Response of the Left Ventricle in Coronary Artery Disease to Postextrasystolic Potentiation By ROBERT
I.
HAMBY, M. D., AGOP AINTABLIAN, M. D., B. GEORGE WISOFF, M.D., AND MARVIN L. HARTSTEIN, M.D.
SUMMARY
Left ventricular volumes and contractile patterns were evaluated during the first sinus beat after a compause resulting from ventricular arrhythmia and were compared to the second sinus beat (control beat) in order to evaluate the effect of postextrasystolic potentiation. Twelve patients had no evidence of heart disease (group I). Fifty patients had coronary artery disease and included 14 patients (group lla) with no prior myocardial infarction and a normal left ventricular contractile pattern and 19 patients (group Ilb) with an abnormal contractile pattern. Seventeen patients (group Ilc) had a documented transmural myocardial infarction as well as an abnormal left ventricular contractile pattern. In all patients the first postextrasystolic sinus beat, when compared to the second sinus beat, demonstrated increases in stroke volume and ejection fraction and decrease in end-systolic volume. There were no qualitative changes in the contractile pattern in the immediate postextrasystolic beat in the patients with normal left ventricular function. In both group lIb and group lIc the changes in end-systolic volume, stroke volume and ejection fraction were significantly greater than observed in groups I and lla. Abnormal wall segments present in the control beat in groups lIb and lIc demonstrated after postextrasystolic potentiation a normal contractile pattern, improved pattern or no change when compared to the control beat. Abnormal wall segments were more likely to revert to normal as a result of postextrasystolic potentiation in group lIb than group lIc. Akinesia was less likely to revert completely to normal than hypokinesia. In 20 of 24 patients the changes in contractile pattern after aortocoronary bypass surgery corresponded to those observed as a result of postextrasystolic pensatory
potentiation.
Additional Indexing Words: Asynergy
Coronary artery surgery
Ejection fraction
Myocardial infarction
Left ventricular function
ABNORMAL CONTRACTION of left ventricular segments is a characteristic finding in patients with coronary artery disease.'`4 Such localized abnormal contractility probably represents the morphologic basis for the disturbed hemodynamics which accompany coronary artery disease. With the introduction of aortocoronary bypass surgery it became relevant to determine whether such disturbances in myocardial wall movement in the individual patient are irreversible. There is some evidence, based on postoperative studies after aortocoronary bypass surgery, that in some patients localized disturbances of wall movement may represent a reversible functional abnormality presumably resulting from chronic ischemia.`8
It has previously been noted that abnormal contractile patterns accompanying chronic ischemia may show evidence of improvement after administration of epinephrine9 and nitroglycerin.'0 The present report describes the effect of postextrasystolic potentiation on left ventricular function in patients with arteriosclerotic heart disease. Evidence will be presented to demonstrate that in many patients the localized disturbance in contraction may be completely reversible and accompanied by improvement in left ventricular function. Furthermore, the changes in wall movement accompanying postextrasystolic potentiation will be compared with the findings observed after aortocoronary bypass surgery. Methods Studies were performed on 62 patients as part of a workup to evaluate recurrent chest pain. Twelve patients (group I) were found to have normal hemodynamics and normal left ventricular angiographic studies by criteria previously reported.'"` The remaining 50 patients (group II), all of whom had angina pectoris, were found to have coronary artery disease on selective coronary angiography and were divided in three groups. Group lla consisted of 14 patients with no prior history of myocardial infarction. The elec-
From the Department of Medicine, Cardiology Division and the Department of Surgery, Cardiovascular Division, Long Island Jewish-Hillside Medical Center, New Hyde Park; Queens Hospital Center Affiliation, Jamaica; and School of Medicine, Health Sciences Center, State University of New York at Stony Brook, New
York. Address for reprints: Robert I. Hamby, M.D., Long Island Jewish-Hillside Medical Center, New Hyde Park, New York 11040. Received August 15, 1974; revision accepted for publication November 7, 1974. 428
Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
LV RESPONSE TO PESP IN CAD trocardiogram on admission revealed no evidence of previous myocardial infarction and left ventricular angiography demonstrated a normal contractile pattern (synergy). Group lIb consisted of 19 patients without prior history of myocardial infarction and whose electrocardiogram on admission did not suggest prior myocardial infarction. However, all patients in group lIb had an abnormal contractile pattern (asynergy) on left ventricular angiographic study. The types of asynergy noted included localized absence of wall movement (akinesia) and diminished localized wall movement (hypokinesia) during systole.9 Group lIc consisted of 17 patients who had a history of prior myocardial infarction documented by abnormal Q waves in the electrocardiogram. The admitting electrocardiogram was diagnostic of an inferior myocardial infarction in nine patients, anterior in six and combined anterior and inferior infarctions in two patients. All 17 patients in group lIc had left ventricular angiograms demonstrating abnormal contractile pattern. Cardiac catheterization was performed in the fasting state and consisted of right and transseptal combined with retrograde left heart catheterization. Pressures were measured in all chambers of the heart and cardiac output was obtained by the direct Fick principle. Left ventricular angiograms were obtained in the right anterior oblique position by injecting 0.50 to 0.75 ml/kg of 90% sodium meglumine diatrizoate over two seconds using a power injector (Viamonte-Hobbs) into the left ventricle through either the transseptal or retrograde catheter. A tracing of lead II of the electrocardiogram was superimposed in the right upper corner of each cine frame (Cinetrace, Electronics for Medicine). Cineangiograms were taken with a 35 mm camera at 60 frames/sec. The X-ray equipment utilized for this study included a dual field 6 inch 3,000 gain, 9 inch 6,000 gain image intensifier (General Electric) with a 35 mm (Photomechanism) synchronous camera utilizing a grid control X-ray tube. When the left ventricular angiogram was completed a grid of known dimension was positioned at the approximate location of the left ventricle and a short film strip taken to permit correction due to magnification. After the completion of the left ventricular angiographic study, selective coronary angiograms were performed. Left ventricular volumes were obtained by the area length method12 and regression equation of Kasser and Kennedy.'3 The cine films were projected with a 35 mm projector (Vanguard Instrument Corp.) on a ground glass screen. The area of the left ventricular cavity was obtained utilizing an electronic digitizer (Graf/Pen, Science Accessories Corp.) interfaced to a digital computer (Hewlett-Packard) for calculating volumes. The left ventricular end-diastolic volume index (EDV) and ejection fraction determined in 20 patients with normal left ventricles using this method were 69 + 19 ml/m' and 0.68 + 10, respectively. All results were expressed as the mean ± one standard deviation of the mean with comparisons between groups determined using unpaired Student's t-test. During selective left ventricular angiography it is common for the injection of contrast material to be accompanied by catheter-induced ventricular ectopic beats. At the completion of the injection of contrast material the ventricular arrhythmia is followed by a compensatory pause and subsequent normal sinus beats."4 In the calculation of ventricular volumes the first sinus beat after the compensatory pause is ignored since it is recognized that the first postextrasystolic sinus beat may have a different volume and ejection fraction compared to subsequent sinus beats. Depend-
429 ing on several factors, including heart rate and the interval separating the ectopic beat from the first normal sinus beat, the postextrasystolic beat may have a larger volume than the second sinus beat." In the present study the injection of contrast material lasted two seconds and was accompanied by one to three ventricular ectopic beats. At the completion of the injection of contrast material there followed a compensatory pause followed by normal sinus rhythm. The first and second beats (2 to 21/2 sec after the beginning of injection of contrast material) after the compensatory pause were utilized to calculate left ventricular volumes. The first sinus beat after the compensatory pause was designated the postextrasystolic beat while the second beat was designated the control beat. The control beat was assumed to represent the normal contractile mechanism and volume for each patient.'4 Patients were selected for this study if ventricular arrhythmia (1 to 3 ventricular ectopic beats) occurred during injection of contrast material, followed by a compensatory pause which was at least one-and-a-half times the R-R interval of subsequent sinus intervals. Furthermore, sufficient contrast material had to remain in the left ventricle after the postextrasystolic beat to permit the determination of the ventricular volumes in the control beat. Ventriculograms were evaluated by the superimposition of the end-diastolic and end-systolic silhouette utilizing the mid-aortic valve and apex as fixed points. Since two consecutive beats (postextrasystolic and control beat) were compared with each other, no attempt was made to correct for rotation of the heart or downward displacement of the base. One transverse hemiaxis was drawn which bisected at right angles the line defining the long axis (mid-aortic-to-apex) of the heart. A normal left ventricular contraction was accompanied by at least a 20% shortening of the long axis and a 50% shortening of the transverse hemiaxis.9 A quantitative comparison between the control beat and the postextrasystolic beat was made on the basis of the percent increase of shortening of the hemiaxis and long axis. Twenty-four patients in groups lIb and lIc were restudied two to four weeks after aortocoronary bypass surgery in the same laboratory utilizing techniques previously described.5 Five of these patients had single, twelve double and seven triple vein bypass procedures which included 22 grafts to the left anterior descending, 19 to the right coronary and nine to the circumflex artery. All grafts were demonstrated to be patent. In order to determine the reliability of the method for calculating the volumes of two consecutive beats, the angiograms of 38 patients were reviewed in which there was no interruption of the sinus rhythm by ectopic beats. Comparison of two such consecutive sinus beats in these 38 patients demonstrated excellent reproducibility in the calculation of the end-diastolic volume (r = 0.985), endsystolic volume (r = 0.984), stroke volume (r = 0.987) and ejection fraction (r = 0.990).
Results
The mean left ventricular hemodynamics of the control beat for the groups studied are shown in table 1. The only abnormality noted in group lla was an elevated left ventricular end-diastolic pressure (>11 mmHg) in five patients. Twelve patients in group IIb had an elevated left ventricular end-diastolic pressure and four had an abnormal ejection fraction (100 ml/m2) in three and the ejection fraction less than 0.50 in seven patients. Figures 1 and 2 compare the volume studies and ejection fractions in the control beat and the postextrasystolic beat in the groups studied. The directional changes in the postextrasystolic beat compared to the control beat were the same in all the groups; however, In
group lIc
was
Volu fme (ml)
170160-
Mean
SEIIN
Control Beat A1Posl -extrasystolic Seal
150-
140
130-
120-
the magnitude of the changes revealed significant differences (table 2). In all the groups there was an increase in the end-diastolic volume and a decrease in the end-systolic volume resulting in an increase in stroke volume and ejection fraction of the postextrasystolic beat. As indicated in table 2, comparing group I with group lla revealed no significant difference between the changes in the end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat compared to the control beat. However, in groups lIb and lIc the changes in endsystolic volume, stroke volume and ejection fraction noted in the postextrasystolic beat were significantly greater compared to changes observed in groups I and lla (table 2). There was no significant difference comparing group Ilb with group lIc. Figures 3 and 4 show a continuous frame-by-frame plot of the volumes of the postextrasystolic and control beats demonstrating that the changes observed in end-systolic volume, group
110End -diastolic Volume 100-
Eleclion
Fraction
90-
*
i Mean ± SIM.
Control seat
A Post-eltrasystolic Beat
0.8080-
70-
0.70Go-
End -systolic volume 50-
0.60-
40-
30. 0.50Group Normal
Group tic ASHO
Group lla ASHO No Infarction
Group 11l ASHO No lnfarction
Intarction
Synergy
Asynergy
Asymergy
Uu, u
Group
Normal
Figure 1
A comparison of the end-diastolic and end-systolic volumes of the control beat (CB) and the postextrasystolic beat (PESB) for the groups studied. Note that in all the groups the end-diastolic volume is greater and the end-systolic volume is smaller in the PESB than the CB. These changes result in an increase in the stroke volume in the PESB as compared to the CB. Each point represents the mean for each group studied. SEM = standard error of the mean.
Group 1Ia ASHO Infarction Synergy
No
11 b ASND Inlarction Asynergy
Group No
Grous fic ASHD lnfarction Asynergy
Figure 2 A comparison of the ejection fraction in the control beat and the postextrasystolic beat for the groups studied. Note that the ejection fraction of the PESB in group IIb is the same as group I and group IIa. Each point represents the mean for each group studied. SEM = standard error of the mean. Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
LV RESPONSE TO PESP IN CAD
431
Table 2 Comparison of Postextrasystolic Beat and Control Beat End-systolic volume (%) (ml)
Change in
Group I
3
12
2
-
8
(ml)
20
Stroke volume
23
8
Ejection fraction
(%)
0.07
9
0.004
9
0.06 0.02 0. 14 - 0.04t 0.15 i 0.0st
i10
-
(%)
7
Group II 12 -4 29 - llt 24 -13*
4 2 16 i7t 19 i11$
a
b c
24 -7 40 - 16* 54 - 26t
19 6 33 Ilt 39 i13$
25 14t 3;; 23t
The above figures represent the mean aid - 1 standard deviation of the difference between the control beat and the postextrasystolic beat. First columni represents the absolute difference aind the second coluimn the percentage (%) change from control. *Statistically significant compared to group I and lla (P < 0.01). tStatistically significant compared to group I and lla (P < 0.005). tStatistically significant compared to group I and lla (P < 0.001).
stroke volume and ejection fraction were not entirely dependent on a change in end-diastolic volume. The over-all contractile pattern in the postextrasystolic beat when compared to that of the control beat revealed no qualitative difference in group I and group lla (fig. 5). However, the abnormal wall segments present in the control beat in groups lIb and lIc demonstrated either normal or improved contractile pattern (fig. 6) or no change in contractility (fig. 7) in the postextrasystolic beat. In 12 of 19 patients (63%) in group lIb and 3 of 17 patients (18%) in group lIc the postextrasystolic beat demonstrated a normal contractile pattern. In these 15 patients in groups lIb and lIc demonstrating a normal contractile pattern in Volume (ml I) 150-
EOV ESV SV LF
1.K.
361e mlig.. ASHO
146 57 89 0.61
Volume (mil) 140-
138 74
64 0.47
N.G. 42 d'
EDO ESO SO EF
133 40 93 0.70
130-
.3.
133
50 83 0.62 J-..
120-
140-
:-
110-
130-
' .1 1v., :
1
too-
.
120-
the postextrasystolic beat there was a 24.6 ± 9.2% increased shortening of the hemiaxis and an 8.8 ± 7.2% increased shortening of the long axis. In the remaining seven patients in group lIb the contractile pattern of the postextrasystolic beat, although not normal, did improve as evident by a 10 ± 5. 1 % increased shortening of the hemiaxis and a 4.1 ± 3.8% increased shortening of the long axis compared to the control beat. In the 14 patients in group lIc who did not have a normal contractile pattern in the postextrasystolic beat, eight demonstrated improvement in contractile pattern as evident by a 12 ± 8.3% increased shorten-
90-
8070-
10090-
60-
80-
50-
40-
70-
605040-
30-
Compensatory Pause
Post - Extrasystolic Beat
Control Beat
20-
Compensatory Pause
Post -Extrasystolic Beat
Control Beat
10t
Figure 3
Figure 4
Continuous plot of the ventricular volumes of two cardiac cycles after a compensatory pause. Each point represents the calculated volume from a single cine frame (60 frameslsec). Note the higher end-diastolic volume in the postextrasystolic beat than the control beat. Note also the changes in end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat as compared to control beat.
Continuous plot of the ventricular volumes of two cardiac cycles after a compensatory pause. Each point represents the calculated volume from a single cine frame (60 frameslsec). Note the similar end-diastolic volume in both the postextrasystolic beat and the control beat. Note also the changes in end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat as compared to the control beat.
Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
43
432
End diastole
1't BEAT
IAI 1BY ET A L.
End systole
Peot. Extrasystolic Beat EDV 214 ISV 50 sv 1 6 [F 0,717
..
_
2nd BEAT Control [DV ESV SV EF
4.1.K.
44
_ Kt:
Beat 184 49 135 0.73
Control Beat
1.J.A.
.k
I11
wh~
7
Post-Extrasystolic Beat
Figure 5 \rigiographiic stidi ojfa patient i7 grioupl) 1la (n)orial it'tiiodtjtictiiiics anriido/ditiic'
sfluidy itif/i do(u/ti/c c'c'csisl corotiairit ariery discasc' lerionisttri f/di cmoiltirtg ft/c piaftfern ii f/i1f) scfcvfictssfo/ic brat and if f/ttfie rc' is tio oiitrol bcal. Itfis c tieorsigriiJifcacnr qusaII lita/ce cha/nige fri f/ic frac fil/c pafft r' of f/i postc vfratj.sfo/ic bc'af c omripardtifo f /ic corrl / beaf.
ing of the hemiaxis and a 3.6 + 2.9%e increased shortening of the long axis. In the remaining six patients in group lle there was little or no change in shortening of the hemiaxis or long axis in the postextrasystolic beat as compared to the control beat. In the 36 patients in groups lIb) and lie there were 32 hvpokinetic and 25 akinetic segments (iniferior, apical and anterior segments). A normal contractile pattern in 15 patients in the postextrasystolic beat was associated with 20 hypokinetic and 4 akinetic segments, whereas the 23 patients in which the postextrasystolic beat demonstrated either improvement or no change was associated with 12 hypokinetic and 21 akinetic segments. Thus, a left ventricle demonstrating an akinetic segment was less likely to be associated with a normal contractile pattern in the postextrasystolic beat (figs. 6 and 7). Twenty-four patients in groups lIb and lIe underxwent aortocoronary bypass surgery and had a postoperative study showing all grafts patent. In nine patients both the postextrasystolic beat and the Figure 6 ( 'ortrip)ri.sori of coif (,2tfr( Eile pattfrcins (of 1orifrol bc'at.s (onl lc'ff) iEifth tliosc*,of 1)osft.vfrasij.stfol/ beats (otn rig/it) Tlie otccr sill/ioicettftcis fic' ridlicisto/ic p/icase and t/ie itriir .silhoiwette is t/ie crl sijsfo/ic' Ia paficrits I ciritl 2 tlftre is t'orrip/etc' rcoc'rsib/iit of t/ic cIp1/lisc' trorriclot contfratile i/cpctfcrrn ii f/he corttrol bIcfat cuici'f int tl/t postfcxtrcisljsftolic bc'rt. in 1altic nrfs .3 and 4 tf/ie abniotrricil corittract ile pat ft nl pr'sc nt in tlic cotitrol bezt is riot reversible, buft imnprotetrcic'ii is eutcicrit in fi1c' )ostexttrisijstolic beat. Circulation, Volume 51 March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
433
IV RESPONSE TO PESlS' IN C\AD4
V
80
E\y
82
.Es
0 1
Figure 7 C(omiparison of the caontatile pattern of the control beat iiti/i that of the postextr.asy.stiolicl)eat Tlis patic t hbatd an ef)tletorocardiogra * t7demolernstraitinig an inferolateral mnilocarchaI in?fairction? i/ic conitractile pattern is ot altc red in the pastes-
K'XPystlot Beat
ILV
tF
80 V
93 0. 54
t
rasi?stolic
/)(ubect. '/'ic 1)postextrcLsi/stolic
heat
and uvolnmrne wis ciastolic sliglt inetvolnmne owiii the tuftctionfractioni. stroke
postoperative stucly demonstrated a normal contractile patterni (fig. 8). In 1)oth the postextrasystolic beat anid postoperative stuidy there was no change in contractile pattern in six patients and improvement in five otthers. In four patients the observations noted in the postextrasystolic beat did not correspond to those found at the postoperative study (fig. 8). Figure 9 shoxws two examples of improvement in contractile pattern in the first postextrasystolic beat and after stuccessful aortocoronary bypass suirgerv.
Changeb *No (Pool op1
A(Pine ~ ~ ~ ~sy0pInergy
W
CB 24
S
Improoed 5
cl
Discussion Left ventricular angiographic studies are commonly utilized to determine left ventricular volumes and contractile patterns with coronary artery disease.1-4 Such studies are commonly associated with catheterinduced ventricular arrhythmias during the injection of the contrast material followed at the termination of the injection by a compensatory pause and normal sinus rhythm. It is generally appreciated that the first sinus beat after the compensatory pause is not representative of the left ventricular function and contractile pattern in a given study and as such is not utilized ini the evaluation of left ventricular volumes and contractile patterns. The present study evaluated, in a selected group of patients, the ventricular volume and contractile pattern in both the first and second sinus beats after a compensatory pause. A control Control Beat
Post-Extrasystolic Beat
Post- Operative Beat
/(Post -Dop) W
No Change
(PESO)ed
\
f
(PESB)
Snergy
N
Figure 8 Relcaticni between 1postcxtrcz.'sstolic' poteitiiatiomi prioptrtlaticeliy amid po.stopercitie resinlt imi 2-4 patieiits. All 24 )atietits hil ciasyniergy clemiioiistratlt( precs;sercitivebi in the control beat (CB). In 20 patients thc p)ostoprt)(iveti( pcitrctile ;atteruI wcis simnilcr to that olbserv.eci1p1reoerci.ativelmi in dte postextrcsijstolic beat. DI flit patients there icas io cagreenieit betwecen thle postoperative toritractile pattetratid the postextrcsystoic' beat preop)erativel.
2 1. H.
Figure 9
Twvo examples of stuidies demonstrating the preoperative contrcictile pattern (con trol beat and postextrasystolic beat.) with that c)f the postoperative stuidy.
Circulation, Volume 51, March 1975 Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
HAMBY ET AL.
434
series demonstrated the reproducibility of ventricular volume determination in two consecutive sinus beats not preceded by a ventricular arrhythmia. One of the difficulties encountered in the present study was the requirement that sufficient amounts of contrast material remain in the left ventricle after the first postextrasystolic beat to permit determination of the end-diastolic and end-systolic volumes in the second beat. Patients with abnormal or low ejection fractions were more likely to have sufficient contrast material remaining in the left ventricle to permit reliable determination of left ventricular volumes in the second beat after the compensatory pause. This study indicates that after a compensatory pause, left ventricular function and contractile pattern may be significantly altered from the subsequent sinus beat. Our observations are consistent with the phenomena of postextrasystolic potentiation"619 and are similar to the findings of Dyke and coworkers.'5 The latter group studied postextrasystolic potentiation in 15 patients with coronary artery disease by electrically introducing an extrasystole with an R-wave coupled stimulator. It has been shown previously'6 19 that a premature beat followed by a compensatory pause results in an increase in the contractile force of the first beat following the pause. This phenomenon has been termed postextrasystolic potentiation. Its basic mechanism is not known. The magnitude of the changes noted after the compensatory pause is dependent directly on the prematurity of the extrasystolic beat and the subsequent lengthening of the compensatory pause.'6- 8 Thus postextrasystolic potentiation may not be angiographically demonstrable in cases not having a long enough compensatory pause after a ventricular arrhythmia. In the present study it was appreciated that in order to obtain a consistent inotropic response of the first postextrasystolic beat the compensatory pause should be at least one-and-a-half times the R-R interval of subsequent sinus beats. The Frank-Starling mechanism may be proposed as playing a contributory mechanism responsible for the increased contractility of the first postextrasystolic beat compared to the second beat. Karliner and coworkers20 observed that abrupt alterations in cycle length in patients with atrial fibrillation were accompanied by changes in contractility which could be directly attributed to the Frank-Starling mechanism. In the present study 51 patients demonstrated an increase in the end-diastolic volume of the first postextrasystolic beat compared to the second sinus beat. This is illustrated in figure 3. An increased enddiastolic volume of the first postextrasystolic beat resulted in an increased ejection fraction when compared to the next sinus beat. However, as illustrated in figure 4, there were 11 patients in the present study in
whom no change occurred in the end-diastolic volume of the first postextrasystolic beat compared to the second sinus beat. In spite of the lack of change in the end-diastolic volume there was an increase in the ejection fraction of the first sinus beat, compared to the second sinus beat, as a result of a decrease in the endsystolic volume of the former beat. Observations in animals indicate that the increase in contractility after a compensatory pause is not dependent on an increase in left ventricular distending pressure or changes in end-diastolic volume.'6-18 These observations indicate that altered preload need not play any role in the inotropic response after a compensatory pause. Finally acute changes in afterload have been observed to affect cardiac performance.21' 22 Although this could not be evaluated in the present study, the observations by Beck and associates23 would indicate that the postextrasystolic ventricular pressure response probably does not play a role in the present study. In the present study the postextrasystolic response of the normal left ventricle included a variable increase in the end-diastolic volume and a decrease in the end-systolic volume resulting in an increase in the stroke volume and ejection when compared to the control beat (figs. 1 and 2). These changes were in no way different from those observed in the group of patients with normal left ventricular function and coronary artery disease (group lla). The most striking changes noted in the first postextrasystolic beat were in the patients with abnormal left ventricular contractile patterns in the control beat (groups lIb and c). This is consistent with previous observations indicating that postextrasystolic potentiation is most readily demonstrated when myocardial function is significantly impaired.'9 The findings observed in group lIb suggest that abnormal left ventricular function in patients with coronary artery disease and no prior myocardial infarction is potentially completely reversible (fig. 2). In the patients with prior transmural myocardial infarction (group lIc) the mean ejection fraction attained a normal level in the first postextrasystolic beat, but still did not reach that of the other groups (fig. 2). The over-all contractile pattern of the postextrasystolic beat in the patients with normal left ventricular function revealed no significant qualitative changes when compared to the control beat (fig. 5). This was in sharp contrast to the response seen in the patients whose control beats demonstrated varying degrees of asynergy. In no patient did the contractile pattern deteriorate in the postextrasystolic beat: it either became normal (fig. 6, patients 1 and 2), improved (fig. 6, patients 3 and 4) or revealed no change (fig. 7) when compared to the control beat. The observation that 63% of the patients in group lIb Circulation, Volume 51. March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
435
LV RESPONSE TO PESP IN CAD
demonstrated a normal contractile pattern in the postextrasystolic beat compared to only 18% in group lIc indicates that abnormal myocardial segments not associated with a transmural myocardial infarction are potentially reversible. These findings are consistent with our previous observations that reversibility of abnormal myocardial segments after aortocoronary bypass surgery is dependent on whether or not the patient has evidence of previous myocardial infarction.5 It is evident from our observations that residual left ventricular function can be detected in patients with coronary artery disease by their response to postextrasystolic potentiation. The limited experience in 24 patients from groups lIb and lIc studied after aortocoronary bypass surgery (fig. 8) suggests that the response of an abnormal myocardial segment to postextrasystolic potentiation may be useful in predicting the response of such a segment to aortocoronary bypass surgery. Preoperative evaluation, which includes the response of the heart to postextrasystolic potentiation, can also be useful in determining the degree of revascularization that should be performed. It seems to us that if a particular myocardial segment demonstrates an irreversible contractile segment in response to postextrasystolic potentiation, probably as a result of extensive myocardial fibrosis, little can be expected from revascularization of such a wall. An Rwave coupled stimulator15 or paired pulse stimulation'9 is a reasonable and predictable method for obtaining postextrasystolic potentiation and would thus be useful in detecting residual myocardial function in patients with coronary artery disease. Acknowledgment The authors would like to thank Dr. Irwin Hoffman for his critical review of this manuscript. Assistance in preparing this manuscript was also given by Jarmilia Dvorak, Ph.D., and staff and Brenda Hamby.
References 1. FEILn BJ, RUSSELL RO JR, DosrLING JT, RACKLEY CE: Regional left ventricular performance in the year following myocardial infarction. Circulation 46: 679, 1972 2. BAXLEY WA, JONES WB, DODGE HT: Left ventricular anatomical and functional abnormalities in chronic postinfarction heart failure. Ann Intern Med 74: 499, 1971 3. RACKLEY CE, DEAR HD, BAXLEY WA, JONES WB, DODGE HT: Left ventricular chamber volume, mass, and function in severe coronary artery disease. Circulation 41: 605, 1970 4. HAIMILTO\N GW, MLRRAY JA, KENNEDY JW: Quantitative angiocardiography in ischemic heart disease. The spectrum
of abnormal left ventricular function and the role of abnormally contracting segments. Circulation 45: 1065, 1972 5. HAXNI RI, TABRAH F, AINTABLIAN\ A, HARTSTEIN ML, WiSOFF BG: Left ventricular hemodynamics and contractile pattern
after aortocoronary bypass surgery. Am Heart J 88: 149, 1974 6. REES G, BluISTOW JD, KREM1KAw EL, GREEN GS, HERR RH, GRIsWrALD HE, STARR A: Influence of aortocoronary bypass surgery on left ventricular performance. N Engl J Med 284: 1116, 1971 7. CHATTERJEE K, SIWAN HJC, PARMLEY WW, SUSTAITA H, MARc.us H, MATLOFF J: Depression of left ventricular function due to acute myocardial ischemia and its reversal after aortocoronary saphenous-vein bypass. N Engl J Med 286: 1117, 1972 8. SA.LTIEL J, LESPERANCE J, BOURASSA MG, CASTONGLAY Y, COMPEAL L, GRONDIN P: Reversibility of ventricular dysfunction following aorto-coronary bypass grafts. Am J Roentgenol 110: 739, 1970 9. HERMIAN MV, HEINLE RA, KLEIN MD, GORLIN R: Localized disorders in myocardial contraction. Asynergy and its role in congestive heart failure. N Engl J Med 277: 222, 1967 10. HELFANT HH, PINE R, MEISTER SG, FELDMAN MS, TROUT RG, BANKA VS: Nitroglycerin to unmask reversible asynergy. Correlation with post coronary bypass ventriculography. Circulation 50: 108, 1974 11. HAANIR3E RI, GCPTA MP, YOUNC. MW: Clinical and hemodynamic aspects of single vessel coronary artery disease. Am Heart J 85: 458, 1973 12. DoDGE HT, SANDLER H, BALLEw DW, LORD JD: The use of biplane angiocardiography for measurement of left ventricular volume in man. Am Heart J 61: 165, 1961 13. KASSER IS, KENNEDY JW: Measurement of left ventricular volumes in man by single plane cineangiocardiography. Invest Radiol 4: 83, 1969 14. HU.NT D, BRDESRHAW JA, BAXLEY WA: Left ventricular volumes during ventricular tachycardia, first post-
tachycardia beat, and subsequent beats in normal rhythm. Br Heart J 36: 148, 1974 15. DN'KE SH, COHN PF, GORLIN R, SONNENBLICK EH: Detection of residual myocardial function in coronary artery disease (CAD) using postextrasystolic potentiation (PSEP). (abstr) Circulation 48 (suppl IV): IV-104, 1973 16. LENDRLM B, FEINBERCG H, BoYD) E, KATZ LN: Rhythm effects on contractility of the beating isovolumic left ventricular. Am J Physiol 199: 1115, 1960 17. SIEBENS AA, HOFFMAN BF, CRANEFIELD PF, BROOK CM: Regulation of contractile force during ventricular arrhythmias. Am J Physiol 197: 971, 1959 18. MEIJLFR FF, Bo(AARD FVD, TIWIEL HVD, DuIRRER D: Postextrasystolic potentiation in isolated rat heart. Am J Physiol 202: 631, 1962 19. FRoMMIER PL, ROBINSON BF, BRAUNIOVALD E: Paired electrical stimulation. A comparison of the effects on performance of the failing and non-failing heart. Am J Cardiol 18: 738, 1966 20. KARxLINER JS, GAULLT JH, BoUCHARrD RJ, HOLZER J: Factors influencing the ejection fraction and the mean rate of cir-
cumferential fibre shortening during atrial fibrillation in man. Cardiovasc Res 8: 18, 1974 21. IMPERIAL ES, LEVY MN, ZIESK H JR: Outflow resistance as an independent determinant of cardiac performance. Circ Res 9: 1148, 1961 22. URSCHEL CW, COX ELL JW, SONNENBLICK EH, Ross J JR, BRA-NWA.oLl) E: Effects of decreased aortic compliance on performance of the left ventricle. Am J Physiol 214: 298, 1968 23. BE( K W, MED M, CHESLER E, SCI IRIRE V: Postextrasystolic ventricular pressure responses. Circulation 44: 523, 1971
Circulation, Volume 51, March 1975 Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
Response of the left ventricle in coronary artery disease to postextrasystolic potentiation. R I Hamby, A Aintablian, G Wisoff and M L Hartstein Circulation. 1975;51:428-435 doi: 10.1161/01.CIR.51.3.428 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1975 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/51/3/428
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
I.
HAMBY, M. D., AGOP AINTABLIAN, M. D., B. GEORGE WISOFF, M.D., AND MARVIN L. HARTSTEIN, M.D.
SUMMARY
Left ventricular volumes and contractile patterns were evaluated during the first sinus beat after a compause resulting from ventricular arrhythmia and were compared to the second sinus beat (control beat) in order to evaluate the effect of postextrasystolic potentiation. Twelve patients had no evidence of heart disease (group I). Fifty patients had coronary artery disease and included 14 patients (group lla) with no prior myocardial infarction and a normal left ventricular contractile pattern and 19 patients (group Ilb) with an abnormal contractile pattern. Seventeen patients (group Ilc) had a documented transmural myocardial infarction as well as an abnormal left ventricular contractile pattern. In all patients the first postextrasystolic sinus beat, when compared to the second sinus beat, demonstrated increases in stroke volume and ejection fraction and decrease in end-systolic volume. There were no qualitative changes in the contractile pattern in the immediate postextrasystolic beat in the patients with normal left ventricular function. In both group lIb and group lIc the changes in end-systolic volume, stroke volume and ejection fraction were significantly greater than observed in groups I and lla. Abnormal wall segments present in the control beat in groups lIb and lIc demonstrated after postextrasystolic potentiation a normal contractile pattern, improved pattern or no change when compared to the control beat. Abnormal wall segments were more likely to revert to normal as a result of postextrasystolic potentiation in group lIb than group lIc. Akinesia was less likely to revert completely to normal than hypokinesia. In 20 of 24 patients the changes in contractile pattern after aortocoronary bypass surgery corresponded to those observed as a result of postextrasystolic pensatory
potentiation.
Additional Indexing Words: Asynergy
Coronary artery surgery
Ejection fraction
Myocardial infarction
Left ventricular function
ABNORMAL CONTRACTION of left ventricular segments is a characteristic finding in patients with coronary artery disease.'`4 Such localized abnormal contractility probably represents the morphologic basis for the disturbed hemodynamics which accompany coronary artery disease. With the introduction of aortocoronary bypass surgery it became relevant to determine whether such disturbances in myocardial wall movement in the individual patient are irreversible. There is some evidence, based on postoperative studies after aortocoronary bypass surgery, that in some patients localized disturbances of wall movement may represent a reversible functional abnormality presumably resulting from chronic ischemia.`8
It has previously been noted that abnormal contractile patterns accompanying chronic ischemia may show evidence of improvement after administration of epinephrine9 and nitroglycerin.'0 The present report describes the effect of postextrasystolic potentiation on left ventricular function in patients with arteriosclerotic heart disease. Evidence will be presented to demonstrate that in many patients the localized disturbance in contraction may be completely reversible and accompanied by improvement in left ventricular function. Furthermore, the changes in wall movement accompanying postextrasystolic potentiation will be compared with the findings observed after aortocoronary bypass surgery. Methods Studies were performed on 62 patients as part of a workup to evaluate recurrent chest pain. Twelve patients (group I) were found to have normal hemodynamics and normal left ventricular angiographic studies by criteria previously reported.'"` The remaining 50 patients (group II), all of whom had angina pectoris, were found to have coronary artery disease on selective coronary angiography and were divided in three groups. Group lla consisted of 14 patients with no prior history of myocardial infarction. The elec-
From the Department of Medicine, Cardiology Division and the Department of Surgery, Cardiovascular Division, Long Island Jewish-Hillside Medical Center, New Hyde Park; Queens Hospital Center Affiliation, Jamaica; and School of Medicine, Health Sciences Center, State University of New York at Stony Brook, New
York. Address for reprints: Robert I. Hamby, M.D., Long Island Jewish-Hillside Medical Center, New Hyde Park, New York 11040. Received August 15, 1974; revision accepted for publication November 7, 1974. 428
Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
LV RESPONSE TO PESP IN CAD trocardiogram on admission revealed no evidence of previous myocardial infarction and left ventricular angiography demonstrated a normal contractile pattern (synergy). Group lIb consisted of 19 patients without prior history of myocardial infarction and whose electrocardiogram on admission did not suggest prior myocardial infarction. However, all patients in group lIb had an abnormal contractile pattern (asynergy) on left ventricular angiographic study. The types of asynergy noted included localized absence of wall movement (akinesia) and diminished localized wall movement (hypokinesia) during systole.9 Group lIc consisted of 17 patients who had a history of prior myocardial infarction documented by abnormal Q waves in the electrocardiogram. The admitting electrocardiogram was diagnostic of an inferior myocardial infarction in nine patients, anterior in six and combined anterior and inferior infarctions in two patients. All 17 patients in group lIc had left ventricular angiograms demonstrating abnormal contractile pattern. Cardiac catheterization was performed in the fasting state and consisted of right and transseptal combined with retrograde left heart catheterization. Pressures were measured in all chambers of the heart and cardiac output was obtained by the direct Fick principle. Left ventricular angiograms were obtained in the right anterior oblique position by injecting 0.50 to 0.75 ml/kg of 90% sodium meglumine diatrizoate over two seconds using a power injector (Viamonte-Hobbs) into the left ventricle through either the transseptal or retrograde catheter. A tracing of lead II of the electrocardiogram was superimposed in the right upper corner of each cine frame (Cinetrace, Electronics for Medicine). Cineangiograms were taken with a 35 mm camera at 60 frames/sec. The X-ray equipment utilized for this study included a dual field 6 inch 3,000 gain, 9 inch 6,000 gain image intensifier (General Electric) with a 35 mm (Photomechanism) synchronous camera utilizing a grid control X-ray tube. When the left ventricular angiogram was completed a grid of known dimension was positioned at the approximate location of the left ventricle and a short film strip taken to permit correction due to magnification. After the completion of the left ventricular angiographic study, selective coronary angiograms were performed. Left ventricular volumes were obtained by the area length method12 and regression equation of Kasser and Kennedy.'3 The cine films were projected with a 35 mm projector (Vanguard Instrument Corp.) on a ground glass screen. The area of the left ventricular cavity was obtained utilizing an electronic digitizer (Graf/Pen, Science Accessories Corp.) interfaced to a digital computer (Hewlett-Packard) for calculating volumes. The left ventricular end-diastolic volume index (EDV) and ejection fraction determined in 20 patients with normal left ventricles using this method were 69 + 19 ml/m' and 0.68 + 10, respectively. All results were expressed as the mean ± one standard deviation of the mean with comparisons between groups determined using unpaired Student's t-test. During selective left ventricular angiography it is common for the injection of contrast material to be accompanied by catheter-induced ventricular ectopic beats. At the completion of the injection of contrast material the ventricular arrhythmia is followed by a compensatory pause and subsequent normal sinus beats."4 In the calculation of ventricular volumes the first sinus beat after the compensatory pause is ignored since it is recognized that the first postextrasystolic sinus beat may have a different volume and ejection fraction compared to subsequent sinus beats. Depend-
429 ing on several factors, including heart rate and the interval separating the ectopic beat from the first normal sinus beat, the postextrasystolic beat may have a larger volume than the second sinus beat." In the present study the injection of contrast material lasted two seconds and was accompanied by one to three ventricular ectopic beats. At the completion of the injection of contrast material there followed a compensatory pause followed by normal sinus rhythm. The first and second beats (2 to 21/2 sec after the beginning of injection of contrast material) after the compensatory pause were utilized to calculate left ventricular volumes. The first sinus beat after the compensatory pause was designated the postextrasystolic beat while the second beat was designated the control beat. The control beat was assumed to represent the normal contractile mechanism and volume for each patient.'4 Patients were selected for this study if ventricular arrhythmia (1 to 3 ventricular ectopic beats) occurred during injection of contrast material, followed by a compensatory pause which was at least one-and-a-half times the R-R interval of subsequent sinus intervals. Furthermore, sufficient contrast material had to remain in the left ventricle after the postextrasystolic beat to permit the determination of the ventricular volumes in the control beat. Ventriculograms were evaluated by the superimposition of the end-diastolic and end-systolic silhouette utilizing the mid-aortic valve and apex as fixed points. Since two consecutive beats (postextrasystolic and control beat) were compared with each other, no attempt was made to correct for rotation of the heart or downward displacement of the base. One transverse hemiaxis was drawn which bisected at right angles the line defining the long axis (mid-aortic-to-apex) of the heart. A normal left ventricular contraction was accompanied by at least a 20% shortening of the long axis and a 50% shortening of the transverse hemiaxis.9 A quantitative comparison between the control beat and the postextrasystolic beat was made on the basis of the percent increase of shortening of the hemiaxis and long axis. Twenty-four patients in groups lIb and lIc were restudied two to four weeks after aortocoronary bypass surgery in the same laboratory utilizing techniques previously described.5 Five of these patients had single, twelve double and seven triple vein bypass procedures which included 22 grafts to the left anterior descending, 19 to the right coronary and nine to the circumflex artery. All grafts were demonstrated to be patent. In order to determine the reliability of the method for calculating the volumes of two consecutive beats, the angiograms of 38 patients were reviewed in which there was no interruption of the sinus rhythm by ectopic beats. Comparison of two such consecutive sinus beats in these 38 patients demonstrated excellent reproducibility in the calculation of the end-diastolic volume (r = 0.985), endsystolic volume (r = 0.984), stroke volume (r = 0.987) and ejection fraction (r = 0.990).
Results
The mean left ventricular hemodynamics of the control beat for the groups studied are shown in table 1. The only abnormality noted in group lla was an elevated left ventricular end-diastolic pressure (>11 mmHg) in five patients. Twelve patients in group IIb had an elevated left ventricular end-diastolic pressure and four had an abnormal ejection fraction (100 ml/m2) in three and the ejection fraction less than 0.50 in seven patients. Figures 1 and 2 compare the volume studies and ejection fractions in the control beat and the postextrasystolic beat in the groups studied. The directional changes in the postextrasystolic beat compared to the control beat were the same in all the groups; however, In
group lIc
was
Volu fme (ml)
170160-
Mean
SEIIN
Control Beat A1Posl -extrasystolic Seal
150-
140
130-
120-
the magnitude of the changes revealed significant differences (table 2). In all the groups there was an increase in the end-diastolic volume and a decrease in the end-systolic volume resulting in an increase in stroke volume and ejection fraction of the postextrasystolic beat. As indicated in table 2, comparing group I with group lla revealed no significant difference between the changes in the end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat compared to the control beat. However, in groups lIb and lIc the changes in endsystolic volume, stroke volume and ejection fraction noted in the postextrasystolic beat were significantly greater compared to changes observed in groups I and lla (table 2). There was no significant difference comparing group Ilb with group lIc. Figures 3 and 4 show a continuous frame-by-frame plot of the volumes of the postextrasystolic and control beats demonstrating that the changes observed in end-systolic volume, group
110End -diastolic Volume 100-
Eleclion
Fraction
90-
*
i Mean ± SIM.
Control seat
A Post-eltrasystolic Beat
0.8080-
70-
0.70Go-
End -systolic volume 50-
0.60-
40-
30. 0.50Group Normal
Group tic ASHO
Group lla ASHO No Infarction
Group 11l ASHO No lnfarction
Intarction
Synergy
Asynergy
Asymergy
Uu, u
Group
Normal
Figure 1
A comparison of the end-diastolic and end-systolic volumes of the control beat (CB) and the postextrasystolic beat (PESB) for the groups studied. Note that in all the groups the end-diastolic volume is greater and the end-systolic volume is smaller in the PESB than the CB. These changes result in an increase in the stroke volume in the PESB as compared to the CB. Each point represents the mean for each group studied. SEM = standard error of the mean.
Group 1Ia ASHO Infarction Synergy
No
11 b ASND Inlarction Asynergy
Group No
Grous fic ASHD lnfarction Asynergy
Figure 2 A comparison of the ejection fraction in the control beat and the postextrasystolic beat for the groups studied. Note that the ejection fraction of the PESB in group IIb is the same as group I and group IIa. Each point represents the mean for each group studied. SEM = standard error of the mean. Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
LV RESPONSE TO PESP IN CAD
431
Table 2 Comparison of Postextrasystolic Beat and Control Beat End-systolic volume (%) (ml)
Change in
Group I
3
12
2
-
8
(ml)
20
Stroke volume
23
8
Ejection fraction
(%)
0.07
9
0.004
9
0.06 0.02 0. 14 - 0.04t 0.15 i 0.0st
i10
-
(%)
7
Group II 12 -4 29 - llt 24 -13*
4 2 16 i7t 19 i11$
a
b c
24 -7 40 - 16* 54 - 26t
19 6 33 Ilt 39 i13$
25 14t 3;; 23t
The above figures represent the mean aid - 1 standard deviation of the difference between the control beat and the postextrasystolic beat. First columni represents the absolute difference aind the second coluimn the percentage (%) change from control. *Statistically significant compared to group I and lla (P < 0.01). tStatistically significant compared to group I and lla (P < 0.005). tStatistically significant compared to group I and lla (P < 0.001).
stroke volume and ejection fraction were not entirely dependent on a change in end-diastolic volume. The over-all contractile pattern in the postextrasystolic beat when compared to that of the control beat revealed no qualitative difference in group I and group lla (fig. 5). However, the abnormal wall segments present in the control beat in groups lIb and lIc demonstrated either normal or improved contractile pattern (fig. 6) or no change in contractility (fig. 7) in the postextrasystolic beat. In 12 of 19 patients (63%) in group lIb and 3 of 17 patients (18%) in group lIc the postextrasystolic beat demonstrated a normal contractile pattern. In these 15 patients in groups lIb and lIc demonstrating a normal contractile pattern in Volume (ml I) 150-
EOV ESV SV LF
1.K.
361e mlig.. ASHO
146 57 89 0.61
Volume (mil) 140-
138 74
64 0.47
N.G. 42 d'
EDO ESO SO EF
133 40 93 0.70
130-
.3.
133
50 83 0.62 J-..
120-
140-
:-
110-
130-
' .1 1v., :
1
too-
.
120-
the postextrasystolic beat there was a 24.6 ± 9.2% increased shortening of the hemiaxis and an 8.8 ± 7.2% increased shortening of the long axis. In the remaining seven patients in group lIb the contractile pattern of the postextrasystolic beat, although not normal, did improve as evident by a 10 ± 5. 1 % increased shortening of the hemiaxis and a 4.1 ± 3.8% increased shortening of the long axis compared to the control beat. In the 14 patients in group lIc who did not have a normal contractile pattern in the postextrasystolic beat, eight demonstrated improvement in contractile pattern as evident by a 12 ± 8.3% increased shorten-
90-
8070-
10090-
60-
80-
50-
40-
70-
605040-
30-
Compensatory Pause
Post - Extrasystolic Beat
Control Beat
20-
Compensatory Pause
Post -Extrasystolic Beat
Control Beat
10t
Figure 3
Figure 4
Continuous plot of the ventricular volumes of two cardiac cycles after a compensatory pause. Each point represents the calculated volume from a single cine frame (60 frameslsec). Note the higher end-diastolic volume in the postextrasystolic beat than the control beat. Note also the changes in end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat as compared to control beat.
Continuous plot of the ventricular volumes of two cardiac cycles after a compensatory pause. Each point represents the calculated volume from a single cine frame (60 frameslsec). Note the similar end-diastolic volume in both the postextrasystolic beat and the control beat. Note also the changes in end-systolic volume, stroke volume and ejection fraction in the postextrasystolic beat as compared to the control beat.
Circulation, Volume 51, March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
43
432
End diastole
1't BEAT
IAI 1BY ET A L.
End systole
Peot. Extrasystolic Beat EDV 214 ISV 50 sv 1 6 [F 0,717
..
_
2nd BEAT Control [DV ESV SV EF
4.1.K.
44
_ Kt:
Beat 184 49 135 0.73
Control Beat
1.J.A.
.k
I11
wh~
7
Post-Extrasystolic Beat
Figure 5 \rigiographiic stidi ojfa patient i7 grioupl) 1la (n)orial it'tiiodtjtictiiiics anriido/ditiic'
sfluidy itif/i do(u/ti/c c'c'csisl corotiairit ariery discasc' lerionisttri f/di cmoiltirtg ft/c piaftfern ii f/i1f) scfcvfictssfo/ic brat and if f/ttfie rc' is tio oiitrol bcal. Itfis c tieorsigriiJifcacnr qusaII lita/ce cha/nige fri f/ic frac fil/c pafft r' of f/i postc vfratj.sfo/ic bc'af c omripardtifo f /ic corrl / beaf.
ing of the hemiaxis and a 3.6 + 2.9%e increased shortening of the long axis. In the remaining six patients in group lle there was little or no change in shortening of the hemiaxis or long axis in the postextrasystolic beat as compared to the control beat. In the 36 patients in groups lIb) and lie there were 32 hvpokinetic and 25 akinetic segments (iniferior, apical and anterior segments). A normal contractile pattern in 15 patients in the postextrasystolic beat was associated with 20 hypokinetic and 4 akinetic segments, whereas the 23 patients in which the postextrasystolic beat demonstrated either improvement or no change was associated with 12 hypokinetic and 21 akinetic segments. Thus, a left ventricle demonstrating an akinetic segment was less likely to be associated with a normal contractile pattern in the postextrasystolic beat (figs. 6 and 7). Twenty-four patients in groups lIb and lIe underxwent aortocoronary bypass surgery and had a postoperative study showing all grafts patent. In nine patients both the postextrasystolic beat and the Figure 6 ( 'ortrip)ri.sori of coif (,2tfr( Eile pattfrcins (of 1orifrol bc'at.s (onl lc'ff) iEifth tliosc*,of 1)osft.vfrasij.stfol/ beats (otn rig/it) Tlie otccr sill/ioicettftcis fic' ridlicisto/ic p/icase and t/ie itriir .silhoiwette is t/ie crl sijsfo/ic' Ia paficrits I ciritl 2 tlftre is t'orrip/etc' rcoc'rsib/iit of t/ic cIp1/lisc' trorriclot contfratile i/cpctfcrrn ii f/he corttrol bIcfat cuici'f int tl/t postfcxtrcisljsftolic bc'rt. in 1altic nrfs .3 and 4 tf/ie abniotrricil corittract ile pat ft nl pr'sc nt in tlic cotitrol bezt is riot reversible, buft imnprotetrcic'ii is eutcicrit in fi1c' )ostexttrisijstolic beat. Circulation, Volume 51 March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
433
IV RESPONSE TO PESlS' IN C\AD4
V
80
E\y
82
.Es
0 1
Figure 7 C(omiparison of the caontatile pattern of the control beat iiti/i that of the postextr.asy.stiolicl)eat Tlis patic t hbatd an ef)tletorocardiogra * t7demolernstraitinig an inferolateral mnilocarchaI in?fairction? i/ic conitractile pattern is ot altc red in the pastes-
K'XPystlot Beat
ILV
tF
80 V
93 0. 54
t
rasi?stolic
/)(ubect. '/'ic 1)postextrcLsi/stolic
heat
and uvolnmrne wis ciastolic sliglt inetvolnmne owiii the tuftctionfractioni. stroke
postoperative stucly demonstrated a normal contractile patterni (fig. 8). In 1)oth the postextrasystolic beat anid postoperative stuidy there was no change in contractile pattern in six patients and improvement in five otthers. In four patients the observations noted in the postextrasystolic beat did not correspond to those found at the postoperative study (fig. 8). Figure 9 shoxws two examples of improvement in contractile pattern in the first postextrasystolic beat and after stuccessful aortocoronary bypass suirgerv.
Changeb *No (Pool op1
A(Pine ~ ~ ~ ~sy0pInergy
W
CB 24
S
Improoed 5
cl
Discussion Left ventricular angiographic studies are commonly utilized to determine left ventricular volumes and contractile patterns with coronary artery disease.1-4 Such studies are commonly associated with catheterinduced ventricular arrhythmias during the injection of the contrast material followed at the termination of the injection by a compensatory pause and normal sinus rhythm. It is generally appreciated that the first sinus beat after the compensatory pause is not representative of the left ventricular function and contractile pattern in a given study and as such is not utilized ini the evaluation of left ventricular volumes and contractile patterns. The present study evaluated, in a selected group of patients, the ventricular volume and contractile pattern in both the first and second sinus beats after a compensatory pause. A control Control Beat
Post-Extrasystolic Beat
Post- Operative Beat
/(Post -Dop) W
No Change
(PESO)ed
\
f
(PESB)
Snergy
N
Figure 8 Relcaticni between 1postcxtrcz.'sstolic' poteitiiatiomi prioptrtlaticeliy amid po.stopercitie resinlt imi 2-4 patieiits. All 24 )atietits hil ciasyniergy clemiioiistratlt( precs;sercitivebi in the control beat (CB). In 20 patients thc p)ostoprt)(iveti( pcitrctile ;atteruI wcis simnilcr to that olbserv.eci1p1reoerci.ativelmi in dte postextrcsijstolic beat. DI flit patients there icas io cagreenieit betwecen thle postoperative toritractile pattetratid the postextrcsystoic' beat preop)erativel.
2 1. H.
Figure 9
Twvo examples of stuidies demonstrating the preoperative contrcictile pattern (con trol beat and postextrasystolic beat.) with that c)f the postoperative stuidy.
Circulation, Volume 51, March 1975 Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
HAMBY ET AL.
434
series demonstrated the reproducibility of ventricular volume determination in two consecutive sinus beats not preceded by a ventricular arrhythmia. One of the difficulties encountered in the present study was the requirement that sufficient amounts of contrast material remain in the left ventricle after the first postextrasystolic beat to permit determination of the end-diastolic and end-systolic volumes in the second beat. Patients with abnormal or low ejection fractions were more likely to have sufficient contrast material remaining in the left ventricle to permit reliable determination of left ventricular volumes in the second beat after the compensatory pause. This study indicates that after a compensatory pause, left ventricular function and contractile pattern may be significantly altered from the subsequent sinus beat. Our observations are consistent with the phenomena of postextrasystolic potentiation"619 and are similar to the findings of Dyke and coworkers.'5 The latter group studied postextrasystolic potentiation in 15 patients with coronary artery disease by electrically introducing an extrasystole with an R-wave coupled stimulator. It has been shown previously'6 19 that a premature beat followed by a compensatory pause results in an increase in the contractile force of the first beat following the pause. This phenomenon has been termed postextrasystolic potentiation. Its basic mechanism is not known. The magnitude of the changes noted after the compensatory pause is dependent directly on the prematurity of the extrasystolic beat and the subsequent lengthening of the compensatory pause.'6- 8 Thus postextrasystolic potentiation may not be angiographically demonstrable in cases not having a long enough compensatory pause after a ventricular arrhythmia. In the present study it was appreciated that in order to obtain a consistent inotropic response of the first postextrasystolic beat the compensatory pause should be at least one-and-a-half times the R-R interval of subsequent sinus beats. The Frank-Starling mechanism may be proposed as playing a contributory mechanism responsible for the increased contractility of the first postextrasystolic beat compared to the second beat. Karliner and coworkers20 observed that abrupt alterations in cycle length in patients with atrial fibrillation were accompanied by changes in contractility which could be directly attributed to the Frank-Starling mechanism. In the present study 51 patients demonstrated an increase in the end-diastolic volume of the first postextrasystolic beat compared to the second sinus beat. This is illustrated in figure 3. An increased enddiastolic volume of the first postextrasystolic beat resulted in an increased ejection fraction when compared to the next sinus beat. However, as illustrated in figure 4, there were 11 patients in the present study in
whom no change occurred in the end-diastolic volume of the first postextrasystolic beat compared to the second sinus beat. In spite of the lack of change in the end-diastolic volume there was an increase in the ejection fraction of the first sinus beat, compared to the second sinus beat, as a result of a decrease in the endsystolic volume of the former beat. Observations in animals indicate that the increase in contractility after a compensatory pause is not dependent on an increase in left ventricular distending pressure or changes in end-diastolic volume.'6-18 These observations indicate that altered preload need not play any role in the inotropic response after a compensatory pause. Finally acute changes in afterload have been observed to affect cardiac performance.21' 22 Although this could not be evaluated in the present study, the observations by Beck and associates23 would indicate that the postextrasystolic ventricular pressure response probably does not play a role in the present study. In the present study the postextrasystolic response of the normal left ventricle included a variable increase in the end-diastolic volume and a decrease in the end-systolic volume resulting in an increase in the stroke volume and ejection when compared to the control beat (figs. 1 and 2). These changes were in no way different from those observed in the group of patients with normal left ventricular function and coronary artery disease (group lla). The most striking changes noted in the first postextrasystolic beat were in the patients with abnormal left ventricular contractile patterns in the control beat (groups lIb and c). This is consistent with previous observations indicating that postextrasystolic potentiation is most readily demonstrated when myocardial function is significantly impaired.'9 The findings observed in group lIb suggest that abnormal left ventricular function in patients with coronary artery disease and no prior myocardial infarction is potentially completely reversible (fig. 2). In the patients with prior transmural myocardial infarction (group lIc) the mean ejection fraction attained a normal level in the first postextrasystolic beat, but still did not reach that of the other groups (fig. 2). The over-all contractile pattern of the postextrasystolic beat in the patients with normal left ventricular function revealed no significant qualitative changes when compared to the control beat (fig. 5). This was in sharp contrast to the response seen in the patients whose control beats demonstrated varying degrees of asynergy. In no patient did the contractile pattern deteriorate in the postextrasystolic beat: it either became normal (fig. 6, patients 1 and 2), improved (fig. 6, patients 3 and 4) or revealed no change (fig. 7) when compared to the control beat. The observation that 63% of the patients in group lIb Circulation, Volume 51. March 1975
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
435
LV RESPONSE TO PESP IN CAD
demonstrated a normal contractile pattern in the postextrasystolic beat compared to only 18% in group lIc indicates that abnormal myocardial segments not associated with a transmural myocardial infarction are potentially reversible. These findings are consistent with our previous observations that reversibility of abnormal myocardial segments after aortocoronary bypass surgery is dependent on whether or not the patient has evidence of previous myocardial infarction.5 It is evident from our observations that residual left ventricular function can be detected in patients with coronary artery disease by their response to postextrasystolic potentiation. The limited experience in 24 patients from groups lIb and lIc studied after aortocoronary bypass surgery (fig. 8) suggests that the response of an abnormal myocardial segment to postextrasystolic potentiation may be useful in predicting the response of such a segment to aortocoronary bypass surgery. Preoperative evaluation, which includes the response of the heart to postextrasystolic potentiation, can also be useful in determining the degree of revascularization that should be performed. It seems to us that if a particular myocardial segment demonstrates an irreversible contractile segment in response to postextrasystolic potentiation, probably as a result of extensive myocardial fibrosis, little can be expected from revascularization of such a wall. An Rwave coupled stimulator15 or paired pulse stimulation'9 is a reasonable and predictable method for obtaining postextrasystolic potentiation and would thus be useful in detecting residual myocardial function in patients with coronary artery disease. Acknowledgment The authors would like to thank Dr. Irwin Hoffman for his critical review of this manuscript. Assistance in preparing this manuscript was also given by Jarmilia Dvorak, Ph.D., and staff and Brenda Hamby.
References 1. FEILn BJ, RUSSELL RO JR, DosrLING JT, RACKLEY CE: Regional left ventricular performance in the year following myocardial infarction. Circulation 46: 679, 1972 2. BAXLEY WA, JONES WB, DODGE HT: Left ventricular anatomical and functional abnormalities in chronic postinfarction heart failure. Ann Intern Med 74: 499, 1971 3. RACKLEY CE, DEAR HD, BAXLEY WA, JONES WB, DODGE HT: Left ventricular chamber volume, mass, and function in severe coronary artery disease. Circulation 41: 605, 1970 4. HAIMILTO\N GW, MLRRAY JA, KENNEDY JW: Quantitative angiocardiography in ischemic heart disease. The spectrum
of abnormal left ventricular function and the role of abnormally contracting segments. Circulation 45: 1065, 1972 5. HAXNI RI, TABRAH F, AINTABLIAN\ A, HARTSTEIN ML, WiSOFF BG: Left ventricular hemodynamics and contractile pattern
after aortocoronary bypass surgery. Am Heart J 88: 149, 1974 6. REES G, BluISTOW JD, KREM1KAw EL, GREEN GS, HERR RH, GRIsWrALD HE, STARR A: Influence of aortocoronary bypass surgery on left ventricular performance. N Engl J Med 284: 1116, 1971 7. CHATTERJEE K, SIWAN HJC, PARMLEY WW, SUSTAITA H, MARc.us H, MATLOFF J: Depression of left ventricular function due to acute myocardial ischemia and its reversal after aortocoronary saphenous-vein bypass. N Engl J Med 286: 1117, 1972 8. SA.LTIEL J, LESPERANCE J, BOURASSA MG, CASTONGLAY Y, COMPEAL L, GRONDIN P: Reversibility of ventricular dysfunction following aorto-coronary bypass grafts. Am J Roentgenol 110: 739, 1970 9. HERMIAN MV, HEINLE RA, KLEIN MD, GORLIN R: Localized disorders in myocardial contraction. Asynergy and its role in congestive heart failure. N Engl J Med 277: 222, 1967 10. HELFANT HH, PINE R, MEISTER SG, FELDMAN MS, TROUT RG, BANKA VS: Nitroglycerin to unmask reversible asynergy. Correlation with post coronary bypass ventriculography. Circulation 50: 108, 1974 11. HAANIR3E RI, GCPTA MP, YOUNC. MW: Clinical and hemodynamic aspects of single vessel coronary artery disease. Am Heart J 85: 458, 1973 12. DoDGE HT, SANDLER H, BALLEw DW, LORD JD: The use of biplane angiocardiography for measurement of left ventricular volume in man. Am Heart J 61: 165, 1961 13. KASSER IS, KENNEDY JW: Measurement of left ventricular volumes in man by single plane cineangiocardiography. Invest Radiol 4: 83, 1969 14. HU.NT D, BRDESRHAW JA, BAXLEY WA: Left ventricular volumes during ventricular tachycardia, first post-
tachycardia beat, and subsequent beats in normal rhythm. Br Heart J 36: 148, 1974 15. DN'KE SH, COHN PF, GORLIN R, SONNENBLICK EH: Detection of residual myocardial function in coronary artery disease (CAD) using postextrasystolic potentiation (PSEP). (abstr) Circulation 48 (suppl IV): IV-104, 1973 16. LENDRLM B, FEINBERCG H, BoYD) E, KATZ LN: Rhythm effects on contractility of the beating isovolumic left ventricular. Am J Physiol 199: 1115, 1960 17. SIEBENS AA, HOFFMAN BF, CRANEFIELD PF, BROOK CM: Regulation of contractile force during ventricular arrhythmias. Am J Physiol 197: 971, 1959 18. MEIJLFR FF, Bo(AARD FVD, TIWIEL HVD, DuIRRER D: Postextrasystolic potentiation in isolated rat heart. Am J Physiol 202: 631, 1962 19. FRoMMIER PL, ROBINSON BF, BRAUNIOVALD E: Paired electrical stimulation. A comparison of the effects on performance of the failing and non-failing heart. Am J Cardiol 18: 738, 1966 20. KARxLINER JS, GAULLT JH, BoUCHARrD RJ, HOLZER J: Factors influencing the ejection fraction and the mean rate of cir-
cumferential fibre shortening during atrial fibrillation in man. Cardiovasc Res 8: 18, 1974 21. IMPERIAL ES, LEVY MN, ZIESK H JR: Outflow resistance as an independent determinant of cardiac performance. Circ Res 9: 1148, 1961 22. URSCHEL CW, COX ELL JW, SONNENBLICK EH, Ross J JR, BRA-NWA.oLl) E: Effects of decreased aortic compliance on performance of the left ventricle. Am J Physiol 214: 298, 1968 23. BE( K W, MED M, CHESLER E, SCI IRIRE V: Postextrasystolic ventricular pressure responses. Circulation 44: 523, 1971
Circulation, Volume 51, March 1975 Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
Response of the left ventricle in coronary artery disease to postextrasystolic potentiation. R I Hamby, A Aintablian, G Wisoff and M L Hartstein Circulation. 1975;51:428-435 doi: 10.1161/01.CIR.51.3.428 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1975 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/51/3/428
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Circulation is online at: http://circ.ahajournals.org//subscriptions/
Downloaded from http://circ.ahajournals.org/ at UNIV OF NORTH DAKOTA on May 20, 2015
