METHOD OF DETECTING AND PREDICTING NEUROCARDIOGENIC SYNCOPE

Abstract

A method of detecting an early onset of neurocardiogenic syncope in a patient uses respiratory functions as a predictor of the syncope. According to the method, at least one sample of baseline minute ventilation, tidal volume and respiratory rate of the patient is obtained. The detection unit is set to detect an increase in tidal volume and in minute ventilation over a predetermined respiratory period. The detecting unit also detects any rate of change in respiratory rate and sends a signal to a microprocessor to determine whether the increase in minute ventilation is a sole function of increased tidal volume. The impending syncope is diagnosed if variance in respiratory rate is less than 25% in relation to the sampled baseline during the predetermined period of time.

Claims

1. A method of detecting an impending neurocardiogenic syncope in a patient, comprising the steps of: obtaining at least one sample of baseline minute ventilation, tidal volume and respiratory rate of the patient; detecting an increase in tidal volume; detecting an increase in minute ventilation over a predetermined respiratory period; detecting any rate of change in respiratory rate; determining whether the increase in minute ventilation is a sole function of increased tidal volume; and diagnosing impending syncope if variance in respiratory rate is less than 25% in relation to the sampled baseline during the predetermined period of time.

2. The method of claim 1, comprising a step of storing at least one data associated with the increase in minute ventilation.

3. The method of claim 1, comprising a step of generating an alarm signal after the impending syncope is diagnosed.

4. The method of claim 1, wherein the step of determining whether the increase in minute ventilation is a sole function of increased tidal volume is performed using data of fixed respiratory rate.

5. The method of claim 1, wherein the step of obtaining at least one sample of baseline minute ventilation, tidal volume and respiratory rate of the patient is performed by measuring transthoracic impedance or directly by exhaled volumes.

6. The method of claim 1, wherein the increase in tidal volume is defined as being more than a 75% increase from baseline.

7. A computer readable medium for storing instructions for performing the method of claim when executed.

8. An apparatus for detecting an impending neurocardiogenic syncope in a patient, comprising a means for obtaining at least one sample of baseline minute ventilation, tidal volume and respiratory rate of the patient; a means for detecting an increase in tidal volume; a means for detecting an increase in minute ventilation over a predetermined respiratory period; a means for detecting any rate of change in respiratory rate; a means for determining whether the increase in minute ventilation is a sole function of increased tidal volume; and a means for generating an alarm signal when variance in respiratory rate is less than 25% in relation to the sampled baseline during the predetermined period of time.

9. The apparatus of claim 8, comprising a microprocessor unit operationally connected to the a means for obtaining at least one sample of baseline minute ventilation, tidal volume and respiratory rate of the patient, to the means for detecting an increase in tidal volume, to the means for detecting an increase in minute ventilation over a predetermined respiratory period, to the means for detecting any rate of change in respiratory rate, to the means for determining whether the increase in minute ventilation is a sole function of increased tidal volume, and to the means for generating an alarm signal.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The accompanying drawings, which are incorporated in and constitute a part of this specification, exemplify the embodiments of the present invention and, together with the description, serve to explain and illustrate principles of the invention. The drawings are intended to illustrate major features of the exemplary embodiments in a diagrammatic manner. The drawings are not intended to depict every feature of actual embodiments nor relative dimensions of the depicted elements, and are not drawn to scale.

[0016] FIGS. 1A and 1B are graphical depictions showing heart rate and blood pressure response with and without syncope;

[0017] FIGS. 2A and 2B are graphical depictions showing fold change from baseline without (FIG. 2A) and with (FIG. 2B) syncope;

[0018] FIG. 3 is a graphical depiction change in minute ventilation from baseline for responders and non-responders;

[0019] FIG. 4 is a graphical depiction of minute ventilation during syncope; and

[0020] FIG. 5 is a flow chart of a process for detecting syncope and/or impending syncope.

[0021] FIG. 6A graphically illustrates change in mean flow velocity in three exemplary trials, and FIG. 6B graphically illustrates change in End Tidal CO.sub.2 measured in normal subjects in whom hypotension was induced with a combination of head-up tilt and lower body negative pressure over three trial on three different days. Also shown are direct measurements of cerebral blood flow in the same subjects at the same times and distinct correlation between cerebral blood flow and End Tidal CO.sub.2.

[0022] FIG. 7 is a block diagram illustrating a worn or fixed device that processes various signals from a subject, processes them, stores them and provides real-time feedback to the subject and/or to an external monitoring system.

[0023] FIG. 8 demonstrates an example of a portable version of the unit at its most simplest. Spirometry data is not collected in this example.

DETAIL DESCRIPTION OF THE INVENTION

[0024] According to one aspect of the invention, a computer readable medium for storing instructions for performing a method, is provided that includes instructions for detecting a series of intrinsic depolarizations of a heart; detecting minute ventilation and respiratory rate; sampling baseline minute ventilation and respiratory rate; detecting an increase in minute ventilation over a predetermined period of time that satisfies a programmed criteria; detecting any rate of change in respiratory rate; determining whether the change in minute ventilation is a sole function of increased tidal volume; and diagnosing a syncopal episode as having a hypotensive etiology if minute ventilation criteria are met without accompanying rhythm disturbances. The computer readable medium may also include storing at least one data item related to the step of detecting an increase in minute ventilation.

[0025] According to another aspect of the invention, an implanted cardiac or subcutaneous apparatus is provided that includes means for detecting a series of intrinsic depolarizations of a heart; means for detecting minute ventilation and respiratory rate; means for sampling baseline minute ventilation and respiratory rate, detecting an increase in minute ventilation over a predetermined period of time that satisfies a programmed criteria, detecting any rate of change in respiratory rate, and determining whether the change in minute ventilation is a sole function of increased tidal volume; and means for detecting impending syncope or altered cerebral perfusion if minute ventilation criteria are met. The implanted apparatus may also include means for storing at least one data item related to the step of detecting an increase in minute ventilation.

[0026] This invention provides a syncope detection method, which uses respiratory input to detect impending neurocardiogenic or hypotensive syncope is described. The methodology provides both a diagnostic option for patients with undiagnosed syncope when coupled to modified event monitors, and diverse monitoring options for individuals in whom monitoring of brain perfusion would be desirable (pilots, astronauts, divers, soldiers, etc.).

[0027] The inventor discovered that a 2 to 3 fold increase in minute ventilation precedes the drop in heart rate and blood pressure in tilt-induced neurocardiogenic syncope. This increase in minute ventilation is driven exclusively by increases in tidal volume (TV) rather than respiratory rate, which allows for easy distinction between impending neurocardiogenic syncope and other physiologic causes of increased minute ventilation (for example, exercise, pain, anxiety, primary respiratory distress, and heart failure). The inventor has also previously described an excellent correlation between cerebral blood flow and end-tidal carbon dioxide. As end-tidal carbon dioxide decreases, so does the cerebral blood flow. The mechanism for the link is not clear, but may have to do with the role of carbon dioxide as a cerebral vasoregulator. This is illustrated in FIG. 6 and has been previously published by the inventor.

[0028] With reference to FIGS. 1A and 1B, a typical heart rate and blood pressure response is shown in patients without syncope (FIG. 1A) and with syncope (FIG. 1B). As shown in FIGS. 1 A and 1B, syncope is marked by a sudden drop in heart rate and blood pressure which results in decreased cerebral perfusion and subsequent loss of consciousness and postural tone. As shown in FIGS. 2A, 2B and FIG. 3, during syncope, there is an increase in minute ventilation (MV) and tidal volume (VO2/VCO2) while the respiration rate remains the same.

[0029] The syncope detection method utilizes respiratory input for early detection of impending syncope, with subsequent warning or triggered therapies or maneuvers to prevent development of syncope. When the detected minute ventilation exceeds a predetermined threshold value without a corresponding increase in respiratory rate, the episode gets labeled as impending syncope and either stored for further analysis or transmitted real-time to the subject and/or remote monitoring stations via audible and/or vibratory alarm.

[0030] FIG. 4 shows the typical evolution of minute ventilation signal (MV) with respect to time in a patient with neurocardiogenic syncope. Note that the respiratory interval (R) remains fixed, while the tidal volume (TV, or TE) increases substantially. As described above, MV is a signal which may be directly obtained from measuring thoracic impedance. Oscillations in thoracic impedance with respect to time allow for the derivation of TV and R.

[0031] The measurement of minute ventilation can be obtained directly by measuring exhaled volumes and rate, or indirectly by changes in thoracic impedance between two electrodes on the skin. The impedance is then measured in response to the application of constant current (e.g., approximately 200 mA) at a fixed frequency (e.g., usually 8 Hz). From this, one can determine the respiratory period (R), or respiratory rate (breaths per minute). The tidal volume (TV) is represented by the area under the curve, and the minute ventilation is the product of (RTV)/min.

[0032] FIG. 5 illustrates a process for detecting decreasing cerebral perfusion, and/or impending syncope and/or syncope. The process is described in the context of a process for measuring transthoracic impedance, such as in the case wearable external monitors, or directly measuring tidal volumes, as could be use with aerospace and hyperbaric applications. It will be appreciated that the method may be used with implantable medical devices as well. In addition, it will be appreciated that the process may vary. The process may include additional steps or fewer steps and the order of the steps may differ.

[0033] Minute ventilation, either by transthoracic impedance measurements or by spirometry, is being constantly sampled in step 501 and analyzed in step 502. If an increase in minute ventilation is detected in step 503, then the respiratory interval is analyzed in step 504. The respiratory interval may be analyzed over a fixed period of time (e.g., any time period or range of time periods between about 10 seconds and about 5 minutes, including less than ten seconds and more than 5 minutes). If the increased minute ventilation is not accompanied by a decrease in respiratory interval (e.g., the respiratory interval does not decrease for a predetermined period of time, e.g., any time period or range of time periods between about 10 seconds and about 5 minutes, including less than ten seconds and more than 5 minutes), then the conditions for impending syncope have been met, as shown in step 505.

[0034] If, on the other hand, the respiratory interval is decreased, then the heart rate and any additional data are analyzed (such as accelerometer or contextual information). Increased minute ventilation, decreased respiratory interval, increased heart rate and detected acceleration indicate increased physical activity or stressor other than decreased cerebral hypoperfusion in step 506. Alternatively, increases in minute ventilation, decreased respiratory interval, heart rate and no detected acceleration would indicate increased physiologic stress without physical activity (for example, heart failure, anxiety, or respiratory distress); this information may be subsequently used for diagnostic purposes. It will be appreciated that the detection algorithm may be applied without the use of accelerometer data. It will also be appreciated that minute ventilation may be based upon measured MV0.sub.2.

[0035] FIG. 6A illustrates change in mean flow velocity and FIG. 6B illustrates changes in end tidal carbon dioxide (CO.sub.2) measured in normal subjects in whom hypotension was induced with a combination of head-up tilt and lower body negative pressure over three trial on three different days. Also shown are direct measurements of cerebral blood flow in the same subjects at the same times. The graph illustrates excellent correlation between cerebral blood flow and End Tidal CO.sub.2 is shown.

[0036] The detection method described above may be applied to any monitoring device, internal or external, portable or fixed, which is outfitted to measure minute ventilation and respiratory rate at a minimum, with additional possible enhancements of accelerometer and heart rate.

[0037] It should be understood that processes and techniques described herein are not inherently related to any particular apparatus and may be implemented by any suitable combination of components. Further, various types of general purpose devices may be used in accordance with the teachings described herein. It may also prove advantageous to construct specialized apparatus to perform the method steps described herein.

[0038] FIG. 7 is a block diagram illustrating the constituent components of the device in accordance with one embodiment of the invention. Any one embodiment may contain some, or all of the input signals represented here, depending on the application for which the build is required. It will be understood by those skilled in the art that the electrical components represented in FIG. 7 are powered by an appropriate battery supply or external power source (not shown). The input devices are connected to a subject 701.

[0039] The input/output circuit 702 contains the operating input and output analog circuits for digital controlling and timing circuits necessary for the detection of electrical signal derived from the heart, such as the surface cardiac electrogram derived from three leads 703, 704 and 705. Thoracic impedance (Z-sense) is derived from current between the surface leads 706. Accelerometer data 707 is derived from a piezoelectric crystal within the unit in the case of portable applications. Additional input is derived from spirometry data in some applications as well as contextual and symptoms reported by the subject via means of voice recording or text input 709. It will be understood by those skilled in the art that various forms of input devices are possible, including microphones and keypads, but they are not illustrated here. These input feed into a microprocessor or microcomputer unit 710. It will be understood by those skilled in the art that the microprocessor unit comprises an on-board circuit and an off-board circuit. On-board circuit includes a microprocessor, a system clock, and on-board RAM and ROM. Off-board circuit includes an off-board RAM/ROM unit providing additional memory. These are not illustrated here.

[0040] Additional input into the microcomputer unit will be from a power-on-reset circuit (POR) 711 which serves to initialize the unit with programmed default settings on power-up, and reset the program values to default states upon detection of an insufficient power supply or transiently in the presence of certain undesirable conditions such as unacceptably high electromagnetic interference. (EMI), for example. A Vref/Bias circuit 712 generates a stable voltage reference and bias currents for the analog circuits of input/output circuit 702.

[0041] An antenna 714 is connected to input/output circuit 702 for purposes of uplink/downlink telemetry through a radio frequency (RF) Transmitter/Receiver Circuit (RF TX/RX) 713. Uplink and downlink telemetry transmission of programming commands and analog and digital data between antenna 714 and an external device, such a monitoring station 716 or storage media 715, can be accomplished employing any of the hardware and operating systems known in the art. Communication between the input/output circuit 702 and storage medium 715 and monitoring station 716 may also be accomplished by direct, wired connections.

[0042] The input/output circuit can additionally provide feedback 710 to the subject 701 in the form of visual and/or auditory and/or vibratory signals.

[0043] FIG. 8 illustrates a non-spirometric application of the invention wherein thoracic impedance, respiratory rate and electrograms are obtained, recorded, stored and transmitted in a portable device 801 incorporating the input/output circuit 702 mentioned previously. Electrodes 804 are placed on the subject's chest and back for measurement of thoracic impendance and, optionally, cardiac electrograms. A belt 803 around the chest will serve the functions of respirometry independent of thoracic impedance and contain an antenna which would increase the range of the unit. In this example, the input/output unit 801 is wired to the subject 802 but transmitting to a storage unit and monitoring unit wirelessly.

[0044] The present invention has been described in relation to particular examples, which are intended in all respects to be illustrative rather than restrictive. Those skilled in the art will appreciate that many different combinations will be suitable for practicing the present invention. Moreover, other implementations of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. Various aspects and/or components of the described embodiments may be used singly or in any combination. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.