multivariate statistical evaluation of intraaortic counterpulsation in pump failure complicating...

Multivariate Statistical Evaluation of lntraaortic

Counterpulsation in Pump Failure Complicating Acute

Myocardial Infarction

PACO LORENTE, MD

RENE GOURGON, MD

PHILIPPE BEAUFILS, MD

CHRISTlANE MASQUET, MD

MICHAEL ROSENGARTEN, MD

ISAAC AZANCOT, MD

ROBERT SLAMA, MD

Paris, France

From the Department of Cardiology and U. 141 INSERM, ti6pital Lariboisiere, Paris, France. This study was supported by the lnstitut National de la Sante et de la Recherche M&kale. Paris, France. Manuscript received May 22, 1979; revised manuscript received December 18, 1979, accepted January 30, 1980.

Address for reprints: Pace Lorente, MD, U. 14 1 INSERM, Hopital Lariboisiere, 2, rue Ambroise Pare, 75475 Paris Cedex 10, France.

Clinical and hemodynamic data from 189 patients sustaining an acute myocardial infarction complicated by pump failure were analyzed with a multivariate analysis method using correspondence analysis. A graphic decision-making system based on survival at 1 month was derived from a set of 101 patients. According to the scatter of patient data points on the factorial plane resulting from analysis, survival and nonsurvival zones were defined, and the position of a given patient within these zones was considered a reliable estimate of likelihood of survival. Then, the decision-making rule was applied to a set of 88 patients. Every new patient whose data fell wfthin the nonsurvival zone was referred for consideration of intraaortic counterpulsation. Thus, 43 patients were predicted to be nonsurvivors; 28 of these (group I) underwent balloon counterpulsation; the remaining 17 formed group II. The two groups were considered comparable. Seven patients in group I and none in group II survived for more than 1 month (probability [p] = 0.02); it was concluded that counterpulsation improves short-term survival. The analysis of baseline measurements demonstrated that a good prediction of short-term survival was feasible in the patients undergoing circulatory assistance. Thus, patients who are salvaged In these circumstances are probably in a less severe condition than others and mechanical assistance may not be of value in every patient predicted to be a nonsurvivor. Of the seven short- term survivors, only three survived for more than 1 year. This low long-term survival rate (11 percent) was related to extensive myocardial and coronary arterial lesions found on angiography in survivors as well as in counterpulsation-dependent patients.

Over the last decade, the efficiency of intraaortic balloon counterpulsation in pump failure complicating acute myocardial infarction has been evaluated by numerous investigators. As a rule, hemodynamic status improves after the initiation of balloon pumping, but the reported effects on long-term survival have varied widely. As Weber and Janickil and Kuhn2 pointed out, the variability of criteria for patient selection and the heterogeneity of studied samples may account for the observed differences in counterpulsation efficiency. In an attempt to obviate the difficulties arising from varying patient selection criteria, we based our indications for intraaortic balloon pumping on a decision-making rule derived from clinical and hemodynamic variables through the use of a multidimensional analysis procedure previously described in studies of pump failure in acute myocardial infarction.:3-g

Multivariate evaluation of patients undergoing circulatory assistance has previously been performed either to define physiologic patterns and

I24 July 1980 The American Journal of CARDIOLOGY Volume 48

time courses of recovery in shock due to myocardial infarctionlOJ1 or to determine prognostic indexes during postcardiotomy balloon pumping.12 In this study, our efforts were directed to the prediction of outcome in order to select the patients needing mechanical support. Clinical and hemodynamic variables were taken into account in a comprehensive study, the likelihood of survival was evaluated and every patient predicted to be a nonsurvivor was referred for consideration of balloon pumping. Our report describes our experience with this procedure and analyze short- and long-term survival in 26 patients undergoing intraaortic balloon counterpulsation.

Methods

Selection of Patients

One hundred eighty-nine consecutive patients with pump failure complicating myocardial infarction confirmed by electrocardiogram and serum enzyme analysis were admitted to the coronary care unit for hemodynamic evaluation. This sample included 138 men and 51 women ranging in age from 36 to 88 years (mean 63). On admission to the unit, the patients were clinically classified13; 9’7 were considered to be in Killip functional class III (frank pulmonary edema) and, the other 92 in class IV (cardiogenic shock). None had any com- plication or any associated cardiac or pulmonary disease other than pump failure; patients with mechanical lesions, such as mitral regurgitation secondary to papillary muscle dysfunction or rupture and ventricular septal perforation, were eliminated. Other possible causes of pump failure, such as hypoxemia, hemodynamically significant arrhythmias, acidosis, severe anemia or hypovolemia, were excluded or corrected.

The elapsed time from the onset of infarction to the first evaluation ranged from 6 hours to 6 days, and baseline measurements were performed before the initiation of any therapy other than administration of oxygen, narcotic agents, sedative drugs or lidocaine. The patients were observed in this unit for a mean period of 66 hours (range 3 to 100). Monitoring was performed with use of an indwelling radial or femoral arterial catheter, a central venous pressure line and a Swan-Ganz flow-directed pulmonary arterial catheter. Systemic arterial, central venous and pulmonary arterial wedge pressures were recorded continuously. Serial measurements of cardiac output were made by the indocyanine green dye-dilution technique. From these data, stroke index, peripheral vascular resistance, total pulmonary resistance, left ventricular stroke work index, right ventricular stroke work index and other indexes were computed as described previously.3-g

Nonsurvival was defined as death occurring only from in- tractable pump failure within 4 weeks after the onset of myocardial infarction. Hence, patients surviving after 4 weeks were considered survivors. Patients whose death was related to cardiac rupture or arrythmia were excluded. Myocardial infarction was classified anterior or inferior on the basis of infarct site. Anterior infarctions included anteroseptal, an- terolateral, lateral and circumferential sites; inferior infarctions included posteroseptal and inferolateral sites.

Statistical Analysis

Learning sample: For the purpose of deriving a prognostic decision-making rule for prediction of outcome, we took into account all the multivariable data sets collected in our patients. Each data set comprised 26 items (Table I)$ all with a common relation in time. The method used to analyze these data has previously been described in detail.“-g Briefly, the initial set of measurements was chosen for analysis because

INTRAACRTIC CWNTERPULSATICN IN MYCCARDIAL INFARCTION-LCPENTE ET AL.

it provided insight into the patient’s status at the time of admission to the shock ward. With the use of correspondence analysis,14J5 data from a learning sample of 101 patients were projected onto a factorial plane. This plane is defined by two factorial axes, fl and f2, which are linear functions of the collected variables. Because this statistical analysis procedure is only descriptive, survival and nonsurvival zones were defined in retrospect by considering the outcome of each indi- vidual patient represented in the scatter diagram.a-g Because of the relatively short overlap between these two zones, the separation between survivors and nonsurvivors was deemed reliable, and prognostic groupings of patients inferred from the data were subsequently formed. The most important variables in the formulation of the factorial axes-that is, in the two dimensional projection of the learning sample-were cardiac index, left and right filling pressures, heart rate, systolic arterial pressure and left ventricular stroke work index; the univariate analysis of these variables was helpful in characterizing prognostic groupings.

Test sample: The factorial plane and the prognostic zones derived from the learning sample were then used as a frame of reference for a new (test) sample of 88 patients. Data from each new patient entering the shock ward were plotted on this plane through a very simple computation with a small desk- top calculators and from the patient’s data point on the scatter diagram, both his pathophysiologic behavior and outcome were predicted. Any patient whose data fell within the nonsurvival zone, the overlap zone or the borderline zone was referred for intraaortic balloon assistance.

This graphic allocation rule was compared with the following prognostic index derived from discriminant analyses previously reported3: Zi = 0.427 + 0.00121 X left ventricular minute work index - 0.00125 X total pulmonary resistance. This index allocates a given patient to the survivor group if the value is positive or to the nonsurvivor group if the value is negative. As a rule, the assessment of prognosis and therapy for these 88 patients was carried out routinely as shown in Figure 1.

In addition, we compared subsets of patients by using the Mann-Whitney test, the Fisher’s test and the two sample

TABLE I

List of Selected Variables

Sex (male/female) Age (years) Previous myocardlal infarction (yes/no) Location of myocardial infarction (anterior/inferior) Conduction disturbances (yes/no) Time of study from probable onset of myocardial infarction (TS) Heart rate (HR) (beatsimin) Cardiac index (Cl) (literslmin per m*) Stroke index (SI) (ml/beat per m*) Systolic aortic pressure (SAP) (mm Hg) Diastolic aortic pressure (DAP) (mm Hg) Mean aortic pressure (MAP) (mm Hg) Peripheral vascular resistance (PVR) (dvnes s crne5 oer m*) Left’ventricular filling pressure (LVFPj (inm Hg) ’ ’ Mean pulmonary arterial pressure (MPAP) (mm Hg) Right ventricular filling pressure (RVFP) (mm Ha3 Total pulmonary resrstance (TPR) (dynes s cm- m*) Left ventricular stroke work index (LVSWI) (g.m/m*) Right ventricular stroke work index (RVSWI) (g.m/m2) Left ventricular minute work index (LVMWI) (g.m/m* ger min) Right ventricular minute work index (RVMWI) (g.m/m Survival/death

per min)

Right ventricular pressure generation index (RVPGI) (dimenslonless)

Ejection time (ET) (ms) Tension-time index (TTI) (mm Hg4min) Urinary flow $2 ur) (ml/mitt) -

July 1990 The American Journal of CARDIOLOGY Volume 46 125

INTRAAORTIC COUNTERF’ULSATlON IN MYOCARDIAL INFARCTION-LORENTE ET AL.

TABLE II

Data on 26 Patlents Undergoing lntraaortlc Balloon Counterpulsation (group I)

Killip Coronary Arterial

Age (yr) Site Functional Duration Lesions* Case & sex of MI Classification IABP (h) LAD LCX RCA Dyssynergy Surgery

A. Survivors (group la)

1 69F A IV 22 .

2 61M A,old I IV 96 3 3 4 Inferior wall akinesia

3 37M A IV 333 3 3 1 Aneurysm of apex lnfarctectomy and adjacent parts of A and I walls

4 62M A IV 120 4 3 4 Paradoxical apicolateral aneurysm; global hypokinesia

5 57M A Ill 216 3 3 3 Global hypokinesia

6 48M A Ill 108 4 4 2 Apical and A wall akinesia

7 64M I,old A Ill 192 4 2 3 Akinesia of I wall, apex and half of A wall

B. Balloon-Dependent Patients (group lb)

a 53M A IV 85 4 3 3 Left A wall akinesia

Inda;;ty;;;,

bypass grafts 9 48M A IV 192 4 3 4 Apical -t A wall

akinesia 10 77F A IV 34 .

11 50F A IV 48

12 64M A,old I

13 37M A

14 73F A

Ill 90

IV 240

IV 264

4 3 4 Apical and I LAD bypass graft dyskinesia; half A wall akinesia

4 3 2 Large apical and A dyskinesia

C. Patients Whose Condition Deteriorated With IABP (orouo Ic)

15 57M

16 62F

17 68M :5 68F

50M

A

I

A,old A

;

20 62M A

21 47M

22 63M

23 58M

24 40M

25 6OF

26 55F

A

A.old I

A

A

A

A

IV

IV 84

IV 72

IV 4

IV 72

IV 6

IV 1

2

10

:: 168

4 3

144 4 3

4 3

3

3

4 Global akinesia

Extensive A wall akinesia

lnfarctectomy

Global akinesia except a narrow segment near to mitral ring

Increased cavity size; A, apical and inferoapical akinesia

lnfarctectomy

l Scale of perfusion: 1 = normal; 2 = moderate obstruction (50 to 75 percent); 3 = severe obstruction (greater than 75 percent); 4 = occlusion.

126 July 1980 The American Journal of CARDIOLOGY Volume 46

INTRAAGRTIC COUNTERPULSATION IN MY~~A~~DIAL INFAROTI~N---L~RENTE ET AL.

TABLE II

(continued)

CaSe Follow-Up Study Necropsy Findings

A. Survivors (group la)

1 Alive 13 months: well controlled heart . . failure, not d&bled; sudden death

2 A;ve&r0fr;; no disability, no therapy: Severe obstruction LCx + RCA, quasi-complete obstruction of LAD; old IMI, aneurysm evolved from recent AMI

3 Alive 4.5 years; no disability, no therapy, . . . active; sudden death

4 Alive 6 weeks; disabled, left heart failure: . . died, ventricular fibrillatloti

5 Alive 2 months; no disability, no therapy; died, ventricular flbrillatlon

6 Alive 3 years: active, no disability, no therapy: resumption of professlonal activity

7 Alive 2 months; mlid left heart failure deteriorating progressively

. . .

.

B. Balloon-Dependent Patients (group lb)

8 Died 48 h after surgery

9 Died after progressive weaning

10 Died while on IABP (sudden death)

11 Died after weaning (ventricular fibrillation)

12 lntraoperative death

13 Died after weaning

14 Died after weaning

Massive ventrlcuiar infarction (circumferential); occlusion of LAD + RCA; partial obstruction of LCx

. .

Massive ventricular infarction (circumferential); occlusion of LCx + RCA; severe obstruction of LAD

Circumferential infarct; occlusion of LMCA

.

Circumferential infarct; occlusion of LAD i- RCA; quasi- complete obstruction of LCx

C. Patients Whose Condition Deteriorated With IABP (group Ic)

15

16

:; 19

Sudden death while on IABP

Progressive deterioration while on IABP

Died while on IABP; pump failure Died while on IABP; pump failure Died while on IABP; pump failure

Circumferential infarct; occlusion of LAD + RCA; severe obstruction of LCx

Large inferior infarction; almost complete three vessel obstruction

.

A and I massive ventricular infarct; high grade obstruction of the three vessels

20 In;ra,p,“ive death; pump .

21

22

23

24

25

26

Died while on IABP; pump failure; pulmonary embolism

Died while on IABP; pump failure; pulmonary embolism

Died while on IABP; pump failure




Massive circumferential infarct; occlusion of LAD

Massive circumferential infarction; occlusion of LAD + RCA; severe obstruction of LCx

Extensive ventricular infarct; occlusion of LAD + RCA: severe obstruction of LCx

. . .

Large anterior infarction; occlusion of LAD and RCA; severe obstruction of LCx

Large circumferential infarction; severe obstruction of the three vessels

A = anterior; AMI = anterior myocardlal infarction: I = inferior: IABP = lntraaortic balloon pumping; LAD = left anterior descending coronary artery: LCX = left circumflex coronary artery; LMCA = left main coronary artery; Ml = myocardial infarction; RCA = right coronary artery.


INTRAAORTIC COUNTERPULSATION IN MYOCARDIAL INFARCTION-LORENTE ET AL

ENTRANCE CLINICAL AND HEMODYNAMIC OBSERVATION

AUTOMATED COMPUTATION OF PATIENT COORDINATES ON THE FACTORIAL PLANE

SURVIVAL NONSURVIVAL

GRAPHIC PREDICTION RULE

CONVENTIONAL INDICATION FOR

THERAPY BALLOON SUPPORT

/

GROUP I: GROUP II: PUMPING PUMPING

PERFORMED NOT PERFORMED

Hotelling T2 statistic.lfi The latter was used to test the null hypothesis of equality of two mean vectors x and v with:

g = (X1, xz, . . XI,)

1 Y=(y,,& ,............. jf!,) ,where

Xi = mean value of the ith parameter measured in the patients of group I (see later).

yi = mean value of the ith parameter measured in the patients of group II (see later).

A stepwise nonlinear discriminant analysis using a Rayes procedure” was performed in an attempt to separate survivors from nonsurvivors undergoing circulatory assistance. The

. NON SURVIVOR

SURVIVOR i ‘-. ; _

,. ‘;

NON . \

SURVIVAL /’ 1 = ’ .~ \_ SURVIVAL ZONE *,’ n . I

. GONE .

. ’ f. .

:‘, 12

.:’ . t n ’

D n . . \‘t;;’ .~, s ‘\,$

.i . .

8. . : .;

:

.

.: ‘\

.

_-’

.

.

.

8’

: P ‘/ \

.,’ \

/ _-

/ /

/ , ”

FIGURE 2. Learning sample projected on the factorial plane (f,,f,). S, D, A and I correspond to the barycenters of survivor, nonsurvivor, anterior and inferior myocardial infarction groups, respectively.

1 FIGURE 1. Protocol followed in the 88 patients in the test sample.

significance of evolutionary changes within groups was evaluated by the Wilcoxon signed rank test.

lntraaortic Balloon Counterpulsation

Group I versus group II: Forty-three patients were graphically predicted to be nonsurvivors. Among these, 26 underwent balloon pumping and formed group I (Table II); in the 17 remaining patients (group II), balloon pumping was not performed. This grouping of patients was not performed in random fashion, owing to ethical considerations. Patients in group II, although as critically ill as those in group I, did not undergo pumping for the following coincidental technical reasons: (1) device failure, (2) lack of staff, or (3) use of the apparatus elsewhere. Patients in whom balloon catheter in- sertion failed because of the presence of iliofemoral atheroma were not included in the study.

Protocol during balloon pumping: The mean delay between onset of pump failure and initiation of counterpulsation was 15 hours (range 3 to 30). Under local anesthesia an AVCO intraaortic balloon catheter was inserted into the right common femoral artery through a sidearm graft and positioned distal to the left subclavian arterial orifice. The timing of inflation and deflation was adjusted to ensure inflation on the dicrotic notch of the monitored radial arterial pressure and deflation before the ascending systolic limb. Heparin was administered during the period of circulatory support and low molecular-weight dextran was given intravenously at 10 ml/hour. No patient received a trial of medical therapy (vasoactive drugs or digitalis) before pumping to assess re- fractoriness of the pump failure. In addition to assessment of the clinical and hemodynamic variables listed in Table I and the electrocardiogram and chest X-ray film, arterial blood gas measurements, blood cell counts, serum and urine electrolytes, blood urea nitrogen and serum enzyme determinations were made. Urinary flow from an indwelling bladder catheter was measured hourly.


INTRAACRTIC CCUNTERWLSATION IN MYCCAROIAL INFARCTION-LCRENTE ET AL.

TABLE III

Univarlate Analysis of Cases (mean f standard deviation)’

Learning Sample (n = 101)

survivors Nonsurvivors

Test Sample (n = 88) Predicted Predicted

P to Survive to Die P

HR (beats/min) 88f 14 98f 18 <0.02 87 f 20 98f 19 <O.Ol Cl (llters/min per m2) 2.30 f 0.58 1.40 f 0.38 <10-s 2.87 f 0.59 1.50 f 0.38 <10-s SAP (mm Hg) 114f25 98 f 22 LVFP (mm Hg) 18.5 f 5.1 22.0 f 5.1 ;$$l 125f25 91 f 18 14.8 f 5.8 22.8 f 8.0 :;;r:

RVFP (mm Hg) 8.3 f 4.1 10.8 f 4.3 <O.Ol 8.1 f 4.2 10.8 f 4.5 <O.Ol

+ No significant difference is observed between learning sample survivors and test sample patients predicted to survive and between learning sample nonsurvivors and test sample patients predicted to survive.

p = probability; other abbreviations as in Table I.

After 24 to 96 hours of therapy, attempts were made to wean patients from balloon assistance as soon as they showed improvement and their condition appeared hemodynamically stable. A stepwise reduction in the frequency of inflation was performed from l:l, to 1:2, to 1:4. Counterpulsation was continued for 3 to 4 hours at each stage of the withdrawal process. A decrease in mean arterial pressure to less than 60 mm Hg, an increase in pulmonary arterial wedge pressure to more than 20 mm Hg, a reduction in cardiac index below 2 liters/min per m2, and recurrence of ischemic pain, pulmonary edema or cardiogenic shock were considered indicators of balloon- dependence.

Coronary and left ventricular angiography and indications for surgery: Whether or not a patient was balloon- dependent he was referred for left ventriculography and coronary angiography while pumping was continued so that coronary lesions amenable to surgery could be identified. However, only 14 patients underwent cardiac catheterization; the procedure was not performed in 8 of the remaining 12 patients because of a reduced time course or a rapid worsening of condition during circulatory assistance, or both, and was not performed in 4 because of failure of the device.

Our criteria for emergency revascularization, derived from those of the Massachussetts General Hospital group, 18-2o were as follows: (1) adequate coronary vessels distally for

“‘“YIVOR ; 0 SURVlVOR

- ION SURVIVOR . .._.

* q SURVIVOR ‘\ 0 NON ,i’ .’ /

SURVIVAL,/’ ;: ‘/ ZONE*/ ‘, . ‘I 0

‘\\,SURVIVAL

0 ‘\ ZONE

& . / I . , 00 ‘* \

Learning sample: Figure 2 depicts the scatter diagram obtained for the patients of the learning sample, projected on the factorial plane defined by fr and fs. They are roughly divided along fl into two groups: nonsurvivor (left) and survivor (right), delineating the survival and nonsurvival zones. The two zones overlap slightly at the upper part of the diagram where inferior infarctions are prevalent. Anterior infarctions prevail in the lower part. As demonstrated in previous publi- cations6vg fl is well correlated with outcome and left ventricular function variables. Hence, the position of a patient’s data point along this axis (that is, his fr coordinate) reflects his likelihood of survival and can be considered a reliable prognostic indicator.

4 MINUTE WORK t TENSION TIME p .

/ ’ q m

0 .

bypass with good peripheral runoff and (2) relative preser- vation of perfusion and contraction in at least four of the six left ventricular segments defined by Leinbach et al.18 A combination of akinesia and avascularity in the same area was considered as a contraindication. The decision for infarctectomy was made either at the time of surgery in addition to revascularization or when there was angiographic evidence of a large paradoxically bulging infarct associated with a good contraction of the myocardium adjacent to the mitral ring. Three patients underwent infarctectomy and two had coronary bypass grafting. One of the latter two also had infarctectomy. Postmortem examination was performed in 12 nonsurvivors and in 1 short-term survivor.

Results

0

INDEX

kgm

$/ P << 0.00

1500

1 P < 0.01

\ -. \ . /’ -___y \ k’-_-___ L_-- .~~~_ -. ,’

.__--/ . BASELINE MEASUREMENTS

FIGURE 3. Projection of the test sample on the factorial plane (f,,fz). Among the patients undergoing intraaortic balloon pumping (IABP), data points for survivors are generally plotted toward the right part of the critical zone as opposed to those of nonsurvivors, which are spread throughout this zone.

o PEAK IMPROVEMENT

FIGURE 4. Graph showing significant improvement of hemodynamic status with intraaortic balloon counterpulsation. kgm = kilogram- meters.

July 1980 The American Journal of CARDIOLDGY Volume 46 129

INTRAAORTIC COUNTERPULSATION IN MYOCARDIAL INFARCTION-LORENTE ET AL.

Survivors and nonsurvivors are characterized by significant intergroup differences between the mean values for heart rate, cardiac index, left and right ventricular filling pressures and systolic aortic pressure (Table III). These variables are precisely those that predominate in the mathematical formulation of the first factorial axis.

Test sample: The scattering of the test sample represented in Figure 3 is comparable with that observed in Figure 2 and shows similar distribution according to outcome and topographic criteria. Analogous differences were observed after plotting for the variables mentioned regarding the patients predicted to die and those predicted to survive (Table III). Furthermore, there was no significant difference between nonsurvivors in the learning sample and patients in the test sample predicted to die or between survivors in the learning sample and patients in the test sample predicted to survive. These comparability tests allow us to assess the consistency of analysis and validate our prognostic decision-making rule.

As mentioned, groups I and II were defined according to whether the critically ill patients were or were not

subjected to circulatory assistance. To assess the effectiveness of counterpulsation, comparisons were made to determine whether group II could be considered as a reference for group I. Only a few significant differences were observed in some variables unrelated to prognosis and left ventricular function, whereas no appreciable difference was noted for prognostic indexes, left ventricular function variables or mean group vectors (Table IV). Thus, the groups were accepted as comparable and suitable for evaluating balloon pump efficacy.

Effectiveness of intraaortic balloon pumping: At the initial stage of balloon assistance, cardiac pump failure was reversed in 23 of 26 patients and the effectiveness of counterpulsation was judged hemodynamically by a significant increase in the minute work index and a significant decrease in the tension-time index (Fig. 4), the peak improvement occurring within a mean of 19 hours.

If one assumes that groups I and II are comparable, testing for the same probability of survival in either group results in the conclusion that intraaortic balloon pumping probably improves short-term survival (Table IV). To evaluate the meaning of this result, three

TABLE IV

Patients Referred for lntraaortic Balloon Pumping: Initial Clinical and Hemodynamic Data

Group I Group II (with IABP) (no IABP)

(n = 26) (n = 17) p

Age 57.3 f 10.5 64.1 f 10.9 <0.05 sex

Male 18 = 0.05 Female 8

1;

Previous MI Yes No 2: 1;

Mi site AMI 24 9 = 0.04 IMI 2 8

Conduction disturbances Yes 10 No :4

272 f 1.7 TS (days) 2.0 f 1.3 HR (beats/min) 103.9 f 15.6 90.8 f 20.9 <0.05 Cl (liters/min m*) per 1.50 f 0.44 1.46 f 0.36 SI (ml/beat m*) per 14.6 f 4.9 16.6 f 4.2 SAP (mm Hg) 89.5 f 12.8 89.3 f 15.8 DAP (mm Hg) 63.0 f 9.8 55.1 f 7.8 <0.02 MAP (mm Hg) 71.2 f 10.5 66.4 f 9.3 PVR (dynes s crnw5 m2) per 3614 f 1296 3198 f 997 LVFP (mm Hg) 22.1 f 6.4 21.1 f 7.7 MPAP (mm Hg) 29.4 f 7.2 28.5 f 12.0 RVFP (mm Hg) 9.2 f 4.0 10.8 f 3.8 TPR (dynes s cm-5 m*) per 1725 f 825 1616 f 788 LVSWI (g.m/m? 10.44 f 4.03 10.86 f 3.53 RVSWI (g.m/m ) 4.34 f 2.08 4.19 f 2.63 LVMWI (g.m/mi min) per 1060 f 385 949 f 285 ;;rGWl (g.m/m per min) 446 2.73 f f 221 1.86 391 1.97 f f 254 1.42

Z -1.30 f 1.35 -1.30 f 1.20 f 1 co-ordinates -364 f 381 -372 f 177

Ho$~~IIP, T* x v F = 1.15:NS

Survival 7 0 = 0.02 Nonsurvival 19 17

Values for continuous variables are expressed as mean values f standard deviation; AMI = anterior myocardial infarction; IABP = intraaortic balloon pumping; IMI = inferior myocardial infarction; MI = myocardial infarction; NS = not significant; Z = prognostic index (see text): other abbreviations as in Table I.



subgroups within group I were retrospectively defined according to follow-up finding: Ia (7 survivors); Ib (7 balloon-dependent patients); and Ic (12 patients with insignificant transient improvement or rapid clinical and hemodynamic deterioration, or both, during balloon pumping).

Baseline measurements for survivors (group Ia) and nonsurvivors (pooled groups Ib and Ic) are compared in Table V. Significant intergroup differences were observed for cardiac index, left ventricular function variables, urinary flow and prognostic indexes, dem- onstrating a worse status in nonsurvivors than in survivors just before the onset of balloon pumping. Dif- ferences between groups Ia and Ic were more striking, and there was no significant difference between groups Ib and Ic.

Then a question arose: Could a precise rule for prediction of survival be derived from baseline measurements in patients referred for balloon pumping? Con- sistent with the results of univariate analysis, a good classification rate of both survivors and nonsurvivors (92 percent) was obtained by the use of a stepwise discriminant analysis (Fig. 5). The first three variables selected were urinary output, left ventricular minute work index and ejection time. The computed proba- bilities gave an estimate of the likelihood of survival leading to the misclassification of only two patients who were erroneously predicted to survive: Patient 12, who

I-

CLASSIFICATION TABLE

GROUP

AllOelTlOW

1 1 --

1 2 3 STEPS

FIGURE 5. Nonlinear stepwise discriminant analysis based on survival at 1 month. Urinary flow (Gur), left ventricular minute work index (LVMWI) and ejection time (ET) are successively selected. Only two patients are misclassified at the third step: They were predicted to survive but died. D = nonsurvival; S = survival.

died intraoperatively, and Patient 8, who died 48 hours after operation.

In contrast, no predictive inferences could be drawn from changes recorded during circulatory assistance. Comparisons between patients in groups Ia and Ib were made at two times (ti and ts) during balloon pumping. Time ti was defined as the 17th hour f 6 (standard

TABLE V

Intergroup Comparisons Between Survivors (group la) and Nonsurvivors (groups lb and ic), Between Survivors and Baiioon- Dependent Patients (group lb), and Between Survivors and Patients Whose Condition Deteriorated (group ic) for initial Clinlcai and Hemodvnamic Data

Variable

Survivors (group la)

(n = 7)

Nonsurvivors la vs. (groups lb •t Ic) lb + Ic

(n = 19) (P)

Group lb (n = 7) +

la vs. lb (P)

Group Ic (n = 12) +

la vs.

fc (P)

Age Duration of IABP (h) ;; (days)

Cl SI SAP DAP MAP PVR LVFP MPAP RVFP TPR LVSWI RVSWI LVMWI

56.9 155 2.9 105.7 1.84 17.3 95.9 65.0 74.4 3009 21.6 30.7 8.7 1356 13.20 5.60 1397 605 3.42

-0.43 -77

57.5 93

.

<‘d.o5

jd.05 . .

57.4 136 1.9 110.9 1.47 14.1 91.6 66.7 73.7 3709 23.7 29.9 8.5 1675 10.26 4.43 1054 460 2.58

-1.25 -373

210 1810 8.6 8.7

. . .

57.5 68 jd.04

<0.05

<0.63

id.05

iiz3.3 1.37 13.8 87.1 62.3 70.1 3836 23.1 29.0 9.3 1861 9.43 3.87 936 387 2.48

-1.62 -470

197 1660 5.3 5.6

!&68 . . . . .

.

.

1.31 13.6 84.5 59.7 67.9

. . . . . .

id.63

3911 22.7 28.5 9.8 1969 8.94 3.55 867 345 2.43

-- 1.84 -527

189 1572 3.4 3.8

. . . . . . .

id.65 co.03 <6.62

<0.05 <0.02 jd.02 id.65

. .

<&!I2 co.03

<O.Ol -

jd.05 . . . . . .

jd.02 <0.02 <0.05

<‘d.Ol -

6 co-ordinates

:I Q ur Mean delay of

survival (days)’

227 1905 19.3

>1 mo -

l Comparison of balloon-dependent patients with patients in group Ic revealed no significance level for any variable except for survival time from onset of the infarct to death (p <O.Ol).

Abbreviations and units as in Table I.



i = 60 , c ,G . z g 40_ *

2 k

ko t 5

1 .“ P< 0.03

FlGURE 6. tiemodynamic changes observed in survivors (open circles) and in balloondependent patients (closed circles) before (b) and during circulatory assistance (1, and t2). The only significant intergroup difference was observed at t, for urinary flow. T, and T2 = 17th and 54th hour (mean) of counterpulsation.

deviation) and ts as the 54th hour f 18 of counterpulsation. In addition, intragroup tests between baseline measurements and data collected at ti and t:! were carried out. No significant difference was observed between patients in groups Ia and Ib except for urinary flow, which was greater at time ti in survivors (64 f 15 ml/ hour) than in balloon-dependent patients (41 f 28 ml/hour, p <0.03). The most meaningful changes within groups Ia and Ib are summarized in Figure 6. A significant improvement was recorded at ti for left ventricular function variables and urinary flow in both groups. Between ti and ts nonsignificant intragroup changes occurred, with both groups attaining a similar plateau of left ventricular function.

Angiographic, pathologic and follow-up studies: The angiographic data (Table II) revealed no significant differences among patient subsets. All but Patient 3 had extensive obstructive three vessel disease and severe impairment of contraction in large areas of myocardium, although dyssynergy appeared to be more marked in patients whose condition deteriorated rapidly during counterpulsation. Of these patients only five were candidates for emergency surgery, and one of these (Patient 3) was a long-term survivor. Among the patients in group Ia, four died within 2 months: two were in New York Heart Association class IV and two were asymptomatic until sudden death occurred. Only three patients were long-term survivors: One is still living after 3 years and has satisfactory exercise tolerance; one had well controlled heart failure, but died suddenly after 13 months; and one had resumed professional activities but died after 4.5 years. The overall long-term survival rate was 11 percent. Autopsy performed in 13 patients

showed massive infarction involving 40 percent or more of the left ventricular myocardium and extensive coronary artery disease with three vessel involvement in 11.

Complications: A variable degree of arterial insufficiency was observed in five patients. In one, the problem was transient and disappeared within 30 minutes. In two patients, ischemia was sufficiently prolonged to warrant removal of the balloon, which was proximally reinserted in one. Arterial emergency surgery was required in one patient because of ischemia after balloon removal, despite the routine Fogarty ex- ploration of the catheterized vessels. In one, acute vascular insufficiency was related to atheromatous emboli originating from aortic lesions as demonstrated by autopsy. Of the five patients with complications two were long-term survivors and one a short-term survivor. In one patient the balloon could not pass through an oc- cluded femoral artery and was inserted through the contralateral artery. Pulmonary emboli were found in three patients at postmortem examination, although all had received adequate anticoagulant therapy during balloon assistance. The external balloon ruptured in one patient, but no patient died as a result of balloon pumping.

Discussion

Reported survival rates after intraaortic balloon pumping: When considering the reported effectiveness of intraaortic balloon pumping in cardiac pump failure complicating acute myocardial infarction, one is im- pressed by the surprisingly wide range of survival rates (11 to 71 percent).21-32 The following factors may account for these large differences. (1) The criteria used for patient selection vary from one study to another.2 (2) The extent of left ventricular dysfunction is not al- ways hemodynamically assessed before circulatory assistance is given, even though not all patients with shock during myocardial infarction have an equal risk of death.’ (3) Sometimes, patients with either pure myocardial dysfunction or mechanical defect are pooled in the same sample, notwithstanding the different pat.hophysiologic features and accompanying prognoses. (4) In most studies, a trial of medical therapy, including administration of catecholamines or other supportive agents, was given and failure to respond to this conventional treatment was considered a criterion for intraaortic balloon pumping.2*-“7~30-s2 But this procedure can entail loss of time whereas early circulatory support is required to stop the vicious cycle of hemodynamic and metabolic deterioration. Furthermore, the deleterious effects of inotropic agents can advance the myocardial ischemic injury.33,34

Selection of patients for balloon pumping: To obviate the drawbacks arising from a heterogeneous selection of patients, we included only patients with myocardial infarction and pump failure who had no mechanical complications and had not undergone a previous trial of medical therapy. In addition, we performed balloon pumping whenever the multivariable



prognostic decision-making rule predicted a low likelihood of survival on the basis of hemodynamic data (irrespective of the patient’s clinical classification).

Our selection of patients for counterpulsation (group I) was not based on a randomization procedure and is thus open to criticism. However, our patients who did not undergo counterpulsation (group II) may be considered to approach a control group because the few differences between groups I and II were unrelated to ventricular function or prognostic index values. Thus, the assumption that the groups are comparable enables us to conclude that intraaortic balloon pumping improves short-term survival.

Survivors versus nonsurvivors of intraaortic balloon pumping: The question arises whether the short-term survivors are really representative of group I or, equivalently, whether survival is independent of the severity of dysfunction within this group. The intergroup comparisons of baseline measurements (Table V) suggest that survivors were in better condition before counterpulsation than were balloon-dependent patients or those who died while undergoing balloon pumping. One can infer that these groupings reflected a variable impairment of cardiac function among the patients treated. The results of this univariate screening were subsequently confirmed by a stepwise discriminant analysis based on survival at 1 month: A high rate of accurate classification was obtained with the first three variables selected. This finding suggests that it may be possible to predict the outcome of patients referred for consideration of circulatory assistance on the basis of initial hemodynamic status. However, this new prognostic decision-making rule could not be validated owing to the small sample sizes involved and the absence of a test sample.

Predictors of survival: In contrast with our results, Dunkman21 and Scheidt and their co-workers22 were unable to predict outcome from initial data, and we were unable to identify balloon-dependent patients within the first 24 hours of counterpulsation as had Ehrich et a1.23 Other workers27,2s found retrospective clues to survival such as the location of the infarct, the absence of a previous infarct, the stabilization of hemodynamic status within 24 hours of balloon pumping2g and the extent of myocardial and coronary lesions visualized on angiography.18>20 These clues were not found in our data. The patients’ functional classification may have

some prognostic value because, among our patients in functional class III, three were survivors, one was balloon-dependent and none was in worse condition during pumping (group Ic): These findings are in good agree- ment with data from other reports.30>31 Nevertheless, urinary flow seems to be the most reliable prognostic indicator, as Scheidt et a1.s2 and Jackson et a1.25 reported. Our data indicate that indexes of left ventricular function are also good predictors of survival.

Long-term survivors: Among our seven short-term survivors, only three were long-term survivors: Two of the three were in Killip class IV and one in class III before balloon pumping. This low long-term survival rate was probably related to extensive ventricular and coronary lesions similar to those observed in the other groups. Such a poor long-term prognosis was previously observed in balloon-dependent patients and also in those who were successfully weaned from circulatory assistance.21,23,27,32 In order to identify surgical candidates, we performed angiography in all balloon-assisted patients whether or not they were balloon-dependent. This procedure was based on the assumption that re- ducing ischemic akinetic areas by myocardial revascularization and suppressing a threatening mechanical factor such as an acute aneurysm could improve prognosis in every patient undergoing pumping.

Clinical implications: Our results lend support to the concept that indications for balloon pumping could be optimized through use of objective indexes of severity of dysfunction. By using these indexes, counterpulsation could reasonably be proposed to patients ranging from those predicted to be survivors with conventional therapy and those predicted to be nonsurvivors with circulatory assistance plus surgery. Similarly, many investigators1~2~25~30 have advocated counterpulsation in randomized patients with less severe dysfunction than those with an expected mortality rate approaching 100 percent. But the difficulties of selecting patients at equal risk lie in defining the objective criteria, in ap- praising the patient’s status and in obtaining truly ho- mogeneous and comparable samples. However, in pro- found cardiogenic shock with an extremely high mortality rate, a fatal outcome is probable unless cardiac transplantation is possible. The latter procedure was recently performed by Reemtsma et al.,35 but it is not generally feasible in all institutions, and all related immunologic problems are not yet solved.

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