Frequency of Left Ventricular Free-Wall Rupture inPatients With Acute Myocardial Infarction Treated

With Primary AngioplastyRaul Moreno, MD, Esteban Lopez de Sa, MD, Jose L. Lopez-Sendon, MD,

Eulogio Garcıa, MD, Javier Soriano, MD, Manuel Abeytua, MD, Jaime Elızaga, MD,Javier Botas, MD, Rafael Rubio, MD, Mar Moreno, MD,

Miguel A. Garcıa-Fernandez, MD, and Juan-Luis Delcan, MD

The main advantage of primary percutaneous trans-luminal coronary angioplasty (PTCA) over throm-

bolytic therapy for the treatment of acute myocardialinfarction (AMI) is the achievement of a higher rate ofcoronary patency with a lower risk of intracranialbleeding, which includes lower mortality and a reduc-tion of the reinfarction rate, especially in high-riskpatients.1,2 Free-wall rupture (FWR) constitutes thesecond most common cause of in-hospital death inpatients with AMI, ranging from 0.8% to 6%.3–5 It hasbeen suggested and even widely accepted that primaryPTCA reduces the risk of FWR, especially when asuccessful result is achieved.6–9 However, the risk ofFWR in patients with AMI treated with primary an-gioplasty has not been studied in detail. This studywas conducted to assess the incidence of FWR inpatients with AMI treated with primary angioplasty,as well as to investigate the clinical and angiographicvariables associated with a higher risk of FWR in thissetting.

• • •Between January 1992 and October 1998, primary

PTCA was performed in our institution in 643 patientswith AMI within the first 12 hours after onset ofsymptoms. All of them had chest pain$30 minutesassociated with ST elevation of$0.1 mV in $2adjacent electrocardiographic leads or complete leftbundle branch block. Fifty-three patients were ex-cluded from the analysis because of prior thrombolytictherapy (n5 46), or no attempt of PTCA (4 withoutsignificant coronary stenosis and 3 submitted foremergency surgical revascularization). The remaining590 patients comprise the population of this study.

In 286 patients primary PTCA was the reperfusionapproach individually selected by the primary physi-cian. The main selection criteria for the patients withAMI for this reperfusion strategy changed over thisperiod of time in our institution. Cardiogenic shock atpresentation and high-risk patients with contraindica-tion to thrombolytics were the leading reasons forselecting primary PTCA; this therapy changed slightlyover time. Additionally, 304 patients were included in

different primary PTCA clinical trials, such as Pri-mary Angioplasty in Myocardial Infarction (PAMI) IIand III, Global Utilization of Streptokinase and tPAfor Occluded arteries (GUSTO) IIb, Controlled Ab-ciximab and Device Investigation to Lower Late An-gioplasty Complications (CADILLAC), and our insti-tution anterior AMI trial.2

Cardiac catheterization was performed by femoralapproach in most patients. The patients routinely re-ceived a bolus injection of 10,000 IU IV of heparin atthe beginning of the procedure. Additional boluseswere given if necessary to maintain an activated clot-ting time (ACT) of .300 seconds. The angiographicresult was considered to be successful with a finalThrombolysis In Myocardial Infarction (TIMI) grade2 or 3 flow and,50% residual stenosis. The femoralsheath was removed within 6 to 10 hours after theprocedure. Aspirin was administered in all patients ina daily dose of 150 to 300 mg. No routine anticoag-ulant therapy was administered after the procedure.Additionally, ticlopidine 250 mg twice daily for 1month was given following stent implantation. Abcix-imab was administered and/or stents were implantedwhen considered appropriate individually or when as-signed on a particular clinical trial.

FWR was diagnosed during hospitalization when 1of the following was present: (1) FWR confirmed atpostmortem examination; (2) FWR confirmed at sur-gery (subacute FWR); and (3) unexpected suddendeath due to electromechanical dissociation with se-vere pericardial effusion (.10 mm in the subcostalview) in a routine echocardiographic study performedduring the resuscitation maneuvers.4 Three patientswho suffered cardiac tamponade secondary to a cor-onary perforation during PTCA were not consideredas having FWR. The status on coronary risk factorswas defined according to the history given by thepatient or patient’s relatives.

Continuous variables are expressed as mean6 SD,and qualitative variables as percentages (proportions).Relation between qualitative variables were studied bychi-square test (Fisher’s test when necessary), andcomparisons between 2 media by Student’st test.Associations were considered statistically significantat p ,0.05.

Baseline characteristics are summarized on TableI. Angiographic successful results were obtained in549 patients (93%), and a final TIMI grade 3 flow in479 patients (81%). At least 1 coronary stent was

From the Division of Interventional Cardiology, Coronary Care Unit,and Echocardiography Laboratory, Department of Cardiology, Hos-pital Gregorio Maranon, Madrid, Spain. Dr. Moreno address is:Division of Interventional Cardiology, Department of Cardiology, Hos-pital Universitario Gregorio Maranon, Doctor Esquerdo, 46, 28007Madrid, Spain. Manuscript received July 28, 1999; revised manu-script received and accepted October 11, 1999.

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placed in 283 cases (48%). Beta blockers were admin-istered in 34% of patients.

Thirteen patients experienced FWR (2.2%). In 7patients (54%), left ventricular FWR was acute and in6 patients (46%) subacute; the latter patients under-went emergency surgical repair. The diagnosis wasanatomically confirmed at surgery or postmortem in 8patients and by echocardiography in 5. Seven of the304 patients (2.3%) enrolled in clinical trials and 6 of286 patients (2.1%) not enrolled in trials had FWR(p 5 NS)

The overall in-hospital mortality rate was 14.1%(83 patients) (3.7%, 7.5%, 28.9%, and 70.8% in pa-tients in Killip classes I to IV, respectively). Patientsenrolled in clinical trials had lower mortality thanpatients who were not in clinical trials (6.6% vs22.0%; p,0.0001). The cause of death was cardio-genic shock in 59 patients (71.1%), FWR in 10 pa-tients (12.0%), and other causes in 16 patients (16.9%)(Table II). Sixteen patients (2.7%) suffered in-hospital

reinfarction; 2 were fatal. All patients with acute and3 with subacute FWR died before discharge (overallFWR mortality rate 77%).

Table III shows the incidence of FWR in the dif-ferent subgroups of patients. The incidence of FWRwas significatively higher in the following groups: age.65 years (4.1% vs 0.3%, p5 0.0007), female gender(5.2% vs 1.5%, p5 0.0292), anterior location (3.1%vs 0.5%, p5 0.0234), nonsmokers (3.7% vs 1.1%,p 5 0.0378), and patients with total occlusion withTIMI flow grade 0 before PTCA (2.7% vs 0%, p50.0211). The incidence of FWR was similar in patientswith or without an angiographically successful pri-mary PTCA (2.2% vs 2.4% respectively, p5 NS).Coronary stenting was not statistically associated witha lower incidence of FWR.

In the 44 patients who were excluded from thestudy because of prior thrombolytic therapy (rescuePTCA), the incidence of FWR was 6.8% (p5 NS vsprimary PTCA). There were no FWR in the 7 patientsin whom primary PTCA was not attempted.

• • •In the present series of 590 patients with AMI

treated with primary PTCA, the incidence of FWRwas 2.2%, and FWR was the direct cause of 12% ofthe in-hospital deaths. These data do not differ fromthat of other series of patients treated with thrombol-ysis5,10 and appear to be lower than reported during

TABLE I Baseline Characteristics (n 5 590)

Age (yrs) 64 6 13Men 472 (80%)Previous AMI 80 (14%)AMI location

Anterior 390 (66%)Inferior 164 (28%)Lateral 25 (4%)Other 11 (2%)

Systemic hypertension 259 (44%)Hypercholesterolemia 208 (35%)Diabetes mellitus 140 (24%)Cigarette smoker 348 (59%)Minutes from onset of symptoms 213 6 153Killip class

I 434 (74%)II 53 (9%)III 38 (6%)IV 65 (11%)

Creatinine phosphokinase-MB (IU) 364 6 153No. of narrowed coronary arteries 1.6 6 0.7Infarct-related artery

Left anterior descending 385 (65.3%)Right 134 (22.8%)Left circumflex 51 (8.6%)Left main 12 (2.0%)Coronary graft 2 (0.3%)Undetermined 6 (1.0%)

Treated segmentProximal 254 (43%)Middle 265 (45%)Distal 71 (12%)

TIMI 0 before coronary angioplasty 481 (82%)Coronary stenting 283 (4%)c7E3 Fab (abciximab) 23 (4%)

TABLE II Causes of In-Hospital Death (n 5 83)

Cardiogenic shock 59 (70%)FWR 10 (12%)Cardiac arrest during coronary angioplasty 3 (4%)Arrhythmia 3 (4%)Bleeding complications 3 (4%)Other 5 (6%)Total 83

TABLE III Incidence of Free-Wall Rupture in DifferentSubgroups of Patients.

FWR (%) p Value

Age 0.0007.65 yrs 4.1#65 yrs 0.3

Men/women 1.5 vs 5.2 0.0292Previous AMI (yes vs no) 1.3 vs 2.4 NSAMI location 0.0234*

Anterior* 3.1Inferior 0.6Lateral 0.0Other 0.0

Systemic hypertension (yes vs no) 3.1 vs 1.5 NSHypercholesterolemia (yes vs no) 1.4 vs 2.6 NSDiabetes mellitus (yes vs no) 2.1 vs 2.2 NSSmoking (yes vs no) 1.1 vs 3.7 0.0378Time from onset NS

,2 h 2.0.2 h 2.4

Killip class NSI 1.4II 6.1III 7.7IV 1.6

Multivessel disease (yes vs no) 2.3 vs 2.1 NSOccluded segment NS

Proximal 3.5Middle 1.7Distal 0.0

TIMI 0 pre-PTCA (yes vs no) 2.7 vs 0.0 0.0146Angiographic success (yes vs no) 2.2 vs 2.4 NSFinal TIMI grade flow (2 vs 3) 2.9 vs 1.9 NSCoronary stenting (yes vs no) 1.8 vs 2.7 NSc7E3 Fab (abciximab) (yes vs no) 4.4 vs 2.0 NSb blockers (yes vs no) 2.0 vs 2.3 NS

758 THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 85 MARCH 15, 2000

the prethrombolytic era.3,4 However, the incidence ofFWR in the present series is clearly higher than thatshown in previous primary PTCA studies. O’Keefe etal6 found no FWR in 500 patients treated with primaryPTCA. In the series of Krikorian et al,7 none of 330patients with AMI treated with primary PTCA suf-fered a FWR. In the study of Rothbaum et al,8 only 1of 151 patients (0.7%) suffered a FWR; in this patient,angiographic success was not achieved, and it wasconcluded that a successful primary PTCA mightavoid the risk of FWR. Similar results are shown inthe study by Kahn et al,9 in which only 2 of 614patients treated with primary PTCA (0.3%) suffered aFWR; in these 2 patients, PTCA was angiographicallyunsuccessful. The incidence of FWR was only 0.4%(5 of 1,184 patients) in a recent study of Brodie et al.11

Finally, in the study of Bedotto et al,12 only 1 of 750patients with AMI (0.1%) suffered a FWR, in whomPTCA was angiographically successful. Therefore, therisk of FWR in previous series on primary PTCAranges from 0% to 0.8%.6–9,11–14

It could be that in our series a selection bias influ-enced the preference for primary PTCA of patients athigher risk for FWR than in other studies. Old age isa proven major risk factor for FWR.15 The age in thepresent study was$5 years older than age in otherstudies.6–9,11–14However, other admitted risk factorsfor FWR, such as female gender, first AMI, single-vessel disease, time to reperfusion, and absence ofbblockers, were similar in the studied group of patientsand in the series of primary PTCA with a lower FWRincidence.6–9,11 Because an association between anti-coagulation and FWR has been suggested,15 it may bethat the high doses of heparin administered duringprimary PTCA could have contributed to the inci-dence of FWR in our series. However, Becker et al10

have recently demonstrated that the intensity of anti-coagulation is not associated with the risk of cardiacrupture.

Older age, hypertension, female gender, anteriorlocation, and absence of prior AMI are the most ac-cepted variables associated with the risk of FWR.15–17

In the present series, elderly patients had a higherincidence of FWR. In all but 1 patient with FWR, theAMI location was anterior, and no patient with FWRhad a previous AMI. Female gender, hypertension,and absence of prior AMI, although without statisticaldifferences, were also more prevalent in patients withFWR. Angiographic success was not significativelyassociated with a lower incidence of FWR. This resultdisagrees with the accepted idea that the few cases ofAMI that are complicated with a FWR are associatedwith an angiographically unsuccessful result.8 In thisstudy, we found that an angiographically successfulprimary PTCA does not avoid the risk of FWR. Asmall beneficial effect of opening the infarct arterycannot, however, be ruled out, and perhaps this issuehas to be evaluated with larger studies. Cheriex et al18

found that most patients with FWR had a nonreper-fused infarct-related artery, suggesting that a completeand maintained coronary occlusion predisposes to thiscomplication. Moreover, some retrospective studies

have suggested that FWR is less frequent in cases witha successful coronary reperfusion.19 All patients withFWR initially had a TIMI flow grade 0, which sup-ports this hypothesis. It could be that some of theangiographically reperfused epicardial coronary arter-ies were not accompanied with complete reperfusedintramyocardial vessels. The role of the presence ofcollateral circulation could not be correctly addressedin all patients due to the retrospective substrate, but itspresence could be a protective factor.20

The frequency of FWR in our series of 590patients with AMI treated with primary PTCA was2.2%, which is not different from that reported inseries of patients treated with thrombolysis. Thisincidence was higher in patients>65 years old,women, nonsmokers, as well as in those with ante-rior location and an initial TIMI grade 0 flow, butit was similar in patients with a successful or un-successful angiographic result.

1. Grines CL, Browne KF, Marco J, Rothbaum D, Stone GW, O’Keefe J, OverlieP, Donohue B, Chelliah N, Timmis GC, et al, for the Primary Angioplasty inMyocardial Infarction Study Group. A comparison of immediate angioplasty withthrombolytic therapy for acute myocardial infarction.N Engl J Med1993;328:673–679.2. Garcıa E, Elızaga J, Pe´rez N, Serrano JA, Soriano J, Abeytua M, Botas J, RubioR, Lopez de Sa´ E, Lopez-Sendo´n JL, Delcan JL. Primary angioplasty versussystemic thrombolysis in anterior myocardial infarction.J Am Coll Cardiol1999;33:605–611.3. Reddy SG, Roberts WC. Frequency of rupture of the left ventricular free wallof ventricular septum among cases of fatal acute myocardial infarction sinceintroduction of coronary care units.Am J Cardiol1989;63:906–11.4. Lopez-Sendo´n JL, Gonza´lez A, Lopez de Sa´ E, Coma-Canella I, Rolda´n I,Domınguez F, Maqueda I, Martı´n-Jadraque J. Diagnosis of subacute ventricularwall rupture after acute myocardial infarction: sensitivity and specificity ofclinical, hemodynamic and echocardiographic criteria.J Am Coll Cardiol1992;19:1145–1153.5. Pollak H, Nobis H, Mlczoch J. Frequency of left ventricular free wall rupturecomplicating acute myocardial infarction since the advent of thrombolysis.Am JCardiol 1994;74:184–186.6. O’Keefe JH Jr, Rutherford BD, McConahay DR, Ligon RW, Johnson WL,Giorgi LV, Crockett JE, McCallister BD, Conn RD, Gura GM, et al. Early andlate results of coronary angioplasty without antecedent thrombolytic therapy foracute myocardial infarction.Am J Cardiol1989;64:1221–1230.7. Krikorian RK, James LV, Beauchamp GD. Timing, mode and predictors ofdeath after direct angioplasty for acute myocardial infarction.Cath CardiovascDiagn 1995;35:192–196.8. Rothbaum DA, Linnemeier TJ, Landin RJ, Steinmetz EF, Hillis JS, HallamCC, Noble RJ, See MR. Emergency percutaneous transluminal coronary angio-plasty in acute myocardial infarction: a 3 year experience.J Am Coll Cardiol1987;10:264–272.9. Kahn JK, O’Keefe HJ Jr, Rutherford BD, McConahay DR, Johnson WL,Giorgi LV, Shimshcak TM, Ligon RW, Hartzler GO. Timing and mechanism ofin-hospital and late death after primary coronary angioplasty during acute myo-cardial infarction.Am J Cardiol1990;66:1045–1048.10. Becker RC, Hochman JS, Cannon CP, Spencer FA, Ball SP, Rizzo MJ,Antman EM. Fatal cardiac rupture among patients treated with thrombolyticagents and thrombin antagonists.J Am Coll Cardiol1999;33:479–487.11. Brodie BR, Stuckey TD, Hansen CJ, Muncy DB, Weintraub RA, Kelly TA,Berry JJ. Timing and mechanism of death determined clinical after primaryangioplasty for acute myocardial infarction.Am J Cardiol1997;79:1586–1591.12. Bedotto JB, Kahn JK, Rutherford BD, McConahay DR, Giorgi LV, JohnsonWL, O’Keefe JH, Shimshak TM, Ligon RW, Hartzler GO. Failed direct coronaryangioplasty for acute myocardial infarction: in-hospital outcome and predictors ofdeath.J Am Coll Cardiol1993;22:690–694.13. De Boer MJ, Hoorntje JCA, Ottenvanger JP, Reiffers S, Suryapranata H,Zijlstra F. Immediate coronary angioplasty versus intravenous streptokinase inacute myocardial infarction: left ventricular ejection fraction, hospital mortalityand reinfarction.J Am Coll Cardiol1994;23:1004–1008.14. Kinn JW, O’Neill WW, Benzuly KH, Jones DE, Grines CL. Primaryangioplasty reduces risk of myocardial rupture compared to thrombolysis foracute myocardial infarction.Cath Cardiovasc Diagn1997;42:151–157.15. Becker RC, Gore JM, Lambrew C, Weaver WD, Rubison RM, French WJ,Tiefenbrunn AJ, Bowlby LJ, Rogers WJ. A composite view of cardiac rupture inthe United States National Registry of Myocardial Infarction.J Am Coll Cardiol1996;27:1321–1326.

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16. Griffith GC, Hedge B, Oblath RW. Factors in myocardial rupture: an analysisof 204 cases at Los Angeles County Hospital between 1924 and 1957.Am JCardiol 1961:8:792–798.17. Mann JM, Roberts WC. Rupture of the left ventricular free wall during acutemyocardial infarction: analysis of 138 necropsy patients and comparison with 50necropsy patients with acute myocardial infarction without rupture.Am J Cardiol1988;62:847–860.18. Cheriex EC, de Swart H, Dijkman LW, Havenith MG, Maessen JG, Engelen

DJM, Wellens HJJ. Myocardial rupture after myocardial infarction is related tothe perfusion status of the infarct-related coronary artery.Am Heart J1995;129:644–650.19. Nakamura F, Minamino T, Higashino Y, Ito H, Fujii K, Fujita T, Nagano M,Higaki J, Ogihara T. Cardiac free wall rupture in acute myocardial infarction:ameliorative effect of coronary reperfusion.Clin Cardiol 1992;15:244–250.20. Lewis AJ, Burchell HB, Titus JL. Clinical and pathologic features ofpostinfarction cardiac rupture.Am J Cardiol1960;23:43–53.

Acute Myocardial Infarction and Vascular RemodelingSteven D. Filardo, MD, MPH, Severin P. Schwarzacher, MD, Sidney T. Lo, MB, BS,Niall A. Herity, MD, David P. Lee, MD, Heike Huegel, MD, William L. Mullen, MD,

Peter J. Fitzgerald, MD, PhD, Michael R. Ward, MB, BS, PhD, and Alan C. Yeung, MD

Recent evidence has suggested that plaque ruptureand outward remodeling may be associated. A

postmortem study, comparing vessel sections from thesame nonbranching femoral arterial segment, foundthat those with the largest vessel area (the greatestamount of outward remodeling) had significantlymore markers of plaque vulnerability (more matrixmetalloproteinase-secreting macrophages and T-lym-phocytes and less collagen-producing smooth musclecells) compared with those with the least remodeling.1

These differences were most marked at the shouldersof the plaques where plaque rupture is most prevalent.Thinning of the fibrous cap has been attributed tocollagen breakdown (due to macrophages and T-lym-phocytes) along with a reduction in smooth musclecells. To examine the strength of this association,other investigators have compared remodeling pat-terns in patients with unstable and stable angina.2–4

However, the heterogenous nature of unstable angina5

coupled with some uncertainty in the location ofplaque rupture means that observer bias may be dif-ficult to avoid in these studies. Such methodologicissues can be overcome by examining remodeling inthe setting of acute transmural myocardial infarction,for which there are firm diagnostic criteria and a moredefinite site of plaque rupture. Therefore, we exploredthis association, using a retrospective case-control de-sign, by comparing the intravascular ultrasound(IVUS) findings of patients with acute myocardialinfarction to those with stable angina.

• • •The IVUS database at Stanford University Medical

Center was searched from June 1993 to February 1999to identify patients who had preinterventional IVUSduring primary angioplasty for acute myocardial in-farction. First, only those patients in whom the precisesite of plaque rupture was identified with reasonablecertainty and annotated during IVUS imaging wereincluded. Charts were reviewed to confirm that those

identified with acute myocardial infarction had isch-emic chest pain and ST elevation consistent withGISSI criteria.6 The diagnosis was confirmed by ele-vation of creatinine kinase to greater than twice theupper limit of normal. Patients who had had priorcoronary artery bypass grafting or interventional pro-cedures in the culprit vessel were excluded. Fourteencases met these strict criteria; for each case a control,who had stable angina, was then selected from thedatabase. Controls were selected by matching in orderof priority for vessel, gender, and age, and selectionwas performed blinded to the IVUS findings. Clinicaldata, nearest available before the time of IVUS exam-ination, were obtained from the patients’ medicalrecord or from their primary care physician; these dataincluded cholesterol profile, smoking history, hyper-tension, diabetes mellitus, and family history of pre-mature atherosclerosis. Tobacco consumption, diabe-tes mellitus, family history, and hypertension wererecorded as binary events.

Selective coronary angiography was performed bya standard Judkins technique. All images were re-corded in multiple views with hand injections of ra-diographic contrast before IVUS examination. In thepatients with infarction (cases), the culprit lesion wasidentified by angiography as the site with the minimallumen diameter after reperfusion had been establishedeither by passage of the guidewire, or subsequently,the IVUS catheter. In the control patients the lesionwas defined as the site with the smallest lumen diam-eter. All patients received nitroglycerin before IVUSexamination. IVUS images were obtained using 30- or40-MHz imaging catheters (2.6Fr to 3.2Fr, Scimed,Maple Grove, Minnesota) before intervention. Imageswere recorded on sVHS tape during a slow manualpullback and off-line analysis was performed usingplanimetric software (Tape Measure, Indec Systems,Mountain View, California). The site with the smallestplaque area, proximal to the lesion, within the samevessel segment (before any branching) was defined asthe reference site. Vessel cross-sectional area (CSAV)was defined as the area within the external elasticlamina. The remodeling index was defined as the ratioof CSAV lesion:CSAV reference. As the thrombusburden of the acute myocardial infarction patientsoften precluded accurate assessment of lesion plaque

From the Division of Cardiovascular Medicine, Stanford University,Stanford, California; and University of Innsbruck, Innsbruck, Austria.Dr. Yeung’s address is: Stanford University School of Medicine, Divi-sion of Cardiovascular Medicine, 300 Pasteur Drive, Stanford, Cali-fornia 94305. E-mail: alan_yeung@cvmed.stanford.edu. Manuscriptreceived August 5, 1999; revised manuscript received and acceptedOctober 13, 1999.

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