a Medizinische Klinik B, Herzzentrum Ludwigshafen, Ludwigshafen, Germany
b Medizinische Klinik II, Klinikum Kassel, Kassel, Germany
c Medizinische Klinik I, Amper-Klinikum Dachau, Dachau, Germany
d Medi-zinische Klinik II, Klinikum Lippe-Detmold, Detmold, Germany
e Medizinische Klinik 8, Klinikum Nürnberg, Nürnberg, Germany
f Medizinische Klinik II, Klinikum Fulda, Fulda, Germany
* Correspondence to: Priv. Doz. Dr Uwe Zeymer, FESC, Herzzentrum Ludwigshafen, Medizinische Klinik B, Bremserstrasse 79, D-67063 Ludwigshafen, Germany. Tel: +49 621 503 4045; Fax: +49 621 503 4002
E-mail address: Uwe.Zeymer{at}t-online.de
Received 20 March 2003; revised 14 November 2003; accepted 4 December 2003
Abstract
Aims Acute myocardial infarction complicated by cardiogenic shock is associated with an exceedingly high mortality, even if patients are treated with early reperfusion therapy. The aim of this study was to evaluate predictors of in-hospital mortality of a large cohort of consecutive patients with cardiogenic shock treated with primary percutaneous coronary intervention (PCI).
Methods and results Between July 1994 and March 2001 all interventions performed in 80 centres in Germany were prospectively entered into the primary PCI registry of the ALKK. A total of 9422 procedures were registered, of these 1333 (14.2%) were performed in patients with cardiogenic shock. Total in-hospital mortality was 46.1% and was dependent on TIMI flow grade after PCI, with mortality rates of 78.2%, 66.1% and 37.4% in patients with TIMI 0/1, TIMI 2 and TIMI 3 flow, respectively. In a multivariate analysis left main disease, TIMI <3 flow after PCI, older age, three-vessel disease and longer time-intervals between symptom onset and PCI were significant independent predictors of mortality. The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 19952000. There was a significant decrease in mortality over the years (P for trend 0.02).
Conclusions In-hospital mortality in patients with acute myocardial infarction complicated by cardiogenic shock remains high, even with early interventional therapy. However, our data demonstrate that the PCI in these high-risk patients is feasible in a wide spectrum of community hospitals with acceptable success rates. Our results seen in connection with the results of the randomized SHOCK study advocate an early invasive approach in younger patients with cardiogenic shock, while the best strategy in elderly patients is still a matter of debate.
Key Words: Cardiogenic shock Acute myocardialinfarction Angioplasty Stents
1. Introduction
Acute myocardial infarction is complicated by cardiogenic shock in 5 to 10% of patients.1,2The mortality rate in these patients is exceedingly high and reaches 7080% in those treated conservatively.1,2Most recent experiences from large thrombolytic trials demonstrate of about 60% mortality in shock patients treated with the most effective thrombolytic regimens.3,4Non-randomized studies report encouraging mortality rates among patients undergoing early interventional therapy.5,6However, these studies were performed in highly specialized centres and a selection bias is most likely.7A randomized study comparing angioplasty with conventional therapy in 55 patients was prematurely terminated and reported no significant mortality difference between the two groups.8The larger randomized SHOCK trial performed in 302 patients showed a trend towards an improved outcome after 30 days inthe early invasive group, and a lower 6-month survival rate in the invasive group.9In the recent guidelines of the European Society for patients with ST elevation myocardial infarction interventional therapy is recommended for cardiogenic shock.10
The purpose of this study was to evaluate the in-hospital mortality rate and to determine independent predictors of mortality in a large cohort of unselected consecutive patients with acute myocardial infarction complicated by cardiogenic shock treated with percutaneous coronary intervention in 80 centres inGermany.
2. Methods
2.1. Structure of the ALKK Registry
The PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK) contains all PCI procedures from 80 centres in Germany since October 1992. Details of the organization of the registry have been published previously.11In brief all interventions were prospectively enrolled in the registry by telephone or fax to the coordinating centre in Kassel. All complications occurring in the catheter room and during the in-hospital phase were prospectively documented. In July 1994, a sub-registry was opened, which includes all PCI procedures in acute myocardial infarction within 24h after symptom onset in more detail than in the general registry.12The procedures in the sub-registry from July 1994 until end of March 2001 were analysed for this report. All data were collected prospectively and analysed centrally.
2.2. Patient selection
All patients undergoing PCI for an acute myocardial infarction within 24h after symptom onset were considered for this analysis. Acute myocardial infarction was confirmed by the presence of symptoms of myocardial ischemia associated with ST-segment elevations, left bundle branch block, or elevation of the creatine kinase >3 times the upper normal range. Patients receiving thrombolysis before PCI were excluded from this analysis. It was recommended to diagnose cardiogenic shock in cases with systolic blood pressure <90mmHg or the need forcatecholamines to maintain a systolic blood pressure >90mmHg.
The use of glycoprotein IIb/IIIa receptor inhibitors was evaluated only in the years 1999 until 2001, and is therefore available only in the minority of the patients and not reported here.
2.3. Statistical analysis
All data shown are observed data except for the odds ratios given in Table 4. Continuous variables were summarized as mean±SD and categorical variables as percentages. Univariate analysis was performed with CHI-square tests. Multivariate analysis was done with logistic regression. Tests for trends were performed with the CochranArmitage test for trends. We performed a multivariate analysis with age, left main disease, three intervals between symptom onset and treatment, TIMI <3 flow after PCI, 3 vessel-disease, female gender, year of intervention (1995, 1996, 1997, 1998, 1999, 2000) and stent implantation, all parameters which were significantly related to mortality in a univariate analysis. All statistical calculations were made with the CSS STATISTICA software package by STATSOFT.
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3.1. Patients
Between July 1994 and April 2001 a total of 9422 patients from 80 hospitals were entered into the primary-PCI registry of the ALKK. Of these 1333 (14.2%) patients were in cardiogenic shock as diagnosed by the local investigator and had not received thrombolysis before PCI. The baseline characteristics of these 1333 patients are shown in Table 1.
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The infarct related artery was the left main in 6.0%, the left anterior descending in 39.5%, the circumflex in 14.8%, the right coronary artery in 37.1% and a bypass graft in 2.0% of the patients. Single, double and triple vessel coronary artery disease was observed in 32.2%, 27.6% and 37.3% of the patients, respectively. The mean time from catheter insertion until achievement of the final TIMI flow was 27.6±20.1min. The mean total fluoroscopy time was 12.0±8.8min. The interventionresulted in a TIMI 3 flow in 76.2% and a TIMI 2 flow in 8.6% of the patients, while 15.1% had a TIMI 0/1 flow in the infarct-vessel after PCI.
A stent was implanted in 741 (55.6%) patients. In patients with stent implantation the incidence of TIMI 3 flow post PCI was significantly higher than in patients with plain balloon angioplasty (85.2% vs 65.0%, P=0.001). Accordingly the rate of patients with a final TIMI 0/1 flow was significantly lower with stent implantation (3.2% vs 26.8%, P<0.001) (Table 2).
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3.3. In-hospital mortality
The total in-hospital mortality rate was 46.1% (614/1333 patients). The impact of TIMI patency after PCI on mortality is given in Table 2, indicating the lowest mortality in patients with TIMI 3 flow. There were no significant differences in mortality in patients within the different TIMI flow grades between balloon angioplasty and stenting (Table 2). Because of the significantly higher incidence of TIMI 3 flow after stenting the total mortality was significant lower compared to balloon angioplasty (39.1% vs 54.7%, P=0.02). The influence of the infarct-related artery on mortality is given in Table 3, revealing the highest mortality in patients with left main disease. Mortality in patients with three-, double- and single-vessel disease was 58.2%, 45.1% and 32.8%, respectively. The mortality in different age groups is shown in Fig. 1with the highest mortality in the patients >75 years. In Fig. 2the impact of the time-interval between symptom-onset and admission is depicted, which shows an increase of mortality with the increasing time-interval.
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3.5. Temporal trends
The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 19952000. There was a significant decrease in mortality over the years (P for trend 0.02) (Fig. 3) in the univariate analysis, which was not significant in the multivariate analysis any more. The use of stents increased from to 24% to over 70%. However, the rate of final TIMI grade 3 flow did not change over time (Fig. 4).
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Cardiogenic shock remains the leading cause of death in patients admitted to a hospital with acute myocardial infarction. The results of the SHOCK trial indicate that an early invasive strategy with revascularization may improve outcome in these high risk patients.9We report about the outcome of a large cohort of consecutive patients treated with primary PCI in 80 German community hospitals for acute myocardial infarction complicated by cardiogenic shock. Therefore this result represents the real world experience of PCI in this high risk subgroup.
The approximate 14% rate of patients with cardiogenic shock in our registry is higher compared to reports in other acute myocardial infarction registries, this is certainly due to a selection bias, since an invasive approach is recommended by the current guidelines and not all centres performed primary PCI in all patients with acute myocardial infarction. In addition a quarter of our patients were transferred from hospitals without catheter laboratories.
Earlier retrospective reports in highly specialized centres showed very low mortality rates of around 30% with PCI in cardiogenic shock. The very encouraging results might be explained at least in part by selection bias.7The 30-day mortality in the early invasive arm of the prospective SHOCK trial was 46.7%,9which is comparable to our in-hospital mortality of 46.1%. Still, these mortality rates are lower compared to patients treated conservatively or with thrombolytic therapy only. Therefore an invasive strategy in patients with cardiogenic shock is recommended in the current guidelines of the European Society of Cardiology for patients with ST elevation myocardial infarction.10
4.1. Procedural success
The mortality of our patients was strongly related to the procedural success of PCI, with an improved mortality observed only in patients with TIMI 3 flow after the intervention. Therefore the achievement of TIMI 3 flow is crucial in this situation. In our registry the rate of final TIMI 3 flow of the infarct-related coronary artery was 76%. This is certainly lower compared to the over 90% TIMI 3 flow rates reported from PCI in patients with AMI without cardiogenic shock.13,14However, in the SHOCK trial the success rate of PCI, defined as TIMI 3 or 2 flow and a residual stenosis of <50%, in the early invasive group was 77%.9This rate was achieved in highly specialized centres, experienced in the care of patients with cardiogenic shock. Therefore our results demonstrate that PCI in this high risk subgroup of patients is feasible and associated with an acceptable success rate in a wide range of community hospitals.
The rate of stenting increased from below 25% to over 70% over the years. However, there was no increase in the rate of TIMI 3 flow with the increased use of stents. Patients receiving a stent had a higher TIMI 3 flow rate and this was associated with a lower mortality. However, selection bias is very probable, since primary failure of the procedure by inability to cross the lesion will certainly preclude from attempting a stent. In addition, difficult anatomical features might have prohibited the use of stents in some patients treated with balloon angioplasty alone. In addition, in randomized trials stenting in patients with acute myocardial infarction did not result in higher TIMI 3 flow rates.13,14Therefore the impact of stenting on the procedural success and clinical outcome in our patients remains uncertain.
In recent reports the adjunctive use of abciximab was associated with an improved TIMI 3 flow rate and an improved myocardial reperfusion rate in patients with PCI for cardiogenic shock.15,16Since we do not have complete data of the use of abciximab in our registry we cannot comment on the influence of this therapy on procedural success. In the prospective REO-SHOCK study of the ALKK the TIMI 3 flow rate was 80% with PCI and abciximab.17Considering the positive effect of this treatment in lower risk patients with unstable angina or STEMI without shock in the CADIILAC and EPISTENT trials,14,18abciximab should be strongly considered in the high risk group with cardiogenic shock. Mechanical support with an intra-aortic balloon pump was used in only 151 (11%) patients, 99 (65.6%) of these died. This high mortality rate in patients with intra-aortic balloon pump might indicate a negative selection bias. The low use of this device reflects the current clinical practice in Germany and is different from the higher use of the intra-aortic balloon pump in United States.19
4.2. Predictors of in-hospital mortality
The total in-hospital mortality in our large series was 46.1%. This is higher compared to most recent reports from single centre experiences, but comparable to a report about the mortality in 200 patients.20The highest mortality was observed in patients with occlusion of the left main stem as the infarct-related artery. Since this anatomic feature is usually not predictable from the admission ECG, these results do not impact the recommendation for an invasive approach. A similar high mortality was observed in patients with PCI failure, that means TIMI <3 flow after the intervention, which underscores the importance of TIMI 3 flow in this setting. Therefore all efforts should be undertaken to restore normal flow in the infarct related artery. The increase in the time-interval between symptom-onset and startof PCI was associated with an increase in mortality, advocating a rapid invasive strategy in shock patients.
4.3. Elderly patients
Mortality in patients with cardiogenic shock and an age >75 years is extremely high even with the early interventional approach. In the SHOCK trial the 6-month mortality in the early invasive group was even higher compared to the conservative group (79% vs 56%). In our registry 63% of the patients older than 75 years patients died. In contrast in the SHOCK registry there was a better outcome in patients >75 years treated with early revascularization therapy.21Therefore the decision for interventional therapy should be carefully weighted in these elderly patients. A strategy of initial medical stabilization and subsequent PCI should be considered and the decision for an early invasive strategy should be carefully weighted on the biological age and the co-morbidity of the individual patient.22
4.4. Temporal trends
There was a significant decrease in mortality over time. This has been reported from other registries as well. There are several possible explanations for this positive trend. First with the growing experience in primary PCI over the last years the technical skills of the operators may have increased. Secondly there was an increase in the use of stents. Although this was not associated with an increase in the rate of TIMI 3 flow, there might be a decrease in the rate of fatal re-infarctions after primarily successful PCI. Thirdly the use of abciximab increased to over 60%. Since we have data only from the last 2 years we were not able to determine the positive impact of the use of abciximab on mortality, which was reported in recently published series.15,16
4.5. Limitations
The diagnosis of cardiogenic shock was made by the local investigator by clinical judgement, there were no strictly pre-specified criteria for the diagnosis of cardiogenic shock. However the high mortality rate and the stable rate of shock patients over the years makes it unlikely that the results were significantly influenced by the inclusion of patients, who would not fulfil the haemodynamic criteria for cardiogenic shock. In addition there were no exclusion criteria with respect to concomitant diseases, therefore this patient population represents the real world experience of cardiogenic shock.
5. Conclusions
PCI in patients with acute myocardial infarction complicated by cardiogenic shock is feasible in a wide spectrum of community hospitals. Despite early PCI the mortality in these patients remains high. Therefore all efforts should be undertaken to prevent the occurrence cardiogenic shock. One strategy seems very early initiation of reperfusion therapy with pre-hospital thrombolysis, which was associated with a reduced rate of cardiogenic shock in the CAPTIM trial.23Once cardiogenic shock has developed in a patient with an acute myocardial infarction an early invasive therapy should be applied. In our large series TIMI 3 flow could be established in over 75% of the patients and mortality in these patients was 37%.
Younger age, absence of three-vessel disease, shorter time between symptom-onset and PCI, and the achievement of TIMI 3 flow were the best predictors of an improved in-hospital mortality. Therefore all efforts should be made to bring younger patients with cardiogenic shock as early as possible in the catheter laboratory and to restore patency and normal flow of the infarct related coronary artery. The decision for interventional therapy in the elderly (>75 years) patients should be carefully weighted on the biological age and the co-morbidity of the individual patient.
Footnotes
1 This paper is dedicated to the memory of Karl-Ludwig Neuhaus (19442000)
References