T6-5 Effect_of_Pacing_Chamber_and_Atrioventricular_Delay_on_Congestive_Heart_Failure
Effect of Pacing Chamber and Atrioventricular Delay on Acute Systolic Function of Paced Patients With
Congestive Heart Failure
Angelo Auricchio,MD,PhD;Christoph Stellbrink,MD;Michael Block,MD;Stefan Sack,MD;
Ju¨rgen Vogt,MD;Patricia Bakker,MD;Helmut Klein,MD;
for the Pacing Therapies for Congestive Heart Failure Study Group;Andrew Kramer,PhD;
Jiang Ding,PhD;Rodney Salo;Bruce Tockman;Thierry Pochet,PhD;Julio Spinelli,PhD;
for the Guidant Congestive Heart Failure Research Group
Background—Previous studies of pacing therapy for dilated congestive heart failure(CHF)have not established the relative importance of pacing site,AV delay,and patient heterogeneity on outcome.These variables were compared by
a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous
ventricular pacing.
Methods and Results—Twenty-seven CHF patients with severe left ventricular(LV)systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle(RV)and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV,aorta,and RV.Patients in normal sinus rhythm were stimulated in the RV,LV,or both ventricles simultaneously(BV)at preselected AV delays in a repeating5-paced/15-nonpaced beat sequence.Maximum LV pressure derivative(LV?dP/dt)and aortic pulse pressure (PP)changed immediately at pacing onset,increasing at a patient-specific optimal AV delay in20patients with wide surface QRS(180?22ms)and decreasing at short AV delays in5patients with narrower QRS(128?12ms) (P?0.0001).Overall,BV and LV pacing increased LV?dP/dt and PP more than RV pacing(P?0.01),whereas LV pacing increased LV?dP/dt more than BV pacing(P?0.01).
Conclusions—In this population,CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing,LV stimulation is required for maximum acute benefit,and the maximum benefit at any site occurs with a patient-specific AV delay.(Circulation.1999;99:2993-3001.)
Key Words:pacingⅢheart failureⅢsystoleⅢhemodynamics
T reatment of congestive heart failure(CHF)with electrical stimulation has been proposed as additional therapy to be used in conjunction with pharmacological treatment.1Although early studies reported short-term2or long-term3,4improvement with right ventricular(RV)pacing,subsequent studies did not reproduce these improvements with similar CHF patients.5,6In contrast,a more uniform,beneficial result of pacing has been reported when the left ventricle(LV)has also been stimulated.7,8 The acute hemodynamic effect of atrial-triggered LV and simul-taneous RV and LV(biventricular)pacing at a fixed AV delay of100ms has also been reported.9In addition to issues about the pacing chamber,there is wide speculation regarding the need and method for optimizing the AV delay.2,4,5
The study objective was to investigate the effect of pacing chamber and AV delay with atrial-synchronous ventricular pacing on hemodynamic function in a specific CHF popula-tion consisting of patients in stable New York Heart Associ-ation(NYHA)class III or IV with severe LV systolic dysfunction,wide QRS complex(?120ms),normal sinus rhythm,and no history of arrhythmia.
Methods
Patients
Twenty-seven patients with NYHA class III or IV heart failure were enrolled in a multicenter prospective,randomized,single-blinded crossover study(Pacing Therapies for Congestive Heart Failure
Received October23,1998;revision received March18,1999;accepted March26,1999.
From the Department of Cardiology,University Hospital,Otto-von-Guericke Universita¨t,Magdeburg,Germany(A.A.,H.K.);Department of Cardiology,RWTH University Hospital,Aachen,Germany(C.S.);Department of Cardiology,University Hospital,Mu¨nster,Germany(M.B.); Department of Cardiology,University Hospital,Essen,Germany(S.S.);Department of Cardiology,Herz-und Diabeteszentrum NRW,Bad Oeynhausen, Germany(J.V.);Heart Lung Institute,University Hospital Utrecht,The Netherlands(P.B.);Guidant Corporation,St.Paul,Minn(A.K.,J.D.,R.S.,B.T., J.S.);and Guidant Corporation,Brussels,Belgium(T.P.).
This work was supported by a grant from Guidant Corporation.
Correspondence to Angelo Auricchio,MD,PhD,Department of Cardiology,University Hospital,Leipzigerstra?e44,D-39120Magdeburg,Germany. E-mail angelo.auricchio@medizin.uni-magdeburg.de
?1999American Heart Association,Inc.
Circulation is available at https://www.wendangku.net/doc/a22989954.html,
2993
[PATH-CHF]).The complete PATH-CHF study inclusion and ex-clusion criteria,study design,and end points have been presented elsewhere.10Main inclusion criteria were dilated cardiomyopathy of any origin;stable NYHA class III or IV with optimal medical therapy,including ACE inhibitors,nitrates,vasodilators,diuretics, digitalis,and?-blockers;a surface ECG QRS duration?120ms; and a PR interval?150ms.Main exclusion criteria were recent history of atrial or ventricular tachyarrhythmia;recent myocardial infarction;recent or pending coronary artery revascularization; severe valve disease;dependence on intravenous inotropes;and conventional indications for pacemaker implantation.
The protocol was approved by the ethical committees at all participating centers,as well as by the competent authorities of their respective countries.The study is monitored by a Patient Data/Safety Committee of independent reviewers.All patients provided written informed consent before participating in the study.
Data Collection
Acute data were collected while the patients were under general anesthesia,including fentanyl,propofol,and O2during pacemaker implantation.Chronic pacing leads were implanted with screw-in leads(Sweet-Tip,Guidant Corp)in the right atrial appendage and RV,and an epicardial lead(model4316,Guidant Corp,or model 4965,Medtronic)was attached to the surface of the LV via a limited thoracotomy.The LV pacing site was most commonly on the apex but could also be on midlateral segments.Two8F dual-transducer pressure catheters(model SPC-780c,Millar Instruments)were placed to measure right atrial,RV,aortic,and LV pressures.Pressure catheters and pacing leads were connected to a custom external pacing computer(FlexStim,Guidant Corp)to acquire hemodynamic signals and execute a transient pacing protocol(FlexStim protocol) as previously described.10The FlexStim protocol is designed to measure the immediate effects of pacing,account for local baseline shifts,and allow statistical comparison of multiple pacing combina-tions within individuals.Briefly,the RV,LV,or both ventricles(BV) were stimulated in a VDD mode(atrial sense followed by ventricular pacing at a predetermined AV delay)at1of5AV delays preset to percentages of the patient’s intrinsic PR interval measured with the pacing leads.Each combination of pacing chamber and AV delay was randomly repeated5times by pacing for5beats separated by15 nonpaced beats.
Raw data were recorded on a digital tape recorder with16-bit resolution at a12000-Hz sampling rate and then downsampled to 500Hz for offline analysis.The following measurements were made automatically with custom software:aortic diastolic pressure,aortic systolic pressure(ASP),pulse pressure(PP?ASP?aortic diastolic
TABLE1.Demographic and Baseline Hemodynamic Data for the Study Population
Patient Sex Age,
y Etiology
NYHA
Class
EF,
%
V O2max,
mL?min?1?kg?1
PR,
ms
QRS,
ms IVCD
LV?dP/dt,
mm Hg/s
ASP,
mm Hg
PP,
mm Hg
1F62CAD422NA173160LBB?LAH NA NA NA 2M54ID32220.3240200LBB?LAH5229136 3F59ID 3.52910.5165160LBB6828428 4F63ID3237.4200220LBB4138240 5M62ID31511.8300190LBB?LAH4329325 6M60ID 3.5189.7210160LBB3607817 7M66CAD 3.51611.0250180LBB4477527 8M61ID 3.51710.5210160LBB89011632 9F66CAD3198.8180140LBB?LAH7098846 10F61ID31610.5165140LBB6158234 11F70ID31511.1250200LBB?LAH3776729 12M64ID32819.0220200LBB4749737 13M67CAD33110.1240120Diffuse7869248 14F51ID3159.3225120Diffuse4847621 15M48ID320NA180160LBB3316624 16M64ID327NA250190LBB?LAH5589124 17M64CAD31513.9218148LBB97513066 18F70ID41116.2200200LBB5149737 19M63ID32913.3270130Diffuse6057529 20F73ID31916.2180170LBB46910931 21M55ID3129.5160200LBB3186820 22F75CAD3328.6184140LBB NA NA NA 23M63ID32514.3260200LBB5979629 24F62ID32715.8160180LBB?LAH76611656 25F62CAD3148.3200120Diffuse96311049 26M60CAD31812.2180160LBB5247725 27M63CAD323 6.9220180LBB6429422 Mean62 3.22111.92111685789033 SD60.36 3.637291871612 EF indicates ejection fraction;IVCD,intraventricular conduction disturbance;CAD,coronary artery disease;LBB,left bundle-branch block;LAH,left anterior hemiblock;NA,data not available;and ID,idiopathic dilated cardiomyopathy.
2994Pacing Parameters for Congestive Heart Failure
pressure),LV pressure-derivative maximum (LV ?dP/dt)and mini-mum (LV ?dP/dt)by the method of Kass et al,11LV end-diastolic pressure (LV EDP),RV maximum pressure derivative (RV ?dP/dt),and RV systolic pressure.LV EDP was measured at the time when dP/dt reached 10%of the maximum.Reported QRS durations are the maximum of leads II,V 1,and V 6measured automatically and validated manually by 2independent observers.
Statistics
Parameters were calculated for each beat of a pacing sequence as a percentage change from their average value during the immediately preceding 6nonpaced beats (ie,local baseline).The first paced beat was always discarded,because its hemodynamic effects were systematically biased by the diastolic behavior of a preceding nonpaced beat and a transitory cycle length decrease caused by the switch to a short AV delay.In addition,beats altered by a premature ventricular complex were discarded.A 3-way ANOVA was applied to individual results to analyze differences between AV delays and pacing chambers while
accounting for the ordered pacing beat number and interaction between the main effects.The AV delay and pacing chamber were considered the treatment variables and the beat number was considered a blocking factor when ANOVA results were reported.A similar 2-way ANOVA was applied to individual results at a selected optimal AV delay for each pacing chamber.We used corresponding 4-way and 3-way ANOVA tests to analyze group results by adding individuals as a treatment variable.Tukey methodology was used to evaluate multi-ple comparisons of the main effects in the full ANOVA models.A paired t test was used to evaluate the effects of pacing compared with no pacing.A P value of 0.0001was considered statistically signifi-cant for ANOVA tests.A P value of 0.05was considered statistically significant before Tukey corrections for individual results,whereas a more stringent P value of 0.01was selected for group results owing to the larger number of sample points.Similarly,P values of 0.001for individual results and 0.0001for group results were considered statistically significant for the t tests.Average data are shown as mean ?SD unless otherwise
noted.
Figure 1.Simultaneous recording of LV pressure waveforms and electrogram during a transient LV pacing sequence in VDD mode.Immediate changes of LV pressure,LV positive dP/dt,and aortic pressure occur when pacing starts (indicated by larger potentials in electrogram);all changes are reversed within a few beats when pacing
stops.
Figure 2.Hemodynamic impulse response plots from 1individual showing immediate percentage change of LV ?dP/dt (left)and aortic PP (right)from baseline.Separate plots are shown for each pacing chamber (RV,LV,and BV)when pacing at the same AV delay.First beat number is ?rst paced beat of a sequence;sixth beat number is ?rst nonpaced beat.
Auricchio et al June 15,19992995
Results
Table1summarizes demographic and baseline hemodynamic data for the27patients enrolled in the study.Two patients (patients1and22)were excluded from further analysis because LV and aortic pressure could not be recorded.All patients were able to tolerate the acute procedure without major complications.
Hemodynamic Impulse Response
Hemodynamic parameter changes during the brief pacing periods of the FlexStim protocol appeared immediately at pacing onset and diminished rapidly during the subsequent nonpacing period(Figure1).This was quantified with im-pulse response plots,which showed the average parameter measurement over all repetitions of a pacing combination in a patient on5paced beats and during the15nonpaced beats that followed pacing(Figure2).Typically for LV?dP/dt and PP parameters,changes from baseline occurred on the first paced beat,reached a maximum change during the next4 paced beats,and then returned to baseline levels within5 nonpaced beats.For all patients,recovery occurred within10 nonpaced beats for every pacing chamber and AV delay combination.The paced-beat number had a statistical effect on parameter variation for most patients even when the first pace was discarded(ANOVA,P?0.0001).
Effects of Pacing Chamber
The statistical significance of the change in LV systolic parameters averaged over all AV delays for each pacing chamber is shown in Table2for each patient.For the population average,pacing in any chamber significantly increased LV?dP/dt(P?0.0001),whereas BV and LV pac-ing significantly increased ASP and PP(P?0.0001).The selection of pacing chamber was a significant determinant of
TABLE2.Percentage Changes in Systolic Parameters When Pacing in Different Chambers Over All AV Delays
Patient Type
LV?dP/dt ASP Aortic PP
RV LV BV RV LV BV RV LV BV
2I 1.38.2*?8.4*??0.8 1.00.9?1.4 2.1 1.4 3I12.3*16.5*?15.4*? 2.6* 3.2* 3.2*8.08.610.1* 4I 1.4*12.5*??11.6*?0.2 4.8*? 4.4*?0.68.4*?7.7*?5I10.2*18.0*?18.4*? 3.6* 5.1*? 5.7*?7.0*13.1*?13.9*?6I7.4*29.6*??26.3*? 1.1* 3.2*?? 2.5*? 4.9*13.3*??11.6*?7I 3.9*36.7*?35.8*? 3.0*13.0*?13.0*? 6.1*28.3*??27.1*?8I 2.220.8*??17.1*??0.7 1.6??0.6? 1.28.0?? 5.3?9I?0.114.1*?15.4*?§?2.1*?2.9*?0.7?§?4.5*§?5.5*?2.1*?§10I9.6*22.8*?25.7*?§ 1.5 6.4*?7.5*? 3.315.4*?16.8*?11I0.89.8*?10.5*??1.2* 2.0*? 1.6*??2.0 6.5*? 5.3*?12I 3.5*§ 1.9* 4.0*§?1.1?0.80.0??0.6?0.80.8 13II?11.0*?7.9*??6.8*?§?6.6*?5.7*?5.1*??8.2*?7.9*?6.0* 14II?15.1*?13.2*??11.8*?§?3.3*?2.2*??2.3*??6.4*?1.9??2.6?15I20.3*33.1*?33.3*?0.1 1.9*? 1.1? 1.0 6.4*? 6.0*?16I7.623.9*?22.8*? 3.5* 6.9*? 6.1*?15.4*17.1*18.8* 17II?12.4*?7.0*??3.1*?§?5.1*?4.4*??4.6*?9.1*?7.6*??8.2*?18I 2.1*20.6*??18.8*??0.8* 2.2*? 1.6*??0.4 5.3*? 4.2*?19II?9.4*?6.0*??6.4*??3.7*?3.2*?3.6*?6.5*??7.0*?7.8* 20I8.0*32.4*??29.0*? 1.3* 4.6*? 4.3*? 2.612.7*??11.5*?21I9.5*45.7*??42.8*? 2.4*10.7*??9.6*? 6.8*25.7*??22.5*?23I 4.1*27.8*?27.3*?0.7 4.6*? 4.0*? 4.715.5*?13.4*?24I7.1*13.7*??11.8*? 1.3* 3.9*? 3.3*? 2.8*8.7*?7.0*?25II?20.1*?1.9???12.7*??3.7*0.2???1.6*??5.7* 1.8???3.1 26I?1.27.6*?? 2.5*??4.2*?2.3*???3.5*??8.1*?3.8*???7.4*?27I13.1*28.0*?28.5*? 5.8*8.7*?8.9*?16.7*23.9*?24.5*?
Group I 6.0*21.4*??20.4*?0.7* 3.9*? 3.6*? 3.0*10.4*?9.7*?Group II?13.4*?7.2*???8.2*??4.5*?3.1*??3.4*??7.2*?4.5*??5.5*?Group All 1.9*15.3*??14.4*??0.4 2.4*? 2.2*?0.97.3*? 6.6*?*Not0,paired t test P?0.001(individual),P?0.0001(group).
??RV,Tukey test P?0.05(individual),P?0.01(group).
??BV,Tukey test P?0.05(individual),P?0.01(group).
§?LV,Tukey test P?0.05(individual),P?0.01(group).
2996Pacing Parameters for Congestive Heart Failure
changes in all3LV systolic parameters(ANOVA, P?0.0001).LV?dP/dt,ASP,and PP changes with BV and LV pacing were significantly greater than the effects of RV pacing for the population;and LV pacing effects on LV?dP/dt were greater than the effects of BV pacing (P?0.01).
Population changes in other hemodynamic parameters averaged over all AV delays for each pacing chamber are shown in Table3.Changes to parameters that partially reflect LV diastolic performance were statistically significant but small and inconsistent.The LV EDP decreased,indicating lowered filling pressures,but the absolute value of LV–dP/dt also decreased,indicating slower relaxation.Average changes in RV systolic parameters were also relatively small and inconsistent.
Interpatient Variability of Pacing Chamber Effects With the FlexStim protocol,the effects of pacing were statisti-cally established for each individual(Table2).Most but not all patients had statistical improvement in short-term hemodynamic function with pacing at some site(P?0.001):RV,LV,or BV pacing significantly increased both LV?dP/dt and PP in15 patients(60%),increased only LV?dP/dt in5patients(20%), and did not increase LV?dP/dt or PP in5patients(20%). Patients in this last group had significantly shorter QRS widths from surface ECG compared with other patients(180?22versus 128?12ms;t test,P?0.0001)and had less incidence of left bundle-branch block(20of20patients versus1of5patients;?2, P?0.0001)but were not statistically different for other demo-graphic measures.Patients in this last group were retrospectively classified as type II,whereas all other patients were classified as type I.As shown in Figure3,all type I patients had significant improvement in LV?dP/dt or PP with pacing in the optimal chamber,and all but2of them had a surface QRS width?150 ms,whereas none of the type II patients had improvement in LV?dP/dt or PP,and all of them had a QRS width?150ms. When patients were divided into type I and type II subgroups, RV-paced changes in ASP and PP reached significant levels for each subgroup(Table2).The statistical differences among pacing chambers were similar for the type I and type II subgroups,although parameter responses were in opposite directions.
Effects of AV Delay
For all patients combined and for type I and type II sub-groups,AV delay was a significant determinant of changes in all LV systolic parameters(ANOVA,P?0.0001).Figure4 shows the paced change in systolic parameters as a function of AV delay for the patient subgroups.For type I patients, LV?dP/dt and PP AV delay functions were positive and unimodal,with a peak at the middle AV delay setting [0.5?(PR–30ms)].For type II patients,AV delay functions were negative for all parameters.For both type I and type
II Figure3.Association of QRS width of each patient and their acute hemodynamic response to pacing in the optimal chamber averaged over5AV delays ranging from0to PR–30ms(from Table2).Patients for whom LV?dP/dt or PP were not increased with optimal chamber pacing were designated type II;all others were designated type I.Left,Association of QRS and percentage change in
LV?dP/dt.Right,Association of QRS and percentage change in PP.
TABLE3.Population Mean(?SD)Percentage Changes in LV Diastolic and RV
Parameters When Pacing in Different Chambers Over All AV Delays
Parameter Baseline RV LV BV
LV EDP18?9mm Hg?7.0?20.5*??7.6?19.8*??9.5?20.4*
LV?dP/dt?637?149mm Hg/s?4.9?10.0*?2.4?12.2*??0.8?12.3?§
RVSP37?20mm Hg?2.6?8.2*?0.6?12.4???2.5?9.8*
RV?dP/dt339?232mm Hg/s0.6?22.60.4?22.6 3.1?26.0*?§
RVSP indicates RV systolic pressure.
*Not0,paired t test P?0.0001.
??RV,Tukey test P?0.01.
??BV,Tukey test P?0.01.
§?LV,Tukey test P?0.01.
Auricchio et al June15,19992997
patients,there was significant interaction between AV delay and pacing chamber (ANOVA chamber/AV delay interac-tion,P ?0.0001).
Interpatient Variability of AV Delay Effects
The detailed relationship between AV delay and LV ?dP/dt or PP varied among individuals (ANOVA chamber/patient and AV delay/patient interactions,P ?0.0001).One way to measure these differences is to compare the peaks of the AV delay functions for each patient,defined as the optimal AV delays.The optimal AV delays for the same pacing chamber and parameter varied widely among patients and often dif-fered for PP and LV ?dP/dt within an individual (examples in Figures 5and 6).On average (Table 4),the optimal AV delays were similar among pacing chambers for peak ASP and PP,but for the type I patients,they were significantly shorter for RV pacing and BV pacing compared with LV pacing for LV ?dP/dt (paired t test,RV ?LV P ?0.008,BV ?LV P ?0.04).The optimal acute benefit attained for each patient group and pacing chamber is shown in Table 5.Statistical results at the optimal AV delays were similar to those over all AV delays (Table 2),except for type II patients,whose optima were near baseline at the longest AV delays.
Discussion
The major finding of this study is that the acute LV systolic function of patients with moderate to severe CHF,LV systolic dysfunction,and prolonged ventricular activation is significantly and consistently improved by ventricular pacing at an optimal combination of AV delay and site,while LV
diastolic and RV systolic parameter changes are relatively small and inconsistent.Patients with QRS ?150ms exhibit large positive LV systolic changes with pacing,whereas patients with QRS ?150ms exhibit predominantly negative LV systolic changes.However,even for these latter patients,LV systolic function could be optimized by individualized selection of AV delay and pacing chamber.In this patient population,which is dominated by LV conduction disorders,LV stimulation alone or in combination with RV stimulation substantially increases LV systolic benefits compared with RV stimulation alone.
Hemodynamic Impulse Response
We found that systolic parameters changed immediately with the onset and cessation of pacing,which confirms an obser-vation made by Blanc et al,9who also showed these changes persist after several minutes of steady-state pacing.Others have shown similar increases in PP 12and LV ?dP/dt 13in CHF patients with steady-state VDD pacing.Furthermore,PP and stroke volume changes were associated with steady-state pacing in a study of CHF patients 13and have been shown to be proportional in animal studies with the FlexStim proto-col.14Thus,the effects of transient and steady-state ventric-ular stimulation appear to be qualitatively similar and prob-ably arise from the same mechanism,which we surmise is a direct change of the ventricular electromechanical activation patterns.Under the conditions of our study (patients under general anesthesia and only transient pacing),the compensa-tory reflex response to stimulation should be small,certainly less than for steady-state stimulation of unsedated
patients,
Figure 4.Average percentage change in systolic parameters as a function of 5normalized AV delays for each pacing chamber (RV,LV,and BV)in type I (top)and type II (bottom)patient groups.Tested AV delays were normalized to the patient’s PR interval minus 30ms.Data points are shown with SE bars.Solid points are signi?cantly different from 0(paired t test,P ?0.0001).Left,Changes in LV ?dP/dt.Middle,Changes in aortic systolic pressure.Right,Changes in aortic PP.
2998Pacing Parameters for Congestive Heart Failure
and therefore the measured effects of ventricular stimulation would tend to be larger and reflect mainly the direct mechanisms.
Pacing Mechanisms
A number of potential mechanisms to explain the positive effects of pacing in CHF patients have been discussed previously.12These mechanisms primarily involve correcting abnormal electrical conduction 15that presumably generates mechanical dysfunction.CHF patients exhibit abnormally short or long left-side mechanical AV delays outside the normal range of 180to 250ms,12resulting in increased mitral regurgitation and reduced effective preload.Similar to our findings,Nishimura et al 16and Auricchio and Salo 12showed that an appropriate AV delay is required to maximize cardiac output in CHF patients.They suggest the optimal AV delay may normalize the mechanical timing between left atrium and LV,thus reducing regurgitation and maximizing effective preload.Our observation that paced changes in PP are a positive unimodal function of AV delay is consistent with this mechanism.
CHF patients also have relatively uncoordinated contrac-tion patterns in the LV,17which could impair systolic func-tion.BV pacing may improve systolic function in the short term by altering the segmental LV and interventricular septal contractile sequence in patients with depressed LV function,18which would be expected to correlate with increased LV ?dP/dt,a global measure of systolic pump performance.
There is a close relationship between abnormal contraction patterns and electrical activation disturbances,such as a wide QRS complex.19This relationship may explain why a suffi-ciently wide QRS and left bundle-branch block tend to predict short-term pacing benefit.Patients may not benefit from pacing unless the conduction disorder and underlying ventricular incoordination are suitably abnormal.It may also explain why stimulation that includes the LV is far better than RV-only stimulation in a population with a high incidence of LV conduction disorders.It is our hypothesis that atrial-synchronous pacing that preexcites the ventricular wall ipsi-lateral to the conduction disorder restores a more normal activation pattern,thus coordinating wall motion and increas-ing pumping effectiveness.
Clinical Implications
Because CHF patients have heterogeneous symptoms,etiol-ogies,and substrates,and pacing may operate through mul-tiple mechanisms requiring individual optimization,it should not be surprising that the previously reported clinical benefit of pacing is ambiguous.Our results show that both positive and negative effects of pacing occur,at least in the short term.The outcome depends on pacing parameters and individual variables.The most important pacing parameter is pacing chamber,but AV delay significantly modulates the result.The most important variable for predicting acute pacing benefit in the present study was QRS width.If the distinction between type I and type II patients also applies to long-term pacing benefit,studies including a mixture of such
patients
Figure 5.Percentage change in systolic parameters as a function of 5AV delays for each pacing chamber (RV,LV,and BV)in 2type I patients.Top,Patient 18.Bottom,Patient 5.Left,Changes in LV ?dP/dt.Right,Changes in aortic PP.
Auricchio et al June 15,19992999
will necessarily have mixed results.The seemingly contra-dictory results regarding the benefit of RV pacing 3,5,6,20might be explained by the weak and strongly patient-dependent hemodynamic effects of RV pacing and fortuitous differences in clinical patient populations.21On the other hand,the consistently reported positive results with LV pacing 7–9,12,13can be understood as a consequence of the large hemody-namic response to left-sided pacing in a majority of studied patients.Thus,it would seem important to account for these individual variations in future studies of pacing therapy for CHF.Selection of the optimal pacing parameters for an individual patient can minimize the negative effects of pacing on type II patients and maximize the positive effects of pacing on type I patients,with optimized cardiac output increase being 2to 4times more than with suboptimal pacing.
Limitations
This was an acute study performed during surgery on patients under general anesthesia,which can affect preload,afterload,and other hemodynamic variables;results may differ for unsedated patients with chronic pacing.Although this study focused on LV systolic function,the chronic response to pacing may depend also on long-term alterations of diastolic function and RV function,although they changed minimally and inconsistently during the acute protocol.The results may not extrapolate to other CHF populations,particularly those with less severe symptoms,nonsystolic dysfunction,parox-ysmal or chronic atrial fibrillation,sick sinus syndrome or complete AV block,or more severe AV conduction blocks.A limitation of our protocol is that the paced-beat number has a significant effect on the hemodynamic response.The
first
Figure 6.Percentage change in systolic parameters as a function of 5AV delays for each pacing chamber (RV,LV,and BV)in 2type II patients.Top,Patient 17.Bottom,Patient 19.Left,Changes in LV ?dP/dt.Right,Changes in aortic PP.
TABLE 4.
Distribution of Optimal AV Delays (Mean ?SD)
Patient Type Baseline AV Delay?
LV ?dP/dt
ASP Aortic PP RV LV BV RV LV BV RV LV BV I 218?5065?3693?32*?76?2696?33103?41100?3288?3895?3699?33II 230?9200?9179?30189?20180?35171?50190?29200?9171?71200?9All
220?45
92?64
110?47
98?52
113?47
117?50
118?48
110?57
110?53
119?51
*?RV,paired t test P ?0.008.??BV,paired t test P ?0.04.
?Measured from intracardiac electrograms.
3000Pacing Parameters for Congestive Heart Failure
beat in a pacing period was excluded from analysis because of expected effects of the initial AV delay shortening.However, the order effects of subsequent beats were unexpected,and although they were accounted for in the ANOVA statistical analysis,results may differ when such systematic beat-number effects are excluded.As a check of the sensitivity of the results to beat number,statistical analyses were repeated with alternative combinations of paced beats.None of our study conclusions changed for these alternative statistical treatments.
Acknowledgments
This study was supported entirely by Guidant Corporation,St.Paul, Minn,and by an unrestricted grant by Guidant to the Department of Cardiology,University Hospital Magdeburg,Germany.We are indebted to the patients who participated in this trial and to the physicians who referred their patients for study inclusion.The investigators gratefully acknowledge the nurses and colleagues at each institution of the ICU,Heart Failure Program,and Surgery without whose help and logistic support this study would not be possible.Dr Auricchio wishes to thank the CHF Research Group of Guidant for the outstanding technological support,with special thanks to Michael Hull,MS,for excellent statistical assistance.
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TABLE5.Percentage Changes in Systolic Parameters When Pacing at Optimal AV Delay
Patient Type
LV?dP/dt ASP Aortic PP
RV LV BV RV LV BV RV LV BV
I11*29*??27*?3*7*?7*?8*18*?17*?
II11*0000010
All9*23*??22*?2*6*?5*?7*15*?13*?
*Not zero,paired t test P?0.001(individual),P?0.0001(group).
??RV,Tukey test P?0.05(individual),P?0.01(group).
??BV,Tukey test P?0.05(individual),P?0.01(group).
Auricchio et al June15,19993001