - FastICA and JADE - and to principal component analysis (PCA). According to simulation results, the best detection performance is obtained with the periodicity-based schemes.

Research paper thumbnail of Comparative Evaluation of Methodologies for T-Wave Alternans Mapping in Electrograms

IEEE Transactions on Biomedical Engineering, 2000

Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessi... more Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessible. T-wave alternans (TWA) is associated with increased vulnerability to ventricular tachycardia/fibrillation and it occurs before the onset of ventricular arrhythmias. Thus, accurate methodologies for time-varying alternans estimation/detection in EGM are needed. In this paper, we perform a simulation study based on epicardial EGM recorded in vivo in humans to compare the accuracy of four methodologies: the spectral method (SM), modified moving average method, laplacian likelihood ratio method (LLR), and a novel method based on time-frequency distributions. A variety of effects are considered, which include the presence of wide band noise, respiration, and impulse artifacts. We found that 1) EGM-TWA can be detected accurately when the standard deviation of wide-band noise is equal or smaller than ten times the magnitude of EGM-TWA. 2) Respiration can be critical for EGM-TWA analysis, even at typical respiratory rates. 3) Impulse noise strongly reduces the accuracy of all methods, except LLR. 4) If depolarization time is used as a fiducial point, the localization of the T-wave is not critical for the accuracy of EGM-TWA detection. 5) According to this study, all methodologies provided accurate EGM-TWA detection/quantification in ideal conditions, while LLR was the most robust, providing better detection-rates in noisy conditions. Application on epicardial mapping of the in vivo human heart shows that EGM-TWA has heterogeneous spatio-temporal distribution.

Research paper thumbnail of Average T-wave alternans activity in ambulatory ECG records predicts sudden cardiac death in patients with chronic heart failure

Heart Rhythm, 2012

BACKGROUND T-wave alternans (TWA) is a well-documented noninvasive electrocardiographic (ECG) met... more BACKGROUND T-wave alternans (TWA) is a well-documented noninvasive electrocardiographic (ECG) method useful for identifying patients at risk for sudden cardiac death (SCD).

Research paper thumbnail of Time Course and Spatial Distribution of T Wave Alternans Induced by Artery Occlusion in Pigs

cinc.org

T-wave alternans (TWA) has been linked to increased vulnerability of the myocardium to ventricula... more T-wave alternans (TWA) has been linked to increased vulnerability of the myocardium to ventricular fibrillation in different clinical conditions, including myocardial ischemia and infarction. TWA induced by acute ischemia has been characterized in patients during balloon occlusion in PTCA [Martınez et al. 2006, IEEE TBME 56 (4) pp. 701-711], which constitutes a good model for the first minutes of acute ischemia. Our aim in this work is to study and characterize TWA in longer occlusions using an animal model of myocardial ...

Research paper thumbnail of A Multilead Scheme Based on Periodic Component Analysis for T-Wave Alternans Analysis in the ECG

Annals of Biomedical Engineering, 2010

T-wave alternans (TWA) is a cardiac phenomenon that appears in the electrocardiogram (ECG) and is... more T-wave alternans (TWA) is a cardiac phenomenon that appears in the electrocardiogram (ECG) and is associated with the mechanisms leading to sudden cardiac death (SCD). In this study, we propose the use of a multilead TWA analysis scheme that combines the Laplacian likelihood ratio (LLR) method and periodic component analysis (pCA), an eigenvalue decomposition technique whose aim is to extract the most periodic sources of the signal. The proposed scheme is evaluated in different scenarios-from synthetic signals to stress test ECGs-and is compared to other reported schemes based on the LLR method. Results demonstrate that the pCA-based scheme provides a superior ability to detect TWA than previously reported schemes, and has the potential to improve the prognostic value of testing for TWA.

Research paper thumbnail of Comparison of Source Separation Techniques for Multilead T-Wave Alternans Detection in the ECG

T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden c... more T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden cardiac death. In this work, we evaluate different source separation techniques for multilead detection of TWA in the electrocardiogram (ECG). Two periodicity-based techniques -periodic component analysis (πCA) and the newly proposed spectral ratio maximization (SRM) -are compared to two independencebased techniques -FastICA and JADE -and to principal component analysis (PCA). According to simulation results, the best detection performance is obtained with the periodicitybased schemes.

Research paper thumbnail of Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PloS one, 2017

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart fai... more Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventric...

Research paper thumbnail of T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure

Journal of the American Heart Association, Jan 19, 2017

Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dis... more Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was sig...

Research paper thumbnail of Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols

Progress in Biophysics and Molecular Biology, 2016

Models of ion channel dynamics are usually built by fitting isolated cell experimental values of ... more Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived * Corresponding author identification of major ionic conductance contributors to steady-state AP markers, including AP D 90 , AP D 75 , AP D 50 , AP D 25 , T riangulation and maximal and minimal values of V and dV /dt during the AP (V max , V min , dV /dt max , dV /dt min ).

Research paper thumbnail of Automatic SVM classification of Sudden Cardiac Death and Pump Failure Death from Autonomic and Repolarization ECG Markers

Journal of Electrocardiology, 2015

Considering the rates of sudden cardiac death (SCD) and pump failure death (PFD) in chronic heart... more Considering the rates of sudden cardiac death (SCD) and pump failure death (PFD) in chronic heart failure (CHF) patients and the cost-effectiveness of their preventing treatments, identification of CHF patients at risk is an important challenge. In this work, we studied the prognostic performance of the combination of an index potentially related to dispersion of repolarization restitution (Δα), an index quantifying T-wave alternans (IAA) and the slope of heart rate turbulence (TS) for classification of SCD and PFD. Holter ECG recordings of 597 CHF patients with sinus rhythm enrolled in the MUSIC study were analyzed and Δα, IAA and TS were obtained. A strategy was implemented using support vector machines (SVM) to classify patients in three groups: SCD victims, PFD victims and other patients (the latter including survivors and victims of non-cardiac causes). Cross-validation was used to evaluate the performance of the implemented classifier. Δα and IAA, dichotomized at 0.035 (dimensionless) and 3.73μV, respectively, were the ECG markers most strongly associated with SCD, while TS, dichotomized at 2.5ms/RR, was the index most strongly related to PFD. When separating SCD victims from the rest of patients, the individual marker with best performance was Δα≥0.035, which, for a fixed specificity (Sp) of 90%, showed a sensitivity (Se) value of 10%, while the combination of Δα and IAA increased Se to 18%. For separation of PFD victims from the rest of patients, the best individual marker was TS≤2.5ms/RR, which, for Sp=90%, showed a Se of 26%, this value being lower than Se=34%, produced by the combination of Δα and TS. Furthermore, when performing SVM classification into the three reported groups, the optimal combination of risk markers led to a maximum Sp of 79% (Se=18%) for SCD and Sp of 81% (Se=14%) for PFD. The results shown in this work suggest that it is possible to efficiently discriminate SCD and PFD in a population of CHF patients using ECG-derived risk markers like Δα, TS and IAA.

Research paper thumbnail of T-wave alternans predicts ICD discharge in MADIT II patients with elevated resting heart rate

In this work we measure T-wave alternans (TWA) using the multilead Laplacian likelihood ratio met... more In this work we measure T-wave alternans (TWA) using the multilead Laplacian likelihood ratio method (mLLR) in MADIT II patients, and we evaluate its ability to predict ventricular tachycardia or ventricular fibrillation events requiring an ICD shock and to predict sudden cardiac death (SCD). Our results indicate that the average TWA measured between 80 and 90 beats/min in resting ECGs is associated with future ICD therapy in MADIT II patients with elevated resting heart rate.

Research paper thumbnail of Comparison of source separation techniques for multilead T-wave alternans detection in the ECG

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2010

T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden c... more T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden cardiac death. In this work, we evaluate different source separation techniques for multilead detection of TWA in the electrocardiogram (ECG). Two periodicity-based techniques - periodic component analysis (πCA) and the newly proposed spectral ratio maximization (SRM) - are compared to two independence-based techniques - FastICA and JADE - and to principal component analysis (PCA). According to simulation results, the best detection performance is obtained with the periodicity-based schemes.

Research paper thumbnail of Comparative Evaluation of Methodologies for T-Wave Alternans Mapping in Electrograms

IEEE Transactions on Biomedical Engineering, 2000

Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessi... more Electrograms (EGM) recorded from the surface of the myocardium are becoming more and more accessible. T-wave alternans (TWA) is associated with increased vulnerability to ventricular tachycardia/fibrillation and it occurs before the onset of ventricular arrhythmias. Thus, accurate methodologies for time-varying alternans estimation/detection in EGM are needed. In this paper, we perform a simulation study based on epicardial EGM recorded in vivo in humans to compare the accuracy of four methodologies: the spectral method (SM), modified moving average method, laplacian likelihood ratio method (LLR), and a novel method based on time-frequency distributions. A variety of effects are considered, which include the presence of wide band noise, respiration, and impulse artifacts. We found that 1) EGM-TWA can be detected accurately when the standard deviation of wide-band noise is equal or smaller than ten times the magnitude of EGM-TWA. 2) Respiration can be critical for EGM-TWA analysis, even at typical respiratory rates. 3) Impulse noise strongly reduces the accuracy of all methods, except LLR. 4) If depolarization time is used as a fiducial point, the localization of the T-wave is not critical for the accuracy of EGM-TWA detection. 5) According to this study, all methodologies provided accurate EGM-TWA detection/quantification in ideal conditions, while LLR was the most robust, providing better detection-rates in noisy conditions. Application on epicardial mapping of the in vivo human heart shows that EGM-TWA has heterogeneous spatio-temporal distribution.

Research paper thumbnail of Average T-wave alternans activity in ambulatory ECG records predicts sudden cardiac death in patients with chronic heart failure

Heart Rhythm, 2012

BACKGROUND T-wave alternans (TWA) is a well-documented noninvasive electrocardiographic (ECG) met... more BACKGROUND T-wave alternans (TWA) is a well-documented noninvasive electrocardiographic (ECG) method useful for identifying patients at risk for sudden cardiac death (SCD).

Research paper thumbnail of Time Course and Spatial Distribution of T Wave Alternans Induced by Artery Occlusion in Pigs

cinc.org

T-wave alternans (TWA) has been linked to increased vulnerability of the myocardium to ventricula... more T-wave alternans (TWA) has been linked to increased vulnerability of the myocardium to ventricular fibrillation in different clinical conditions, including myocardial ischemia and infarction. TWA induced by acute ischemia has been characterized in patients during balloon occlusion in PTCA [Martınez et al. 2006, IEEE TBME 56 (4) pp. 701-711], which constitutes a good model for the first minutes of acute ischemia. Our aim in this work is to study and characterize TWA in longer occlusions using an animal model of myocardial ...

Research paper thumbnail of A Multilead Scheme Based on Periodic Component Analysis for T-Wave Alternans Analysis in the ECG

Annals of Biomedical Engineering, 2010

T-wave alternans (TWA) is a cardiac phenomenon that appears in the electrocardiogram (ECG) and is... more T-wave alternans (TWA) is a cardiac phenomenon that appears in the electrocardiogram (ECG) and is associated with the mechanisms leading to sudden cardiac death (SCD). In this study, we propose the use of a multilead TWA analysis scheme that combines the Laplacian likelihood ratio (LLR) method and periodic component analysis (pCA), an eigenvalue decomposition technique whose aim is to extract the most periodic sources of the signal. The proposed scheme is evaluated in different scenarios-from synthetic signals to stress test ECGs-and is compared to other reported schemes based on the LLR method. Results demonstrate that the pCA-based scheme provides a superior ability to detect TWA than previously reported schemes, and has the potential to improve the prognostic value of testing for TWA.

Research paper thumbnail of Comparison of Source Separation Techniques for Multilead T-Wave Alternans Detection in the ECG

T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden c... more T-wave alternans (TWA) is a cardiac phenomenon associated with the mechanisms leading to sudden cardiac death. In this work, we evaluate different source separation techniques for multilead detection of TWA in the electrocardiogram (ECG). Two periodicity-based techniques -periodic component analysis (πCA) and the newly proposed spectral ratio maximization (SRM) -are compared to two independencebased techniques -FastICA and JADE -and to principal component analysis (PCA). According to simulation results, the best detection performance is obtained with the periodicitybased schemes.