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US-12616412-B2 - Method for the identification of cardiac fibrillation drivers and/or the footprint of rotational activations using single optical or electrical signals without requiring panoramic simultaneous acquisition

US12616412B2US 12616412 B2US12616412 B2US 12616412B2US-12616412-B2

Abstract

This invention relates to an ex vivo use of the instantaneous frequency modulation (iFM) signal of cardiac activations and to an ex vivo use of the instantaneous amplitude modulation (iAM) signal obtained from the sequence of amplitude excursions of said activations for detecting ‘driver’ or ‘high-hierarchy’ regions and/or the cardiac spots that display the footprint of rotational activations in the heart of a subject with cardiac fibrillation without requiring panoramic simultaneous acquisition.

Inventors

  • Jorge GARCÍA QUINTANILLA
  • David FILGUEIRAS RAMA
  • Nicasio PÉREZ CASTELLANO
  • Julián PÉREZ-VILLACASTÍN DOMÍNGUEZ

Assignees

  • CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.)
  • FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL CLÍNICO SAN CARLOS

Dates

Publication Date
20260505
Application Date
20191011
Priority Date
20181011

Claims (17)

  1. 1 . A medical apparatus, comprising at least a probe or catheter configured to insert into a heart of a subject with cardiac fibrillation, wherein the probe comprises an elongated body, and one or more mapping electrodes or optical fibers disposed on a distal portion of the body, a memory having one or more programs stored therein, a display, and a processor linked to the display and coupled to access the memory to execute the programs, wherein the processor is connectable to receive an input provided by the mapping electrodes or optical fibers, wherein the one or more programs, when executed by the processor, cause the processor to perform the steps of obtaining a single or multiple electrical unipolar signals or optical signals from a single target or multiple sequential targets in the heart via the mapping electrodes or optical fibers, generating an electroanatomical map based on the assigned electrical or optical data at a single or multiple cardiac spots, and wherein the one or more programs, when executed by the processor, cause the processor to perform the following steps: a. detecting activations over i) the electrical unipolar signals or ii) the optical signals; b. obtaining an instantaneous frequency modulation (iFM) signal from the activations of step a) for each i) unipolar electrical signal or ii) optical signal, by calculating a reciprocal of one or more intervals between consecutive activations, and obtaining an instantaneous amplitude modulation (iAM) signal from sequence of amplitude excursions of i) the negative deflections that contain activations in each unipolar electrical signal or ii) the optical phases O that contain activations in each optical signal: wherein the lower an amplitude excursion, the higher its corresponding value in the iAM signal and vice versa; c. detecting intervals that display the footprint of rotational activity wherein A) simultaneous increase in iFM and iAM is indicative of drifting rotors approaching a cardiac spot or B) simultaneously high iAM and iFM values is indicative of stationary rotors or rotors meandering around a cardiac spot; d. calculating the mean, median or a specific percentile value of each iFM signal obtained in step b), and obtaining a map by interpolating such values at each of the points used to generate the map, and using such a map to detect cardiac spots wherein such mean, median or specific percentile values are higher than those in their surroundings, such cardiac spots being considered to be the regions potentially driving cardiac fibrillation; and e. presenting the electroanatomical map to guide ablation of at least one area of tissue of the subject on the display in any way in which the regions potentially driving cardiac fibrillation detected in step d) and the cardiac spots displaying the footprint of rotational activity detected in step c) can be identified in the heart of the subject.
  2. 2 . The medical apparatus of claim 1 , wherein the step of detecting intervals that display the footprint of rotational activity comprises selecting intervals upon compliance with at least one of the conditions A or B specified below; Condition A: a simultaneous increase in iFM and iAM, which is indicative of drifting rotors approaching a cardiac spot, wherein the following logical condition is fulfilled, Increasing iFM(t) for at least parameter_1 cycles AND [(increasing iAM(t) with a minimum excursion of parameter_2% for at least parameter_3 cycles reaching at least parameter 4%) OR iAM(t)≥parameter_4%]; or Condition B: simultaneous high iAM and iFM values, which is indicative of stationary rotors or rotors meandering around a cardiac spot, wherein the following logical condition is fulfilled: iFM(t)≥parameter_5 percentile AND iAM(t)≥parameter_4% for at least 2 cycles.
  3. 3 . The medical apparatus according to claim 1 , wherein the activations of step a) are detected by first calculating i) an absolute negative slope (ANS) signal/s that is/are obtained as the absolute value of a time derivative of a single or multiple electrical unipolar signal/s obtained via a single or multiple mapping electrode/s, in the intervals with negative slopes and assigning a O value in the intervals with positive slopes; or by first calculating ii) an absolute positive slope (APS) signal/s that is/are obtained as the absolute value of the time derivative of a single or multiple optical signal/s obtained via a single or multiple optical fiber/s, in the intervals with positive slopes and assigning a O value in the intervals with negative slopes.
  4. 4 . The medical apparatus according to claim 1 , wherein the cardiac fibrillation is atrial fibrillation, and wherein the intervals between consecutive atrial activations during atrial fibrillation to provide the iFM signal are calculated by first detecting and excluding false atrial negative deflections due to ventricular electrical far-field in an electrical unipolar signal acquired from an atrium of a heart of a subject during atrial fibrillation, wherein such exclusion of the false atrial negative deflections comprises the following steps: a. obtaining a bipolar electrical signal from 2 atrial unipolar electrical signals acquired from two atrial locations in the heart of the subject during atrial fibrillation via at least two electrodes, and obtaining a simultaneous surface ECG signal or a simultaneous ventricular signal acquired in the same heart via at least one electrode; and b. detecting intervals containing false unipolar atrial negative deflections as intervals when simultaneously: i) the unipolar electrical signals from the atria acquired in step a) present negative slope; ii) the simultaneous surface ECG signal or the simultaneous ventricular signal acquired in step a) display ventricular activation; and iii) the bipolar electrical signal indicated in step a) contains negligible voltages; wherein the instantaneous frequency modulation (iFM) signal is then calculated as the reciprocal of the intervals between consecutive atrial activations during atrial fibrillation after discarding activations contained in the false unipolar atrial negative deflections detected in step b).
  5. 5 . The medical apparatus according to claim 1 , wherein the cardiac fibrillation is atrial fibrillation, and wherein atrial activations in unipolar electrical signals acquired from the atria of a subject with atrial fibrillation to provide the iFM signals are detected by a method which comprises the following steps: a. obtaining a bipolar electrical signal from 2 atrial unipolar electrical signals acquired from two atrial locations in the heart of the subject during atrial fibrillation via at least two electrodes, and obtaining a simultaneous surface ECG signal or a simultaneous ventricular signal acquired in the same heart via at least one electrode; b. applying a ventricular far-field subtraction method to the atrial unipolar signal acquired in step a); c. calculating the absolute negative slope (ANS) signal from the signal obtained after performing step b), wherein the ANS signal/s is/are obtained as the absolute value of the time derivative of a single or multiple electrical unipolar signal/s obtained via a single or multiple mapping electrode/s, in the intervals with negative slopes and assigning a O value in the intervals with positive slopes; d. detecting local maxima in the ANS signal; wherein the times at which the local maxima are detected are considered potential atrial activations; e. rejecting the false atrial activations contained in the residual false atrial negative unipolar deflections detected as by first detecting and excluding the false atrial negative deflections due to ventricular electrical far-field in an electrical unipolar signal acquired from an atrium of a heart of a subject during atrial fibrillation, wherein such exclusion of the false atrial negative deflections comprises the following steps: i) obtaining a bipolar electrical signal from 2 atrial unipolar electrical signals acquired from two atrial locations in the heart of the subject during atrial fibrillation via at least two electrodes, and obtaining a simultaneous surface ECG signal or a simultaneous ventricular signal acquired in the same heart via at least one electrode; and ii) detecting intervals containing false unipolar atrial negative deflections as intervals when simultaneously: i) the unipolar electrical signals from the atria acquired in step a) present negative slope: ii) the simultaneous surface ECG signal or the simultaneous ventricular signal acquired in step a) display ventricular activation; and iii) the bipolar electrical signal indicated in step a) contains negligible voltages; wherein the instantaneous frequency modulation (FM) signal is then calculated as the reciprocal of the intervals between consecutive atrial activations during atrial fibrillation after discarding activations contained in the false unipolar atrial negative deflections detected in step b); and f) identifying the activations used to calculate the iFM signal.
  6. 6 . The medical apparatus according to claim 5 wherein said local maxima according to step d) are selected upon compliance with both condition A, a minimum height and prominence, and condition B, a minimum separation from the previous and next detected local maxima: Minimum height and prominence=max{parameter_1,parameter_2 ·P 95th (ANS)} Condition A: wherein 95 th percentile of ANS signal values is used as reference instead of the maximum value, and parameter_1 is used as noise level threshold, and wherein parameter_1=0.03 and parameter_2=0.05; Condition B: Min . separation ⁢ between ⁢ activitions == max ⁢ { parameter_ ⁢ 3 ⁢ ms , 1000 parameter_ ⁢ 4 · median ⁢ { DF UNI , DF ANS , DF BIP } ⁢ ms } or alternatively, condition B: Min . separation ⁢ between ⁢ activitions == max ⁢ { parameter_ ⁢ 3 ⁢ ms , 1000 parameter_ ⁢ 4 · m ⁢ in ⁢ { DF UNI , DF ANS , DF BIP } ⁢ ms } wherein DF UNI is the dominant frequency of the unipolar electrical signal, DF ANS the dominant frequency of the ANS signal and DF BIP the dominant frequency of the bipolar electrical signal, and wherein parameter_3=50 and parameter_4=1.95, DF UNI , DF ANS , and DF BIP are calculated as the frequencies with the highest peak in the Fourier transform or the power spectral density (PSD) of the unipolar, ANS and bipolar signals, respectively, wherein PSD is calculated by any known method.
  7. 7 . The medical apparatus according to claim 1 , wherein the cardiac fibrillation is atrial or ventricular fibrillation, wherein cardiac activations are detected in optical signals acquired from the heart of a subject with cardiac fibrillation, to provide the iFM signals, using the following steps: a. Calculating the APS signal/s as described in claim 3 from one or more optical signal/s from the heart, or from a portion of the heart such as one atrium, both atria, one ventricle or both ventricles, of the subject obtained via a device with one or more optical fiber/s embedded; and b. Detecting local maxima in the APS signal/s, wherein the times at which the local maxima are detected are considered potential cardiac activations, wherein the absolute positive slope (APS) signal/sis/are obtained as the absolute value of the time derivative of a single or multiple optical signal/s obtained via a single or multiple optical fiber/s, in the intervals with positive slopes and assigning a 0 value in the intervals with negative slopes.
  8. 8 . The medical apparatus according to claim 7 , wherein said local maxima according to step b) are selected upon compliance with both condition A, a minimum height and prominence, and condition B, a minimum separation from the previous and next detected local maxima: Minimum height and prominence=parameter_ I·P 95th_ (APS) Condition A: wherein 95 th percentile of APS signal values is used as reference instead of the maximum value, and wherein parameter_1=0.02; Condition B: Min . separation ⁢ between ⁢ activitions == max ⁢ { parameter_ ⁢ 2 ⁢ ms , 1000 parameter_ ⁢ 3 · m ⁢ in ⁢ { DF Optical , DF APS } ⁢ ms } wherein DF Optical is the dominant frequency of the optical signal and D FAPs the dominant frequency of the APS signal, and wherein parameter_2=50 and parameter_3=1.95, DF Optical and DF APS are calculated as the frequencies with the highest peak in the Fourier transform or the power spectral density (PSD) of the optical signal and APS signal respectively and PSD is calculated by any known method.
  9. 9 . A non-transitory computer-readable medium storing one or more programs comprising instructions that, when executed by at least one processor of a computing device, cause the at least one processor to perform operations comprising: obtaining a single or multiple electrical unipolar signals or optical signals from a single target or multiple sequential targets in the heart via the mapping electrodes or optical fibers, generating an electroanatomical map based on the assigned electrical or optical data at a single or multiple cardiac spots, and wherein the programs, when executed by the processor, cause the processor to perform the following steps: a. detecting activations over i) the electrical unipolar signals or ii) the optical signals; b. obtaining an instantaneous frequency modulation (iFM) signal from the activations of step a) for each i) unipolar electrical signal or ii) optical signal, by calculating a reciprocal of one or more intervals between consecutive activations, and obtaining an instantaneous amplitude modulation (iAM) signal from a sequence of amplitude excursions of i) the negative deflections that contain activations in each unipolar electrical signal or ii) the optical phases 0 that contain activations in each optical signal: wherein the lower an amplitude excursion, the higher its corresponding value in the iAM signal and vice versa; c. detecting intervals that display the footprint of rotational activity wherein A) simultaneous increase in iFM and iAM is indicative of drifting rotors approaching a cardiac spot or B) simultaneously high iAM and iFM values is indicative of stationary rotors or rotors meandering around a cardiac spot; d. calculating the mean, median or a specific percentile value of each iFM signal obtained in step b), and obtaining a map by interpolating such values at each of the points used to generate the map, and using such a map to detect cardiac spots wherein such mean, median or specific percentile values are higher than those in their surroundings, such cardiac spots being considered to be the regions potentially driving cardiac fibrillation; e. presenting the electroanatomical map to guide ablation of at least one area of tissue of the subject on a display in any way in which the regions potentially driving cardiac fibrillation detected in step d) and the cardiac spots displaying the footprint of rotational activity detected in step c) can be identified in the heart of the subject.
  10. 10 . The medical apparatus of claim 1 , wherein the cardiac fibrillation is atrial fibrillation.
  11. 11 . The medical apparatus of claim 1 , wherein the cardiac fibrillation is persistent atrial fibrillation.
  12. 12 . The medical apparatus of claim 1 , wherein the intervals between consecutive activations is in seconds.
  13. 13 . The medical apparatus of claim 1 , wherein the percentile value is 90 th percentile.
  14. 14 . The medical apparatus of claim 5 , wherein applying a ventricular far-field subtraction method to the atrial unipolar signal comprises using principal component analysis to estimate the ventricular far-field signal.
  15. 15 . The medical apparatus of claim 6 , wherein the PSD is calculated by Welch's periodogram.
  16. 16 . The medical apparatus of claim 7 , wherein the cardiac fibrillation is atrial fibrillation.
  17. 17 . The medical apparatus of claim 7 , wherein the cardiac fibrillation is persistent atrial fibrillation.

Description

TECHNICAL FIELD OF THE INVENTION This invention relates generally to minimally invasive treatment of organs inside the body. More particularly, this invention relates to determination of ablation sites for ablation treatments applied to cardiac tissue. BACKGROUND OF THE INVENTION There is evidence of a progressive increase in overall burden of atrial fibrillation (AF), its incidence, prevalence, and associated mortality between 1990 and 2010. Only in Europe, the current prevalence of AF is 2%, twice as many as the last decade. Given that AF is associated with significant morbidity and mortality, this increasing number of individuals with AF will have major public health implications. Indeed, the average lifetime risk of AF has been recently reported as 37%. Pulmonary vein isolation (PVI) is still considered the cornerstone of catheter ablation for treating AF. However, radiofrequency-based ablation of AF during persistent stages (persistent AF: AF episodes lasting ≥7 days, PersAF) is challenging and associated with less favourable outcomes than paroxysmal AF (AF episodes lasting <7 days). The latter is a consequence of the fact that many more mechanisms and different atrial regions can play an important role in PersAF maintenance. To improve outcomes, ablation targeting the substrate that allegedly maintains PersAF was often added to PVI. The two most common techniques for substrate modification were the creation of linear lesions in the left atrium (LA) or targeting “complex fractionated atrial electrograms” (CFAEs). However, the STAR-AF II trial concluded that there was no incremental benefit of these two techniques in addition to PVI. In this context, new approaches such as the ablation of areas with spatiotemporal dispersion, or costly multielectrode (64-256) simultaneous panoramic acquisition systems (MESPAS, e.g. RhythmView™, Abbott/Cardiolnsight™, Medtronic) are being increasingly used in addition to the mandatory conventional electroanatomical mapping system to improve outcomes in PersAF. Such approaches aim at detecting and ablating alleged drivers (rotational or centrifugal) using propriety algorithms. These alleged drivers are ablated regardless their activation frequency dynamics which, for some, may be justified because previous attempts to guide ablation using dominant frequency (DF) yielded suboptimal results in PersAF. However, this might make these approaches potentially unspecific. In addition, sensitivity and specificity of the MESPAS used to detect rotational activations (rotors) and/or centrifugal activations (foci) are further limited by multiple technical aspects. Thus, current clinical outcomes obtained with those systems are controversial and a matter of debate. Moreover, the use of these propriety MESPAS and their own expendable materials considerably increases the cost of AF ablation procedures. From the foregoing, it is clear that incorporating single-signal algorithms capable of detecting rotational activations (rotors) and/or cardiac fibrillation (preferably AF) ‘high-hierarchy’ driver regions into a standard electroanatomical mapping system without the need of costly simultaneous panoramic acquisition systems would significantly improve, simplify and make more cost-effective these patient-tailored, mechanistically-based ablation procedures for cardiac fibrillation (preferably AF, or PersAF). BRIEF DESCRIPTION OF THE FIGURES FIG. 1. A. Concept of AM/FM used in radio broadcasting. Note that in FM the increases in the blue modulatING signal make the sinusoid oscillate proportionally faster and vice versa. B. AM and FM are present during cardiac fibrillation due to scroll-wave/rotor drifting. A schematic representation of a piece of cardiac tissue is displayed in red. When a drifting scroll-wave filament/rotor core approaches the blue square spot, the amplitude of the action potentials decreases resulting in an increased iAM (in red). Simultaneously, as the wave-emitting source (scroll-wave filament/rotor core) is approaching, the perceived iFM (in blue) at the spot increases (Doppler Effect). In this schematic representation, this situation occurs at 1.8 and 4.4 seconds. Therefore, a simultaneous iAM/iFM increase is indicative of drifting scroll-waves/rotors in the surroundings. At the same time, the areas with the highest values of average (mean/median) iFM would be those hierarchically driving fibrillation (drivers). The right panel shows the estimation of such average iFM by its median/mean values (8 Hz both) and with the conventional Dominant Frequency (DF) spectral approach (5.6 Hz). Note that the time intervals with the highest iFM usually display the lowest amplitudes and viceversa. The latter affects the height of their corresponding power spectral peaks. This and other issues limit hierarchical approaches based on DF. C. Schematic representation of the translational approach performed to develop this invention. FIG. 2. Examples of iAM/iFM from an optical movie of a sheep