United States Patent: (10) Patent No .: US 10, 182, 729 B2

US010182729B2
(12) United States Patent ( 10) Patent No.: US 10 ,182,729 B2

Zielinski et al. (45) Date of Patent: Jan. 22, 2019
(54 ) SYSTEMS AND METHODS FOR (52) CPC
U .S. CI.........
MONITORING HEMODYNAMIC STATUS A61B 5 /02108 (2013 . 01) ; A61B 5 /0002
(2013 .01); A61B 5 / 0031 ( 2013 .01); A61B
( 71 ) Applicant: Medtronic, Inc., Minneapolis, MN 5 / 021 ( 2013 .01 ); A61B 5 / 0205 ( 2013 .01) ;
(US) A61B 5 /0261 (2013 .01 ) ; A61B 5 /02125
(2013 .01); A61B 5 /0402 ( 2013 .01 ); A61B 5/ 08
(72) Inventors: Todd M . Zielinski, Ham Lake, MN ( 2013 .01 ); A61B 5 /686 (2013.01); A61B 5 /746
(US); David A . Anderson , Stanchfield , ( 2013.01)
MN (US ); Tom D . Bennett, Shoreview , (58 ) Field of Classification Search
MN (US ); James K . Carney , Roseville , CPC . A61B 5 / 02108 ; A61B 5 / 0002; A61B 5 / 0004 ;
MN (US ); Can Cinbis , Salt Lake City , A61B 5 /0006 ; A61B 5 /0031; A61B
UT (US ) ; Yong K . Cho, Excelsior, MN 5 /0205 ; A61B 5 /021; A61B 5 /02125 ;
(US); Jonathan L . Kuhn , Ham Lake, A61B 5 / 0261; A61B 5 /0402; A61B 5 /08;
MN (US) ; Brian B . Lee , Golden Valley, A61B 5 /686 ; A61B 5 /746
MN (US ); Richard J. O ' Brien , Hugo , See application file for complete search history.
MN (US ) ; Eduardo N . Warman , (56 ) References Cited
Maple Grove, MN (US ); Vinod
Sharma, Maple Grove ,MN (US ) U . S. PATENT DOCUMENTS
(73 ) Assignee : Medtronics , Inc., Minneapolis , MN 8 , 147 ,416 B2 4 /2012 Fayram et al.
(US ) 8 , 162 ,841 B2 4 / 2012 Keel et al .
8 ,313 ,439 B2 11/ 2012 McCombie et al.
( * ) Notice : Subject to any disclaimer, the term of this (Continued )
patent is extended or adjusted under 35 OTHER PUBLICATIONS
U . S .C . 154 (b ) by 0 days .
Yano et al., “ Nocturnal Blood Pressure , Morning Blood Pressure
(21) Appl. No.: 15 /253,229 Surge , and Cerebrovascular Events ,” Current Hypertension Reports ,
Jun . 2012 ; 14 (3):219 -227. Available online Apr. 22 , 2012 .
( 22 ) Filed : Aug . 31, 2016 (Continued )
(65 ) Prior Publication Data Primary Examiner - George Manuel
US 2018 /0055386 A1 Mar. 1, 2018 (57 ) ABSTRACT
The exemplary systems and methods may monitor one or
(51) Int. ci. more signals to be used to assess the hemodynamic status of
A61B 5 / 04 ( 2006 .01) a patient. The one ormore signalsmay be used to calculate ,
A61B 5 /021 ( 2006 .01 ) or determine, a plurality of pulse transit times. The plurality
A61B 5 /00 ( 2006 .01) of pulse transit times may be used to determine hemody
A61B 5 / 0205 ( 2006 .01) namic status values that may be indicative of a patient' s
A61B 5 / 026 ( 2006 .01) aggregate hemodynamic status.
(Continued ) 21 Claims, 23 Drawing Sheets
*
*
US 10 ,Page
182,2729 B2
(51) Int . Cl.

A61B 5 /0402 ( 2006 .01)
A61B 5 / 08 ( 2006 .01)
(56) References Cited
U . S . PATENT DOCUMENTS
8, 574 ,161 B2 11/2013 Banet et al.
9 ,037, 208 B2 5 / 2015 Furman
9 .408 ,542 B18 /2016 Kinast et al.
2004 /0133081 A1 * 7 /2004 Teller A61B 5 /01
600 / 300
2008/0183083 A1 7 / 2008 Markowitz et al.
2009 /0216132 AL 8 / 2009 Orbach
2010 /0160798 A1 6 / 2010 Banet et al.
2011/0009754 AL 1 / 2011 Wenzel et al.
2011/0224520 AL 9 /2011 Skerl et al.
2013 / 0041269 A1 * 2 / 2013 Stahmann .............. A61B 5 /686
600 /484
2014 /0088385 A1 * 3 / 2014 Moon ................... A61B 5 / 1118
600 / 324
2014 /0187941 A1 7/2014 Shusterman
2014 /0249398 A1 9 / 2014 Morris et al.
2014 /0276123 A1 9 / 2014 Yang
2015 /0051467 AL 2 /2015 Corbucci et al.
2015 / 0088216 A1 3/ 2015 Gordon et al.
2017 / 0055845 Al * 3/ 2017 Mirov ................. A61B 5 /0205
OTHER PUBLICATIONS
(PCT/US2017 /049537) PCTNotification of Transmittal of the Inter
national Search Report and the Written Opinion of the International
Searching Authority, dated Nov . 9 , 2017 , 13 pages.
* cited by examiner
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US 10 ,182 ,729 B2
SYSTEMS AND METHODS FOR device such that external monitoring device can calculate a
MONITORING HEMODYNAMIC STATUS pulse transit time from the data .
One exemplary system for use in assessment of a patient' s
The present disclosure pertains to systems and methods hemodynamic status may include one or more devices (e. g.,
for monitoring the hemodynamic status ofpatients using one 5 implantable devices, subcutaneously implantable devices,
or more devices (e .g ., implantable devices ) and an external etc .) and an external monitoring device . The one or more
monitoring device . devices may include a first sensor to measure a first signal
Blood pressure may increase with worsening heart failure . from tissue of a patient, and a second sensor to measure a
As blood pressure increases, blood vessel diameter may second signal from tissue of the patient from a different
increase and blood vessels may become less compliant ( e . g ., 10 location along a circulatory path from the patient' s heart
stiffen ). During clinical examination of heart failure patients, than the first sensor. The one or more devices may be
echocardiography can be used to monitor blood vessel configured to periodically measure the first and second
diameter as an indicator of cardiac health . signals over a monitoring time period (e .g ., the monitoring
time period is greater than or equal to 1 hour ). The external
SUMMARY 15 monitoring device may be wirelessly operatively coupled to
the one or more devices and configured to receive data
The exemplary systems and methods described herein representative of the first and second signals from the one or
may generally be described as monitoring at least two more devices and determine a pulse transit timebased on the
signals from tissue from a patient located in proximity to a data representative of the first and second signals for each
blood vessel such as an artery . A first signal may be 20 measurement of the first and second signals resulting in a
measured in tissue closer to theheart (e .g ., closer to the heart plurality of pulse transit times for the monitoring time
along a circulator path ) than the second signal. A fiducial period . The external monitoring device may be further
point such as , e . g ., a maximum peak value, etc ., may be configured to determine a surrogate hemodynamic status
selected for each signal, and the time between the fiducial value based on the plurality of pulse transit times represen
points in the signals may be determined , which is a pulse 25 tative of the patient' s aggregate hemodynamic status for the
transit time. Pulse transit times may be periodically mea monitoring time period .
sured over a monitoring time period such as, e. g ., half day, One exemplary system for use in assessment of a patient' s
a whole day , nighttime, daytime, etc . The pulse transit times hemodynamic status may include one or more devices ( e . g .,
may then be analyzed to determine, or assess , the hemody - implantable devices , subcutaneously implantable devices,
namic status of the patient. For example , a hemodynamic 30 etc .) and an external monitoring device . The one or more
status value may be generated based on the pulse transit devices may include a first sensor to measure a first signal
times measured during a monitoring time period . Thus , a from tissue of a patient, and a second sensor to measure a
hemodynamic status value may be generated for each moni- second signal from tissue of the patient from a different
toring time period , and the hemodynamic status values may location along a circulatory path from the patient's heart
be plotted over time such that a user to can view and analyze 35 than the first sensor. The one or more devices may be
trends, the system may compare the hemodynamic status configured to periodically measure the first and second
values to baseline values to generate alerts , etc . In one or signals over a monitoring time period ( e . g ., the monitoring
more embodiments, the hemodynamic status value may be time period is greater than or equal to 1 hour ). The one or
a surrogate aggregate blood pressure value. more devices may be further configured to determine a pulse
The exemplary systemsand methods may use one ormore 40 transit time based on the data representative of the first and
implantable devices ( e. g ., subcutaneously, paravascular second signals for each measurement of the first and second
devices ) and / or one or more non - implantable devices to signals resulting in a plurality of pulse transit times for the
measure the at least two signals from the tissue of the patient monitoring time period and determine a surrogate hemody
and an externalmonitoring device . The one or more implant namic status value based on the plurality of pulse transit
able and /or non - implantable devices may be wirelessly 45 times representative of the patient' s aggregate hemody
operably coupled to the externalmonitoring device to trans - namic status for the monitoring time period . The external
fer data therebetween . In at least one embodiment, the one monitoring device may bewirelessly operatively coupled to
or more implantable and /or non -implantable devices may the one or more devices and configured to receive the
transfer a digital representation of the first and second surrogate hemodynamic status value and/ or data represen
signals to the external monitoring device such that external 50 tative of the first and second signals from the one or more
monitoring device can calculate a pulse transit time from the devices .
digital representation of the first and second signals. In at One exemplary method for use in assessing a patient' s
least one embodiment, the one or more implantable and /or hemodynamic status may include periodically measuring a
non - implantable devices may transfer a time stamp repre - first signal from tissue of a patient and a second signal from
sentative of the time at which a fiducial point occurred in the 55 tissue of the patient in a different location along a circulatory
first and second signals to the external monitoring device path from the patient 's heart than where the first signal is
such that external monitoring device can calculate a pulse measured over a monitoring time period ( e. g ., themonitor
transit time from the time stamps. In at least one embodi- ing time period may be greater than or equal to 1 hour ),
ment, an implantable and /or non -implantable devices may receiving data representative of the first and second signals
issue a pulse associated with a fiducial point in the first 60 using an external monitoring device , determining a pulse
signal, and then transfer a time stamp representative of the transit time based on the data representative of the first and
time at which the pulse was delivered to the external second signals for each measurement of the first and second
monitoring device . Another implantable and /or non - im signals resulting in a plurality of pulse transit times for the
plantable device may either transfer a digital representation monitoring time period, and determining a hemodynamic
of the second signal (which , e .g., may include the pulse ) or 65 status value based on the plurality of pulse transit times
a time stamp corresponding to when the pulse is sensed , or representative of the patient' s aggregate hemodynamic sta
occurs, in the second signal to the external monitoring tus for the monitoring time period.
US 10, 182 ,729 B2
One exemplary system for use in assessment of a patient's In one or more embodiments , the second signal may
hemodynamic status may include one or more devices ( e .g ., include one or more of an impedance signal sensed , an
implantable devices, subcutaneously implantable devices, optical signal sensed , an acoustic signal sensed, and an
etc .) and an external monitoring device . The one or more accelerometer signal.
devices may include a pulse generator to generate a pulse in 5 One exemplary system for use in assessment of a patient' s
tissue of a patient and a sensor to measure a signal from hemodynamic status may include one ormore devices ( e.g .,
tissue of the patient from a different location along a etc implantable devices, subcutaneously implantable devices,
circulatory path from the patient's heart than the pulse . ) and an external monitoring device . The one or more
generator. The one or more devices may be configured to devices may include a first sensor to measure a first signal
periodically deliver a pulse and measure the signal over a 10 second
from tissue of a patient, and a second sensor to measure a
monitoring timeperiod . The externalmonitoring device may location signalalong
from tissue of the patient from a different
a circulatory path from the patient' s heart
be wirelessly operatively coupled to the one or more devices than the first sensor . The one or more devices may be
and configured to receive a time stamp corresponding to the configured to periodically measure the first and second
delivery of the pulse and data representative of the signal 15 signals over a first monitoring time period and a second
from the one or more devices , and determine a pulse transit monitoring time period ( e. g., the monitoring time periods
time based on the time stamp and the data representative of may be greater than or equal to 1 hour). The external
the signal for each pulse delivery and measurement of the monitoring device may be wirelessly operatively coupled to
signal resulting in a plurality of pulse transit times for the the one or more devices and configured to receive data
monitoring time period . The externalmonitoring device may 20 representative of the first and second signals from the one or
be further configured to determine a surrogate hemodynamic more devices and determine a pulse transit time based on the
status value based on the plurality of pulse transit times data representative of the first and second signals for each
representative of the patient's hemodynamic status for the measurement of the first and second signals resulting in a
monitoring time period. plurality of pulse transit times for the first and second
In one or more embodiments , the external monitoring 25 monitoring time periods. The external monitoring device
device may be further configured to execute or the method may be further configured to receive a plurality of blood
further includes monitoring the hemodynamic status values pressure values of the patient synchronized to the plurality
for a plurality of monitoring time periods and determining of pulse transit times over at least the first monitoring time
whether the hemodynamic status of the patient has changed period and the second monitoring time period , generate a
based on the hemodynamic status values over the plurality 30 pulse transit time- blood pressure relationship between the
ofmonitoring time periods. Further , an alert may be issued plurality of pulse transit times and the plurality of blood
if the hemodynamic status of the patient has changed based pressure values and for each of the first monitoring time
on the hemodynamic status values . period and the second monitoring time period, and deter
In one or more embodiments , the external monitoring mine whether the hemodynamic status of the patient has
device may be further configured to execute or the methodh z35 changed based on a change in the pulse transit time-blood
pressure relationship over the first and the second monitor
further includes receiving a plurality of blood pressure ing time periods.
values of the patient synchronized to the plurality of pulse One exemplary method for use in assessing a patient' s
transit times over the monitoring time period , modelling a hemodynamic status may include receiving a plurality of
relationship between the plurality of blood pressure values 40 pulse transit times of a patient over at least a first monitoring
and the plurality of pulse transit times, monitoring the time period and a second monitoring time period , receiving
relationship between the plurality of blood pressure values a plurality of blood pressure values of the patient synchro
and the plurality of pulse transit times for at least two nized to the plurality of pulse transit times over at least the
monitoring time periods, and determining whether the first monitoring time period and the second monitoring time
hemodynamic status of the patient has changed based on a 45 period , generating a pulse transit time-blood pressure rela
change in the relationship between the plurality of blood tionship between the plurality of pulse transit times and the
plurality of blood pressure values and for each of the first
pressure values and the plurality of pulse transit times over monitoring
the at least two monitoring time periods. time period and the second monitoring time
period , and determining whether the hemodynamic status of
In one or more embodiments , the one or more devices
may include a first device including the first sensor and a 50 the patienthas changed based on a change in the pulse transit
second device including the second sensor. In one or more time-blood pressure relationship over the first and the sec
embodiments, the one ormore devices may include a single ond monitoring time periods.
implantable device including the first sensor and the second One exemplary system may include a plurality of implant
sensor. able and /or non - implantable devices to measure sensed
waveforms to determine hemodynamic status. The system
In one or more embodiments, the first signal may include may be configured to measure a primary signal on a device
one or more of an electrocardiography signal and an imped located in a specific anatomical region of the body and
ance signal. Further, in at least one embodiment, the data measure a secondary signal on a second device or plurality
representative of the first signal may include a digital of devices located in different anatomical regions of the
representation of one of an electrocardiography signal, an 60 body. The primary signal may include sensed waveform
impedance signal, an acoustic signal, an optical signal, and parameter ( s ) associated with the cardiac and /or respiratory
an accelerometer signal. Still further, in at least one embodi- cycle . The secondary signal may include a sensed
ment, the data representative of the first signal may include waveform (s ) or timing interval(s ) associated with the pri
a time stamp corresponding to a fiducial point within one of mary signals sensed waveform relative to a cardiac and / or
an electrocardiography signal, an impedance signal, an 65 respiratory cycle . Both signals can be measured with a
optical signal sensed , an acoustic signal, and an accelerom - device electrode array placed in the subcutaneous tissue in
eter signal. close proximity to the heart, artery, vein , and /or capillary
US 10 ,182,729 B2
bed , within the heart, artery , vein , and /or capillary bed , or BRIEF DESCRIPTION OF THE DRAWINGS
combination thereof. Waveform fiducial points and timing
intervals can be measured and compared between the pri FIG . 1A depicts an exemplary system for monitoring
mary and secondary signals. Communication between the hemodynamic status of a patient including a single implant
devices may include direct radio - frequency tissue commu- 5 able device implanted proximate the patient 's heart and an
nication schemes or other communication schemes utilizing external monitoring device .
an external device as a central hub ( such as a cell phone) for FIG . 1B depicts an exemplary system for monitoring
independent communication with the implanted devices and hemodynamic status of a patient including a single implant
subsequent data transmission to a call center or health care able device implanted away from the patient' s heart in the
provider. 10 patient' s arm and an external monitoring device .
One exemplary system may include a plurality of devices FIG . 1C depicts an exemplary system for monitoring
to measure a pulsed timing signal and a sensed waveform to hemodynamic status of a patient including two implantable
determine hemodynamic status. The system may be config - devices and an external monitoring device .
ured to monitor a primary signal on a device located in a FIG . 2 is a functional block diagram of the exemplary
specific anatomical region of the body. The primary signal 15 implantable devices of FIGS. 1A - 1C .
may include sensed waveform parameter (s ) associated with FIG . 3 is a functional block diagram of the exemplary
the cardiac and/or respiratory cycle ( e.g ., R -wave in an external monitoring device of FIGS. 1A - 1C .
electrocardiogram ). A subsequent pulse associated with the FIG . 4 is a flow diagram of an exemplary method of
timing of the aforementioned sensed waveform ( s ) may be monitoring hemodynamic status of a patient using, e . g ., the
transmitted to a secondary device or plurality of devices. 20 systems and devices of FIGS . 1 - 3 .
The secondary device or plurality of devices located in FIGS. 5A -5B depict exemplary systems for monitoring
different anatomical regions of the body can sense the hemodynamic status of a patient including a single implant
primary devices transmitted pulsed signal and use the pulsed able device having two sensors.
signal to perform an action or use the pulsed signal as a FIGS. 5C -5D depict exemplary systems for monitoring
timing reference or time stamp. The secondary signal may 25 hemodynamic status of a patient including a single implant
include sensed waveform ( s ) and/or timing interval (s ) asso - able device having one sensor and one pulse generator.
ciated with the primary signals pulsed timing waveform FIGS. 6A -6C depict exemplary systems for monitoring
relative to a cardiac and/or respiratory event sensed by the hemodynamic status of a patient including a two implantable
primary device . Both signals can be measured with a device devices .
electrode array placed in the subcutaneous tissue in close 30 FIG . 7 is a graph of exemplary arterial waveforms over
proximity to the heart , artery , vein , and / or capillary bed , time including a plurality of selected fiducial points for use
within the heart, artery, vein , and / or capillary bed , or com with the exemplary systems and methods of FIGS . 1 -6 .
bination thereof. Waveform fiducial points and timing inter - FIG . 8 depicts a plurality of graphs showing how a
vals can be measured and compared between the primary plurality of pulse transit times may be converted into a
and secondary signals or between the primary devices 35 surrogate hemodynamic status value and plotted over time.
pulsed timing signal and the secondary signals. Communi- FIG . 9 is a graph of a surrogate hemodynamic status value
cation between the devices may include direct radio -fre - over time.
quency tissue communication schemes or other communi FIG . 10 is a graph of 24 hours of pulse transit time data
cation schemes utilizing an external device as a central hub versus systolic blood pressure measured during experimen
( such as a cell phone) for independent communication with 40 tal testing for calibration .
the implanted devices and subsequent data transmission to a FIG . 11 is a graph of daily average actual systolic pressure
call center or health care provider . and surrogate hemodynamic status values using the calibra
One exemplary embodiment may include a single device tion data depicted in FIG . 10 .
to measure hemodynamic status. The system may be con - FIG . 12 is a graph of weekly actual average systolic
figured to monitor a primary signal on the single device 45 pressure and surrogate hemodynamic status values using the
located in a specific anatomical region of the body. The calibration data depicted in FIG . 10 .
primary signal may include sensed waveform parameter (s) FIG . 13 is a graph of exemplary day and night pulse
associated with the cardiac and /or respiratory cycle. A transit time data over time determined using, e .g ., the
secondary signal may also be measured on the same device . exemplary systems and methods of FIGS. 1 - 6 .
The secondary signal may include sensed waveform (s ) or 50 FIG . 14 is a graph of exemplary day and night pulse
timing interval(s ) associated with the primary signals sensed transit time data for “ dipper ” and “ non -dipper” patients over
waveform relative to a cardiac and /or respiratory cycle. Both time determined using, e .g., the exemplary systems and
signals can be measured with a device electrode array placed methods of FIGS . 1 -6 .
in the subcutaneous tissue in close proximity to the heart, FIG . 15 is a graph of exemplary change in hemodynamic
artery , vein , and/ or capillary bed , within the heart , artery, 55 status value over time determined using, e . g ., the exemplary
vein , and /or capillary bed, or combination thereof. Wave systems and methods of FIGS. 1 -6 .
form fiducial points and timing intervals can be measured FIG . 16 is a block diagram of a centralized data system for
and compared between the primary and secondary signals . use the exemplary systems and methods of FIGS . 1 -6 .
Communication between the device and an external device FIG . 17 is a graph of pulse transit time data versus systolic
( such as a cell phone ) may be used for data transmission to 60 blood pressure measured during a first time period and a
a call center or health care provider. second time period .
The above summary is not intended to describe each
embodiment or every implementation of the present disclo DETAILED DESCRIPTION OF EXEMPLARY
sure . A more complete understanding will become apparent EMBODIMENTS
and appreciated by referring to the following detailed 65
description and claims taken in conjunction with the accom Exemplary methods, apparatus, and systems shall be
panying drawings. described with reference to FIGS. 1 - 17 . It will be apparent
US 10 , 182,729 B2
to one skilled in the art that elements or processes from one low frequency component may provide indicators of respi
embodiment may be used in combination with elements or ratory rate and lung compliance . Still further, for example ,
processes of the other embodiments , and that the possible the DC or mean component may provide an indicator of
embodiments ofsuch methods , apparatus , and systems using patient fluid status.
combinations of features set forth herein is not limited to the 5 Applications for diagnostic monitoring may have over
specific embodiments shown in the Figures and / or described lapping cardiovascular disease specific indications for use as
herein . Further, it will be recognized that the embodiments a potential surrogate to measure cardiac function and /or
described herein may include many elements that are not blood flow or global fluid status . For example , hypertension
necessarily shown to scale . Still further , it will be recognized may be a precursor to , or aggravating factor for, heart
that timing of the processes and the size and shape of various 10 failure . A variety of cardiovascular pressures, e . g ., intracar
elements herein may be modified but still fall within the diac , arterial , and venous pressures, etc., may also be used
scope of the present disclosure , although certain timings, as indicators of the progression of maladies such as heart
one or more shapes and/ or sizes, or types of elements, may failure and hypertension as well as the hemodynamic status
be advantageous over others. of patient in general, although methods to measure the
The human arterial system can be associated with a vast 15 aforementioned parameters may often use invasive sensor
array of distensible tubes ( e. g., blood vessels such as arteries techniques. The exemplary systems, devices, and methods
capillaries ), designed to distribute blood volume throughout described herein may be described as using less invasive
the body . A blood volume impulse generated by the heart sensor measurement methods , which may be useful to
distributes a blood volume pulse along the system of tubes monitor asymptomatic chronic diseases such as, e . g ., hyper
at a velocity which is determined by the properties of the 20 tension .
tube and the fluid contained within . The principal property Chronic methods to monitor relative cardiac function
of the tube can be associated with vessel stiffness and the and/ or blood flow using implantable and/or non - implantable
velocity of the generated pulse traveling through the system sensors as a relative hemodynamic surrogate may provide
of tubes. Stiffness of the arterial vasculature is directly clinical utility for monitoring the onset and progression or
associated with the pressure measured within the artery . The 25 regression of cardiovascular disease based on sensor mea
Moens -Korteweg equation defines the velocity of the propa- surement algorithms that can determine relative cardiovas
gating pulse as pulse wave velocity (PWV) as follows: cular parameters by measurement of waveform specific
fiducial parameters or time duration measurements between
fiducial waveform parameters and /or sensed and /or device
30 pulsed waveforms relative to time points specific to the
PWV = cardiac and /or respiratory cycles . In one such example , pulse
transit time calculation methods may be used . Pulse transit
time may be generally described as the time it takes a
where E is Young ' s modulus of the arterial wall that defines pulsation (e. g ., pressure pulsation ) to travel between two
the elastic properties of the arterial wall per unit area , h /2r 35 blood vessel ( e .g ., arterial) sites , one of such sites located
is the arterialwall thickness divided by the arterial diameter , further along a circulatory path from the heart than the other
and p is the density of blood. such site . For example , the interval between the peak of the
Similar to pulse wave velocity is pulse transit time (PTT) . R -wave on an electrocardiogram and the onset of the cor
Pulse transit time may generally described as the time it responding pressure pulse at a distal anatomical location
takes for a pressure or flow wave to propagate between two 40 (e.g ., distal along a circulatory path ) may be used for pulse
arterial sites. Daily variation in blood pressure and associ - transit time. Pulse transit times and /or one or more values
ated variation in pulse transit timemay occur naturally as the derived therefrom such as a hemodynamic status values as
body adjusts blood volume distribution to the body by described herein may be a valuable metric for chronic
regulation of vasoconstriction and vasodilation properties of hemodynamic monitoring of a patient.
arterial vessels . This variation can be related to changes in 45 Multiple electrode vector configurations may be used , or
autonomic tone due to activity , diet, medication , stress, selected to be used , to measure pulse transit time as
anxiety , sleeping and the like. The exemplary systems
na, described herein . Electrode configurations may include elec
devices , and methods described herein may account for this trodes isolated to a specific device or electrodes in combi
naturally occurring variation in blood pressure and associ - nation with a plurality of devices to detect sensed or pulsed
ated pulse transit time to , e . g ., provide a hemodynamic 50 waveforms.
status of a patient. For example , the exemplary systems, This disclosure herein describes methods for detecting
devices , and methods described herein may be described as changes in a patient' s hemodynamic status in healthy
calculating a statistical parameter that represents a surrogate patients or unhealthy patients ( e . g ., cardiovascular , disease ,
hemodynamic status value from a plurality of pulse transit etc .). Further , this disclosure further describes the use of a
times sensed over a predetermined data collection period . 55 single implantable device or plurality of devices implanted
The processes of calculating a surrogate hemodynamic in subcutaneous tissue in various anatomical locations.
status value from the plurality pulse transit times may Diagnostic applications using the exemplary methods and
account for the continuous variation in blood pressure . devices may include monitoring cardiac function , cardiac
Sensor waveforms ( e . g ., impedance waveforms, optical anomalies , respiratory rate , respiratory anomalies, thoracic
waveforms, etc .) measured cutaneously , subcutaneously, 60 and peripheral limb fluid shifts, circadian fluid shift varia
intravascular, paravascular, intracardiac , or a combination tion , etc .
thereof may contain a high frequency cardiac component In one or more exemplary embodiments, an implantable
superimposed on a low frequency respiratory component medical device or a plurality of devices (e . g ., implantable ,
and a DC or mean component. Each of these components wearable, etc .) may monitor sensor values of an electric ,
may have clinical diagnostic utility. For example , the high 65 optical , or acoustic field path that is between sensors that
frequency cardiac component may provide indicators of traverse the heart, a blood vessel, and/or capillary bed ,
cardiac or hemodynamic function . Further, for example , the within the heart, a blood vessel, and/or capillary bed , and
US 10 , 182 ,729 B2
10
next to theheart, a blood vessel, and /or capillary bed . Itmay also be used to perform the same or similar functionality as
be described that the sensed signal of such a path may be described further herein . The implantable devices 10 will be
correlated with and varies in substantially the same manner described in further detail herein with respect to FIG . 2 and
as the blood flow within a vessel or capillary bed and/or the external monitoring device 20 will be described in
various hemodynamic parameters associated with the car - 5 further detail herein with respect to FIG . 3 .
diac or respiratory cycles . Thus, the sensed signal of the An exemplary system 5 including a single implantable
electric , optical, or acoustic field path may be monitored as device 10 implanted proximate the heart of a patient 1 and
a surrogate for cardiac function or flow in a vessel or an externalmonitoring device 20 is depicted in FIG . 1A . The
capillary bed, and variations in the signal over time may implantable device 10 may be implanted in subcutaneous
indicate changes in hemodynamic performance in a manner 10 tissue in close proximity to , or within , the heart, an artery, a
analogous to conventional techniques used to identify
changes to hemodynamic performance . Further, the signal vein , arterial capillary bed , venous capillary bed , or combi
nation thereof. For example , the implantable device 10 may
may be also be described as an index of cardiac function , be described as being implanted paravascular in proximity to
vessel distensibility, or vessel compliance .
Sensor values of an electric , optical, or acoustic field path 15 an artery (e . g ., located in the chest proximate the heart ) so
may define a periodic function , e.g ., waveform . The period as to be able to monitor two or more signals from tissue
of the periodic function may be correlated with the cardiac proximate the artery . As will be described further herein , the
cycle and heart rate of a patient in much the same manner single implantable device 10 may include at least two
that a cardiovascular pressure waveform defines a periodic sensors, e.g ., so as to be able to monitor two signals for the
function. The exemplary systems described herein including 20 calculation, or determination , of pulse transit times. Further,
one or more devices may monitor changes in the arterial one of the at least two sensors may be described as being
and / or venous waveform over a number of periods . For further along a circulatory path from the patient 's heart than
example , the device or plurality of devices may compare a the other sensor so as to , e . g ., monitor signals for the
sensed or pulsed signal of a first period or a referenced time calculation , or determination , of pulse transit times .
point to a sensed signal of a subsequent period. Further, the 25 The implantable device 10 may further be wirelessly
exemplary device or devices may also compare a range operably coupled to the external monitoring device 20 via a
( corresponding to magnitude or time differences in wave wireless channel 6 as indicated by the waveform symbols
form fiducial points ) of a first period or referenced time point extending between the devices 10 , 20 . The wireless operable
to a range of subsequentperiods . Still further, the exemplary coupling 6 between the implantable device 10 and the
device or devices may also compare a range of sensor values 30 externalmonitoring device 20 may allow data to be trans
measured between the heart or artery and the corresponding ferred between the two devices 10 , 20 such as , e . g ., mea
vein or capillary bed of a first period to a range of a surement initiation signals, time synchronization signals ,
subsequent period . Regardless , in one or more embodi- signal data , data representative of signal data , pulse transit
ments, the exemplary device or devices may determine times , any data usable to determine pulse transit time,
whether the hemodynamic status of the patient has changed 35 waveforms, waveform digital representations, analog wave
based on a daily, weekly , etc . basis based on comparisons forms, etc. The implantable device 10 and the external
between monitoring periods covering the day and night, or monitoring device 20 may be continuously or intermittingly
combinations thereof. wirelessly coupled for data transfer therebetween . For
It may be further described that the exemplary systems example , data may flow continuously between the two
may be configured to determine various conditions related to 40 devices 10 , 20 or data may be exchanged , or transferred ,
cardiovascular performance of the patient. For example , the between the two devices 10 , 20 at selected intervals or
exemplary systems may determine a change in hemody - whenever the devices 10 , 20 come within a particular range
namic performance, stroke volume, peripheral fluid accu - of each other. In at least one embodiment, data is down
mulation , afterload , systolic function , or other characteris- loaded from the implantable device 10 to the external
tics of cardiovascular performance . In some examples, the 45 monitoring device 20 once a day.
one or more devices (e . g ., implanted devices , wearable An exemplary system 5 including a single implantable
devices, etc .) may be communicatively coupled to another device 10 implanted away from the heart of a patient 1 in the
medical device or an independent external device , which patient 's arm and an external monitoring device 20 is
may receive pulse transit time-related data from the devices, depicted in FIG . 1B . The implantable device 10 may be
start or stop a measured timing intervals , trigger or send an 50 implanted in subcutaneous tissue in close proximity to an
alerts in response to a determined change in cardiovascular artery , a vein , arterial capillary bed , venous capillary bed , or
performance , etc . combination thereof. For example , the implantable device
Moreover, the exemplary one ormore devices may use a 10 may be described as being implanted paravascular in
combination of sensor technologies such as electrical (e .g., proximity to an artery in the patient's 1 arm so as to be able
electrocardiogram , impedance , etc. ), optical, pressure, or 55 to monitor two or more signals from tissue proximate the
acoustic processes to measure waveform fiducial time points artery . As will be described further herein , the single
and/ or time intervals between fiducial time points associated implantable device 10 may include at least two sensors , e. g .,
with the cardiac and /or respiratory cycles . so as to be able to monitor two signals for the calculation ,
As described herein , the exemplary systems and methods or determination , of pulse transit times. Further , one of the
described herein may include or use one or more implant- 60 at least two sensors may be described as being further along
able and /or non - implantable devices for monitoring one or a circulatory path from the patient' s heart than the other
more signals to determine pulse transit times for using in sensor so as to , e . g ., monitor signals for the calculation , or
assessing a patient' s hemodynamic status. Exemplary sys - determination , of pulse transit times. The implantable device
tems 5 including one or more implantable devices 10 and an 10 and the externalmonitoring device 20 of FIG . 1B may be
external monitoring device 20 are depicted in FIGS. 1A - 1C . 65 wirelessly operably coupled in a similar manner as the
Although only implantable devices 10 are depicted in FIGS . implantable device 10 and the externalmonitoring device 20
1A - 1C , it is be understood that non - implantable devices may of FIG . 1A .
US 10 , 182 ,729 B2
12
An exemplary system 5 including two implantable device The device 10 may further include pulse delivery module
10 and an externalmonitoring device 20 is depicted in FIG . 50 for delivering pulses, such as electrical stimulations /
1C . One implantable device 10 is implanted in the same, or pulses under the control of timing and control circuitry 52
similar location , to the implantable device 10 shown in FIG . for use in measuring pulse transit times. The pulse delivery
1A , and the other implantable device 10 is implanted in the 5 module 50 may include various apparatus configured to
same, or similar location , to the implantable device 10 deliver pulses such as, e. g ., electrical pulses (e . g ., to contract
shown in FIG . 1B . As will be described further herein , each tissue to cause a pressure pulse within a blood vessel or
of the implantable devices 10 of FIG . 1C may include at vasculature, etc .), pressure pulses, acoustic pulses, ultra
sound pulses, etc ., to a patient' s tissue . Generally, the pulse
least one sensor, e. g., so as to be able to monitor at least one
signal for the calculation , or determination , of a pulse transit 10
deliver module 50 may be described as being configured to
deliver, or initiate , mechanical, or physical, pulses to a
time. Further, a sensor of the device 10 located in the arm of patient's blood vessel (e. g., an artery or a vein ). The pulse
the patient may be described as being further along a delivery module 50 may include a pulse - generating circuitry
circulatory path from the patient's heart than the sensor of for generating therapeutic electrical stimulation pulses (e .g .,
the device 10 in the patient's torso so as to , e. g ., monitor 15 bursts of electrical stimulation pulses ) under the control of
signals for the calculation , or determination , of pulse transit timing and control circuitry 52 . The pulse delivery module
times . Each of the implantable devices 10 and the external 50 may be further coupled to two or more electrodes 68 via
monitoring device 20 of FIG . 1C may be wirelessly operably a switch matrix 58 that is used for selecting which electrodes
coupled in a similar manner as the implantable device 10 and and corresponding polarities are used for delivering electri
the external monitoring device 20 of FIG . 1A . 20 cal pulses .
FIG . 2 is a functional block diagram of the exemplary As described herein , the device 10 includes memory 56
implantable devices 10 shown in FIGS. 1A - 1C . The exem - for storing a variety of processes and methods used to drive
plary implantable devices 10 may generally include an the operation of the device 10 . The memory 56 may also be
operating system that may employ microprocessor 54 to used for storing data , e.g ., data monitored using the elec
control device functions. The microprocessor 54 and asso - 25 trodes 68 and sensors 70 , intermediate data or other values
ciated memory 56 may be coupled to the various compo (e.g., time stamps, etc.) calculated or determined by the
nents of device 10 via a data /address bus 55 . microprocessor 54 based on sensor data , data compiled from
The devices 10 may include electrodes 68 used for at least sensed signals and /or relating to device operating history
sensing electrical signals within the body such as , e . g ., ( e .g ., for use in delivering, adjusting , controlling , initiating ,
cardiac signals ( e . g ., electrocardiogram signals ) , impedance 30 and / or terminating pulses), and /or data for communicating
values , and / or any electrical signal associated with a physi - such data outside of the patient ( e . g ., using telemetry com
ological parameter for use in pulse transit time calculation or munication ). It may be described that the device 10 may
measurement. The electrical signals may be measured , or include a control module or controller, which may include
sensed , from any tissue (e .g ., a tissue bed ) where a hemo- the microprocessor 54 and memory 56 .
dynamic pulse is observable (e . g ., subcutaneously paravas - 35 The implantable device 10 further includes telemetry
cular , etc .) . In at least one embodiment, the electrodes 68 circuitry 64 and an antenna 65 . Data and commands may be
may be used to measure cardiac signals , impedance values , transmitted and received during uplink or downlink telem
and /or any electrical signal associated with a physiological etry between the device 10 using the telemetry circuitry 64
parameter from tissue proximate a blood vessel ( e.g ., arterial and antenna 65 and the externalmonitoring device 50 . In at
tissue, venous tissue, etc . ). The electrodes 68 used for 40 least one embodiment, the wireless operable coupling
sensing and electrodes used for stimulation may be selected between the device 10 and the externalmonitoring device 50
via a switch matrix 58 . When used for sensing, electrodes 68 may use one or more wireless ( e. g ., radio frequency ) data
are coupled to a signal processor, or processing circuitry , 60 transmission protocols such as, e. g ., BLUETOOTH , WI- FI,
via the switch matrix 58 . The signal processor , or processing any protocol in the ultra high frequency (UHF) band , any
circuitry , 60 may include sense amplifiers and may include 45 protocol in the super high frequency (SHF) band , low
other signal conditioning circuitry and an analog - to - digital frequencies , etc .
converter. In essence , the device 10 may include a sensing FIG . 3 is a functional block diagram of the exemplary
module , e .g ., that includes switch matrix 58 , signal process external monitoring devices 20 shown in FIGS . 1A - 1C . In
ing circuitry 60, etc . for monitoring one or more signals that one or more embodiments, the external monitoring device
may be used by microprocessor 54 or transmitted to another 50 20 may be located at home with a patient or with the patient
device such as , e. g ., the external monitoring device 20 , for at most, if not all, times , and used with the one or more
use in determining pulse transit times , in determining a implantable devices 10 implanted in the patient. Further, in
patient' s hemodynamic status ( e . g ., chronic hemodynamic at least one embodiment, the external monitoring device 20
status) , etc . is a cellular telephone . In one or more embodiments , the
The device 10 may further include one or more additional 55 external monitoring device 20 may be located in a clinic or
sensors 70 such as pressure sensors , accelerometers , flow other medical facility and used for wirelessly communicat
sensors , blood chemistry sensors , activity sensors , acoustic ing with multiple implantable devices 10 for multiple
sensors, posture sensors, respiration sensors , etc. that may be patients.
used for the determination , or calculation , of pulse transit The external monitoring device 20 shown in FIG . 3
time. The sensors 70 may be coupled to the remainder of the 60 includes a telemetry circuit 72 and an antenna 73 for
device 10 via a sensor interface 62 which provides sensor bidirectional communication with the implantable devices
signals to signal processing circuitry 60 . Signals monitored , 10 shown in FIGS. 1A - 1C . As described herein , data and
or measured , using the additional sensors 70 may be used by commands may be transmitted and received during uplink or
microprocessor 54 or transmitted to another device such as , downlink telemetry between the device 10 using the telem
e .g ., the externalmonitoring device 20 , for use in determin - 65 etry circuitry 64 and antenna 65 and the externalmonitoring
ing pulse transit times , in determining a patient 's hemody - device 50 using the telemetry circuit 72 and the antenna 73.
namic status (e. g., chronic hemodynamic status ), etc . In at least one embodiment, the wireless operable coupling
US 10 , 182 ,729 B2
13 14
between the device 10 and the externalmonitoring device 50 first and second signals may be measured in a location
may use one or more wireless ( e . g ., radio frequency ) data physically further away from the patient ' s heart than the
transmission protocols such as, e .g ., BLUETOOTH , WI- FI, other location where the other signal is measured . It is to be
any protocol in the ultra high frequency (UHF ) band , any understood that implantable device (s ) may be initiated to
protocol in the super high frequency (SHF) band , low 5 perform the signal measurements from an external monitor
frequencies , etc . ing device and /ormay be self - initiated to perform the signal
The external monitoring device 20 may be described as measurements ( e . g ., the implantable device ( s )may not need
being a microprocessor- controlled device, and thus, may to be initiated to perform signalmeasurements from another
include a microprocessor 74 . The microprocessor 74 may device ). The exemplary method 40 will be further described
operate with associated memory 78 for controlling various 10 herein with respect to the exemplary system 5 depicted in
processes and functions of the externalmonitoring device 20 FIG . 5A .
including initiating one or more measurements using the An exemplary system 5 for monitoring hemodynamic
implantable devices 10, and wirelessly transferring data and status of a patient including a single implantable device 10
commands between the implantable devices 10 and the is shown in FIG . 5A . The device 10 of FIG . 5A is shown
external monitoring device 20 . The microprocessor 74 may 15 implanted in tissue 2 of a patient proximate an artery 3 . The
be further configured to store data from the implantable device 10 includes a first sensor 12 configured to measure a
devices 10 , calculate or determine various metrics or values first signal from tissue 2 proximate the artery 3 and a second
such as , e . g ., hemodynamic status, or index , values, pulse sensor 14 configured to measure a second signal from tissue
transit times , one or more fiducial points located within 2 proximate the artery 3 that is located further along a
waveforms (e . g ., electrocardiograms, impedance wave - 20 circulator path from the patient 's heart than where the first
forms, acoustic signals , pressure signals, etc . ), issue alerts or sensor 12 is measuring the first signal.
messages in view of various determinations, etc . Each of the first and second sensors 12 , 14 may include
Thememory 78 may be used alone or in combination with a pair of electrodes 13. The pair of electrodes 13 may be
the memory 56 of the implantable devices 10 to store sensed used to monitor various different types of signals with the
data ( e. g., impedance data , electrocardiogram data , pressure 25 tissue 2 proximate artery 3 . For example , the electrodes 13
signals data , acoustic signal data , optical signal data , etc .) as may measure impedance signals, electrocardiogram signals ,
well as information used in telemetry link control opera - and /or any electrical signal associated with a physiological
tions. Such telemetry link information may include condi parameter. In other exemplary devices 10 , the first and
tions for verifying a telemetry session is active or inactive , second sensors 12 , 14 may include , or use , other sensing
time intervals for monitoring for such conditions, and mes- 30 apparatus other than electrodes such as optical sensors ,
sages that may be displayed during a telemetry termination pressure sensors, acoustic sensors, accelerometers, flow
operation . sensors , blood chemistry sensors , activity sensors , posture
In order for a person to interact with the external moni sensors, respiration sensors, etc . Regardless of the sensing
toring apparatus 20, the external monitoring apparatus 20 modality, the first and second sensors 12 , 14 may sense and
may include a user interface 71 coupled to microprocessor 35 generate a first and second signal, respectively , that includes
74 . The user interface 71 may include a touchscreen , a a natural pulse originating from the heart or an artificial
keyboard , graphical user interface , and/ or combinations pulse originating from a pulse generator than traverses the
thereof. Further, the external monitoring apparatus 20 may patient ' s tissue, blood vessel structure , etc . Further , as
include a display 76 . The user interface 71 may allow a user shown , the second sensor 14 measures the second electrical
to view and/ or manipulate data on the display 76 and allow 40 signal in a location further along a circulatory path from the
a user to interact with the implantable medical devices 10 . patient's heart than the where the first sensor 12 measures
The external monitoring apparatus 20 may further include a the first electrical signal.
speaker 77 for broadcasting audible tones or messages used The exemplary method 40 may transmit and receive data
to communicate with a user regarding , e.g ., a hemodynamic 42 representative of the first and second signals measured
status of the user, alerts , alarms, etc. 45 using the first and second sensors 12 , 14 of the device 10 .
The externalmonitoring apparatus 20 may further include More specifically, data representative of the first and second
a communications module 79 used for transferring data signals may be transmitted from the implantable device 10
( e .g ., over the internet, over a network , etc .) to a central to the external monitoring device 20. For example, as shown
database or communicating with other patient management in the exemplary system 5 of FIG . 5A , the first signal 16 and
systems such as the centralized system described herein with 50 the second signal 17 have been transmitted to the external
references to FIG . 16 . The external monitoring apparatus 20 monitoring device 20 and are now displayed on the display
may further include an interface 75 for coupling peripheral 76 of the external monitoring device 20 . It is to be under
devices which may include external monitoring equipment stood that the first and second signals 14 , 16 may not be
such as electrocardiogram leads , blood pressure monitor, displayed on the display 76 on the external monitoring
etc . 55 device 20 during general usage of the system 5 and is shown
A flow diagram of an exemplary method 40 ofmonitoring in the examples of FIGS . 5 -6 for explanatory purposes.
aggregate hemodynamic status of a patient using, e . g ., the Nonetheless , the signals 16 , 17 could be displayed on the
systems and devices of FIGS . 1 - 3, is depicted in FIG . 4 . The display 76 of the external monitoring device 20 is a user
exemplary method 40 may include measuring a first signal desired to do so ( e .g ., through some user interaction ).
from tissue of a patient and a second signal from tissue of the 60 In other words, exemplary systems and processes to
patient 41. The first and second signals may be measured measure a timing interval from a single device are shown in
from tissue of the patient in different locations. More spe - FIG . 5A . A first signal 16 may be sensed from the first sensor
cifically, one of the first and second signalsmay be measured 12 and either a digital representation of the first signal 16 or
in a location further along a circulatory path from the a time stamp corresponding to a fiducial point of the first
patient' s heart than the other location where the other signal 65 signal 16 may be sent via a remote communication pathway
is measured such that the signals may be used to determine to the externalmonitoring device 20 ( e. g ., a cell phone ). The
a pulse transit time. In one or more embodiments, one of the second signal 17 may be sensed by, or from , the second
US 10 , 182 ,729 B2
15 16
sensor 14 on the same device 10 , and either a digital Since the heart' s native impulse may be too weak to sense
representation of the second signal 17 or a time stamp in venous tissue (and in some arterial tissue ), the device 10
corresponding to a fiducial point of the second signal 17 may of FIG . 5C may include a pulse generator, or activator, 19
be sent via a remote communication pathway to the external (e. g., the pulse delivery module 50 ) configured to generate
monitoring device 20 ( e . g ., a cell phone ) . A pulse transit time 5 a pressure wave within the vein 4 of the tissue 2 . A time
calculation may be derived from the difference in time s tamp may be associated with the delivery of the pressure
between fiducial points in the two signals 16 , 17 and/ or two wave , which may be used as the first signal 16 . As shown in
time stamps/markers . Additionally, in one or more embodi- the display 76 of the monitoring device 20 , the time stamp
ments, single device calculations, such as pulse transit time is represented by a square wave within the first signal 16 . In
calculations , can also be used in place of transmitting data 10 at least one embodiment, the pulse generator 19 may include
representative of the first and second signals 16 , 17 to the a piezoelectric crystal configured to generate and deliver the
external monitoring device 20 , and subsequently , the pulse pressure wave within the venous tissue . In other embodi
transit times can be transmitted to the external monitoring ments , the pulse generator 19 may be configured to deliver
device 20 . pulses such as , e .g ., electrical pulses ( e. g., to contract tissue
It is described that the data representative of the first and 15 to cause a pressure pulse within a blood vessel or vascula
second signals 16 , 17 is transmitted from the implantable ture , etc .), pressure pulses, acoustic pulses, ultrasound
medical device 10 to the external monitoring device 20 pulses , etc ., to a patient's tissue . Generally , the pulse gen
because , at least in some embodiments , the actual signals erator 19 may be described as being configured to deliver , or
themselves may not be transmitted to the external monitor - initiate , mechanical, or physical, pulses to a patient's blood
ing device 20 . Instead , for example , a digital representation 20 vessel (e .g ., an artery or a vein ).
of the signals 16 , 17 may be transmitted to the external The first sensor 12 of the device 10 of FIG . 5C may
monitoring device . More specifically , the first and second include a pair of electrodes to measure the second signal 17 ,
signals 16 , 17 may be sampled a particular sampling rate , or which in this embodiment, is an impedance waveform . As
frequency, and the data points representative of the signals shown, the sensor 12 measures the second signal 17 in a
16 , 17 may be the data that is transferred to the external 25 location further along a circulatory path from the patient 's
monitoring apparatus 20 . Further, for example , a time stamp heart than the where pulse generator, or activator, 19 delivers
corresponding to a particular fiducial point along the first a pressure wave or pulse . A pulse transit time may be
and second signals 16 , 17 may be transferred to the external calculated by the monitoring apparatus 20 between the
monitoring apparatus 20 . Regardless , the data representative square wave of the first signal 16 and a fiducial point
of the first and second signals 16 , 17 is such that the external 30 representative of the propagated pulse within the second
monitoring apparatus is capable to determine , or calculate , a signal 17 . Please note that the first peak in the second signal
pulse transit time therefrom . 17 may be a stimulus pulse artifact from the activator.
Additional system configurations including a single Additionally, the system 5 of FIG . 5C can also be used to
implantable device 10 or two implantable devices 10 using measure pulse transit time within venous and arterial tissue
a variety of different sensors are depicted in FIGS. 5 -6 . It is 35 such as shown in FIG . 5D . The device 5 of FIG . 5D is
to be understood the configurations depicted in FIGS. 5 -6 do substantially similar to the device 5 of FIG . 5C except that
not represent or depict all of the configurations that are be the device 5 is located proximate both a vein 2 and an artery
considered by this disclosure . Instead , the system configu - 3 . In this embodiment, the second signal 17 includes a
rations depicted in FIGS. 5 -6 are merely a few examples. propagated arterial pulse and a propagated venous pulse . As
The exemplary system 5 of FIG . 5B is similar to the 40 shown, the propagated arterial pulse is faster than the
system 5 of FIG . 5A . For example , the system 5 of FIG . 5B propagated venous pulse , and an arterial pulse transit time,
includes a single implantable device 10 that has a pair of Atl , and a venous pulse transit time, At2 , may be calculated
sensors 12 , 14 and an externalmonitoring device 20 . In this using the same signals 16 , 17 . Again , as before the first peak
system 5 of FIG . 5B , however, the first sensor 12 is an in the second signal 17 may be a stimulus pulse artifact.
electrocardiography sensor including a pair of electrodes 13 45 Exemplary systems 5 for monitoring hemodynamic status
for measuring an electrocardiography signal and the second of a patient including two implantable devices 10 are
sensor 14 is an optical sensor including a light emitter 21 and depicted in FIGS. 6A - 6C . As described herein , one of the
a light detector 22 formeasuring an arterial pulse waveform . implantable devices 10 may be located ( e . g ., implanted
As shown , the second sensor 14 measures the arterial pulse subcutaneously, implanted paravascular , etc .) closer to the
waveform in a location further along a circulatory path from 50 patient' s heart along a circulatory path than the other
the patient 's heart than the where the first sensor 12 mea - implantable device . In at least one embodiment, one of the
sures the electrocardiography signal. The first signal 16 , implantable devices 10 may be located physically closer to
which is an electrocardiogram signal, and the second signal the patient ' s heart than the other implantable device . As
17, which is an optically - acquired arterial pulse waveform , shown in the examples of FIGS. 6A -6C , the implantable
are displayed on the display 76 of the external monitoring 55 device 10 located on the left side of the figures is located
device 20 . As shown, a pulse transit timemay be measured closer to the patient ' s heart along the circulatory path than
between the peak of the R -wave in the first signal 16 to the the implantable device 10 located on the right side . Each of
minimum value in the second signal 17 . the devices 10 of FIGS. 6A -6C include a pair of electrodes
The systems 5 of FIGS. 5A - B may rely, or use , the heart' s 13 configured to measure an impedance waveform and/ or an
native impulse that may be too weak to be detected in large 60 electrocardiogram signal. Further, each of the device 10 of
and small veins. The systems5 of FIGS. 5C -5D may extend FIGS. 6A -6C may be wirelessly operably coupled to at least
the exemplary methods and devices from measurement of the external monitoring apparatus 20 for data transfer ther
arterial tissue to the measurement of venous tissue (e .g ., the ebetween and may be wirelessly operably coupled to each
stiffness /compliance of venous tissue ). The addition of other for data transfer therebetween .
venous measurements may assist clinician in determining 65 In FIG . 6A , the first signal 16 measured by the first sensor
which types ofmedication intervention is most suitable for 12 of the first device 10 is an electrocardiogram signal and
the patient such as , e. g., diuretics or nitrates. the second signal 17 measured by the second sensor 14 of
US 10 ,182 ,729 B2
the second device 10 is an impedance signal. As shown , the second signal 17 measured by the second sensor 14 of the
second sensor 14 measures the second signal 17 in a location second device 10 is also an impedance signal. As shown, the
further along a circulatory path from the patient' s heart than second sensor 14 measures the second signal 17 in a location
the where the first sensor 12 measures the first signal 16 . As further along a circulatory path from the patient' s heart than
before, a pulse transit time, At, may be determined between 5 the where the first sensor 12 measures the first signal 16 .
the peak of the R -wave of the first signal 16 and the Each signal 16 , 17 may be transmitted , or delivered , to the
minimum of the second signal 17 . In other words, FIG . 6A external monitoring device 20 . As before , a pulse transit
depicts exemplary systems and processes to measure a time, At,may be determined between the minimum value of
timing interval from a plurality of devices 10 . A sensed ECG the first signal 16 and the minimum value of the second
R - wave signal and/ or a corresponding time stamp may be 10 signal 17 as depicted on display 76 of the external moni
transmitted , or sent, from a primary device 10 via a remote toring device 20 .
communication pathway to the externalmonitoring device Thus, the exemplary method 40 may further include
20 ( e . g ., cell phone). A signal from a distal secondary device determining a pulse transit time 43 based on the data
10 may be subsequently sensed , and the signal and /or a representative of the first and second signals 16 , 17 . In one
corresponding time stamp of this sensed signalmay also sent 15 or more embodiments , the pulse transit time may be calcu
via a remote communication pathway to the external moni- lated by measuring the time between a selected fiducial point
toring device 20 . A pulse transit time calculation may be in the first signal 16 and a selected fiducial point in the
derived from the difference in timebetween the two fiducial second signal 17 . An exemplary arterial waveform over time
points in the signals 16 , 17 and /or time stamps /markers including a plurality of selected fiducial points is depicted in
related thereto . In at least one embodiment, intrabody com - 20 FIG . 7 .
munication between the two devices 10 can also be used in Potential arterial waveform parameters for identifying
place of remote device telemetry . one or more fiducial points are depicted about the arterial
In FIG . 6B , the first sensor 12 of the first device 10 may waveform 91 of FIG . 7 that may be used for pulse transit
be measure an electrocardiogram signal, an impedance sig - time determination, which may be used to assess the hemo
nal, and /or any other signal indicative of a pressure pulse , 25 dynamic status of a patient. For example , the minimum
and then the first device 10 may transmit a time stamp value ( A ) indicative of minimum vessel distention associ
represented by a square wave of in the first signal 16 ated with diastole and the maximum value ( B ) indicative of
corresponding to a fiducial point within with the measured maximum vessel distention associated with systole may be
signal to the external monitoring device 20 . In another used as fiducial points. As shown , the time between the
embodiment (not depicted ), the first device 10 may transit a 30 minimum values ( A ) may provide cardiac cycle time (C ) .
pulse ( e . g ., electrical pulse , pressure pulse , etc .) into the Further , for example , the maximum slope ( D ) indicative of
blood vessel tissue ( e . g., into the artery ) , and subsequently, the maximum rate of vessel distention and the minimum
transmit a time stamp represented by a square wave in the slope ( E ) indicate of the minimum rate of vessel relaxation
first signal 16 corresponding to the moment when the pulse may also be used as fiducial points.
was transmitted into the blood vessel tissue to the external 35 The exemplary fiducial points identified in FIG . 7 may be
monitoring device 20 . As shown, the second signal 17 used to determine a pulse transit time by identifying a
measured by the second sensor 14 of the second device 10 selected fiducial point on the first signal 16 , identifying a
is an impedance signal. Further, the second sensor 14 selected fiducial point on the second signal 17 , and calcu
measures the second signal 17 in a location further along a lating, or determining , the time between the two fiducial
circulatory path from the patient ' s heart than the where the 40 points occurring . For example , as shown in FIG . 5A , the
first sensor 12 measures the first signal 16 . As before , a pulse selected fiducial points for each of the first and second
transit time, At, may be determined between the square wave signals 16 , 17 are the minimum values. The time between
of the first signal 16 and the minimum of the second signal the minimum value of the first signal 16 and the minimum
17 . value of the second signal 17 , At, may be used as the pulse
In other words, FIG . 6B depicts exemplary systems and 45 transit time.
processes to measure a timing interval from a plurality of As described herein , the data representative of the first
devices 10 . A cardiac event may be sensed by a primary signal 16 may be a digital representation of the first signal
device 10 using sensor 12 , and a corresponding time stamp 16 or a time stamp, and likewise, the data representative of
of this event may be sent via a remote communication the second signal 17 may be a digital representation of the
pathway to the external monitoring device 10 ( e . g ., a cell 50 second signal 17 or a time stamp. It is to be understood that
phone ). Or, a pulsed signal may be administered secondary a time stamp is essentially the time at which a selected
to a sensed cardiac event from the primary device 10 and a fiducial point occurs within a waveform or signal. Thus, the
corresponding time stamp of this pulsed signal may be sent implantable device 10 may be performing the fiducial point
via a remote communication pathway to the external moni analysis in these examples where a time stamp is transmitted
toring device 10 . A signal from a distal secondary device 10 55 to the external monitoring device 20 . The external monitor
(or plurality of devices 10 ) may be subsequently sensed , and ing device 20 may calculate the pulse transit time using one
data representative of the second signal 17 (e. g ., a digital or more time stamps . For example , in at least one embodi
representation of the second signal 17 , a corresponding time ment , the data representative of the first signal 16 may be a
stamp of this signal 17 ) may also sent via a remote com - timestamp while the data representative of the second signal
munication pathway to the external monitoring device 20 . A 60 17 may be a digital representative of the second signal 17 .
pulse transit time calculation may be derived from the Thus, in this embodiment, a fiducial point may be deter
difference in time between the time stamp of the first signal mined in the second signal 17 , and the fiducial time stamp
16 (e .g., the square wave) and either a fiducial point within (i.e., the time at which the fiducial point occurs ) may be used
the second signal 17 or a time stamp from the second sensor with the time stamp of the first signal 16 to determine the
14 . 65 pulse transit time. Further, for example , in at least another
In FIG . 6C , the first signal 16 measured by the first sensor embodiment, the data representative of the first signal 16
12 of the first device 10 is an impedance signal and the may be a time stamp and the data representative of the
US 10 ,182 ,729 B2
20
second signal 17 may be a time stamp. In this embodiment, box 41. In other words , if the monitoring time period has not
the time between the two time stamps may be the pulse expired , the method 40 may loop back to measuring 41 first
transit time. and second signals 16 , 17 , transmitting /receiving 42 , and
In at least another embodiment, the implantable device 10 determining the pulse transit times 43. This measurement
may calculate the pulse transit time by comparing time 5 41, transmission / reception 42 , and pulse transit time deter
stamps from fiducial points that the device 10 itself deter m ination 43 may occur periodically over the monitoring
mined, or calculated , in this first and second signals 16 , 17 . time period . For example , these processes 41 , 42, 43 may
In this example , the implantable device 10 may transmit the occur about every 5 seconds to about every 60 seconds, and
pulse transit time to the externalmonitoring device 20 . this period of time may be referred to as a monitoring time
The first and second signals 16 , 17 may be measured 41 10 period . In one or more embodiments , the monitoring time
and transmitted /received 42 , and pulse transit times may be period may be greater than or equal to about 5 seconds ,
determined 43 over the course of a monitoring time period . greater than or equal to about 10 seconds , greater than or
Generally , the monitoring timeperiod is selected to be a time equal to about 20 seconds, greater than or equal to about 30
period that is useful for assessment of the chronic hemody - seconds , greater than or equal to about 60 seconds, greater
namic health of a patient (as opposed to an acute measure - 15 than or equal to about 120 seconds, greater than or equal to
ment). As will described further herein , hemodynamic status about 5 minutes, greater than or equal to about 10 minute ,
values (e .g ., daily surrogate hemodynamic status values , greater than or equal to about 20 minutes, greater than or
weekly surrogate hemodynamic status values, nighttime equal to about 30 minutes seconds , etc . and /or less than or
surrogate hemodynamic status values, daytime surrogate equal to about 60 minutes, less than or equal to about 45
hemodynamic status values, etc . ) will be generated based on 20 minutes , less than or equal to about 35 minutes , less than or
the pulse transit times determined over the monitoring time equal to about 25 minutes, less than or equal to about 15
period . In other words, the monitoring time period may minutes , less than or equal to about 8 minutes, less than or
provide hemodynamic status values that may be described as equal to about 3 minutes , less than or equal to about 100
being aggregate values over a time period so as to be able to seconds, less than or equal to about 75 seconds , less than or
assess the chronic hemodynamic health of the patient. 25 equal to about 45 seconds , less than or equal to about 35
In one or more embodiments , the monitoring time period seconds , less than or equal to about 25 seconds, less than or
is about 5 minutes to about 2 months. For example , the equal to about 15 seconds, etc . Additionally , it is to be
monitoring time period may be greater than or equal to about understood that the transmission / reception and pulse transit
5 minutes , greater than or equal to about 7 minutes, greater time determination processes 42 , 43 may not occur every
than or equal to about 10 minutes, greater than or equal to 30 time a measurement process 41 occurs , and instead , the data
about 12 minutes, greater than or equal to about 15 minutes, from the measurement processes 41 may be transmitted /
greater than or equal to about 20 minutes, greater than or received 42 periodically over multiple monitoring time
equal to about 25 minutes , greater than or equal to about 30 periods.
minutes, greater than or equal to about 45 minutes, greater If the monitoring time period has expired , the method 40
than or equal to about 1 hour, greater than or equal to about 35 may progress to determining a surrogate hemodynamic
2 hours, greater than or equal to about 4 hours , greater than status value 45 (for the monitoring time period from the
or equal to about 6 hours , greater than or equal to about 8 pulse transit times calculated during the monitoring time
hours , greater than or equal to about 10 hours , greater than period ). As described herein , a hemodynamic status value
or equal to about 12 hours, greater than or equal to about 14 may be indicative of the hemodynamic health , or status, of
hours , greater than or equal to about 16 hours , greater than 40 a patient. Further, the hemodynamic status value may be
or equal to about 18 hours, greater than or equal to about 20 described as an aggregate value because the hemodynamic
hours , greater than or equal to about 22 hours, greater than status value represents, or is derived from , a plurality of
or equal to about 1 day, greater than or equal to about 2 days , pulse transit times over the monitoring time period . In other
greater than or equal to about 1 week , greater than or equal words , the hemodynamic status value represents a period of
to about 2 weeks , greater than or equal to about 3 weeks, etc . 45 time, i. e ., the monitoring time period , as opposed to an
and /or less than or equal to about 17 minutes , less than or individual point in time.
equal to about 27 minutes, less than or equal to about 40 B efore converting the pulse transit times to a surrogate
minutes, less than or equal to about 50 minutes, less than or hemodynamic status value , one or more processes may be
equal to about 1 .5 hours, less than or equal to about 3 hours, performed on the plurality of pulse transit times for the
less than or equal to about 5 hours , less than or equal to 50 monitoring time period . For example , the plurality of pulse
about 7 hours , less than or equal to about 9 hours , less than transit times may be averaged to provide a mean pulse transit
or equal to about 11 hours , less than or equal to about 13 time value . Further, additional processes that may be per
hours , less than or equal to about 15 hours , less than or equal formed on the plurality of pulse transit times for the moni
to about 17 hours, less than or equal to about 19 hours , less toring time period may include one or more of generating a
than or equal to about 21 hours , less than or equal to about 55 median , generating a mode , filtering , generating ranges,
23 hours , less than or equal to about 25 hours, less than or removing outliers, generating standard deviations, etc .
equal to about 1.5 weeks, less than or equal to about 2.5 A plurality of graphs showing how a plurality of pulse
weeks, less than or equal to about 3 . 5 weeks, less than or transit times may be converted into a surrogate hemody
equal to about 1 month , less than or equal to about 2 months, namic status values and plotted over time are depicted in
etc . Further, as described further herein , in some embodi- 60 FIG . 8 . As shown, for each day, a plurality of pulse transit
ments, the monitoring time period may correspond to day - time times 95 are plotted and an average pulse transit time
time and nighttime. 96 is calculated . A linear regression equation as plotted by
The first and second signals 16 , 17 may be measured 41 line 97 may be used to convert the mean pulse transit time
and transmitted /received 42 , and pulse transit times may be to a surrogate hemodynamic status value 98 . Further, in one
determined 43 over the course of a monitoring time period 65 or more embodiments, the pulse transit times may be cali
in a periodic fashion until the monitoring time period expires brated with respect to blood pressure values (e . g ., for
44 as indicated by the arrow from process box 44 to process generating linear regression equations for converting pulse
US 10, 182 ,729 B2
21 22
transit times to hemodynamic status values ) is described A graph of 24 hours of pulse transit time data versus
herein with respect to the FIGS. 10 - 12 . The surrogate systolic blood pressure measured during experimental test
hemodynamic status values 98 may be plotted over time as ing is shown in FIG . 10 . From this data taken over 24 hours ,
shown in graph 99 , which may be used to identify and assess a linear regression equation was fitted to the data, which is
trends in the patient' s aggregate hemodynamic health . 5 y = 0 . 299 - 0 . 0007x with an r - value of 0 . 80 . A graph of daily
Thus, using the exemplary processes depicted in FIG . 8 , actual systolic pressure and surrogate hemodynamic status
the exemplary method 40 may determine a hemodynamic value using the linear regression equation from the data
status value 45 based on the plurality of pulse transit times depicted in FIG . 10 is shown in FIG . 11 . As shown , the
representative of the patient 's aggregate hemodynamic sta - surrogate hemodynamic status values relatively closely
tus for the monitoring time period . In some embodiments , 10 tracked the actual systolic data over the 26 days . In this
the hemodynamic status value may merely be the average , example , each daily surrogate hemodynamic status value
or other statistic , representative of the plurality of pulse plotted in FIG . 11 was generated by measuring pulse transit
transit times determined of the monitoring time period . time for each heartbeat for 10 minutes each hour of the day.
Regardless of the mathematical operations or conversations, Three pulse transit times were selected from each 10 minute
the hemodynamic status value may be representative of the 15 period ( e . g ., as being representative of the 10 minute
plurality of pulse transit timesmeasured during, or over, the period ), and the selected pulse transit times from each 10
monitoring timeperiod and may be used , at least, to identify minute period for the entire day were then averaged to
trends of multiple monitoring time periods that may be generate the surrogate hemodynamic status value for the
indicative of the patient 's hemodynamic health . After deter - day . A graph of weekly actual systolic pressure and surrogate
mination of the hemodynamic status value, the hemody - 20 hemodynamic status value using the linear regression equa
namic status value may be stored 46 in memory, and the tion from the data depicted in FIG . 10 is shown in FIG . 12 .
method 40 may continue for another monitoring time period In this example , each weekly surrogate hemodynamic status
as indicated by the arrow looping back to the measurement value plotted in FIG . 12 was generated by averaging one
process 41 . week of daily surrogate hemodynamic status values . As
The hemodynamic status valuemay be determined by one 25 shown, the surrogate hemodynamic status values relatively
or both of the implantable devices 10 and the monitoring closely tracked the actual systolic data over the nine weeks .
device 20 . For example, the implantable devices 10 may As described herein , the monitoring time period may
determine the hemodynamic status value from the plurality include a portion of a day such as nighttime and daytime.
of pulse transit times, and then transfer the hemodynamic The hemodynamic status values for daytime and nighttime
status value to the monitoring device 20 . Further , for 30 may provide additionalmetrics or data thatmay be useful in
example , the plurality of pulse transit times, or data thereof, assessing a patient's hemodynamic status. For example , a
may be transferred to the monitoring device 20 , and the graph of exemplary daytime and nighttime pulse transit time
monitoring device 20 may determine, or calculate, the data over time determined using, e . g., the systems and
hemodynamic status value. In other words, step 45 may be methods of FIGS. 1 -6 is shown in FIG . 13. In this example ,
performed by one or both of the implantable devices 10 and 35 themonitoring timeperiod included each nighttime and each
the monitoring device 20 . Still further , the pulse transit times daytime, and an average pulse transit time was calculated , or
may be determined by the one ormore devices 10 from the determined , for each nighttime and daytime. By plotting the
first and second signal data , and then transferred to the daytime and nighttime average pulse transit times , the
monitoring device 20 . In sum , any of the one or more difference, or changebetween , the average pulse transit time
devices 10 and the external monitoring device 20 may 40 for daytime and nighttime is visualized . This daytime/
perform any one or more of the steps described with nighttime blood pressure change, as approximated by the
reference to method 40 . daytime/nighttime pulse transit times , may be useful to
Additionally , the method 40 may optionally be configured detect patterns , which may be indicative of the patient's
to compare the determined hemodynamic status value to a hemodynamic health . For example , as shown in this graph ,
baseline or another metric , and issue an alarm to the patient 45 the difference between daytime and nighttime pulse transit
47. For example , the method 40 may determine from the times are decreasing, which may indicate an overall blood
trend of the hemodynamic status values that a patient's pressure increase , a decrease in the patient' s hemodynamic
blood pressure has likely increased and needs medical health , a change in medication ( e . g ., a change in type , dose ,
attention , and thus , issue an alarm 47 to the external moni- etc .) that the patient is taking , non - compliance with treat
toring device 20 . Further, for example , the method 40 may 50 ment options ( e. g ., failure to take medication , etc .), poor
determine from the trend of the hemodynamic status values sleep , change in sleep patterns, stress , any other physiologi
that a patient's blood pressure has likely increased and needs cal changes, etc . Additionally, as shown in this graph, both
medical attention , and thus, may instruct the patient ( e . g ., the daytime and nighttime pulse transit time values dropped
through a message on the device 20) to perform a clinical at around 100 days, which could indicate to a practitioner
action ( e . g ., take a medication ), visit a clinician , go to an 55 that an event occurred such as, e . g ., an increase in sodium
emergency room , etc. The externalmonitoring apparatus 20 intake, etc .
may play a sound, display the alert, and/ or vibrate to indicate A graph of exemplary daytime and nighttime pulse transit
to the user that an alarm and / or instruction is or has occurred . time data for “ dipper ” and “ non - dipper” patients over time
Another graph of a surrogate hemodynamic status values determined using, e .g ., the systems and methods of FIGS.
plotted over time is depicted in FIG . 9 . In this depiction , 60 1 -6 is shown in FIG . 14 . For example , if a hemodynamic
surrogate hemodynamic status values are displayed in mul- status values as derived from the pulse transit time data , does
tiple ways to provide additional information to a practitioner not decrease , or dip , 15 % from daytime to nighttime, this
when identifying and assessing trends in the patient's hemo- lack of decrease may be indicative of a higher risk of
dynamic health . More specifically , the actual surrogate cardiovascular disease .
hemodynamic status values , a moving average of the sur- 65 A graph of exemplary change in surrogate hemodynamic
rogate hemodynamic status values , and a range of the status value over time determined using, e . g ., the systems
surrogate hemodynamic status values are plotted over time. and methods of FIGS. 1-6 is shown in FIG . 15 . This
US 10 , 182 ,729 B2
23 24
simplified graph may be an exemplary interface that is 102 has been plotted for the second time period. In other
configured to be used by the patient and /or clinicians to view words, a pulse transit time-blood pressure relationship 100 ,
overall hemodynamic health trends withoutmuch clutter and 102 has been generated between the pulse transit times and
unnecessary numerical data or complication . As shown , the systolic blood pressure values for each time period .
simplified graph displays a percentage change in raised 5 As shown , the second line 102 is different, or has
surrogate hemodynamic status value over time such that a changed , from the first line 100 , which may indicate that the
user may easily ascertain increases or decreases in their hemodynamic status of a patient has changed (indicated by
general hemodynamic health . arrow 105 ) . The exemplary methods and systems described
The information obtained by the systems, devices , and herein may be configured to determine whether a hemody
methods described herein can be integrated into a central- 10 namic status as changed based on a change in the pulse
ized system 900 for remote monitoring and analysis , allow - transit time-blood pressure relationship from the first time
ing easier use for the patient and caregivers as shown in FIG . period to the second time period ( e . g ., over the first and
18 . As described herein , pulse transit times or data repre - second time periods ). One numerical process to determine
sentative of pulse transit times may be transmitted ( e. g ., whether the relationship between pulse transit time and
transmitted wireless from ) from one or more implantable 15 blood pressure has changed 105 may be to compare the
devices 905 to an external monitoring device 906 . The slopes 101, 103 of the relationships to each other, and if the
external monitoring device 906 can determine hemody - difference in slopes 101, 103 exceeds a threshold value , then
namic status values, which can then upload the hemody - the exemplary systems, methods, and devices described
namic status value data as well as pulse transit timedata into herein may determine that a significant hemodynamic status
the system 900 . This data can then be stored with informa- 20 change has occurred .
tion from all data sources 901, including enrollment data All patents, patent documents, and references cited herein
907, follow - up data 908 , device and registrant tracking data are incorporated in their entirety as if each were incorpo
909, consumer data 910 , and other data sources 911 . The rated separately . This disclosure has been provided with
data can then be transferred to a data collection subsystem reference to illustrative embodiments and is not meant to be
902. This subsystem 902 can extract, transform and load the 25 construed in a limiting sense . As described previously, one
data 912 , into a source warehouse 913 . Copies of the data skilled in the art will recognize that other various illustrative
subsets 914 can be distributed by the data distribution applications may use the techniques as described herein to
subsystem 903 , taking into account appropriate business take advantage of the beneficial characteristics of the appa
rules 915 and privacy laws 916 . This information can then ratus and methods described herein . Various modifications
be transferred to data marts 917. The data from the data 30 of the illustrative embodiments , as well as additional
marts 917 can then be transferred to a data analysis subsys - embodiments of the disclosure , will be apparent upon ref
tem 904 . The data analysis subsystem then makes data erence to this description .
inferences 918 , for each of the data marts to give the
analyzable data 919 , 920 , 921. The data 919 , 920 , 921 can What is claimed :
then be analyzed , including any analytics applications 925 , 35 1. A system for use in assessment of a patient's hemody
to give analyzed information 922 , 923 , and 924 . All of this namic status comprising:
can be done utilizing the data warehousing and analytics one or more devices comprising :
services components 926 . a first sensor to measure a first signal from tissue of a
As described with respect FIGS. 8 and 10 , a plurality of patient, and
pulse transit timesmay be time correlated , or synchronized , 40 a second sensor to measure a second signal from tissue
to a plurality of blood pressure measurements, and a rela of the patient from a different location along a
tionship , or function , such as, e . g ., a linear regression , may circulatory path from the patient' s heart than the first
be generated based on the plurality of pulse transit times and sensor, wherein the one or more devices are config
the plurality of blood pressure measurements. Such relation ured to periodically measure the first and second
ship may be used to convert a pulse transit time to an 45 signals over a monitoring time period ; and
estimated blood pressure , and vice versa . an external monitoring device wirelessly operatively
A change in the relationship between pulse transit time coupled to the one or more devices and configured to :
and blood pressure may also be useful in determining the receive data representative of the first and second
hemodynamic status of a patient. For example , if the rela signals from the one or more devices ;
tionship between pulse transit time and blood pressure 50 determine a pulse transit time based on the data repre
changes, it may indicate an overall blood pressure increase , sentative of the first and second signals for each
a decrease in the patient 's hemodynamic health , a change in measurement of the first and second signals resulting
medication ( e . g ., a change in type , dose , etc .) that the patient in a plurality of pulse transit times for the monitoring
is taking, non -compliance with treatment options (e. g ., fail time period ; and
ure to take medication, etc .), poor sleep, change in sleep 55 determine a surrogate hemodynamic status value based
patterns , stress , any other physiological changes, etc . on the plurality of pulse transit times representative
Pulse transit time data versus systolic blood pressure of the patient' s aggregate hemodynamic status for
measured during a first and second time period is depicted the monitoring time period .
in FIG . 17 . In other words , a plurality of pulse transit times 2 . The system of claim 1 , wherein the monitoring time
and systolic blood pressure values have been monitored over 60 period is greater than or equal to 1 hour.
first and second time periods and such times and values have 3 . The system of claim 1 , wherein the external monitoring
been plotted . As shown, a relationship 100 , 102 , or more device is further configured to :
specifically, a linear regression function , has been generated / monitor the hemodynamic status values for a plurality of
modelled and plotted among the data points of pulse transit monitoring time periods ; and
time versus systolic pressure for each of the first time period 65 determine whether the hemodynamic status of the patient
and the second time period .More specifically , a first line 100 has changed based on the hemodynamic status values
has been plotted for the first time period and a second line over the plurality of monitoring time periods.
US 10 , 182,729 B2
25 26
4 . The system of claim 3 , wherein the externalmonitoring 15 . The method of claim 13 further comprising :
device is further configured to issue an alert if the hemody monitoring the hemodynamic status values for a plurality
namic status of the patient has changed based on the ofmonitoring time periods; and
hemodynamic status values . determining whether the hemodynamic status of the
5 . The system of claim 1 , wherein the external monitoring 5 patient has changed based on the hemodynamic status
device is further configured to : values over the plurality ofmonitoring time periods.
receive a plurality of blood pressure values of the patient
synchronized to the plurality of pulse transit times over alert16 .ifThe
themethod of claim 15 further comprising issuing an
hemodynamic status of the patient has changed
the monitoring time period ,
model a relationship between the plurality of blood pres - 10 based
17 .
on the hemodynamic status values.
The method of claim 15 further comprising :
sure values and the plurality of pulse transit times ; receiving a plurality of blood pressure values of the
monitor the relationship between the plurality of blood patient synchronized to the plurality of pulse transit
pressure values and the plurality of pulse transit times times over the monitoring time period ;
for at least two monitoring time periods; and
determine whether the hemodynamic status of the patient 15 modelling a relationship between the plurality of blood
has changed based on a change in the relationship pressure values and the plurality of pulse transit times ;
between the plurality of blood pressure values and the monitoring the relationship between the plurality of blood
plurality of pulse transit times over the at least two pressure values and the plurality of pulse transit times
monitoring time periods. for at least two monitoring time periods ; and
6 . The system of claim 1,wherein the one or more devices 20 determining
comprises :
whether the hemodynamic status of the
patient has changed based on a change in the relation
a first device comprising the first sensor; and ship between the plurality ofblood pressure values and
a second device comprising the second sensor. the plurality of pulse transit times over the at least two
7. The system of claim 1,wherein the one or more devices monitoring time periods .
18 . The method of claim 13 , wherein the first signal
comprises a single implantable device comprising the first 25 comprises
sensor and the second sensor. one of an electrocardiography signal, an imped
8 . The system of claim 1, wherein the one or more devices ance signal, an optical signal, an acoustic signal, and an
are subcutaneously implantable devices. accelerometer signal.
9 . The system of claim 1, wherein the first signal com 19 . The method of claim 13 , wherein the data represen
prises one or more of an electrocardiography signal and an 30 tative of the first signal comprises a digital representation of
one of an electrocardiography signal, an impedance signal ,
impedance signal.
10 . The system of claim 1 , wherein the data representative an optical signal, an acoustic signal, and an accelerometer
of the first signal comprises a digital representation of one ofF signal.
20 . The method of claim 13 , wherein the data represen
an electrocardiography signal , an impedance signal, an stative
acoustic signal, an optical signal, and an accelerometer 35 !ing to of the first signal comprises a time stamp correspond
a fiducial point within one of an electrocardiography
signal.
11 . The system of claim 1,wherein the data representative signal
signal
, an impedance signal , an optical signal, an acoustic
, and an accelerometer signal.
of the first signal comprises a time stamp corresponding to
a fiducial point within one of an electrocardiography signali , n dynamic system
21 . A
status
for use in assessment of a patient's hemo
comprising :
an impedance signal, an optical signal, an acoustic signal, 40 dyn
and an accelerometer signal. one or more devices comprising:
12 . The system of claim 1, wherein the second signal a pulse generator to generate a pulse in tissue of a
comprises one or more of an impedance signal, an optical patient, and
signal, an acoustic signal, and an accelerometer signal. a sensor to measure a signal from tissue of the patient
13 . A method for use in assessing a patient's hemody - 45 from a different location along a circulatory path
namic status comprising : from the patient's heart than the pulse generator,
periodically measuring a first signal from tissue of a wherein the one or more devices are configured to
patient and a second signal from tissue of the patient in periodically deliver a pulse and measure the signal
a different location along a circulatory path from the over a monitoring time period ; and
patient ' s heart than where the first signal is measured 50 an external monitoring device wirelessly operatively
over a monitoring time period ; coupled to the one or more devices and configured to :
receiving data representative of the first and second receive a time stamp corresponding to the delivery of
signals ; the pulse and data representative of the signal from
determining a pulse transit time based on the data repre the one or more devices ;
sentative of the first and second signals for each mea - 55 determine a pulse transit time based on the time stamp
surement of the first and second signals resulting in a and the data representative of the signal for each
plurality of pulse transit times for the monitoring time pulse delivery and measurement of the signal result
period ; and ing in a plurality of pulse transit times for the
determining a hemodynamic status value based on the monitoring time period; and
plurality of pulse transit times representative of the 60 determine a surrogate hemodynamic status value based
patient's aggregate hemodynamic status for the moni on the plurality of pulse transit times representative
toring time period . of the patient's hemodynamic status for the moni
14 . The method of claim 13 , wherein the monitoring time toring time period.
period is greater than or equal to 1 hour.

United States Patent: (10) Patent No .: US 10, 182, 729 B2

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United States Patent: (10) Patent No .: US 10, 182, 729 B2

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US010182729B2

(12) United States Patent ( 10) Patent No.: US 10 ,182,729 B2

(51) Int . Cl.

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Systolic Pressure (mmHg )

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