certain embodiments as disclosed herein provide for a method and system for automatic determination of hemodynamically desirable cardiac pacing parameter values . embodiments are employed , for example , but not limited to , in a pacing system analyzer ( psa ) or external cardiac pulse generator ( temporary cardiac pacemaker ). after reading this description it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications . however , although various embodiments of the present invention will be described herein , it is understood that these embodiments are presented by way of example only , and not limitation . fig1 shows a patient 10 and his stylized heart containing four chambers : right atrium 12 , right ventricle 14 , left atrium 16 and left ventricle 18 . in the preferred embodiment shown , surface ecg - type electrodes as part of an electrode array are attached to the patient &# 39 ; s right side of neck and the left side of lower thorax . the outer surface electrodes 20 , 22 are connected to the alternating current ( ac ) source 122 of the heart monitor 120 , which is part of the optimization apparatus 100 . the inner surface electrodes 24 , 26 are connected to the voltmeter 124 of the heart monitor 120 . the heart monitor 120 determines from the ratio of the ac applied by 122 and the voltage measured by 124 the thoracic electrical bioimpedance . alternatively , the heart monitor 120 determines from the reciprocal ratio of the ac applied by 122 and the voltage measured by 124 the thoracic electrical bioadmittance . this method is described in the above - mentioned osypka ep application no . 02007310 . 2 which is herein incorporated by reference , which describes how the continuous measurement of thoracic electrical bioimpedance is used to determine stroke volume and cardiac output . alternatively , the thoracic electrical bioimpedance ( or bioadmittance ) can be measured using different electrode configurations , including a second electrode array , and electrodes located on an esophageal catheter / probe , all described in osypka ep application no . 02007310 . 2 . furthermore , a cardiac pacemaker 130 integrated into 100 is connected to at least two heart chambers of right atrium ( ra ) 12 , right ventricle ( rv ) 14 , left atrium ( la ) 16 and left ventricle ( lv ) 18 . in the event the optimization apparatus 100 is used for pacing system analysis , the connection of the heart chambers and the apparatus is accomplished by permanent pacing leads ( indicated by the dashed part of the connection 30 to the right atrium 12 , the dashed part of the connection 32 to the right ventricle 14 , the dashed part of the connection 34 to the left atrium 16 , and the dashed part of the connection 36 to the left ventricle 18 ), all of which are later connected to an implantable pacemaker , and extension cables ( indicated by the solid part of the connection 30 to the right atrium 12 , the solid part of the connection 32 to the right ventricle 14 , the solid part of the connection 34 to the left atrium 16 , and the solid part of the connection 36 to the left ventricle 18 ). the processing unit 110 of the optimization apparatus 100 processes the permutations of the pacing parameter values , i . e . the pacing parameter values applied by cardiac pacemaker 130 , such as heart rate ( pacing or stimulation rate output by the pacemaker ), and atrioventricular ( av ), inter - atrial ( aa ) and inter - ventricular ( also known as bi - ventricular ) ( vv ) delays , and records the corresponding measurements of stroke volume , cardiac output , ejection fraction ( ef ) and other indices of ventricular performance in a data storage module of the processing unit . an input device ( not illustrated ) is connected to the optimization apparatus for operator input of pacing parameters , variation ranges , and variation step widths to define an optimization cycle . according to one embodiment , a specific optimization cycle , triggered by an operator or upon the expiration of a preset time interval , automatically varies one or more pacing parameters , such as av delays , inter - atrial delay , inter - ventricular delay , or heart rate , within operator - defined ranges , and determines at each parameter setting hemodynamic parameters , such as stroke volume ( sv ), cardiac output ( co ), and other indices of ventricular performance . each application of set pacing parameters is applied , for example , but not limited to , for a period in the range of 30 to 120 seconds . the processing unit records the hemodynamic parameters with each permutation of pacing parameter values , and , upon completion of the optimization cycle , indicates the permutation of pacing parameter values leading to optimal stroke volume , cardiac output and other indices of ventricular performance . the results are numerically of graphically shown on a display 140 . in the event the display 140 features a touch screen , patient demographic parameters , such as name , age , and weight , can be entered via the touch screen . alternatively , the optimization apparatus 100 features an interface 150 to a keyboard or a port allowing communication with peripheral devices . typical applications for the aforementioned preferred embodiment are , but not limited to , pacing system analysis ( psa ) with permanent pacing leads connected to the apparatus , temporary pacing ( t . p .) after cardiac surgery using temporary myocardial pacing leads ( heart wires ), and temporary pacing treatment of congestive heart failure ( chf pacing ). fig2 illustrates a second embodiment which employs , for example , but not limited to , in a combination of a permanent cardiac pacemaker and a corresponding external programmer for permanent pacemakers , with or without an pacing system analyzer ( psa ) integrated into the programmer . with regards to temporary pacing , this embodiment is employed , for example , but not limited to , in a combination of a temporary cardiac pulse generator ( temporary cardiac pacemaker ) and a hemodynamic measurement unit interfacing with the pulse generator . fig2 shows the patient 10 after implantation of a permanent cardiac pacemaker 170 . the cardiac pacemaker 170 is connected to at least two heart chambers of right atrium ( ra ) 12 via a permanent pacing lead 172 , right ventricle ( rv ) 14 via a permanent pacing lead 174 , left atrium ( la ) 16 via a permanent pacing lead 176 , and left ventricle ( lv ) 18 via a permanent pacing lead 178 . fig2 shows the connections from the permanent cardiac pacemaker to the heart chambers , i . e . the pacing leads , by dashed lines to indicate that these pacemaker leads are implanted into the patient and , thus , not part of the optimization apparatus . the optimization apparatus 100 incorporates a heart monitor 120 , a display 140 , an interface 150 , all controlled by a control module of processing unit 110 . the optimization apparatus communicates with the permanent cardiac pacemaker through the interface 150 and an external pacemaker telemetry unit 160 , which , for example , is provided by the manufacturer of the permanent cardiac pacemaker 170 . alternatively , the telemetry unit 160 is integrated into the optimization apparatus , which is indicated by the dashed lines 162 extending the apparatus 100 . the communication between the optimization apparatus 100 and the permanent pacemaker 170 is important to synchronize any new permutation of pacing parameter values with the corresponding hemodynamic parameter measurements performed by the optimization apparatus 100 . if no communication can be established , then , at least , the physician programming the cardiac pacemaker 170 and operating the optimization apparatus 100 must know and record the related set pacing and measured hemodynamic parameters . in the embodiment shown , surface ecg - type electrodes as part of an electrode array are attached to the patient &# 39 ; s right side of neck and the left side of lower thorax . the outer surface electrodes 20 , 22 are connected to the alternating current ( ac ) source 122 of the heart monitor 120 , which is part of the optimization apparatus 100 . the inner surface electrodes 24 , 26 are connected to the voltmeter 124 of the heart monitor 120 . the heart monitor 120 determines from the ratio of the ac applied by 122 and the voltage measured by 124 the thoracic electrical bioimpedance . alternatively , the heart monitor 120 determines from the reciprocal ratio of the ac applied by 122 and the voltage measured by 124 the thoracic electrical bioadmittance . the above - mentioned osypka ep application no . 02007310 . 2 , which is herein incorporated by reference , describes how the continuous measurement of thoracic electrical bioimpedance is used to determine stroke volume and cardiac output . alternatively , the thoracic electrical bioimpedance ( or bioadmittance ) can be measured using different electrode configurations , including a second electrode array , and electrodes located on an esophageal catheter / probe , all described in the above - mentioned osypka ep application no . 02007310 . 2 . typical applications for the aforementioned preferred embodiment are , but not limited to , the examination of a pacemaker patient upon a follow - up visit , and hemodynamic optimization during temporary pacing after cardiothoracic surgery . fig3 illustrates a flowchart about the various steps of the optimization process . fig3 illustrates a generalized flowchart about the preparation steps of the optimization cycle , i . e . the process which executes the defined number of permutations of pacing parameter values and leads to a permutation of pacing parameter values providing the patient with maximum stroke volume , cardiac output , and other indices of ventricular performance , or any combination thereof . upon start 300 of the procedure , the patient is at rest . in order to provide immediate pacing therapy , if required , the pacemaker , which mayor may not be an integral part of the optimization apparatus , is connected to the pacing leads . in the event of pacemaker patient follow - up , the pacing leads are already part of the implanted pacemaker system . the cardiac pacemaker is stimulating on demand , or , asynchronously to the heart rhythm , with a fixed pacing rate 302 . the physician decides whether the heart monitor integrated into the optimization apparatus utilizes the transthoracic electrical bioimpedance approach , where the alternating current is applied , and the resulting voltage measured , through surface electrodes 304 . alternatively , in patients who are already intubated , the esophageal approach is utilized , where the alternating current is applied , and the resulting voltage measured , through electrodes located on an esophageal catheteprobe 306 . the operator defines the pacing parameter , namely the heart rate 310 , defines or determines the variation range for the value of the pacing parameter , and the variation step width for stepping through the variation range of the heart rate 310 . for example , the later optimization cycle for the heart rate shall begin with a heart rate of 70 , then increase the heart rate by 5 beats per minute ( variation step width = 5 ), until a heart rate of 80 beats per minute . alternatively , the heart rate can be set to a fixed value , with no range to vary . the operator determines the variation range , and the variation step width , for the atrioventricular ( av ) delay 312 . in this context , with av - delay meant to be the right - sided av - delay , the time delay applied between sensing or stimulation in the right atrium and stimulation in the right ventricle . for example , the later optimization cycle of the optimization cycle shall begin with an av - delay of 150 ms , then increase the av - delay by 50 ms ( variation step width = 50 ms ), until an av - delay of 250 ms is reached . alternatively , the av - delay can be set to a fixed value , with no range to vary . the operator determines the variation range , and the variation step width , for the inter - atrial ( m ) delay 314 . in this context , with m - delay meant to be the time delay applied between sensing or stimulation in the right atrium and stimulation in the left atrium . for example , the later optimization cycle shall begins with an m - delay of 0 ms , then increase the m - delay by 5 ms ( variation step width = 5 ms ), until an m - delay of 10 ms is reached . alternatively , the m - delay can be set to a fixed value , for example to 0 ms , with no range to vary . the operator determines the variation range , and the variation step width , for the left - sided atrioventricular ( lav ) delay 316 . in this context , lav - delay is meant to be the left - sided av - delay , the time delay applied between sensing or stimulation in the left atrium and stimulation in the left ventricle . for example , the later optimization cycle shall begin with an lav - delay of 150 ms , then increase the lav - delay by 50 ms ( variation step width = 50 ms ), until an lav - delay of 250 ms is reached . alternatively , the lav - delay can be set to a fixed value , with no range to vary . the operator determines the variation range , and the variation step width , for the inter - ventricular ( vv ) delay 314 . in this context , with vv - delay meant to be the time delay applied between sensing or stimulation in the right ventricle and stimulation in the left ventricle . for example , the later optimization cycle shall begin with an w - delay of 0 ms , then increase the w - delay by 5 ms ( variation step width = 5 ms ), until a vv - delay of 10 ms is reached . alternatively , the vv - delay can be set to a fixed value , for example to 0 ms , with no range to vary . the operator determines the time interval between a variation of pacing parameter values 320 . upon a new permutation of pacing parameter values applied for therapy , the patient &# 39 ; s hemodynamic response may take several cardiac cycles to establish . consequently , the measurement of hemodynamic parameters immediately after the application of a new permutation of pacing parameter values may not reflect the actual hemodynamic changes induced by the changed pacing therapy . for example , within the later optimization cycle , each permutation of pacing parameters shall be held constant for 30 seconds , and measurements of the first cardiac cycles upon each permutation applied may be ignored . the order of setting the variation ranges and variation step width for heart rate 310 , m - delay 314 , av - delay 316 , vv - delay 318 and time interval 320 is arbitrary and can be changed . when setting the variation ranges and variation step widths , as well as the time interval , the physician must take into account that there is a compromise between wide ranges and close step widths of pacing parameters values , and the time the automatic optimization cycle will take , that is , the time the patient can be exposed to the measurements . upon set pacing parameter variation ranges and variation step widths , an optimization module or optimization means of the optimization apparatus calculates and displays the time required for the automatic optimization cycle or scan 330 . depending on the calculated time and the time restrictions the patient &# 39 ; s state of heath or situation mandates , the physician is able to readjust the previously set ranges and step widths . in the event the time required for the automatic optimization cycle is acceptable , the physician confirms the start of the automatic optimization cycle through the predefined pacing parameter variation ranges with the predefined variation step widths . the optimization apparatus stores the default set of pacing parameters prior to the start of the automatic optimization cycle , which can be reset upon termination of the automatic optimization cycle . upon termination of the optimization cycle 340 , the hemodynamic parameter values obtained are displayed with the corresponding permutations of pacing parameter values . the results are displayed in form of a table , with the permutation of pacing parameter values leading to maximum stroke volume , cardiac output , ejection fraction and other indices of ventricular performance , marked . alternatively , two - or three - dimensional graphs are utilized to display a spectrum of pacing parameter value sets and their therapeutical impact on this particular patient . the physician then has the choice of applying a preferred permutation of pacing parameter values parameter set , or a modification of it , for therapy , or return to the previously used and stored default set of pacing parameter values 350 . during pacing system analysis , any new placement of permanent pacing leads may suggest the execution of a new automatic optimization cycle 360 . the physician has the option to reprogram the previously set pacing parameter value ranges and variation step widths 362 , or initiate a new automatic optimization cycle with the pacing parameter ranges and step widths previously used 364 . alternatively , the pacemaker optimization is ended 370 . fig4 illustrates schematically the sensing and pacing sequence of the avv - mode . fig4 illustrates schematically the four heart chambers , and their respective sensing and pacing channels , right atrium ( ra ) 200 , right ventricle ( rv ) 202 , left atrium ( la ) 204 , and left ventricle ( lv ) 206 , and a preferred operating mode ( avv mode ) of the cardiac pacemaker integrated into the optimization apparatus of fig1 . the pacemaker provides the functions to measure ( sense ) in each heart chamber the intrinsic activity , if extant , and to deliver a pacing stimulus . in this context , the av - delay 210 is the programmed atrioventricular pacing interval , initiated by an atrial stimulus . the m delay 212 is the programmed inter - atrial pacing interval , initiated by an atrial stimulus . the w - delay 214 is the programmed inter - ventricular pacing interval , initiated by a ventricular stimulus . fig4 illustrates the most complex sensing and pacing therapy the avv mode provides . by disabling the pacing and sensing in specific heart chambers , the function of the complex cardiac is reduced to known and established pacing modes . in the event that no left - atrial sensing and stimulation is required , or applicable , the left - atrial channel is disabled . the three heart chambers remaining , and their respective sensing and pacing channels 216 , right atrium ( ra ) 200 , right ventricle ( rv ) 202 , and left ventricle ( lv ) 206 , are of particular interest in pacing therapy addressing congestive heart failure , known as biventricular , or chf , pacing . to our knowledge , the application of a vv - delay , which can assume a positive or negative value , has neither been published nor investigated . upon disabling pacing and sensing in the left ventricle , the two heart chambers remaining , and their respective sensing and pacing channels 218 , right atrium ( ra ) 200 , and right ventricle ( rv ) 202 , are of particular interest in classical physiological pacing therapy , known as dual - chamber , or ddd , pacing . fig5 illustrates schematically the sensing and pacing sequence of the avav - mode . fig5 illustrates schematically the 4 heart chambers , and their respective sensing and pacing channels , right atrium ( ra ) 200 , right ventricle ( rv ) 202 , left atrium ( la ) 204 , and left ventricle ( lv ) 206 , and another preferred operating mode ( avav mode ) of the cardiac pacemaker integrated into the optimization apparatus of fig1 . the pacemaker provides the functions to measure ( sense ) in each heart chamber the intrinsic activity , if extant , and to deliver a pacing stimulus . in this context , the av - delay 210 is the programmed right - sided atrioventricular pacing interval , initiated by an atrial stimulus . the aa delay 212 is the programmed inter - atrial pacing interval , initiated by an atrial stimulus . the lav - delay 220 is the programmed left - sided atrioventricular pacing interval , initiated by a left - atrial stimulus . upon disabling pacing and sensing in the left atrium ( la ) 204 and ventricle ( lv ) 206 , the 2 heart chambers remaining , and their respective sensing and pacing channels 218 , right atrium ( ra ) 200 , and right ventricle ( rv ) 202 , are of particular interest in classical physiological pacing therapy , known as dual - chamber , or ddd , pacing . as indicated above , it is not only the stroke volume ( sv ) that can be used in order to optimize or improve the pacing parameters to be programmed onto the pacemaker . in general , most indices of left - ventricular cardiac performance may be suitable measures for optimization . the optimization apparatus measures in any event the heart rate ( hr ). therefore , cardiac output ( co ), instead of stroke volume ( sv ) may be used for the optimization process : where sv = stroke volume measured in milliliters ( ml ); co = cardiac output measured in liters / minute ; hr = heart rate measured in beats / minute . for the calculation of the stroke volume ( sv ), the following equation of the above - mentioned osypka ep application no . 02007310 . 2 can be used ( but not limited to ): sv = v eff · c 1 (  ( ⅆ z ⁡ ( t ) ⅆ t ) min  z o ) n · ( 1 t rr ) m · t lve or , in a special form with n = m = 0 . 5 and c 1 = 1 : sv = v eff ·  ( ⅆ z ⁡ ( t ) ⅆ t ) min  z o · f tc  ( ⅆ z ⁡ ( t ) ⅆ t ) min  z 0 = maximum ⁢ ⁢ rate ⁢ ⁢ ⁢ of ⁢ ⁢ change ⁢ ⁢ of ⁢ ⁢ impedance ; z 0 = base impedance ; t rr = r − r interval ; t lve = left - ventricular ejection time ; ft c = corrected flow time ; ft c = t lve / t rr v eff is a factor , which is typical for a particular patient , as it is derived , among other factors , from the patient &# 39 ; s weight . v eff is considered quasi - constant , because , according to the afore - mentioned osypka ep application no . 02007310 . 2 , v eff depends also on the basic impedance z 0 . considering the scope of possible applications , which require only several minutes for the optimization process , z 0 varies , if at all , only by a small margin , and has practically no measurable influence on the sv or co measured . if z 0 and , consequently , v eff being constant during the entire application for a particular patient , optimization without compromising accuracy can be achieved without knowledge of the patient &# 39 ; s weight and , thus , v eff . for example , a “ stroke index ” si 1 can be determined : si 1 = (  ( ⅆ z ⁡ ( t ) ⅆ t ) min  z o ) n · ( 1 t rr ) m · t lve with 0 . 15 ≦ n ≦ 0 . 8 and 0 m 1 . 5 according to the aforementioned osypka ep application . a special “ stroke index ” si 1 is determined with n = m = 0 . 5 : the only shortcoming of such processing is that the user does not obtain ( simple ) absolute indication of the range in which patient &# 39 ; s stroke volume is determined while the patient is undergoing the various permutations of pacing parameter values . the user , however , obtains relative values of “ stroke indices ” to compare . with z 0 considered constant , z 0 may be omitted from the equation . the following simplified equation can be used to calculate another form of “ stroke index ” si 2 : a special “ stroke index ” si 2 is determined with n = m = 0 . 5 : a further simplification but compromise in accuracy is to substitute corrected flow time ft c for left - ventricular ejection time ( known also as systolic flow time ) t lve or even fully omit ft c or t lve . accordingly , a “ stroke index ” si 3 is determined : alternatively , a “ stroke index ” si 4 is determined by normalizing stroke volume , cardiac output and the aforementioned “ stroke indices ” are , within their constraints , suitable hemodynamic parameters for determination of the optimal setting of pacing parameters . alternatively , ( left - ventricular ) ejection fraction ( ef ) is an at least as suitable hemodynamic index for pacing parameter optimization . in the above description , stroke volume is calculated based on bioimpedance ( z ). stroke volume ( and the associated stroke indices ) can alternatively be calculated based on bioadmittance ( y ), as described in the above mentioned osypka ep application no . 02007310 . 2 . admittance is related to impedance as follows : y ⁡ ( t ) = 1 z ⁡ ( t ) t 0 = 1 z 0 and ⁢ ( ⅆ y ⁡ ( t ) ⅆ t ) max ≅ 1 z 0 2 ⁢  ( ⅆ z ⁡ ( t ) ⅆ t ) min  the stroke volume equation in the previous paragraph which is based on bioadmittance can be used in exactly the same way as described above for bioimpedance to derive a similar stroke index si y based on bioadmittance : si y = ( ( ⅆ y ⁡ ( t ) ⅆ t ) max y 0 ) n · ( 1 t rr ) m · t lve where 0 . 15 & lt ; n & lt ; 0 . 8 and 0 ≦ m ≦ 1 . 5 . this eliminates the term v eff from the sv equation above , since this term will be constant during an entire application for a particular patient . in view of the above relationship between y 0 and z 0 , v eff is dependent also on the basic admittance . if y 0 and consequently v eff are substantially constant during an entire application for a particular patient , optimization can the achieved without compromising accuracy and without knowledge of a patient &# 39 ; s weight , using the above stroke index equation in which the term v eff is eliminated . a special stroke index is derived from the above equation with n = m = 0 . 5 , as follows : si y ⁢ ⁢ 1 = ( ⅆ y ⁡ ( t ) ⅆ t ) max y 0 · ft c ( a ) if y 0 is considered constant , it can be eliminated from the above equation . the following simplified equation can be used to calculate another form of stroke index , si y2 : si y ⁢ ⁢ 2 = ( ⅆ y ⁡ ( t ) ⅆ t ) max ω · ft c ( b ) in order to produce a further simplification but a compromise in accuracy , the term ft c can be eliminated from either equation a or b above to produce the following alternative stroke indices : the above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention . various modifications to these embodiments will be readily apparent to those skilled in the art , and the generic principles described herein can be applied to other embodiments without departing from the spirit or scope of the invention . thus , it is to be understood that the description and drawings presented herein represent a presently preferred embodiment of the invention and are therefore representative of the subject matter which is broadly contemplated by the present invention . it is further understood that the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and that the scope of the present invention is accordingly limited by nothing other than the appended claims .
for cardiac rhythm management , a combination of cardiac pacing and a noninvasive heart monitoring is proposed for the determination of a set of programmable pacing parameters hemodynamically beneficial to the patient . the apparatus incorporates a cardiac pacemaker and a thoracic electrical bioimpedance heart monitor . this combination allows the creation of a closed - loop system that obtains pacing parameter settings providing hemodynamically beneficial pacing therapy to the patient as determined by measuring and recording of stroke volume , cardiac output , and other indices of ventricular performance by the heart monitor during an optimization cycle automatically employing different permutations of values of pacing parameters such as atrioventricular delays , inter - atrial delay , inter - ventricular delay , or heart rate , that are sequentially programmed to the pacemaker . the hemodynamically beneficial permutation of pacing parameter values is determined from all recordings and programmed to the pacemaker for permanent or temporary pacing therapy .