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European Journal of Heart Failure 2003 5(1):73-79; doi:10.1016/S1388-9842(02)00112-5
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© 2002 European Society of Cardiology

Effect of early revascularisation in cardiogenic shock complicating acute myocardial infarction. A single center experience

M.G. Lindholm, J. Aldershvile, C. Sundgreen, Erik Jørgensen, Kari Saunamäki and S. Boesgaard*

Medical Department B 2142, Rigshospitalet, University of Copenhagen Blegdamsvej 9, DK-2100 Copenhagen, Denmark

* Corresponding author. Tel.: +45-3545-2347; fax: +45-3545-2513 E-mail address: boesgaard{at}heartfailure.dk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 References
 
Background: Five to 10% of patients with acute myocardial infarction develop cardiogenic shock and the majority of these patients are expected to die within the first few weeks. In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect of early invasive revascularisation on mortality.

Methods: Thirty-six consecutive patients who developed cardiogenic shock less than 48 h after MI were retrospectively evaluated and divided into two treatment groups. One group received early invasive revascularisation (n=24) and the other group had no early invasive revascularisation, but received similar conventional intensive care medical treatment (n=12).

Results: Baseline characteristics and hemodynamic variables were similar in both groups. Apart from invasive revascularisation and the use of intra aortic balloon counterpulsation (IABP), treatment strategies did not differ between the two groups. Thirty-day mortality was 21% in the revascularised group of patients and 58% in the non-revascularised group (P<0.05).

Conclusions: Our data support previous observations suggesting that an aggressive treatment strategy including early invasive revascularisation and IABP is associated with improved short and long-term survival in patients with cardiogenic shock. Since early revascularisation appears safe with a considerable treatment benefit, this approach must be considered in patients with short shock duration early after MI.

Key Words: Cardiogenic shock • Myocardial infarction • PTCA • Revascularisation

Received April 10, 2001; Revised December 20, 2001; Accepted January 4, 2002


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 References
 
Despite recent advances in diagnosis and monitoring of patients with cardiogenic shock complicating acute myocardial infarction (MI), the prognosis is still dismal and cardiogenic shock is the most common cause of death among patients admitted to hospital with MI [1–4]. Five to 10 percent of patients with MI develop cardiogenic shock and (more than) 2/3 of these patients are expected to die within the first few weeks [1–4]. Modern intensive care treatment including the use of inotropic drugs has not been shown to improve survival [5–7] and although, the incidence of shock is reduced in thrombolysed patients, even the effect of thrombolytics is limited in fully developed cardiogenic shock [8–11].

During the last 5–10 years, observations from randomized studies comparing thrombolysis with primary percutaneous transluminal coronary angioplasty (PTCA), suggest that high-risk patients may do better with invasive revascularisation due to a higher degree of reperfusion of the infarct-related artery [12–14]. The importance of reperfusion is further substantiated by observational data showing that mortality among patients with cardiogenic shock referred to PTCA is markedly reduced in patients with a successful procedure as compared to those where reperfusion can not be satisfactorily re-established (30 vs. 78%)[12–14]. In fact, a likely benefit of an early invasive approach to shock treatment is in line with data from a recent randomized clinical trial [15].

In this study, we review our recent experience in the management of patients with cardiogenic shock complicating MI and examine the effect on mortality of an aggressive treatment approach including early invasive revascularisation.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Statistical analysis
 4. Results
 5. Discussion
 References
 
2.1. Patients
The records of all patients transferred from another hospital to our institution from June 1998 to October 2000 with the diagnosis of cardiogenic shock were retrospectively evaluated. Inclusion criteria were: (1) MI within the previous 48 h; (2) short shock duration with the possibility to perform early invasive revascularisation within 18 h after development of shock; (3) cardiogenic shock defined as systolic blood pressure (SBP) of <90 mmHg for at least 30 min or the need for supportive measures to maintain a SBP >90 mmHg; (4) clinical shock symptoms including cool and clammy extremities, oliguria, high respiratory rate, shallow respiration, sinus tachycardia, or a change in mental status; and (5) survival for at least 1 h after arrival to our department. All five criteria had to be present in each individual patient.

Eighty-two patients with cardiogenic shock were identified. Thirty-four patients did not meet the inclusion criteria (primarily because of shock due to decompensated chronic heart failure, myocarditis or late shock >48 h after MI). A total of 46 patients fulfilled the inclusion criteria defined above. Among those, 10 patients with a primary mechanical complication (ventricular septal defect, rupture of a papillary muscle with severe mitral incompetence and cardiac tamponade due to cardiac rupture) were excluded. The remaining 36 patients were classified into two treatment groups, with and without early revascularisation.

2.2. Data collection
All baseline demographic data were collected from the medical files of the referring hospital and our department. Hemodynamic and clinical data were collected during the first hour after arrival to the intensive care unit at our institution and before any attempts to make revascularisation. ‘Mixed venous saturation (SvO2)’ was collected from the right atrium. Medical treatment is listed as dopamine, dobutamine, epinephrine, norepinephrine, nitroglycerin, isoprenaline. Thrombolytic treatment was noted whenever a thrombolytic agent was administered.

2.3. Clinical strategy
All patients were monitored by both non-invasive (continuous ECG, arterial blood gas analyses, central and peripheral temperatures, urine output) and invasive methods (continuous arterial blood pressure, central venous pressure). Pulmonary artery catheter was placed in five patients and thus not used routinely. After arrival, all patients received additional vasopressor and/or inotropic agents to improve the circulatory condition. In hypotensive patients, dopamine was used as a first-line drug. In severe hypotension, norepinephrine/epinephrine was added. When circulatory stability was obtained, dobutamine or a phosphodiesterase inhibitor could be added.

The decision to perform early invasive procedures [angiography, PTCA, intra-aortic balloon counterpulsation (IABP), by-pass surgery (CABG)] was made at the discretion of the cardiologist in charge. In 1998, a shift from a general conservative and non-invasive treatment approach to a more invasive approach was decided at our department. However, during the present study period both early invasive revascularisation and continued medical treatment without early revascularisation were equally accepted treatment options. Therefore, patients received treatment in a non-randomized manner depending on personal preferences in the actual clinical situation. Use of IABP was encouraged, preferable with start of IABP treatment before any administration of intracoronary contrast agents. PTCA and stent implantation was performed according to our routines for primary infarct PTCA procedures with special efforts directed towards re-establishing of flow in the infarct-related coronary artery.


   3. Statistical analysis
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
4. Results
 5. Discussion
 References
 
Differences in distribution of characteristics between: (1) patients treated with early invasive revascularisation and those that were medically treated; and (2) patients who survived to be discharged and those who died, were studied with the use of Fisher's exact test and chi-square tests for categorical variables. Student's t-tests for the comparison of the mean of normally distributed numerical data with equal variances and the alternate Welch's t-test for continuous variable with significant difference in variances was used. Categorical variables were analyzed with the use of chi-square tests and Fisher's exact test. Differences in survival between study groups were estimated using the Kaplan Meier method and evaluated with the Log–Rank test. Because of the study design and the small size of the sample we did not perform multivariate analysis to identify factors that were associated with a differential effect within subgroups. All numerical data are expressed as median values and range. All the categorical data are expressed in percent. Two-sided P values were considered significant when P<0.05.


   4. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
5. Discussion
 References
 
Thirty-six patients constituted the study population. Twenty-four patients with cardiogenic shock were revascularised within 18 h of shock development. Shock had to develop less than 48 h after an MI. A strategy without early revascularisation but including conventional intensive care monitoring/treatment was decided for the remaining 12 patients. Two of these patients underwent PTCA several days after admission. IABP was used in 50% of the patients with early revascularisation as compared to none of the medical treated patients.

4.1. Baseline characteristics
Patient history, clinical status and treatment on arrival are shown in Table 1. Except for a slight difference in heart rate no significant baseline differences were noted between the groups on arrival to the department. A non-significant trend towards an increased appearance of risk factors is found among the patients treated with early revascularisation. Among the total of 36 patients, one had no inotropic treatment at arrival despite a systolic blood pressure below 90 mmHg. All patients had continuous furosemide infusion at the time when the first hourly diuresis was measured. With one exception in each group, all patients were below the age of 75.


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  		Table 1 Baseline characteristics at arrival of the eligible study patients according to treatment group

 
4.2. Survival
Table 2 and Fig. 1 show in-hospital mortality and 30-days survival. In-hospital mortality was 50% in the medical treated group with one additional death occurring during the first 30 days (58%). Thirty-day mortality was significantly lower (21%) in the group that underwent early invasive revascularisation. Twenty-three of the 24 patients in the revascularised group underwent PTCA. Culprit-lesion TIMI II or TIMI III flow was obtained in 21 patients (91%). All 23 patients received one or more intracoronary stents. Abciximab (glycoprotein 2b/3a inhibitor) was used in 30% of the procedures. One patient was referred to CABG.


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  		Table 2 Hospital management and clinical outcome according to treatment group

 


Figure 1
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  		Fig. 1 30-day survival in two groups of patients with cardiogenic shock complicating acute myocardial infarction.

 
Long-term survival data with a mean follow-up of 214 days is shown in Table 2. No additional deaths were seen among the medical treated patients, whereas an additional two deaths were seen in the revascularised group. Thus, long-term mortality was 58 and 29%, respectively. Heart transplantation or left ventricular assist devices were not used in any of the patients. For patients surviving in the medical therapy group, median hospital stay was 10 days (range 8–17 days) and for those who had early revascularisation median stay was 12 (range 3–48 days). Comparisons between surviving and dead patients are shown in Table 3. Blood pressure and transcutaneous oxygen saturation were significantly lower and heart rate significantly higher among those who died. In addition, a trend towards decreased SvO2, higher age and more severe kidney dysfunction was found. However, the sample sizes may be too small to detect statistical significance.


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  		Table 3 Hospital management of the eligible study patients according to whether they survived to discharge or died in the hospital

 
All surviving patients were started on an ACE inhibitor. Within the first 30 days, betablocker therapy was started in 60% of the patients in the medical treated group and 68% of the patients in the early revascularised group. No patients died from complications (e.g. cerebral or peripheral vascular events) related to the use of IABP and revascularisation.


   5. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
References
 
Even though treatments of both MI and congestive heart failure have improved substantially, the management of cardiogenic shock following acute MI remains a major problem. Death from cardiogenic shock is the main contributor to in-hospital mortality after myocardial infarction, accounting for more than 60% of all deaths in major thrombolytic trials. Thus, efforts should be made to [1] prevent the development of cardiogenic shock and/or [2] to reduce mortality of patients in cardiogenic shock.

Appropriate treatment of every MI is essential to achieve this goal. Although thrombolytic therapy reduces the incidence of cardiogenic shock in clinical trials [8,9], the incidence of cardiogenic shock in the total MI population has not changed much during the last decades and is still approximately 7% [1]. Whereas thrombolytic agents have been shown to reduce mortality in high-risk MI patients, their efficacy in cardiogenic shock is questionable due to a significantly reduced reperfusion rate in this condition [4,11,13,16]. Attempts to improve efficacy of thrombolytic agents by augmentation of arterial blood pressure and coronary perfusion have been promising but not evaluated in conclusive clinical trials [17–19].

In this study, 30-day mortality was significantly reduced in patients with cardiogenic shock undergoing a more aggressive approach including early revascularisation and IABP as compared to a more conventional medical therapy. Despite the retrospective and non-randomized nature of the study, baseline characteristics and hemodynamic variables were almost identical in the two groups of patients and, apart from revascularisation and the use of IABP, treatment strategies were identical in both groups. However, since IABP was used only in the revascularised group, the improved results in this group may not be solely related to the revascularisation procedure, but probably a consequence of the combined use of revascularisation and an assist device. The 30-day mortality rate of 58% in the medical treated group and the lack of inter-group significant differences in baseline variables confirm that the included patients constitute a very high-risk MI population.

The clinical inclusion criteria used in the present study deliberately resemble inclusion criteria used in the large randomized SHOCK trial i.e. a recent myocardial infarction and a short shock duration [15]. In that study, the pre-specified subgroup analysis of patients younger than 75 years (comparable to the present study population) showed a similar 30-day mortality of 57% in the non-revascularised group and a 30-day mortality of 41% in the revascularised group of patients (P<0.05). While the 30-day mortality rates were similar in the non-revascularised groups in this study and the SHOCK-trial, our mortality in the revascularised group (21%) is much lower than in the SHOCK-trial. We cannot exclude the influence of pre-selection bias or the play of chance due to the small numbers. However, both stenting and glycoprotein 2b/3a inhibition were used more frequently in the present study. Consequently, TIMI II or TIMI III flow was achieved in 91% of patients as compared with 77% in the SHOCK-trial [15]. In another recent single-center report [20], similar high rates of TIMI II/III flow (94%) were reported in a group of PTCA treated cardiogenic shock patients where 47% received a stent. In that study, in-hospital mortality was 26% [20]. In addition, recent data suggest that glycoprotein 2b/3a inhibition may favorably influence survival of patients in cardiogenic shock [21]. Among 1257 non-randomized patients, evaluated in several mainly older studies, PTCA treatment was associated with a 44% mortality rate [22].

In general, introduction of new treatments should be based on evidence-based medical practice. During the last 10 years, several attempts have been made to provide evidence in favor of an aggressive approach to the treatment of cardiogenic shock. Two recent randomized controlled trials in Europe have been prematurely stopped due to slow patient recruitment [19,23]. In these trials, it was only possible to include 57 and 55 patients despite efforts to increase inclusion rate. The SHOCK trial included 302 patients during a 5-year period [15]. Probably, due to an early interventional hazard the primary (30-day mortality) end-point was negative in this trial. However, several secondary endpoints, including 6-month mortality were significantly improved. After 1 year, the potential overall gain from early revascularisation was 130 lives saved per 1000 treated patients, which is higher than any other documented treatment in cardiovascular disease [24]. Despite the lack of confirmatory evidence, it is currently unlikely that we will see new large-scale randomized controlled trials of early revascularisation for cardiogenic shock.

Therefore, based on our present knowledge, high-risk MI patients in pre-shock states and younger patients with early shock presentation and ongoing ischemia seem ideal candidates for invasive revascularisation and IABP. However, this strategy is invariably accompanied by a high rate of peri- and post-procedural complications, and a fully staffed and dedicated intensive cardiology care environment as well as skilled and experienced interventional cardiologists are a necessary prerequisite for these procedures to succeed [25].

Despite the methodological limitations, our data support previous observations suggesting that an aggressive treatment strategy, including early invasive revascularisation and IABP, is associated with improved short and long-term survival in patients with cardiogenic shock. Since this strategy appears safe with a considerable treatment benefit, early revascularisation must be considered in patients with short shock duration early after MI.


   Acknowledgements
 
This study was supported by a grant from the Jørgen Møller Foundation.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Statistical analysis
 4. Results
 5. Discussion
 References
 

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