One-Year Clinical Outcome of Elderly Patients Undergoing Angioplasty for ST-Elevation Myocardial Infarction Complicated by Cardiogenic Shock: The Importance of 3-Vessel Disease and Final TIMI-3 Flow Grade

Abstract: Background. The influence of age on clinical results of primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarctions (STEMI) complicated by cardiogenic shock (CS) is poorly investigated. Methods. In this study, we evaluated the outcome of 216 consecutive all-comer patients with STEMI and CS undergoing PCI who were divided into 2 groups according to age: <75 years (n = 131) or ≥75 years (n = 81). The study endpoint was the incidence of death at 1-year follow-up. The predictors of mortality at 1 year were also investigated. Results. The group <75 years had a significantly lower incidence of death compared with the group ≥75 years at 30 days (39% vs 69%; P=.01) and 1 year (51% vs 79%; P<.001). Cox proportional hazards model identified: age (adjusted hazard ratio [HR] = 1.02; 95% confidence interval [CI], 1.00-1.03; P=.02), 3-vessel disease (HR = 1.47; 95% CI, 1.00-2.17; P=.05), post-PCI TIMI flow grade 0-1 (HR = 2.48; 95% CI, 1.66-3.70; P=.01) and grade 2 (HR = 1.68; 95% CI, 1.01-2.80; P=.05) after PCI as independent predictors of death at 1-year follow-up. Conclusions. Patients ≥75 years with STEMI complicated by CS and treated by PCI have higher 1-year mortality compared with younger counterparts. Final TIMI 0-2 and 3-vessel disease are strong predictors of death. This finding may be valuable in risk stratification of these patients.  

J INVASIVE CARDIOL 2014;26(3):114-118

Key words: cardiogenic shock, old age, primary angioplasty

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The treatment of ST-elevation acute myocardial infarction (STEMI) in patients >75 years old is an important challenge as the elderly represent a rising population and have an increased risk of mortality.^1-3 Cardiogenic shock (CS) is the most important complication in STEMI patients as it is associated with extremely high mortality rates.⁴ Primary coronary angioplasty (PCI) is a useful strategy of treatment in STEMI patients complicated by CS,⁵ but its benefits in patients ≥75 years are still debated.^6-12

The aim of the present study is to compare clinical outcomes of patients ≥75 years versus patients <75 years undergoing primary PCI for STEMI complicated by CS. We also analyzed the clinical, angiographic, and procedural characteristics of the two groups in order to identify the predictors of adverse outcome during 1-year follow-up.

Methods

The study included all patients with STEMI and CS admitted to our catheterization laboratory. The diagnosis of STEMI was established on the basis of typical chest pain lasting >30 minutes, unrelieved by sublingual nitrates, associated with  ST-segment elevation (≥1 mV in ≥2 limb leads or ≥0.2 mV in ≥2 contiguous precordial leads) or left bundle branch block of new onset on surface electrocardiogram. Cardiogenic shock was defined as systolic blood pressure <90 mm Hg for >30 minutes or requiring inotropes to maintain systolic blood pressure >90 mm Hg, evidence of low cardiac output and end-organ hypoperfusion (eg, resting tachycardia, urine output <30 mL/hour, cold extremities, or altered mental status), and/or elevated filling pressures (eg, pulmonary congestion on examination or chest x-ray). 

All patients received intravenous aspirin 300-500 mg and unfractionated heparin 60 UI /kg body weight, and were pretreated with 300 or 600 mg clopidogrel. Abciximab was administrated at the discretion of the operator: an intravenous preprocedural bolus of 0.25 mg/kg body weight followed by a continuous infusion of 0.125 µg kg^-1 min^-1 for 12 hours (up to a maximal dose of 10 µg/min). During PCI, intravenous boluses of unfractionated heparin were given to maintain an activated clotting time of at least 300 seconds (250 seconds in case of abciximab administration). All patients who were discharged alive were treated with aspirin (100 mg) indefinitely and clopidogrel (75 mg) daily for 6-12 months. 

The number of critically narrowed coronary arteries was evaluated. Angiographic analysis was done on end-diastolic frames demonstrating the stenosis on its more severe view. The view with the least foreshortening was selected for the analysis. Initial and final flow in the infarct-related artery was graded according to TIMI classification. 

Follow-up protocol included evaluation at hospital discharge and a clinical visit thereafter at 1, 6, and 12 months. The study endpoint was the 1-year incidence of death. 

Statistical analysis. A retrospective analysis of data prospectively collected according to our internal protocol was performed. Data are presented as mean ± standard deviation (SD) or percentages. Comparisons between groups were performed using t-test for continuous data and the chi-square test or Fisher’s exact test for categorical data. Logistic regression was performed to determine the independent correlates of death at 30-day follow-up. The Cox proportional hazards model was used to determine the independent correlates of the primary endpoint at 1 year. Linearity and proportionality assumptions were verified according to the Mantel-Haenszel method. Adjusted survival curves were developed using the Kaplan-Meier method. The C-statistic was calculated to evaluate the goodness of fit of the multivariable model. Analyses were performed using the SPSS version 17.0 statistical package (Insightful Corporation). Statistical significance was accepted at a P<.05.

Results

From January 2002 to October 2011, a total of 216 consecutive patients (mean age, 69 ± 12 years) with STEMI complicated by CS underwent coronary angiography and immediate attempt to perform PCI at our institution.

Patients were divided into two groups according to age: <75 years (average, 61 ± 9 years; range, 37-74 years) and ≥75 years (average, 81 ± 5 years; range, 75-96 years), P<.001, including 135 and 81 patients, respectively.

Baseline characteristics are shown in Table 1. The group ≥75 years included a significantly higher number of women. Angiographic and procedural variables are shown in Table 2. Multivessel coronary disease was present in 148 patients (68%) without significant differences between the groups. Multivessel PCI was performed in 47 patients (22%). Patients ≥75 years were less likely to receive abciximab and intraaortic balloon pump.

At 30-day and 1-year follow-up, there were 109 deaths (50%) and 128 deaths (61%), respectively. Patients ≥75 years had a higher incidence of death in comparison with patients <75 years at 30 days  (56 [69%] and 53 [39%], respectively; P<.001) and at 1 year (63 [79%] and 65 [51%], respectively; P<.001). Eight patients (4%) were lost at 1-year follow-up without differences in patients <75 or ≥75 years (7 patients [5%]  and 1 patient [1%], respectively; P=.26). 

The following variables, with enter P-value <.05 and remove P-value <.10 in univariate analysis, were included in the multivariate logistic regression model: age, sex, target vessel, 3-vessel disease, abciximab, pacemaker, and orotracheal intubation. Logistic regression identified age, TIMI 0-1, 2, and 3 after procedure, 3-vessel disease, and orotracheal intubation as predictors of death at 30 days (Table 3). The following variables, with enter P-value <.05 and remove P-value <.10 in univariate analysis, were included in the multivariate Cox proportional hazard model: age, TIMI flow 0-1, 2, and 3 after PCI, and 3-vessel disease. The Cox proportional hazards model identified age, TIMI flow grade after PCI, and 3-vessel disease as independent predictors of death at 1-year follow-up (Table 4). The C-statistic for the whole model was 0.80.

The 1-year survival rates were 30.7% in patients <75 years and 20.8% in patients ≥75 years (P<.02) (Figure 1). The 1-year survival rates were 12.4%, 19.1%, and 35.8% in patients with final TIMI flow grade 0-1, 2, and 3, respectively (P<.05) (Figure 2). The 1-year survival rates were 14.6%, 28.2%, and 41.9% in patients with 3-, 2-, and 1-vessel disease, respectively (P<.05) (Figure 3). 

Discussion

The present study shows that among patients undergoing primary PCI for STEMI complicated by CS: (1) those ≥75 years have a higher 1-year mortality rate in comparison with younger counterparts; (2) age, 3-vessel disease, and post-PCI TIMI flow grade 0-2 are independent predictors of death during 1-year follow-up.

In our series of “all-comer” patients undergoing primary PCI for STEMI complicated by CS, 37% were ≥75 years old, a result comparable with previous reports.^10,11 In this population, 30-day and 1-year overall mortality rates were higher than described in some studies,^9-11 but closer to the data of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte) European PCI registry.¹³ This may be explained by the high risk profile of our population. We included a higher number of anterior STEMI (as well as left anterior descending artery involvement) and lower percentage of inferior STEMIs than previously reported. It is well known that the vagal reaction accompanying inferior infarction may be confused with CS; conversely, anterior STEMIs are often larger infarctions with a higher incidence of CS and a poorer clinical course. The time from pain to PCI is longer, including patients with prolonged CS who have worse prognosis.¹³ Ejection fraction values of our patients were lower than other studies. In contrast to other reports,^10,11 we did not include non-STEMI patients, whose survival can be better than STEMI.⁹  

We found age to be an independent predictor of death. This is in line with some studies,^9,13-15 but not with other reports.^10-12 The discrepancy may be due to power limitations, major bias in the clinical inclusion of elderly, and differences in selection criteria and study protocol. Factors that explain the higher incidence of death in the elderly include age itself, but also associated comorbidities. Moreover, delayed arrival at the hospital, severity of coronary artery disease, procedural failure, and increased non-cardiac complications may have an adverse impact on survival. Our population of elderly does not differ very much in clinical baseline characteristics from younger patients. In line with previous reports, the elderly patients in our study were more frequently female,^10,11 were less likely to be treated with abciximab,¹¹ and were less likely to have TIMI-3 flow after PCI. In the elderly, there was also a tendency to less use of intraaortic balloon pump, which was probably due to a higher incidence of peripheral artery disease in this population. However, the prognostic role of aortic counterpulsation on 30-day clinical outcome in CS has been questioned in a recent study.¹⁶ Apart from the above-mentioned factors, we did not find any difference between the two age groups either regarding other baseline clinical-angiographic characteristics (prevalence of multivessel disease, infarct-related artery, baseline TIMI grade flow), employed techniques (use of stents or thrombus aspiration systems), or procedural results (multivessel PCI).

Failure to obtain adequate postprocedural epicardial flow is associated with in-hospital^11,13 and 1-year follow-up¹¹ high mortality rates. Our results are in line with Sutton et al,¹⁷ who found that failed reperfusion also predicts higher in-hospital mortality in patients with CS. In our study, TIMI-2 flow grade was also a predictor of negative outcome,¹³ underlining that attempts to restore TIMI-3 flow grade should be strongly undertaken. This seems to be more difficult to obtain in the elderly, as they had lower final TIMI-3 flow rates (58%) in comparison with younger patients in our study. This finding is in line with Gasior et al,⁹ who reported final TIMI-3 flow grade in 67% of the elderly, but it is difficult to compare with previous studies, as TIMI-2 flow grade after PCI was considered a marker of successful procedure and analyzed together with TIMI-3.¹⁰

Multivessel coronary disease is a well-known characteristic associated with higher risk of CS among patients with STEMI referred to primary PCI.¹⁸ Additionally, multivessel coronary disease itself is a risk factor for hard endpoints and unfavorable left ventricular remodeling.¹⁹ Given its prognostic relevance, attempts to achieve complete revascularization have been advocated in patients with STEMI and CS.²⁰ Despite these findings, multivessel disease has not been found as a predictor of death in some studies,⁹ nor tested at multivariable analysis in others.^10-12,15 A novel finding of our study is that 3-vessel but not 2-vessel disease was a relevant predictor of death at both 30-day and 1-year follow-up; this may justify the discrepancies with previous reports in which these two groups were analyzed as a single group. In our opinion, this important result might be taken into account in the risk stratification and management of elderly patient with STEMI complicated by CS undergoing primary PCI.

CS represents a catastrophic complication associated with extremely high mortality rates in elderly patients with STEMI. In these patients, primary PCI provides lesser results than in the other subset. Our study suggests that the elderly with STEMI and CS should not be excluded from the potential benefits of primary PCI, but we should recognize that they obtain limited advantages after this procedure. PCI with contemporary devices may be poorly effective in patients with STEMI and CS, above all in elderly patients. The use of advanced left ventricular support systems (Impella, Tandem Heart) and extracorporeal membrane oxygenator (ECMO) might be considered.²¹ They could help to stabilize the patient’s clinical conditions, contribute to improve final TIMI flow grade, and obtain more complete revascularization by PCI and/or coronary artery bypass, especially in old patients with 3-vessel disease. However, further studies are needed to verify the effectiveness of left ventricular supports in old patients with CS, since few data are available in this subgroup of patients.^22,23 

Study limitations. The study is retrospective but, in our view, adds important information about the outcome of a real-world cohort of elderly undergoing PCI for STEMI and CS. The low number of old patients (although not different from reported in previous studies) could have affected the results. A number of these patients were treated before the introduction of drug-eluting stents and thrombus aspiration systems. Information about serum lactate, kidney function, and rates of cardiac arrest with resuscitation prior to admission were not available in all patients. The incidence of ultrafiltration was not recorded. Charlson index was not available, since comorbidities were not assessed due of the difficulty to clearly identify them in old patients with in-hospital death. Finally, although all patients with STEMI and CS admitted to our hospital were referred to the catheterization laboratory, we have no data about the process of selection of patients who were transferred to our center; for this reason, the validation of our results should be obtained through a multicenter study in order to exclude the bias of transfer decision. 

Conclusion

Elderly patients with STEMI complicated by CS undergoing primary PCI have a worse prognosis in comparison with younger patients. Final TIMI 0-2 flow grade and 3-vessel disease identify the patients at highest risk. 

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