Search

Respiratory rate (RR) is an important biomarker of cardiopulmonary status. Its role is particularly evident in conditions like obstructive sleep apnea, which significantly increase risk of heart disease. Electrocardiogram (ECG)-derived RR is an emerging alternative to traditional RR measurement, which requires cumbersome and specialized equipment. Here, we developed a novel algorithm to estimate instantaneous RR using only single-lead body-surface ECG. We comprehensively tested the influence of sex, age, and body mass index on the efficacy of ECG-derived RR. ECG and RR waveforms were obtained from 50 patients enrolled in a polysomnography sleep study. Algorithm-based ECG-derived RR estimates were compared with reference RR measurements from the sleep study. A close linear correlation between the reference and algorithmic RR estimates was observed across the entire cohort of patients. The mean absolute RR estimation error was 0.8±0.9 breaths/min. Importantly, the algorithm's accuracy was independent of the patient's age, sex, and body habitus. Our algorithm provides a robust estimation of RR and holds promise for remote pulmonary assessment in patients with respiratory disorders.

Background: Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity., Objective: The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF., Methods: Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin., Results: Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001)., Conclusion: PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Studies of ventricular fibrillation (VF) in humans are limited because of the short available duration. We sought to study surface ECG waveforms and effect of ablation in long-lasting VF in patients with left assist devices., Methods: Continuous 12-lead ECG of 5 episodes of long-lasting VF occurring in 3 patients with left ventricular assist device were analyzed. Spectral analysis (dominant frequency) and quantification of waveform amplitude, regularity (Unbiased Regularity Index), and complexity (Nondipolar Index) were performed over a median of 24 minutes of VF. Radiofrequency ablation was performed during VF in 2 patients., Results: There was a significant increase in dominant frequency between VF onset and termination but none of the other parameters significantly changed. Some VF parameters varied from patient to patient and from lead to lead. Dominant frequency decreased after radiofrequency ablation in both cases and VF terminated spontaneously shortly after ablation in one case. The previously incessant VFs in these 2 patients did not recur afterward., Conclusions: VF rate increases over time in patients with left ventricular assist devices and is lowered by ablation. Long-lasting VF may be modified or even terminated by ablation.

Background: With increasing clinical use of Electrocardiographic Imaging (ECGI), it is imperative to understand the limits of this technique. The objective of this study is to evaluate a potential-based ECGI approach for activation and repolarization mapping in sinus rhythm., Method: Langendorff-perfused pig hearts were suspended in a human-shaped torso tank. Electrograms were recorded with a 108-electrode sock and ECGs with 256 electrodes embedded in the tank surface. Left bundle branch block (LBBB) was developed in 4 hearts through ablation, and repolarization abnormalities in another 4 hearts through regional perfusion of dofetilide and pinacidil. Electrograms were noninvasively reconstructed and reconstructed activation and repolarization features were compared to those recorded., Results: Visual consistency between ECGI and recorded activation and repolarization maps was high. While reconstructed repolarization times showed significantly more error than activation times quantitatively, patterns were reconstructed with a similar level of accuracy. The number of epicardial breakthrough sites was underestimated by ECGI and these were misplaced (>20 mm) in location. Likewise, ECGI reconstructed activation maps demonstrated artificial lines of block resulting from a W-shaped QRS waveform that were not present in recorded maps. Nevertheless, ECGI allowed identification of regions of abnormal repolarization reasonably accurately in terms of size, location and timing., Conclusions: This study validates a potential-based ECGI approach to noninvasively image activation and recovery in sinus rhythm. Despite inaccuracies in epicardial breakthroughs and lines of conduction block, other important clinical features such as regions of abnormal repolarization can be accurately derived making ECGI a valuable clinical tool., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Activation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior invasive studies, and both methods have not been thoroughly confronted in a clinical setting., Objective: The goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures., Methods: Fifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors., Results: The mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation -0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs., Conclusion: Overall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF)., Background: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood., Methods: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed., Results: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m 2 . The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008)., Conclusions: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.

From the dawn of the twentieth century, the electrocardiogram (ECG) has revolutionized the way clinical cardiology has been practiced, and it has become the cornerstone of modern medicine today. Driven by clinical and research needs for a more precise understanding of cardiac electrophysiology beyond traditional ECG, inverse solution electrocardiography has been developed, tested, and validated. This article outlines the important progress from ECG development, through more extensive measurement of body surface potentials, and the fundamental leap to solving the inverse problem of electrocardiography, with a focus on mathematical methods and experimental validation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Here, we investigate the mechanisms underlying the onset of conduction-related arrhythmias in a three-dimensional (3D) computational model of acute regional ischaemia., Methods: Ischaemia was introduced by realistic gradients of potassium, pH, oxygen and electrical coupling in a 3D slab of ventricular tissue using the LRd model. We focused on a specific stage (10-15 min after occlusion) at which an intramural non-conductive ischaemic core (IC) surrounded by a border zone (BZ) has formed., Results: At pacing frequencies greater than 4.5 Hz, we observed narrow areas (0.5 mm wide) of 2:1 conduction blocks at the periphery of the IC. As the pacing frequency increased, the area of block widened to 9 mm and gave rise to reentry at the periphery of the BZ. Alternating conduction blocks produced discordant action potential duration (APD) alternans throughout the slab and T-wave alternans in pseudo-ECG. Slowing the recovery of the calcium current broadened the range of pacing frequencies at which blocks were observed. Hyperkalaemia alone was sufficient to induce the alternating blocks., Conclusion: Computer modelling predicts that ischaemia-related arrhythmias are triggered by calcium-mediated alternating conduction blocks in the ischaemic border zone. Alternating conduction blocks lead to intramural reentry and APD alternans.

BackgroundRight ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT.MethodsWe conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics.ResultsWe found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (P=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (P=0.034) and partially reversed action potential duration at 80% repolarization shortening (P=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (P=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT.ConclusionsHuman RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.

Background: Cardiovascular magnetic resonance T1ρ mapping may detect myocardial injuries without exogenous contrast agent. However, multiple co-registered acquisitions are required, and the lack of robust motion correction limits its clinical translation. We introduce a single breath-hold myocardial T1ρ mapping method that includes model-based non-rigid motion correction. Methods: A single-shot electrocardiogram (ECG)-triggered balanced steady state free precession (bSSFP) 2D adiabatic T1ρ mapping sequence that collects five T1ρ-weighted (T1ρw) images with different spin lock times within a single breath-hold is proposed. To address the problem of residual respiratory motion, a unified optimization framework consisting of a joint T1ρ fitting and model-based non-rigid motion correction algorithm, insensitive to contrast change, was implemented inline for fast (~ 30 s) and direct visualization of T1ρ maps. The proposed reconstruction was optimized on an ex vivo human heart placed on a motion-controlled platform. The technique was then tested in 8 healthy subjects and validated in 30 patients with suspected myocardial injury on a 1.5T CMR scanner. The Dice similarity coefficient (DSC) and maximum perpendicular distance (MPD) were used to quantify motion and evaluate motion correction. The quality of T1ρ maps was scored. In patients, T1ρ mapping was compared to cine imaging, T2 mapping and conventional post-contrast 2D late gadolinium enhancement (LGE). T1ρ values were assessed in remote and injured areas, using LGE as reference. Results: Despite breath holds, respiratory motion throughout T1ρw images was much larger in patients than in healthy subjects (5.1 ± 2.7 mm vs. 0.5 ± 0.4 mm, P < 0.01). In patients, the model-based non-rigid motion correction improved the alignment of T1ρw images, with higher DSC (87.7 ± 5.3% vs. 82.2 ± 7.5%, P < 0.01), and lower MPD (3.5 ± 1.9 mm vs. 5.1 ± 2.7 mm, P < 0.01). This resulted in significantly improved quality of the T1ρ maps (3.6 ± 0.6 vs. 2.1 ± 0.9, P < 0.01). Using this approach, T1ρ mapping could be used to identify LGE in patients with 93% sensitivity and 89% specificity. T1ρ values in injured (LGE positive) areas were significantly higher than in the remote myocardium (68.4 ± 7.9 ms vs. 48.8 ± 6.5 ms, P < 0.01). Conclusions: The proposed motion-corrected T1ρ mapping framework enables a quantitative characterization of myocardial injuries with relatively low sensitivity to respiratory motion. This technique may be a robust and contrast-free adjunct to LGE for gaining new insight into myocardial structural disorders. [ABSTRACT FROM AUTHOR]

Background: Non-invasive electrocardiographic imaging (ECGI) is a promising tool to provide high-resolution panoramic imaging of cardiac electrical activity noninvasively from body surface potential measurements. Current experimental methods for ECGI validation are limited to comparison with unipolar electrograms and the relatively low spatial resolution of cardiac mapping arrays. We aim to develop a novel experimental set up combining a human shaped torso tank with high-resolution optical mapping allowing the validation of ECGI reconstructions. Methods: Langendorff-perfused pig hearts (n = 3) were suspended in a human torso-shaped tank, with the left anterior descending artery (LAD) cannulated on a separate perfusion. Electrical signals were recorded from an 108-electrode epicardial sock and 128 electrodes embedded in the tank surface. Simultaneously, optical mapping of the heart was performed through the anterior surface of the tank. Recordings were made in sinus rhythm and ventricular pacing (n = 55), with activation and repolarization heterogeneities induced by perfusion of hot and cold solutions as well as Sotalol through the LAD. Fluoroscopy provided 3D cardiac and electrode geometries in the tank that were transformed to the 2D optical mapping window using an optimization algorithm. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGI and validated using optical activation and repolarization maps. Results: The transformation and alignment of the 3D geometries onto the 2D optical mapping window was good with an average correlation of 0.87 ± 0.10 and error of 7.7 ± 3.1 ms with activation derived from the sock. The difference in repolarization times were more substantial (error = 17.4 ± 3.7 ms) although the sock and optical repolarization patterns themselves were very similar (correlation = 0.83 ± 0.13). Validation of ECGI reconstructions revealed ECGI accurately captures the pattern of activation (correlation = 0.79 ± 0.11) and identified regions of late and/or early repolarization during different perfusions through LAD. ECGI also correctly demonstrated gradients in both activation and repolarization, although in some cases these were under or over-estimated or shifted slightly in space. Conclusion: A novel experimental setup has been developed, combining a human-shaped torso tank with optical mapping, which can be effectively used in the validation of ECGI techniques; including the reconstruction of activation and repolarization patterns and gradients. [ABSTRACT FROM AUTHOR]

The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi-atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1 year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non-invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat-to-beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient-specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo) plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. [ABSTRACT FROM AUTHOR]