Bioimpedance

for detection

of heart ischemia (infarction).

Andres Kink

Energy

as product of low temperature burning of food products inside the body

To maintain life, every living animal organism must have additionalenergy inflow of food and oxygen.

To save excess of food for future is possible due to intracellular systems.

But this is not possible for oxygen. Oxygen is gaseous and to accumulate it inside the body in reasonable quantity will take to much energy.

Here we will focus on energy as energy units (joule) or as units of used oxygen to get energy.

Oxygen and food substrate delivery system for cells

Most of animals (not included fish) have specialized oxygen carrying system to maintain body tissues oxygenation.

Blood as solute to carry oxygen

Lungs as barrier between atmosphere and blood.

Circulation system as tubing system to carry oxygen rich blood to every cell in body and to collect waste from it.

Cellular system to produce ATP from energetic substances and oxygen.

Ischemia definition

Myocardial ischemia is an imbalance between myocardial oxygen supply and demand.

A decrease in the blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of the blood vessels.

A narrowing of the coronary artery(s) sufficiently to prevent adequate blood supply to the myocardium (ischemia). This narrowing may progress to a point where heart muscle is damaged (infarction).

MYOCARDIAL ISCHEMIA

TRANSIEN TREVERSIBLE

DYSFUNCTIO N O F SUBCELLULAR M ECHANISM SNO PERM ANENT STRUCTURAL DAM AG E

PERM ANENT STRU CTURAL DAM AG E

G LO BAL M YO CARDIAL ISCHEM IA

Ishemia as energy imbalance

Energy imbalance is result of non-equal oxygen supply related to oxygen consumption.

Ischemia with myocardial cell damage is often described in heart as myocardial infarction.

Myocardial infarction is not reversible process, cell necrosis is healed by scar formation.

Short time myocardial ischemia is not dangerous, because myocardial has limited protection against lack of oxygen.

Epidemiology

Heart ischemic conditions are most leading reason for mortality in world.

Silent myocardial ischemia is dangerous condition witch leads very offen to myocardial infarction (muscle tissue necrosis)

Ischaemic heart disease world mapDALY - WHO 2004

Epidemiology (cont.)

Heart anatomy

Cardiovascular system, coronary circulation

Coronary artery physiology

Coronary artery disease

Coronary reserve

Special Features of Coronary Circulation

At rest, Coronary BF = 5% of CO = 250ml/min = 60-80ml/100gm/min

During exercise ↑ by 2-5 times (coronary vasculature has a high vasodilator reserve capacity)

Coronary Blood Flow is phasic

Total Coronary flow is greater during diastole

Therefore, the most crucial factors for perfusing coronary arteries are

aortic pressure

duration of diastole

Myocardial O2 Demand

The cardiac muscle always depends on aerobic oxydation of substrates even during heavy exercise

The cardiac muscle has the highest O2 uptake (VO2) compared to other tissues of the body (12-15 volume%; 7 - 9 ml O2/100gm/min)

This is achieved by a dense network of capillaries, all is perfused at rest (no capillary reserve)

Maximal extraction of O2 from RBCs (almost no O2 extraction reserve)

Pressure volume area inside of ventricles (left ventricle)

Cardiac cycle and

pressure-volume area

Cardiac Output (CO) determined thru

Heart Rate (HR) and Stroke Volume (SV)

Frank Starling Curves Ability of the heart to change force of contraction

in response to changes in venous return

If EDV increases, there is a corresponding increase in stroke volume, suggesting heart failure and inotropy

Reduced stroke volume suggests increased preload and decreased ejection fraction

Cardiac Output

Cardiac Output is the volume of blood (in liters) ejected by the heart in one minute

Stroke Volume is the volume of blood (in liters) ejected by the heart in one beat

When the body is under stress (physical, emotional), the heart tries to increase cardiac output … by increasing the rate according to this formula

Cardiac Output = Heart Rate x Stroke Volumeor

CO = HR x SV

Bradycardia or “low heart rate”

Artifical heart assisting devices

The first artificial pacemaker to maintain heart rhythm was induced by Steiner from Germany to avoid cardiac arrest as a side effect of chloroform.Steiner's study (1871) was performed in chloroform arrested hearts of horses, donkey, dogs, cats and rabbits.

In the next year same method was used in humans by Green in United Kingdom.

First pacemakers had interrupted galvanic (direct-current) stimuli and connected by 13 cm long needles directly to myocardium.

Modern era of implantable pacemakers

The first implanteble pacemaker was made by Swedish inventor Dr. Rune Elmqvist, and was implanted in 1958 by Dr. Ake Senning.

The first demand pacemaker was introduced by Berkovits in June 1964.

The demand pacemaker has additional sensing unit to avoid competition with heart’s own pacemaker (sinus node), and to save battery energy.

Pacemakers

Sensory systems

ECG based interval measurements Movement analysis (acceleration, ..) Temperature measurement Impedance based

Lung impedance Intraventricular impedance, mostly right

ventricle Myocardial impedance

Rate adaptive pacing

Heart rate is regulated to maintain body energetic needs

In the first generation pacemakers the target was simple - reduction of heart rate in night time

The pacemakers of new generation are multisensor based (accelometer, ECG, temperature, bioimpedance based, …) to achieve optimal heart rate calculation

Why Rate Response?

Rate response is the pacemaker’s ability to increase the pacing rate in response to physical activity or metabolic demand

Rate response mimics the healthy heart

Special sensor(s) required Accelerometer Piezoelectric crystal Minute ventilation (transthoracic impedance) Blood temperature Single or combination

Intracardiac bioimpedance measurement

Normal Chronotropic Response

Chronotropic Incompetence

If the patient’s heart cannot increase its rate appropriately in response to increased activity, the patient is chronotropically incompetent

Chronotropic incompetence definitions: Maximum heart rate < 90% x (220 minus age) Maximum heart rate < 120 bpm

The causes can be Aging Drugs Heart disease

Chronotropic Incompetence (cont.)

Sensors

Rate-responsive pacemakers rely on sensor(s) to detect patient activity

The ideal sensor should be Physiologic Quick to respond Able to increase the rate proportionally to the patient’s need Able to work compatibly with the rest of the pacemaker Able to work well with minimum energy demands

or current drain Easy to program and adjust

Types of Sensors

Activity sensors Vibration sensors (piezoelectric sensors) Accelerometers

Physiologic sensors Minute ventilation Temperature Evoked response QT interval Closed loop system (CLS)

Virtual sensors

Activity Sensor/Vibration

Responds rapidly No special pacing leads required Easy to manufacture and program Can be “fooled” by pressure on the can or footfalls (like walking

downstairs)

Activity/ Accelerometer

Responds rapidly No special pacing leads required Easy to manufacture and program Cannot be “fooled” by pressure on the can

Minute Ventilation

Minute Ventilation

Uses low-level electrical signals to measure resistance across the chest (“transthoracic impedance”)

Requires no special sensorRequires bipolar pacing leadsMetabolic

Temperature

A thermistor is mounted in the lead (not the can)Requires a special pacing leadMetabolicResponse time can be slow

Evoked ResponseMeasures the QRS depolarization area

Theory:

the QRS depolarization decreases in area with exercise

Requires no special leadsMay be affected by changes in postureOnly works when the device is pacing

QT Interval

Measures the interval between the pacing spike and the evoked T-wave

Theory:

This interval shortens with exercise

No special pacing lead is required Works only when the device is pacing

Rate-Responsive Parameters to Program

Base rateMaximum tracking rate (in DDDR devices)Maximum sensor rateThresholdSlopeReaction timeRecovery time

Rate-Responsive Pacing

Threshold

Threshold is the amount of activity needed to cause sensor activity

Can also be set to AUTO Measures variations in the last 18 hours of

activity Adjusts threshold automatically Displays Measured Average Sensor value

when pacemaker is interrogated Offset values can be programmed for more

fine-tuning

Threshold in Action

Threshold Programming Considerations

AUTO allows the pacemaker to automatically adjust to the patient’s changing activity levels Updates every 18 hours

AUTO with Offset can further fine-tune the settings A negative value makes it more sensitive (less activity is

needed to start rate response) A positive value makes it less sensitive (more activity is

needed to start rate response)Considerations

Patient age, lifestyle, everyday activities Patient’s fitness level (how likely is he to go jogging?) How well patient tolerates higher-rate pacing

Slope

Slope describes the sensor-drive pacing rate for a given level of activity

AutoSlope Based on recent activity levels

Slope in Action

Slope Programming Considerations

Slope determines “how much” rate response is given for a specific activity

Slope factors: The patient’s age, activities, lifestyle How well he can tolerate rapidly paced

activity How much rate response he needs

Reaction Time

When the sensor determines the patient needs rate response, the Reaction Time parameter regulates how quickly rate response is delivered

Programmable to: Fast, Medium, SlowConsider the patient’s age, lifestyle, activities,

and how quickly he would need rate response Athletic patients probably need a faster

reaction time than couch potatoes Younger, fitter patients probably need a faster

reaction time than older, sedentary patients

Reaction Time in Action

Recovery Time

Recovery time determines the minimum time it will take the sensor-driven rate at the maximum sensor rate to go back down to the programmed based rate

Similar to Reaction TimeProgrammable as Fast, Medium, Slow, and Very SlowProgramming considerations are the usual:

Patient age, lifestyle, activity levels Tolerance of rate transitions (can he tolerate

a rapid change in rate?)

Recovery Time in Action

Maximum Sensor Rate

Maximum Sensor Rate is the fastest possible rate the pacemaker will pace in response to sensor input

It does not have to be the same setting as Maximum Tracking Rate (fastest rate the pacemaker will pace the ventricle in response to sensed atrial activity)

The Maximum Sensor Rate must be a rate that the patient can tolerate Maximum heart rate formula (220-age) x .90 is highest

possible setting But if patient cannot tolerate the maximum heart rate,

set the Maximum Sensor Rate to a rate he can tolerate

Threshold

Threshold defines how much activity must occur before the sensor “sees” activity

Most patients do well with AUTOIf AUTO needs some further adjustment, use

the offset feature If sensor seems to react too often or too quickly,

program a positive offset If sensor does not seem to react soon enough or at all,

program a negative offset

Reaction and Recovery Times

Reaction time determines how fast rate response goes to work If the patient does not tolerate abrupt changes in

rate, program this to SLOWRecovery time determines how quickly a sensor-

driven rate goes back to the base rate MEDIUM is a good setting for most patients SLOW can expose the patient to prolonged

periods of pacing at a higher-than-necessary rate

Slope

Slope is “how much” rate response a patient receives once the sensor determines rate response is needed

AUTO is a good middle-of-the-road choice

Problem

How to control the pacing rate avoiding imbalance between energy consumption and energy supply of the myocardium, estimating:

minute volume (MV) of ventilation

relative stroke volume (SV)

diastolic time (tdiast)

AVOID ISCEMIA, NOT TO MEASURE IT !

Cardiovascular System with a Rate Adaptive Pacemaker

Measurement of Cardiac (ŻC) and Respiratory (ŻR) Impedances

Possible gates for heart rate control

No gates, fixed heart rate Heart rate (slope control) Ventricular volume, minimal stroke volume to

maintain body needs Energy based control:

ratio of PVA to myocardial perfusion index during cardiac cycle

Control system

Optimal v. min-max rate control

Optimal heart rate Mostly technical, not from

real heart physiology Underestimates heart rate

variability importance

Min-max rate gateso Allows to act as supervisory

system for other control algorithms

o Possibility to increase patient cardiovascular system adaptation

Energy Balance

kAVDVE mc

diastmc tR

PV

SVPWE

myocardial myocardial blood volumeblood volume

oxygen uptake oxygen uptake (art(artererio-venous io-venous

differdiffereence)nce)

energetical energetical coefficientcoefficient

(balance)(balance)

hydraulic coronary resistance hydraulic coronary resistance (energy balance(energy balance))

SV

tkAVDR diast

Simplified Calculations

Simplified Calculations (cont.)

kSV

kSV

AVDt

AVDt

R

RCRR

restdiast

restrestdiastrest

,

CRSV

SV

t

t

restdiast

restdiast ,

6to2max CRRR

RCR

min

rest

coronary resistance ratiocoronary resistance ratio

coronary reservecoronary reserve healthy hearthealthy heartarteriosclerosisarteriosclerosis

the condition for the condition for mymyoocardium’s energy cardium’s energy balancebalance

Volume Measurement - Theory

Gmeas = Gblood + Gp

Gp is parallel conductance of muscle and must be removed to estimate volume

Hypertonic saline bolus injection

Conductance signal increases

Gb-ED & Gb-ES both increase

Conductivity of blood changes but not the conductivity of the muscle

Experimental setup with an isolated pig’s heart

“ISHEMIA” data processing

Ischemic damage of myocardial cells

ECGEasy to measure,

Lots of data

SV, coronary perfusionDifficult to measureSmall pieces of data

INFORMATION:LIVE/DEAD

Rhythm type

Diff. to get prognosis

INFORMATION:Pump function

Ischemic status of cells

Easy to get prognosis

Conclusions

Rate response is almost a “standard feature” today

Pacemaker patients often suffer from at least a degree of chronotropic incompetence Many who are not chronotropically incompetent now

will become chronotropically incompetent with disease progression

There is no “perfect” sensor

Gate based control is important to avoid “overpacing”

Conclusions (cont.)

Our experimental studies and theoretical speculations confirm that: Increased concern over maintenance

of energy balance within the heart may be addressed by novel pacing control algorithms that require only relative stroke volume information, derivable from bioimpedance measurements.

New impedance measurement methods can permit more reliable results to make such feedback systems feasible for rate control.