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PTCA in Q Wave AMI. Predictors of
In-Hospital Mortality

Torresani, E.M.; Weisshein, N.; Martino, G.;
Hrabar, A.; Fernández, A.; Bujan, L.;
De Benedetti, L.; Alvarez, C.;
Cohen, M.; Leguizamón, J.H.

Dpto. de Cardiología, Sanatorio Modelo Quilmes, Buenos Aires, Argentina

SUMMARY
The purpose of this study is to determine those factors that are predictive of In-Hospital mortality in patients (pts) treated with Primary (PA) or Rescue (RA) PTCA in Q wave AMI. From 8/94 until 8/99, 239 pts with AMI < 12 hrs were admitted; 84 pts were treated with PA and 155 pts with Streptokinase, of which 32.9% underwent RA. Stent was implanted in 40.7 % due to suboptimal result (recoil, dissection and/or > 30% residual stenosis). All Killip-Kimball (KK) 4 were also treated with IABP.A global in-hospital mortality of 11.1% for PTCA pts was due to Cardiogenic Shock (n=8), Cardiac Rupture (n=2), Gastrointestinal Bleeding (n=2), Retroperitoneal Hemorrhage (n=1), Sepsis (n=1) and Coronary Reclusion (n=1). There were no significant differences in gender, risk factors, previous AMI, infarct territory, angiographic factors including ostial or bifurcational involvement, calcification, difficult access, lesion length, or vessel diameter; neither were in Stent utilization. Mortality was highest in older pts (<50 yrs: 2.9%; 50-70 yrs:11.1%; >70yrs: 25%- p<0.04), with multi-vessel disease (MVD) (1 vessel:5.1%; MVD:19.2%-p<0.021), among those admitted late (<4hrs:5.8%;4-6hrs: 7.5%; >6hrs: 25.8% - p<0.012) and with worse KK [KK1(1.8%), KK2(4.7%), KK3(9.09%), KK4(39.2%)-p<0.00001]. Multivariate analysis demonstrated that a worse KK (OddsRatio: 3.61-p<0.0015)and a prolonged time interval to admission (Odds Ratio: 2.97-p<0.027) are independent risk factors. The impact of time delay was greatest in KK4 pts (< 4 hrs:16.6%; 4-6 hrs: 25%; >6 hrs:87.5%-p<0.004). A subgroup of 94 pts with previous "complete" coronary arteriograms that allowed evaluation of collateral circulation (CC) to the infarct territory showed CC+: 13.8% with 0% In-Hospital mortality.
Conclusions: 1) Although PTCA of the culprit vessel in AMI reduces mortality, new adjunctive strategies are needed for patients with KK4 class, elderly, MVD and delayed hospitalization. 2) The presence of CC to the infarct territory is apparently protective.

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INTRODUCTION
   The guiding principle underlying current treatment strategies in acute myocardial infarction (AMI) is to direct all efforts toward opening the culpable artery with thrombolysis or angioplasty (PTCA) (1-5). Nevertheless, although there have been incremental improvements in reperfusion methods, the global mortality from AMI continues being high (6). The purpose of this study is to determine factors that are predictive or possibly predictive of in-hospital mortality in patients treated with primary coronary angioplasty (PA) or rescue coronary angioplasty (RA) in AMI.

MATERIAL AND METHOD
   From 8/94 until 8/99, 239 pts with AMI < 12hs were admitted. Of these, 84 pts [84/239 (35.1%)] were treated with primary angioplasty and 155 pts with streptokinase (SK) 1.500.000 UI in 1 hs. Of the SK patients, 51/155 (32.9%) underwent rescue angioplasty for failure to reperfuse with thrombolytic therapy alone. Aspirin was administered 325mg via oral to the entrance in all the cases. The PTCA was carried out by femoral boarding in all the cases. Then, was administered initial bolus of sodium heparin of 150 UI/Kg in those PA and 100 UI/Kg in the RA with later dose adjustment according to the KPTT. All patients in this study undergoing PA or RA were treated with balloon PTCA alone (n=135), being supplemented with Stent in cases of suboptimal PTCA results, which included recoil, dissection and/or residual stenosis > 30%. The obtained result was controlled by angiography during 15´ at 30´ later to the last insufflations, and in the face of loss for recoil, dissection or re-occlusion, were optimized with bigger time of insufflations, balloon of more size, placement and/or re-impactation of the Stent. The Stent was selected according to the size of the vessel, lesion length and access type, being generally used tubular Stent. Concluded the procedure, the introducers were retired in the first 24 hs. During this period the patients were treated with sodium heparin and a doses adjustment was made with KPTT control. In the patients in that Stent was used the treatment was supplemented with Ticlopidine 250 mg/day during 1 month and the rest of the medication were used following the limits of the ACC/AHA Guidelines for the AMI patients (7). All Killip-Kimbal (KK) 4 patients were also treated with intraortic balloon pump counterpulsation (IABP).

   Definition of primary success: It was considered primary success a residual obstruction < 30% with TIMI 3 flow and without major complications.
   Definition of failure: The failure was defined as the impossibility of achieving primary success for difficulty in to cross or to dilate the obstruction appropriately or not to achieve TIMI 3 flow in absence of major complications.
   Definition of major complication: Death, emergency surgical revascularization or worsening of the clinical picture (Killip-Kimbal to grades 3-4).
   Statistical analysis: Were used the Chi square test with Yate`s correction, Fisher`s test, Mann-Whitney`s test, Walk's test, and the multivariate analysis with logistical regression technique with multiple variables with quasi Newton method and maximum probability technique, to determine the statistical significance (p level < 0.05). The proportions were analyzed by means of the determination of differences among standard error. The continuous variables were expressed as mean ± 1 SD.

RESULTS
   The primary success was of 90.3%. Were consigned 13 failures due to TIMI < 2 flow [8/13 (61.5%)], non dilatable artery [1/13 (7%)] or not to cross the occlusion with the guide-wire [4/13 (30.7%)]. Global in-hospital mortality of 11.1% (15/135) for PTCA patients was due to cardiogenic shock (n=8), cardiac rupture (n=2 ), gastrointestinal bleeding (n=2), retroperitoneal hemorrhage (n=1), sepsis (n=1) and coronary re-occlusion (n=1). Among treatment groups, there were no significant differences in gender, risk factors, previous AMI, infarct territory, angiographic factors including ostial or bifurcation involvement, calcification, difficulty of access, lesion length, or vessel diameter. Neither were there differences in primary or rescue strategies or Stent utilization (Tables 1 - 2 - 3 - 4).

   In the univariate analysis, mortality was greatest in older patients with multiple vessel disease, among those admitted late and with worse KK classification (Tables 5 - 6). There was to tendency to smaller mortality when the culprit vessel was the right coronary artery and bigger when it was a saphenous by-pass graft (Table 6). Also bigger hospital mortality was consigned when comparing the PTCA failures (F) with the successful (PS) cases {F: 5/13 [38.4%]; PS: 10/122 [8.1%] (p < 0.0065)}.

   Multivariate analysis with multiple logistic regression confirmed that worse KK and greater time interval to admission are independent risk factors for mortality (Table 7).

   The impact of time delay on mortality was greatest in the patients admitted in cardiogenic shock (KK 4) (Table 8). Finally, a subgroup of 94 patients had previous complete arteriograms (in the rest was completed when PTCA concluded) that permitted evaluation of the collateral circulation to the infarct territory. Although, collaterals to the territory were present in only 13.8%,this subgroup had 0% mortality in the current study.

DISCUSSION
   From the Hartzler`s reports (4), the PTCA in the AMI has demonstrated to be a sure method, with a high recanalization rate, improvement of the ventricular function and decrease of the mortality (4-5,8-10). In our practice their use rate was of 56.4% of all the AMI admission between 1994 and 1999, being stationary at the present time. The hospital global mortality was in this study of 11.1%. The absence of inclusion/exclusion criteria for to be an observational retrospective non randomized study shows the results in the daily life including subgroups of increased risk like patients with cardiac failure, multiple vessel disease, older and / or those admitted late to the reperfusion treatment. The population's 20.7% in study presented cardiogenic shock to the moment of its admission. All they received hemodynamic support with IABP during the PTCA, in spite of it the hospital mortality was of 39.2%. When we analyze the impact of the interval time delay in this subgroup we observes that its influence was decisive after the 6 hs specially related to the impossibility of achieving TIMI 3 flow in spite of not having residual obstruction in the treated place. It is probable that these patients could benefit with IIb-IIIa inhibitors or another pharmacological support and/or multiple vessel PTCA. The early indication of treatment bears smaller mortality during the in-hospital phase (11). Is important to stress the low mortality in rescue PTCA (5.8%) that is the same in our experience historically (12-13)and differ substantially with the reported by others (14-15). We believe in this sense that the different concept of primary success marked by the evolution of the knowledge in the time is a reasonable explanation. The use of Stent diminishes the restenosis and necessity of later revascularization (16-17) but evidently it doesn't influence decisively on the mortality (18). The non obtaining of an appropriate perfusion flow (the one that should become independent of the residual obstruction) it was a clear marker of more intra-hospital mortality, being the main reason of our failures. From the initial observations of Rentrop (19) the coronary collateral circulation has been found like protective factor before a sharp ischemic event. In this series the patients with collateral circulation of some grade toward the occluded vessel, overcame the internment successfully, independently of any clinical or angiographic variable analyzed concordant fact with that reported by others authors (20).

CONCLUSIONS

1) Although PTCA of the culprit vessel in AMI reduces mortality, new adjunctive strategies are needed for patients with Killip Kimbal 4 class, elderly, multiple vessel disease and delayed hospitalization.
2) The presence of collateral circulation to the infarct territory is apparently protective.

REFERENCES

1. Koren GT, Hasin Y, Appelbaum D, et al: Prevention of myocardial damage in acute myocardial ischemia by early treatment with intravenous Streptokinase. N Engl J Med 1985 ; 313 : 1384 - 1389.

2. Fibrinolytic Therapy Trialist's (FIT) collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1.000 patients. Lancet 1993 ; 342:759-766.

3. GUSTO Angiographic Investigators: The effects plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction.N Engl J Med 1993 ; 329 : 1615 - 1622.

4. Hartzler GO, Rutherford BD, Mc Conahay DR et al: Percutaneous Transluminal Coronary Angioplasty with and without Thrombolytic therapy for treatment of acute myocardial infarction. Am Heart J 106 : 965 - 973 , 1983.

5. Grines CL, Browne KF, Marco J, for the Primary Angioplasty in Myocardial Infarction Study Group : A Comparison of inmediate angioplasty with thrombolytic therapy for acute myocardial infarction. N Engl J Med 328 : 673 - 679 ,1993.-

6. Hirschson Prado A.,Trivi M, Tajer C, y col:Infarto Agudo de Miocardio en la Argentina. Tercera encuesta nacional. SAC 1996.Rev Arg de Cardiol 1998;66(1):63-72.

7. Ryan ET, Bauman W, Kennedy J et al: ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction. J Am Coll Cardiol 1996;Vol.28,N° 5,November 1:1328-428G.

8. García E, Elízaga J, Pérez N, et al. Primary angioplasty versus systemic thrombolysis in anterior myocardial infarction. J Am Coll Cardiol 1999;33:605-611.

9. Ellis SG, Ribeiro da Silva E, Heyndrickx G,et al for the RESCUE Investigators. Randomized Comparison of Rescue Angioplasty With Conservative Management of Patients With Early Failure of Thrombolysis for Acute Anterior Myocardial Infarction. Circulation 1994;90:2280-2284.

10. Stone GW, Grines CL, Browne KF, et al for the PAMI Trial Investigators. Predictors of In-Hospital and 6-Month Outcome After Acute Myocardial Infarction in the Reperfusion Era: The Primary Angioplasty in Myocardial Infarction(PAMI) Trial. J Am Coll Cardiol 1995;25:370-7.

11. Lincoff AM and Topol EJ. Illusion of Reperfusion. Does Anyone Achieve Optimal Reperfusion During Acute Myocardial Infarction? Circulation 1993;88:1361-1374.

12. Leguizamón JH, Nauwerk R, Torresani EM ,y col: Angioplastia Coronaria en 115 pacientes cursando un IAM: 4 años de experiencia. Parte I: Angioplastia de Rescate. Rev Arg de Cardiol 1991; Vol.59,nº5,TLP 5.

13. Torresani EM, Martino G, Hrabar A, y col: ¿Es útil la Angioplastia de Rescate? Estudio Comparativo con Angioplastia Primaria. Rev Arg de Cardiol 1997;Vol 65,Sup4,TL 167,pag 136.

14. Mc Kendall GR,Forman S,Sopko G,et al :Value of Rescue Percutaneous Transluminal Coronary Angioplasty Following Unsuccessful Thrombolytic Therapy in Patients With Acute Myocardial Infarction. Am J Cardiol 1995; 76:1108-1111.

15. Gibson CM,Cannon CP,Greene RM et al for the TIMI 4 Study Group.Rescue Angioplasty in the Thrombolysis in Myocardial Infarction(TIMI)4 Trial. Am J Cardiol 1997;80:21-26.

16. Fischman DL, Leon MB, Baim DS ,for the STRESS investigators. A randomized comparison of coronary artery stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1997;331:496-501.

17. Serruys PW, de Jaegere P, Kiemeneij F, for the Benestent Study Group. A comparison of balloon-expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 1994 ; 331 : 489 -495.

18. Stone GW, Brodie BR, Griffin JJ, for the PAMI Stent Pilot Trial Investigators. Prospective ,Multicenter Study of the Safety and Feasibility of Primary Stenting in Acute Myocardial Infarction: In-Hospital and 30-Day Results of the PAMI Stent Pilot Trial. J Am Coll Cardiol 1998;31:23 - 30.

19. Rentrop KP, Cohen M, Blanke H, et al: Changes in collateral channel filling inmediately after controlled coronary artery occlusion by an angioplasty balloon in human subjets. J Am Coll Cardiol 1985;5:587-592.

20. Pérez-Castellano N, García EJ, Abeytua M, et al: Influence of Collateral Circulation on In-Hospital Death From Anterior Acute Myocardial Infarction. J Am Coll Cardiol 1998;31:512-8.

 

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2nd Virtual Congress of Cardiology

Dr. Florencio Garófalo
Steering Committee
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Dr. Raúl Bretal
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