Author + information
- Received January 28, 2018
- Revision received June 28, 2018
- Accepted July 17, 2018
- Published online September 17, 2018.
- Michał Hawranek, MDa,∗ (, )
- Marek Gierlotka, MDa,b,
- Damian Pres, MDa,
- Marian Zembala, MDc and
- Mariusz Gąsior, MDa
- a3rd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Silesian Centre for Heart Disease in Zabrze, Zabrze, Poland
- bDepartment of Cardiology, University Hospital in Opole, Faculty of Natural Sciences and Technology, University of Opole, Opole, Poland
- cDepartment of Cardiac, Vascular and Endovascular Surgery and Transplantology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Silesian Center for Heart Diseases in Zabrze, Zabrze, Poland
- ↵∗Address for correspondence:
Dr. Michal Hawranek, Medical University of Silesia, Katowice, School of Medicine with the Division of Dentistry in Zabrze, Silesian Centre for Heart Disease in Zabrze, 3rd Department of Cardiology, ul. Sklodowskiej-Curie 9, 41-800 Zabrze, Poland.
Objectives The authors sought to compare outcomes of patients with myocardial infarction and cardiogenic shock (CS) treated with percutaneous coronary intervention (PCI) with or without intra-aortic balloon pump (IABP) support according to final epicardial flow in the infarct-related artery.
Background A routine use of IABP is contraindicated in patients with myocardial infarction and CS. There are no data regarding the subpopulation of patients who may benefit from such support besides patients with mechanical complications of myocardial infarction.
Methods Prospective nationwide registry data of patients with myocardial infarction and CS treated with PCI between 2003 and 2014 were analyzed. Patients were initially stratified into 2 groups according to final infarct-related artery Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI: those with successful primary PCI (TIMI flow grades 2 or 3) and those with unsuccessful primary PCI (TIMI flow grades 0 or 1). Outcomes of patients with or without IABP treatment in each group were analyzed and compared.
Results In the unsuccessful PCI group, patients in whom IABP was applied had lower in-hospital, 30-day, and 12-month mortality. IABP support in this group of patients was an independent predictor of lower 30-day mortality (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.59 to 0.89; p = 0.002). Conversely, in patients with successful PCI, IABP was an independent predictor of higher 30-day mortality (HR: 1.18; 95% CI: 1.08 to 1.30; p = 0.0004).
Conclusions IABP is associated with a lower risk of 30-day mortality in patients with myocardial infarction complicated by CS, in whom primary PCI was unsuccessful.
Cardiogenic shock (CS) is the greatest challenge in the treatment of myocardial infarction. Despite application of early reperfusion therapy, with percutaneous coronary intervention (PCI) or coronary artery bypass grafting, mortality in the acute phase of CS remains high (1–3). Mechanical circulatory support seems to be one of therapeutic options that can improve treatment results. Until recently, intra-aortic balloon pump (IABP) was the most frequently used device, recommended by the Class IC guidelines (4). Since publication of the results of large meta-analyses and the IABP-SHOCK II (Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock) study results, the routine use of IABP is contraindicated in this patient population (5–7). IABP should be applied in case of mechanical complications of myocardial infarction (7).
According to the results of the large registries, application of IABP in CS is associated with decreased mortality among patients without reperfusion treatment and treated with fibrinolysis, whereas in patients who had undergone primary PCI, it is associated with increased risk of death (6,8). In the IABP-SHOCK II study, application of IABP in patients in cardiogenic shock (CS) who had undergone early revascularization did not bring any benefits. More than 90% of patients, both in the control group and in the group treated with IABP, obtained successful reperfusion treatment defined as final Thrombolysis In Myocardial Infarction (TIMI) flow grade 2/3 in the infarct-related artery (IRA) (5). The effect of IABP on prognosis in patients either with or without successful epicardial reperfusion has not been evaluated so far. It is known that successful reperfusion of the IRA is the strongest prognosis-determining factor (1).
As we have at our disposal a large group of consecutive patients with CS in the course of myocardial infarction who were treated with primary PCI, both with and without the application of IABP, we decided to check whether the prognosis of patients who undergo IABP differs depending on the obtained final TIMI flow grade in the IRA.
The PL-ACS registry
We analyzed the data from ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation myocardial infarction (NSTEMI) patients in the PL-ACS registry (Polish Registry of Acute Coronary Syndromes), which is an ongoing, prospective, observational, nationwide registry of consecutive patients hospitalized with acute coronary syndromes (ACS) in Poland. It was a joint initiative of the Silesian Center for Heart Diseases and the Polish Ministry of Health. The registry methodology and analyses for STEMI patients with CS had been previously published (9–11). In brief, all of the admitted patients with suspected ACS were screened for their eligibility to enter the registry, but they were not enrolled until ACS was confirmed. STEMI and NSTEMI were defined according to the Third Universal Definition of Myocardial Infarction (12). The skilled physicians who were in charge of each individual patient collected the data. Internal checks for missing or conflicting data and values markedly out of the expected range were implemented using the registry software. In the Silesian Center for Heart Diseases data management and analysis center, further checks were applied if necessary. If the patient was transferred via the regional hospital to a primary PCI center and both hospitalizations were reported, they were combined into 1 record for the final data management. The registry was approved by the local ethics committee and meets the conditions of the Declaration of Helsinki.
Patients and definitions
The sample for the current analysis consisted of patients hospitalized between October 1, 2003, and June 30, 2014. The inclusion criteria were STEMI or NSTEMI presentation on admission complicated by CS, and PCI as the final method of reperfusion treatment. The exclusion criterion was unknown final TIMI flow grade status (n = 91).
According to the protocol, CS was defined as: 1) hypotension (systolic blood pressure <90 mm Hg for at least 30 min or the need for pharmacological support to maintain systolic blood pressure above 90 mm Hg); and 2) signs and symptoms of end-organ hypoperfusion. In-hospital major cardiovascular adverse events were all-cause death, recurrent myocardial infarction (defined as an ischemic event that met criteria for reinfarction and was evidently clinically distinct from the index event at the time of admission), stroke (defined as an acute neurological deficit that lasted >24 h and affected the ability to perform daily activities or resulted in death), recurrent PCI (defined as unplanned PCI performed as an urgent procedure due to new acute ischemic symptoms), major bleeding (defined as bleeding with hemoglobin/hematocrit drop of 5 g/dl/0.15 U, leading to hemodynamic instability or requiring blood transfusion; intracranial hemorrhage; or retroperitoneal bleeding), and resuscitated cardiac arrest (defined as sudden cardiac arrest due to ventricular fibrillation, ventricular tachycardia, electromechanical dissociation, or asystole). The vital status at 30 days and 12 months was obtained from the official mortality records from the government databases and was available for all the patients with the exact date of death.
Patients were initially stratified into 2 groups according to final IRA TIMI flow grade after PCI: those with successful primary PCI (TIMI flow grades 2 or 3) and those with unsuccessful primary PCI (TIMI flow grades 0 or 1). Outcomes of patients with or without IABP treatment were analyzed and compared. The study flowchart is available in the online materials (Online Figure S1). The primary outcome measure was 30-day mortality. Secondary outcome measures were in-hospital major cardiac adverse events and 12-month mortality.
Continuous variables were reported as mean ± SD. Categorical variables were expressed as percentages. Student’s t-test was used for the comparison of continuous variables. Normality of distribution was checked with the Shapiro-Wilk test. To compare categorized variables, the chi-square test was used. Follow-up mortality was analyzed using the Kaplan-Meier method, and the differences between the groups were compared with the log-rank test. A multivariate logistic regression was used to present the impact of the selected parameters on the IABP usage in CS patients, and the results were presented as odds ratios with 95% confidence intervals (CIs). A multivariate Cox proportional hazard model regression was performed to adjust the influence of IABP on 30-day and 12-month mortality, and the results were presented as hazard ratios and 95% CIs. A 2-sided p value ≤0.05 was considered significant. For all the calculations, STATISTICA 12.5 software (StatSoft, Tulsa, Oklahoma) was used.
A total of 7,243 patients with myocardial infarction complicated by CS were included into the analysis. Baseline characteristics and outcomes of the whole group are available in the online materials (Online Tables S1 to S3). The majority of patients (>80%) had STEMI as the initial diagnosis. The proportion of successful PCI amounted to 86.3% (6,252 patients), whereas lack of epicardial reperfusion in the IRA (TIMI flow grade 0 to 1) was observed in 13.7% of patients (n = 991). IABP was applied in 1,116 patients (17.8%) with successful PCI, and in 154 patients (15.5%) with unsuccessful PCI, respectively.
Clinical and angiographic characteristics
The patients with successful PCI, in whom IABP was applied, were older. Moreover, a higher proportion of patients with prior myocardial infarction and prior revascularization in their medical history, significantly lower systolic and diastolic blood pressure, and higher heart rate on admission were observed. In coronary angiography, the left anterior descending coronary artery and left main coronary artery were significantly more often infarct-related arteries. In addition, a higher proportion of patients with initial TIMI flow grade 0 to 1 in the IRA, multivessel coronary artery disease, and glycoprotein IIb/IIIa inhibitor use were observed compared with the patients without IABP. Moreover, diabetes mellitus and lower left ventricular ejection fraction occurred significantly more often in patients with IABP, both in the groups with successful and with unsuccessful PCI. Clinical and angiographic characteristics are presented in Tables 1 and 2⇓⇓. Multivariate analysis of parameters associated with IABP use is presented in the Online Appendix (Online Table S4).
Adverse cardiovascular events
The application of IABP, both in patients with successful and unsuccessful PCI, was associated with higher rates of serious bleeding, recurrent myocardial infarction, and recurrent PCI during index hospitalization. The proportion of major bleeding in the whole group of patients with IABP amounted to 7.6%. Of note is that the proportion of major cardiovascular adverse events was significantly higher in the patients with IABP in the successful PCI group, and was comparable, regardless of the fact of IABP support application, in the patients with unsuccessful PCI (Table 3).
In the unsuccessful PCI group with final TIMI flow grade 0 to 1 in the IRA, patients in whom IABP was applied had lower in-hospital, 30-day, and 12-month mortality (Table 3). The aforementioned relationships concerning the 30-day death rate were confirmed by the multivariate analysis (Table 4). Conversely, in the group of patients with successful PCI, IABP insertion was associated with higher in-hospital, 30-day, and 12-month mortality compared with the patients without IABP (Table 3). In the multivariate analysis, IABP application was an independent predictor of higher 30-day mortality (Table 5). Kaplan-Meier estimates for death rates at 30 days and after 12 months are presented in Figure 1. In-hospital, 30-day, and 12-month mortality in the whole group with CS were 45.6%, 57.4%, and 65.9%, respectively.
The most important findings of our analysis are as follows: 1) application of IABP is associated with lower 30-day risk of death in patients with myocardial infarction complicated by CS in whom primary PCI was unsuccessful; 2) application of IABP is related to higher risk of death among patients with successful primary PCI; and 3) these differences persist at the 12-month follow-up.
Until recently, IABP was the most frequently used mechanical circulatory support in patients with myocardial infarction complicated by CS. Publication of the results of meta-analyses and the IABP-SHOCK II study caused the frequency of using IABP for this indication to significantly decrease (13). On the other hand, in many centers, it is still the only device that can be used, when primary PCI and pharmacological treatment are insufficient (14). Moreover, the application of IABP, especially following unsuccessful PCI of IRA, can be particularly important in patients with multivessel disease. In such patients, coronary perfusion to the noninfarcted segments of myocardium is particularly important because there is a chance of maintaining cardiac output through the compensatory hyperkinesis of these segments. In case these segments are supplied by the stenotic artery, IABP can improve the coronary perfusion pressure. The results of the CULPRIT-SHOCK (PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock) study do not justify intervention within these vessels, but on the other hand, show that patients with CS and multivessel disease are at risk of the worst outcome (10,14).
The IABP-SHOCK II study is the largest randomized study so far, assessing the effect of IABP application on short-term prognosis in patients with myocardial infarction complicated by CS, treated with early reperfusion therapy. It has been shown in a large population of patients that the outcomes of patients in whom IABP had been applied are similar to the outcomes of those in whom it was not applied. Due to the lower than expected incidence of death in the control group at 30 days after the acute phase (41.3% toward the expected 56%), the study turned out to be underpowered with respect to the power of verification of the primary hypothesis. Moreover, 10% of patients in the control group and 4.2% of patients in the IABP group were not treated per protocol. Additionally, in the majority of patients, IABP was inserted after the performance of primary PCI (86.6% vs. 13.4%). The aforementioned doubts do not downgrade the quality of the study, but rather leave space for further analyses.
Lack of epicardial reperfusion (unsuccessful PCI)
In the current analysis, patients after unsuccessful PCI in whom IABP was applied were younger, but they exhibited a worse clinical profile compared with the patients in whom IABP was not used. Despite worse clinical characteristics and higher rate of in-hospital major bleeding, the frequency of the primary endpoint was significantly lower in the group treated with IABP. A similar difference was observed at the 12-month follow-up. Data concerning the application of IABP in myocardial infarction complicated by CS are diverse. In the meta-analysis of observational studies, it was shown that IABP decreased the risk of death in patients who received conservative and fibrinolytic treatment. It was confirmed that coronary perfusion pressure is important for the effectiveness of fibrinolytic treatment, which increases with an increase in this pressure (15). IABP increases mean aortic pressure, which translates to higher perfusion pressure in coronary arteries. In the case of primary PCI, vessel patency is not associated with perfusion pressure, but rather with mechanical restoration of patency and dilatation of the stenosis (16). Thus, an increase in the mean pressure may not provide additional benefit in these patients. In the case when, after mechanical restoration of the vessel patency, the epicardial flow according to TIMI flow grade is 0 or 1, there is no myocardial reperfusion. In such patients, coronary autoregulation is exhausted, and coronary flow is dependent on perfusion pressure (17). In relation to this, an increase in coronary perfusion pressure resulting from IABP action can translate into better myocardial perfusion and stabilization of the patient’s clinical condition. Data from the experimental studies concerning lower incidence of no-reflow phenomenon during the IABP therapy can support this hypothesis (18). In addition, a beneficial effect of IABP in this group of patients may result from decreasing the preload and lowering oxygen demand (19,20). It seems that the application of IABP in patients with unsuccessful PCI can reflect the situations observed in the analyses of patients who received conservative or fibrinolytic treatment. In both cases, there is a lack of reperfusion at the epicardial level, or it is incomplete.
In the 12-month follow-up, a slight increase in mortality was observed compared with the 30th day, by 4.0% and 6.5% in the groups with IABP and without IABP, respectively. This observation is in agreement with the published data and confirms that in patients in CS, an early period after the CS occurrence is essential for the prognosis (5). Thus, a difference in mortality found after 12 months is probably associated with the observed difference up to the 30-day follow-up.
Adequate epicardial reperfusion (successful PCI)
Similar to the patients with lack of adequate reperfusion, the patients with successful PCI, in whom IABP was applied, had a worse clinical profile. However, in contrast to patients with unsuccessful PCI, they had significantly higher mortality at 30-day and 1-year follow-up. Results of the analysis in this subgroup of patients are in accordance with the data concerning IABP use during primary PCI, published in meta-analyses and large registries (6,8). IABP insertion was associated with the increased risk of death on the 30th day in the NRMI-2 registry (National Registry of Myocardial Infarction 2) (8). In the meta-analysis of observational data, including the aforementioned registry, the application of IABP during primary PCI was associated with an increased risk of death by 6% at 30-day follow-up. In the meta-analysis of randomized studies, similar to the IABP-SHOCK II study, the application of IABP was not beneficial (5,6). It has been shown that the strongest factor improving the prognosis in patients with myocardial infarction complicated by CS is the successful restoration of patency of the IRA (1). The IABP potential to increase cardiac output does not exceed 0.5 l/min. What is more, up to now, it has not been shown that devices with greater supportive potential would be significantly beneficial for the patients in CS (21). Perhaps the effect obtained by the effective restoration of vessel patency and restored myocardial perfusion exceeds the potential benefits associated with an increase in coronary perfusion pressure achieved with IABP. More frequent vascular complications could additionally influence worse prognosis of patients treated with IABP.
In our analysis, regardless of the effectiveness of the primary PCI procedure, IABP insertion was associated with a significantly more frequent occurrence of major hemorrhagic complications during the in-hospital period. The obtained results are in accordance with the data from the large observational studies and meta-analyses, but different from the results of the IABP-SHOCK II study. In the meta-analysis of the randomized studies, the application of IABP increased the risk of major bleeding by 6% in patients with myocardial infarction (6). However, in the IABP-SHOCK II study, the frequency of life-threatening bleeding was similar in both groups (5). Similar observations were obtained from the randomized studies conducted in populations other than STEMI patients with CS (16,22). The aforementioned differences can result from inconsistent definitions of major bleeding, different clinical presentation, and the mode (elective/urgent) of IABP insertion. Additionally, it is emphasized that both the safety and effectiveness of IABP use can be associated with the experience of the treatment team (23).
The presented analysis derives from an observational study and should be considered as hypothesis-generating only. The obtained results support contraindication of the routine use of IABP, because IABP insertion was associated with increased risk of death in the group with successful PCI. It cannot be excluded that IABP insertion was in part a marker of severity of the initial clinical condition of these patients. On the other hand, the patients with unsuccessful PCI in whom IABP was used, initially also in worse clinical condition, had a better prognosis than patients without IABP support. Taking into account the heterogeneous results of studies on IABP, it seems that it is necessary to develop a risk scale that will help to choose patients who would benefit from the additional support of the circulatory system. Such personalization of the therapeutic process can increase the effectiveness of applied devices and improve the prognosis in this difficult group of patients. Perhaps patients with unsuccessful PCI belong to such a subpopulation of patients.
Because this analysis is an observational study, all limitations associated with a nonrandomized setting apply to it. Moreover, we did not have any data concerning the moment of IABP insertion (before or after the primary PCI), and thus, this important aspect was not analyzed. It cannot be excluded that in some patients in both successful and unsuccessful PCI groups, IABP was not inserted due to an initially extremely poor clinical condition.
IABP is associated with a lower risk of 30-day mortality in patients with myocardial infarction complicated by CS, in whom primary PCI was unsuccessful. These results are only hypothesis-generating and require prospective studies.
WHAT IS KNOWN? The routine use of IABP is contraindicated in patients with myocardial infarction and cardiogenic shock. It can be considered in selected patients with profound cardiogenic shock when other devices are not available, are contradicted, or cannot be placed.
WHAT IS NEW? IABP support is associated with better prognosis in patients with cardiogenic shock complicating myocardial infarction treated with primary PCI without epicardial reperfusion.
WHAT IS NEXT? It is necessary to develop a risk scale that will help to choose patients who would benefit from the additional mechanical support of the circulatory system. Such personalization of the therapeutic process can increase the effectiveness of applied devices and improve the prognosis in this difficult group of patients.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute coronary syndromes(s)
- confidence interval
- cardiogenic shock
- intra-aortic balloon pump
- infarct-related artery
- non–ST-segment elevation myocardial infarction
- percutaneous coronary intervention
- ST-segment elevation myocardial infarction
- Thrombolysis In Myocardial Infarction
- Received January 28, 2018.
- Revision received June 28, 2018.
- Accepted July 17, 2018.
- 2018 American College of Cardiology Foundation
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