Predictors of long-term cardiac survival in patients with multivessel coronary artery disease undergoing percutaneous transluminal coronary angioplasty

The

CORONARY ARTERY DISEASE

American Journal of Cardiology

JANUARY1, 1991,VOL. 67, NO. 1

Predictors of Long-Term Cardiac Survival in Patients with Multivessel Coronary Artery Disease Undergoing Percutaneous Transluminal Coronary Angioplasty Michel Vandormael, MD, Ubeydullah Deligonul, MD, Sue Taussig, RN, and Morton J. Kern, MD

The predictors of S-year cardiac survival in patients with muitivessei coronary artery disease (CAD) undergoing percutaneous transiuminai coronary angkpiasty (PTCA) were analyzed in a series of 637 consecutive patients. The average age was 59 f 11 years in 472 men and 165 women. Diabetes meiiitus, previous myocardiai infarction and unstabie angbra were present in 119 (19%), 261 (41%) and 305 (47%) patients, respectively. Angiographkaiiy, 460 patknts had 2-vessei and 177 pathts had t-vessei CAD. The left ventricuiar contraction score was 212 in 55 patients. Angiographic success (
dictor of cardiac mortality was the iefi ventricular scoreof 212. in conciusion, ieft ventrkuiar function was the most important determinant of cardiac survival in patients with muitfvessei CAD undergoing PTCA, independent of the ciinkai success of the procedure. Advanced age and diabetes meiiitus were associated with additional risk in the overail group, but not in the succe&uiiy treated group. in patknts with muitivessei CAD, S-year survival after PTCA is excellent in the absence of these adverse prognostic factors. (Am J Cardioi 1991;67:1-6)

lthough percutaneoustransluminal coronary angioplasty (PTCA) is now being widely applied in patients with multivesselcoronary artery disease (CAD), many questions regarding indications, patient selection and long-term outcome remain unanswered. Several studies with intermediate-term follow-up (average 15 to 31 months) have shown a mortality rate of 2% and a nonfatal myocardial infarction rate of 2 to 3% during the first 2 years after the procedure.1-8In these series, a second revascularization procedure was required in 25 to 30% of patients, most often during the first year. The secondrevascularization procedure performed was coronary artery bypass surgery in approximately two-thirds of patients and repeat PICA in others. There are only limited data on longer (24 years) follow-up after PICA in patients with multivessel CAD. The follow-up results are often presentedonly in patients with clinically successfulprocedures,with less emphasison the impact of unsuccessfulor complicated FTCA on the overall long-term outcome. Although several factors have been related to survival. with medical From the Cardiology Division, St. Louis University Hospital, St. Louis, or surgical treatment of CAD, the determinants of surMissouri 63110. Manuscript received June 11, 1990; revised manu- vival after PTCA in patients with multivessel CAD are script receivedand acceptedAugust 24, 1990. Address for reprints: Ubeydullah Deligonul, MD, Cardiac Cathe- not well known. In this study, we analyzed the predictors for longterization Laboratory, St. Louis University Hospital, 3635 Vista Aveterm survival in a large series of consecutive patients nue at Grand, St. Louis, Missouri 63110.

A

THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1991

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TABLE I Clinical and Angiographic Characteristics

Total Age Male/female Diabetes mellitus* Systemic hypertension* Cigarette smoking* Previous (>l week) myocardial infarction Unstable angina Angina 1 (Canadian Cardiac Society) class Ill Two-vessel CAD All proximal narrowings Proximal LAD + proximal LC Proximal LAD + proximal right Proximal LC + proximal right One proximal narrowing Total occlusion Proximal Distal Three-vessel CAD All proximal narrowings One or more proximal narrowing Total occlusion Proximal Distal LVscore 212

No.

%

637 59 f 11(29-94) 472/165 119 284 246 261 305

74/26 19 44 39 41 47

403 460 137 18 74 45 260 123 104 19 177 21 152 74 48 26 55

63 72 30

57 27

28 12 86 42

9

* Definition of coronaryrisk factorsis based on patienthistory; diabetes mellitus = treatment by diet. oral antidiabetic drugs or insulin of elevated blood sugar: systemic hypertension = a previous diagnosis of high blood pressure or treatment by diet Or antihypertensive therapy. or both: cigarette smoking = any tobacco smoking habit continued within 1 year of percutaneous transluminal coronary angioplasty. CAD = coronary artery disease; LAD = k?fl anterior descending artery; LC = left crcumflex artery: LV = left ventricular.

with multivessel CAD undergoing PTCA to provide guidelines for better selection and follow-up care of the patients. METHODS Patienk: Six hundred and thirty-seven consecutive patients with multivessel CAD underwent initial PTCA at our institution between May 1983 and June 1988. The patient selection criteria, cardiac catheterization and coronary angioplasty procedures have been previously described.* Briefly, the patients were selectedon the basis of suitability of culprit lesion(s) to PICA. In general, all patients were surgical candidates,although a small number of “salvage” PTCA procedures were performed. The patients with prior coronary bypasssurgery and those with acute transmural myocardial infarction within 1 week of PTCA were not included in this study. Angiographic evaluation: Multivessel coronary diseasewas defined as diameter stenosisof 250% of 2 major coronary arteries as determined by averaging the caliper measurementsin 2 views. Patients with narrowings in the diagonal brancheswere consideredas having left anterior descendingCAD. Patients with stenosisin the obtusemarginal brancheswere consideredas having circumflex CAD. Thus, when a patient had dilatation of diagonal and left anterior descendingcoronary narrowings, this patient was considered to have had l-vessel, multilesion dilatation. The lesion location was classified as proximal (proximal, mid- and distal segments of 2

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67

right coronary artery, left anterior descendingartery before first septal branch and left circumflex artery before first obtuse marginal branch) and distal (posterior descending and posterolateral branches of right coronary artery, mid- and distal segmentsof left anterior descendingand diagonal branches,and marginal branches and distal part of the left circumflex artery). The extent of residual coronary diseaseimmediately after the PTCA procedurewas evaluatedby the number, severity (50 to 69, 70 to 99 and lOa) and location (proximal versus distal) of lesions. The presenceof L70% proximal left anterior descendingartery narrowings was also included in the analysis as a separatevariable. Left ventricular function was assessedon 30° right anterior oblique ventriculograms by using a contraction score according to the Coronary Artery Surgery Study coding system.gA left ventricular contraction score of 112 was selected to identify patients with significant left ventricular dysfunction. In the Coronary Artery Surgery Study registry, a left ventricular score of 2 12 was a predictor of poor outcome in medically treated patients.lO Left ventricular ejection fraction was not available in all patients; therefore, it was not included in the analysis. Evaluation of percutaneous transluminal coronary angioplasty resul& Angiographic and clinical success

and degree of revascularization were defined as previously described.5Briefly, coronary artery narrowings were consideredsuccessfullydilated when a 30% reduction in luminal diameter stenosiswas obtained and the residual narrowing was <50%. Clinical successwas defined as successfuldilatation of the critical stenosisor of all attempted lesionswithout exacerbation of symptoms and without major in-hospital complications, such as myocardial infarction, the need for coronary bypass grafting or death. Complete revascularization was defined as successfuldilatation of all major coronary or branch vesselsand absenceof residual stenosisof >50% in a major coronary vessel.Our strategy was to attempt dilation of all significant narrowings during the same procedure. Dilation of occluded vesselsthat supplied akinetic left ventricular segmentswas not routinely attempted. Follow-up: All patients were eligible for 11 year of follow-up. The functional status of the patients and presenceor absenceof cardiac events (acute myocardial infarction, coronary bypasssurgery, repeat PTCA) were prospectively determined by questionnaire, telephone interview or clinic visit at 6 months and 1 year after the PTCA and then at l-year intervals. The medical records (discharge summary, catheterization or PTCA reports, operative records) were obtained to document the occurrence of nonfatal events. Only 7 patients (6 with a second revascularization and 1 with myocardial infarction) refused to releasetheir medical information. Therefore, the events in these 7 patients were defined according to the patient’s descriptions.The deaths that occurred as a result of clearly described noncardiac causes (such as cancer, accidents, and so forth) were classified as noncardiac deaths and the remaining deaths were accepted as cardiac deaths. No

TABLE III Five-Year Outcome of Percutaneous Transluminal Coronary Angioplasty in Multivessel Disease

TABLE II Results of Percutaneous Transluminal Coronary Angioplasty No. Total No. of lesions dilated/attempted Clinical success Complete revascularization Incomplete revascularization Reason for incomplete revascularization Total occlusion >70% narrowing 50-70% narrowing Remaining narrowing(s) after PTCA Single narrowing Multiple narrowings Proximal narrowing Proximal total occlusion Proximal LAD >70% Complications Procedure-related death* Emergency coronary bypass surgery No myocardial infarction With myocardial infarction Q-wave myocardial infarction

%

637 1,133/1,343 526 177 349

85 83 34 66

171 88 90

49 25 26

274 75 196 97 13

79 21 56 28 4

9

1.4

34 10 6

5.3 1.6 0.9

* Procedure-related death was defined as death occurring immediately in the catheterization laboratory or later in the hospital as a documented, direct result of a complicabon of PTCA. LAD = left anterior descending artery; PTCA = percutaneous translumlnal coronary angroplasty.

verification of causeof death was attempted other than available records and family’s description. Statistical analysis: All statistical analyseswere performed using the BMDP program.” Survival analysis was performed by the Kaplan-Meier method. The noncardiac deaths were censoredat the time of death. The group survival differences were compared using the Mantel-Cox test. Clinical, angiographic and procedural factors included in Tables I and II were analyzed in a Cox regression model for cardiac survival. The angiographic and procedural variables were selectedfor analysis to indicate the extent and severity of CAD before and after PTCA. Cox regression analysis was performed in the overall patient group (including patients who had successfuland unsuccessfulPTCA) by forcing the clinical successvariable into the regression model and then entering other variables in a stepwisefashion to determine additional independent effects on survival. A secondanalysis was performed only in clinically successful patients to determine the predictors of out-ofhospital survival. Relative risk ratio for each independent variable was calculated from relative risks for favorable and unfavorable values of each variable-i2 RESULTS The clinical and angiographic characteristics of the patients are summarized in Table I. Seventy-two percent of patients had 2-vesseland 28% of patients had 3vesselCAD. Immediate percutaneous transluminel coronary angioplasty results: An angiographic success was ob-

tained in 85% of narrowings and clinical successwas obtained in 83% of patients (Table II). Complete revascularization was obtained in 177 of 526 patients who

Whole Group (n = 637)

Successfully Treated Group (n - 526)

Cardiac Events*

No.

%

No.

%

With complete follow-upt Noncardiac death Cardiac death Nonfatal myocardial infarction Emergency coronary bypass surgery Elective coronary bypass surgery Repeat PTCA

608 12 61 36 44 114 73

95 1.9 10 5.9 7.2 18.7 12

503 10 40 20 58 72

96 1.9 7.6 3.9 11 13.7

* Mutually exclusive categories in listed order. t Fifteen additional patients had incomplete follow-up, no events: 5 additional patients had incomplete follow-up, events not included in this table; 9 patients were lost to follow-up. PTCA = percutaneous transluminal coronary angioplasty.

had clinical success(34%) (Table II). The major complications of the PTCA procedure are listed in Table II. Follow-up results: A total of 608 patients (95%) had complete follow-up data with 11 year of follow-up updated within 6 months of the study deadline. Twenty additional patients had incomplete follow-up, 5 of whom had various events(coronary bypasssurgery in 4 and PTCA in 1) that were not included in the analysis. Nine patients were completely lost to follow-up. The incidencesof cardiac events (mutually exclusive) for the whole group and for the group with clinically successful PTCA are listed in Table III. The 30-day mortality rate for the whole group was 3.2% (21 patients). PTCA was performed as a salvageprocedure in 4 of these 21 patients. The indication for second revascularization in 130 patients with an initially successfulPTCA procedure was restenosisin 67 (51%), progressionof CAD in 21 (16%) and combined restenosisand progression in 22 (17%). Incomplete revascularization at the initial PTCA was the indication for second revascularization in only 13 (10%) patients. In 6 patients, angiography was not performed or was unavailable, and 1 patient underwent valve surgery after successfulPTCA. Predictors of cardiac mortality: The cardiac survival estimatedby the Kaplan-Meier analysis was 93 f 1,92 f 1,90 f 1,88 f 1 and 86 f 2% at 1 through 5 years, respectively, in the overall group. The number of patients at risk for theseestimateswere 509,419, 307, 175 and 62 at 1 through 5 years, respectively. Clinical successwas associatedwith more favorable 5-year cardiac survival (88 f 2%) compared with survival in patients with unsuccessfulPTCA (77 f 5%) (p
3

I

TABLE IV Predictors of Cardiac Mortality in 637 Patients with Multivessel Disease Undergoing Percutaneous Transluminal Coronary Angioplasty Percent Cardiac Survival Estimated by Kaplan-Meier Method*

I Variable No. at Risk Immediate outcome of PTCA Successful Failed Left ventricular contraction score L 12: Yes No Diabetes mellitus Yes No Age 265 years Yes No * Survival estimate + Global chi-square.

* standard

1 Year (n = 509)

3 Years (n = 307)

5 Years (n = 62)

Improvement (Chi-Square)

p Value

96fl 82f4

92*1 8of4

8%*2 77f5

11.9t


95fl 78f6

92fl 64f7

89ct2 59zk8

23.8


87f3 95ztl

82f4 93fl

72f9 90f2

9.8

0.002

90*2 95*1

84f3 93fl

79f5 9of2

8.2

0.034

error of the estimate.

There is an increasedprocedural risk of death in patients with multivessel CAD undergoing PTCA. Ellis et a1,13in a large seriesof patients, found the presenceof multivesselCAD to be a significant independentpredictor of in-hospital mortality. Similarly, the National Heart, Lung, and Blood Institute PTCA Registry reported a higher in-hospital mortality in patients with multivessel CAD than in those with l-vessel disease.i4 In the current study, failed PTCA was associated with lower survival, mostly becauseof higher early morDISCUSSION In this large consecutiveseriesof patients with mul- tality (Figure 1). We were also able to identify additiontivessel CAD undergoing PTCA (including unsuccess- al risk factors for increased mortality independent of ful procedures), the estimated 5-year survival was ap clinical successof the procedure. The presenceof these proximately 90%. There was a relatively stable and low risk factors will increasethe likelihood of death should yearly attrition rate of 1 to 2% beyond the first year PTCA fail. Among the variables analyzed, old age and after PTCA. Becauseof the selection criteria applied, it the presenceof diabetes mellitus were significant cliniis difficult to comparethe survival in this seriesto previ- cal predictors of mortality after PTCA. The risk of ously published survival of surgical or medical series. PTCA has been reported to be increasedin elderly padition to the immediate outcome of PTCA (successful or failed). Estimated ratio of risks for eachof thesevariables are listed in Table V. When the analysis was repeatedin the group of patients with clinically successfulPTCA results, the only significant independent predictor of cardiac mortality was a left ventricular contraction scoreof L 12, with an estimated relative risk ratio of 6.2 (p
PTCA IN MULTIVESSELCORONARY DISEASE/ loo-m,I.-,..,---=-mm-m.wh,m 1 -=-=-=-m-m~m-. -=-I p=o.o002 -4

$j

60--

+ FAILED PTCA K 40-304 0 F AT RISK: SUCCESS 503 FAILURE 105

4

1

2

3

4

I 5

256 51

141 34

44 18

YEARS 426 63

346 73

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67

tients.i5 Age is also a known predictor of mortality and morbidity after coronary bypasssurgeryal The relation of diabetes mellitus to increasedrisk of mortality after PTCA has also been noted previously.13Diabetes mellitus is a well known risk factor for restenosis after PTCA.i7J8 The presenceof diabetesis generally associated with a poorer outcome in patients with CAD19 or in those undergoing coronary artery bypassgraftings20 Importance of kfl ventricular dysfunction as a predlctar of mortality: In the overall seriesof patients un-

dergoing PTCA for multivessel CAD, the presenceof left ventricular dysfunction was the most important predictor of mortality (Figure 2, Tables IV and V). The negative impact of left ventricular dysfunction on survival persistedafter successfulPTCA: The estimated 5year survival in patients with and without left ventricular dysfunction was 90 f 2 and 64 f lo%, respectively (p
I FIGURE 2. Kaplan-W

&year

TABLE V Estimated Relative Risk Ratios for Independent

Variables* Independent Variable Immediate outcome of PTCA Failed Successful Left ventricular contraction score 212 <12 Diabetes mellitus Present Absent ripe (years) 70 5cJ * See Table IV. PTCA = percutaneous

transluminal

coronary

Relative Risk

Ratio of Risks

1.74 0.89

1.96

4.1 0.88

4.65

2.04 0.84

2.43

1.47 0.71

2.07

angioplasty.

with multivessel diseasewho had only mild angina and a left ventricular ejection fraction 134% but GO% was 84% for surgically treated and 70% for medically treated patients.22The difference between medically and surgically treated patients was only significant in those with 3-vesseldisease(65 vs 88%). The important question is whether PTCA in patients with multivessel disease and left ventricular dysfunction would provide a similar survival benefit to that expected from surgical revascularization. In patients with left ventricular regional wall motion abnormalities before PTCA, we observedthat regional systolic function was more likely to improve in patients without restenosis.23 Therefore, it is possiblethat restenosismay offset some of the possible survival benefit gained by PTCA revascularization. The effect of the baselineextent of CAD, classified as 2- or 3-vesselCAD according to the usual clinical terminology, on cardiac survival after PTCA for multivessel CAD has not been well defined. Although the natural history of patients with 3-vesselCAD is charac-

PTCA IN MULTIVESSEL

CORONARY

DISEASE

survival

arVerforpOUNltSWithmultlwudcorO-

naryarterydiseasewithIeftventrkuhr (LV) contraction scars 212 (poor LV functian) and <12 (good LV fumdon). llw numbersofpdentsatriskineshgroup ate4htimeintervalaregivenattheboC tomoftheiigurehTheleRve&kWgram was missing in 1 patient.

+ POOR LV FUNCTION

THE AMERICAN JOURNAL OF CARDIOLOGY JANUARY 1, 1991

5

terized by a lower survival than in those with 2-vessel CAD,l” the selection processfor PTCA probably excludes patients with 3-vesselCAD with worse prognostic characteristics, thus creating a bias toward a similar survival after PTCA in patients with 2- and 3-vessel CAD. The routine clinical “2- or 3-vesselCAD” stratification probably is not a satisfactory method to classify the severity of CAD in patients undergoing PTCA. A myocardial jeopardy scorebasedon the size of territory supplied by each vesselmay have more prognostic value.24The degree of revascularization (complete versus incomplete) obtained with PTCA was not a predictor of survival in our study. The follow-up data from the National Heart, Lung, and Blood Institute PTCA Registry25 showed that patients with incomplete revascularization had a higher mortality, with an estimatedrisk of 1.63, than those with complete revascularization. However, when a logistic regressionmodel was used to adjust for significant differences in baseline,including an ejection fraction <50%, the adjusted estimate of risk of death was no longer different betweenpatients with incomplete and complete revascularization. Clinical implications: Our study indicates that in patients with multivessel CAD who undergo PTCA, left ventricular function is the most important determinant of cardiac survival, independent of the immediate successor failure of PTCA. Old age and diabetesmellitus were also important when failed and successfulPTCA caseswere analyzed together. Theseresults may provide important clinical guidelines for selecting patients with multivessel CAD for PTCA. In future studies evaluating long-term outcome after PTCA, the effects of these variables must be taken into consideration. Acknowledgment: We wish to thank the J. Gerard Mudd Cardiac Catheterization Team and Donna Sander for manuscript preparation.

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