Marianna Meo

Spatial Variability of the 12-Lead Surface ECG as a Tool for Noninvasive Prediction of Catheter Ablation Outcome in Persistent Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia encountered in clinical practice. Radiofrequency catheter ablation (CA) is increasingly employed to treat this disease, yet the selection of persistent AF patients who will benefit from this treatment remains a challenging task. Several parameters of the surface electrocardiogram (ECG) have been analyzed in previous works to predict AF termination by CA, such as fibrillatory wave (f-wave) amplitude. However, they are usually manually computed and only a subset of electrodes is inspected. In this study, a novel perspective of the role of f-wave amplitude as a potential noninvasive predictor of CA outcome is adopted by exploring ECG interlead spatial variability. An automatic procedure for atrial amplitude computation based on cubic Hermite interpolation is first proposed. To describe the global f-wave peak-to-peak amplitude distribution, signal contributions from multiple leads are then combined by condensing the most representative features of the atrial signal in a reduced-rank approximation based on principal component analysis (PCA). We show that exploiting ECG spatial diversity by means of this PCA-based multilead approach does not only increase the robustness to electrode selection, but also substantially improves the predictive power of the amplitude parameter.

Late Na + current and protracted electrical recovery are critical determinants of the aging myopathy

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.

Non-invasive prediction of catheter ablation outcome in persistent atrial fibrillation by exploiting the spatial diversity of surface ECG

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice. Radiofre-quency catheter ablation (CA) is becoming one of the most widely employed therapies. Yet selection of patients who will benefit from this treatment remains a challenging task. Previous works have examined several electrocardiogram (ECG) parameters as potential predictors of CA success, such as fibrillatory wave (f-wave) amplitude. However, they require a manual computation and consider only a subset of electrodes, so inter-lead spatial variability of the 12-lead ECG is not fully exploited. The present study puts forward an automatic procedure for f-wave amplitude computation to non-invasively predict CA outcome. An extension of this quantitative measure to the whole set of leads is also proposed, based on Principal Component Analysis (PCA). We show that exploiting the spatial diversity present in the surface ECG not only improves the robustness to electrode selection but also increases the predictive power of the amplitude parameter.

Catheter ablation outcome prediction in persistent atrial fibrillation using weighted principal component analysis

Radiofrequency catheter ablation (CA) is increasingly employed to treat persistent atrial fibrillation (AF), yet selection of patients who would positively respond to this therapy is currently a critical problem. Several parameters of the surface 12-lead electrocardiogram (ECG) have been analyzed in previous works to predict AF termination by CA. Nevertheless, they are affected by some limitations, such as manual computation and the examination of a single ECG lead while neglecting contributions from other electrodes. AF spatio-temporal organization has been described on surface ECG by means of the normalized mean square error (NMSE) between consecutive atrial activity (AA) signal segments and their reduced-rank approximations based on principal component analysis (PCA). However, these features do not show to be correlated with CA outcome. In this study, such descriptors are adequately adapted and applied to CA outcome prediction. An NMSE index is put forward, computed over the set of eight linearly independent ECG leads after AA signal rank-1 approximations determined by weighted principal component analysis (WPCA). The final predictor is able to discriminate between successful (70.76 ± 17.74) and failing CA procedures (37.54 ± 20.01) before performing the ablation (p-value = 0.0013, AUC = 0.91). The proposed WPCA-based technique emphasizes the most descriptive components of AF electrophysiology by selectively enhancing contributions coming from the most representative ECG leads. Our investigation confirms that ECG spatial diversity exploitation in this WPCA-based framework not only endows the NMSE index with clinical value in the context of CA outcome prediction, but it also improves classification accuracy and increases robustness to ECG lead selection.

Hyperglycemia induces defective Ca2+ homeostasis in cardiomyocytes

Diabetes and other metabolic conditions characterized by elevated blood glucose constitute important risk factors for cardiovascular disease. Hyperglycemia targets myocardial cells rendering ineffective mechanical properties of the heart, but cellular alterations dictating the progressive deterioration of cardiac function with metabolic disorders remain to be clarified. In the current study, we examined the effects of hyperglycemia on cardiac function and myocyte physiology by employing mice with high blood glucose induced by administration of streptozotocin, a compound toxic to insulin-producing β-cells. We found that hyperglycemia initially delayed the electrical recovery of the heart, whereas cardiac function became defective only after ~2 mo with this condition and gradually worsened with time. Prolonged hyperglycemia was associated with increased chamber dilation, thinning of the left ventricle (LV), and myocyte loss. Cardiomyocytes from hyperglycemic mice exhibited defective Ca2+ transients before the appearance of LV systolic defects. Alterations in Ca2+ transients involved enhanced spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR), reduced cytoplasmic Ca2+ clearance, and declined SR Ca2+ load. These defects have important consequences on myocyte contraction, relaxation, and mechanisms of rate adaptation. Collectively, our data indicate that hyperglycemia alters intracellular Ca2+ homeostasis in cardiomyocytes, hindering contractile activity and contributing to the manifestation of the diabetic cardiomyopathy. NEW & NOTEWORTHY We have investigated the effects of hyperglycemia on cardiomyocyte physiology and ventricular function. Our results indicate that defective Ca2+ handling is a critical component of the progressive deterioration of cardiac performance of the diabetic heart.

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Background Diabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization. Methods and Results Diabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K+ and L‐type Ca2+ currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes. Conclusions Reductions in the repolarizing K+ currents may contribute to electrical disturbances of the diabetic heart.

Myocyte repolarization modulates myocardial function in aging dogs

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions.

Non-invasive prediction of catheter ablation outcome in persistent atrial fibrillation by fibrillatory wave amplitude computation in multiple electrocardiogram leads

BACKGROUND Catheter ablation (CA) of persistent atrial fibrillation (AF) is challenging, and reported results are capable of improvement. A better patient selection for the procedure could enhance its success rate while avoiding the risks associated with ablation, especially for patients with low odds of favorable outcome. CA outcome can be predicted non-invasively by atrial fibrillatory wave (f-wave) amplitude, but previous works focused mostly on manual measures in single electrocardiogram (ECG) leads only. AIM To assess the long-term prediction ability of f-wave amplitude when computed in multiple ECG leads. METHODS Sixty-two patients with persistent AF (52 men; mean age 61.5±10.4years) referred for CA were enrolled. A standard 1-minute 12-lead ECG was acquired before the ablation procedure for each patient. F-wave amplitudes in different ECG leads were computed by a non-invasive signal processing algorithm, and combined into a mutivariate prediction model based on logistic regression. RESULTS During an average follow-up of 13.9±8.3months, 47 patients had no AF recurrence after ablation. A lead selection approach relying on the Wald index pointed to I, V1, V2 and V5 as the most relevant ECG leads to predict jointly CA outcome using f-wave amplitudes, reaching an area under the curve of 0.854, and improving on single-lead amplitude-based predictors. CONCLUSION Analysing the f-wave amplitude in several ECG leads simultaneously can significantly improve CA long-term outcome prediction in persistent AF compared with predictors based on single-lead measures.

Nonnegative matrix factorization for noninvasive prediction of catheter ablation outcome in persistent atrial fibrillation

Despite the increasing popularity of catheter ablation (CA) for treating atrial fibrillation (AF), the identification of patients who would actually benefit from the therapy remains a challenging open issue. This study aims at noninvasively predicting CA outcome by quantifying the spatio-temporal variability of the atrial activity (AA) signal measured on the standard 12-lead electrocardiogram. The normalized mean square error (NMSE) between consecutive atrial segments and their principal component approximations is computed for each lead, as a recent noninvasive index of AF organization. In the present work, the multilead NMSE array is decomposed by means of a nonnegative matrix factorization (NNMF) with two different initializations. The reconstruction error between the original NMSE matrix and its low-rank NNMF approximation is taken as a classification feature. A dataset of persistent AF patients undergoing CA reveals that the proposed feature is able to predict the therapy outcome with a notably higher level of statistical significance than recent single-lead indices.

Variability in pulmonary vein electrophysiology and fibrosis determines arrhythmia susceptibility and dynamics

Success rates for catheter ablation of persistent atrial fibrillation patients are currently low; however, there is a subset of patients for whom electrical isolation of the pulmonary veins alone is a successful treatment strategy. It is difficult to identify these patients because there are a multitude of factors affecting arrhythmia susceptibility and maintenance, and the individual contributions of these factors are difficult to determine clinically. We hypothesised that the combination of pulmonary vein (PV) electrophysiology and atrial body fibrosis determine driver location and effectiveness of pulmonary vein isolation (PVI). We used bilayer biatrial computer models based on patient geometries to investigate the effects of PV properties and atrial fibrosis on arrhythmia inducibility, maintenance mechanisms, and the outcome of PVI. Short PV action potential duration (APD) increased arrhythmia susceptibility, while longer PV APD was found to be protective. Arrhythmia inducibility increased with slower conduction velocity (CV) at the LA/PV junction, but not for cases with homogeneous CV changes or slower CV at the distal PV. Phase singularity (PS) density in the PV region for cases with PV fibrosis was increased. Arrhythmia dynamics depend on both PV properties and fibrosis distribution, varying from meandering rotors to PV reentry (in cases with baseline or long APD), to stable rotors at regions of high fibrosis density. Measurement of fibrosis and PV properties may indicate patient specific susceptibility to AF initiation and maintenance. PV PS density before PVI was higher for cases in which AF terminated or converted to a macroreentry; thus, high PV PS density may indicate likelihood of PVI success.