Open-source software for respiratory rate estimation using single-lead electrocardiograms.

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing a non-proprietary method that uses minimal ECG leads, generally available from mobile cardiac monitors is highly desirable. Here, we introduce an open-source and well-documented Python-based algorithm that estimates RR requiring only single-stream ECG signals. The algorithm was first developed using ECGs from awake, spontaneously breathing adult human subjects. The algorithm-estimated RRs exhibited close linear correlation to the subjects' true RR values demonstrating an R2 of 0.9092 and root mean square error of 2.2 bpm. The algorithm robustness was then tested using ECGs generated by the ischemic hearts of anesthetized, mechanically ventilated sheep. Although the ECG waveforms during ischemia exhibited severe morphologic changes, the algorithm-determined RRs exhibited high fidelity with a resolution of 1 bpm, an absolute error of 0.07 ± 0.07 bpm, and a relative error of 0.67 ± 0.64%. This optimized Python-based RR estimation technique will likely be widely adapted for remote lung function assessment in patients with cardiopulmonary disease.

Tissue Preparation Techniques for Contrast-Enhanced Micro Computed Tomography Imaging of Large Mammalian Cardiac Models with Chronic Disease.

Structural remodeling is a common consequence of chronic pathological stresses imposed on the heart. Understanding the architectural and compositional properties of diseased tissue is critical to determine their interactions with arrhythmic behavior. Microscale tissue remodeling, below the clinical resolution, is emerging as an important source of lethal arrhythmia, with high prevalence in young adults. Challenges remain in obtaining high imaging contrast at sufficient microscale resolution for preclinical models, such as large mammalian whole hearts. Moreover, tissue composition-selective contrast enhancement for three-dimensional high-resolution imaging is still lacking. Non-destructive imaging using micro-computed tomography shows promise for high-resolution imaging. The objective was to alleviate sufferance from X-ray over attenuation in large biological samples. Hearts were extracted from healthy pigs (N = 2), and sheep (N = 2) with either induced chronic myocardial infarction and fibrotic scar formation or induced chronic atrial fibrillation. Excised hearts were perfused with: a saline solution supplemented with a calcium ion quenching agent and a vasodilator, ethanol in serial dehydration, and hexamethyldisilizane under vacuum. The latter reinforced the heart structure during air-drying for 1 week. Collagen-dominant tissue was selectively bound by an X-ray contrast-enhancing agent, phosphomolybdic acid. Tissue conformation was stable in air, permitting long-duration microcomputed tomography acquisitions to obtain high-resolution (isotropic 20.7 µm) images. Optimal contrast agent loading by diffusion showed selective contrast enhancement of the epithelial layer and sub-endocardial Purkinje fibers in healthy pig ventricles. Atrial fibrillation (AF) hearts showed enhanced contrast accumulation in the posterior walls and appendages of the atria, attributed to greater collagen content. Myocardial infarction hearts showed increased contrast selectively in regions of cardiac fibrosis, which enabled the identification of interweaving surviving myocardial muscle fibers. Contrast-enhanced air-dried tissue preparations enabled microscale imaging of the intact large mammalian heart and selective contrast enhancement of underlying disease constituents.

Noncontact whole-chamber charge density mapping of the left ventricle: Preclinical evaluation in a sheep model.

BACKGROUND: Conventional contact-based electroanatomic mapping is poorly suited for rapid or dynamic ventricular arrhythmias. Whole-chamber charge density (CD) mapping could efficiently characterize complex ventricular tachyarrhythmias and yield insights into their underlying mechanisms. OBJECTIVE: The purpose of this study was to evaluate the feasibility and accuracy of noncontact whole-chamber left ventricular (LV) CD mapping and to characterize CD activation patterns during sinus rhythm, ventricular pacing, and ventricular fibrillation (VF). METHODS: Ischemic scar as defined by CD amplitude thresholds was compared to late gadolinium enhancement criteria on magnetic resonance imaging using an iterative closest point algorithm. Electrograms recorded at sites of tissue contact were compared to the nearest noncontact CD-derived electrograms to calculate signal morphology cross-correlations and time differences. Regions of consistently slow conduction were examined relative to areas of scar and to localized irregular activation (LIA) during VF. RESULTS: Areas under receiver operating characteristic curves (AUCs) of CD-defined dense and total LV scar were 0.92 ± 0.03 and 0.87 ± 0.06, with accuracies of 0.86 ± 0.03 and 0.80 ± 0.05, respectively. Morphology cross-correlation between 8677 contact and corresponding noncontact electrograms was 0.93 ± 0.10, with a mean time difference of 2.5 ± 5.6 ms. Areas of consistently slow conduction tended to occur at scar borders and exhibited spatial agreement with LIA during VF (AUC 0.90 ± 0.02). CONCLUSION: Noncontact LV CD mapping can accurately delineate ischemic scar. CD-derived ventricular electrograms correlate strongly with conventional contact-based electrograms. Regions with consistently slow conduction are often at scar borders and tend to harbor LIA during VF.

Spectral Analysis of Tissue Displacement for Cardiac Activation Mapping: Ex Vivo Working Heart and In Vivo Study.

Characterizing myocardial activation is of major interest for understanding the underlying mechanism of cardiac arrhythmias. Electromechanical wave imaging (EWI) is an ultrafast ultrasound-based method used to map the propagation of the local contraction triggered by electrical activation of the heart. This study introduces a novel way to characterize cardiac activation based on the time evolution of the instantaneous frequency content of the cardiac tissue displacement curves. The first validation of this method was performed on an ex vivo dataset of 36 acquisitions acquired from two working heart models in paced rhythms. It was shown that the activation mapping described by spectral analysis of interframe displacement is similar to the standard EWI method based on zero-crossing of interframe strain. An average median error of 3.3 ms was found in the ex vivo dataset between the activation maps obtained with the two methods. The feasibility of mapping cardiac activation by EWI was then investigated on two open-chest pigs during sinus and paced rhythms in a pilot trial of cardiac mapping with an intracardiac probe. Seventy-five acquisitions were performed with reasonable stability and analyzed with the novel algorithm to map cardiac contraction propagation in the left ventricle (LV). Sixty-one qualitatively continuous isochrones were successfully computed based on this method. The region of contraction onset was coherently described while pacing in the imaging plane. These findings highlight the potential of implementing EWI acquisition on intracardiac probes and emphasize the benefit of performing short time-frequency analysis of displacement data to characterize cardiac activation in vivo.

Profibrillatory Structural and Functional Properties of the Atrial-Pulmonary Junction in the Absence of Remodeling.

Background: Sole pulmonary vein (PV) isolation by ablation therapy prevents atrial fibrillation (AF) in patients with short episodes of AF and without comorbidities. Since incomplete PV isolation can be curative, we tested the hypothesis that the PV in the absence of remodeling and comorbidities contains structural and functional properties that are proarrhythmic for AF initiation by reentry. Methods: We performed percutaneous transvenous in vivo endocardial electrophysiological studies and quantitative histological analysis of PV from healthy sheep. Results: The proximal PV contained more myocytes than the distal PV and a higher percentage of collagen and fat tissue relative to myocytes than the left atrium. Local fractionated electrograms occurred in both the distal and proximal PVs, but a large local activation (>0.75 mV) was more often present in the proximal PV than in the distal PV (86 vs. 50% of electrograms, respectively, p = 0.017). Atrial arrhythmias (run of premature atrial complexes) occurred more often following the premature stimulation in the proximal PV than in the distal PV (p = 0.004). The diastolic stimulation threshold was higher in the proximal PV than in the distal PV (0.7 [0.3] vs. 0.4 [0.2] mA, (median [interquartile range]), p = 0.004). The refractory period was shorter in the proximal PV than in the distal PV (170 [50] vs. 248 [52] ms, p < 0.001). A linear relation existed between the gradient in refractoriness (distal-proximal) and atrial arrhythmia inducibility in the proximal PV. Conclusion: The structural and functional properties of the native atrial-PV junction differ from those of the distal PV. Atrial arrhythmias in the absence of arrhythmia-induced remodeling are caused by reentry in the atrial-PV junction. Ablative treatment of early paroxysmal AF, rather than complete isolation of focal arrhythmia, may be limited to inhibition of reentry.

Localized Pulmonary Vein Scar Promotes Atrial Fibrillation in High Left Atrial Pressure.

BACKGROUND: Pulmonary vein (PV) ablation is unsuccessful in atrial fibrillation (AF) patients with high left atrial (LA) pressure. Increased atrial stretch by increased pressure is proarrhythmic for AF, and myocardial scar alters wall deformation. We hypothesized that localized PV scar is proarrhythmic for AF in high LA pressure. METHODS: Radiofrequency energy was delivered locally in the right PV of healthy sheep. The sheep recovered for 4 months. Explanted hearts (n = 9 PV scar, n = 9 controls) were perfused with 1:4 blood:Tyrode's solution in a four-chamber working heart setup. Programmed PV stimulation was performed during low (∼12 mmHg) and high (∼25 mmHg) LA pressure. An AF inducibility index was calculated based on the number of induction attempts and the number of attempts causing AF (run of ≥ 20 premature atrial complexes). RESULTS: In high LA pressure, the presence of PV scar increased the AF inducibility index compared with control hearts (0.83 ± 0.20 vs. 0.38 ± 0.40 arb. unit, respectively, p = 0.014). The diastolic stimulation threshold in high LA pressure was higher (108 ± 23 vs. 77 ± 16 mA, respectively, p = 0.006), and its heterogeneity was increased in hearts with PV scar compared with controls. In high LA pressure, the refractory period was shorter in PV scar than in control hearts (178 ± 39 vs. 235 ± 48 ms, p = 0.011). CONCLUSION: Localized PV scar only in combination with increased LA pressure facilitated the inducibility of AF. This was associated with changes in tissue excitability remote from the PV scar. Localized PV ablation is potentially proarrhythmic in patients with increased LA pressure.

Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications.