Journal Logo

Article: Systematic Review and Meta-Analysis

Intra-Aortic Balloon Pump May Grant No Benefit to Improve the Mortality of Patients With Acute Myocardial Infarction in Short and Long Term

An Updated Meta-Analysis

Su, Dan MD; Yan, Bin MD; Guo, Litao MD; Peng, Liyuan MD; Wang, Xue MD; Zeng, Lingfang PhD; Ong, HeanYee MRCP; Wang, Gang MD, PhD

Section Editor(s): Lymperopoulos, Anastasios

Author Information
doi: 10.1097/MD.0000000000000876



Cardiogenic shock is the most common cause of death in patients with acute myocardial infarction (AMI), even following early revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).1–3 Intra-aortic balloon pump (IABP) counterpulsation can increase coronary blood supply while at the same time support patients with cardiogenic shock by maintaining cardiac output4 hemodynamically. However, the efficacy of IABP has been controversial since its first application during the early 1960s. Current literature demonstrates wide inconsistency of the indications for IABP utilization and outcomes. A meta-analysis by Sjauw et al5 found conflicting outcomes when randomized studies, cohort studies, and observational data were pooled and analyzed. Consistent with another meta-analysis carried out in 2013,6 Sjauw et al5 also demonstrated the benefit of IABP may vary due to the adjunctive therapies, thrombolysis or PCI.

The use of IABP for high risk PCI was recommended as a class IIb (level of evidence C) indication in ACCF/AHA/SCAI guidelines.7 However, in a recent randomized trial (IABP-SHOCK II), IABP support did not reduce the 30-day mortality in patients with AMI and cardiogenic shock, compared without IABP support.8 In addition, the same study found that IABP did not reduce 6- and 12-month mortality rate compared with the control group, despite early revascularization and optimum medical therapy in both groups.9 Therefore, in the 2014 ESC/EACTS myocardial revascularization guidelines, IABP was only granted an IIIA recommendation and recommended as a bridge to surgery for patients with mechanical complications.10 Our current updated meta-analysis has collected all published randomized trials to date, aiming to evaluate the potential short- or long-term benefits and risks of IABP therapy in AMI with or without cardiogenic shock.


To identify all randomized controlled trials (RCTs) of IABP therapy, public databases including MEDLINE (1966–2014) and EMBASE (1980–2014) were searched. Keywords and medical subject headings are as follows: IABP, IABC (intra-aortic balloon counterpulsation), AMI, heart infarction, coronary artery disease, ischemic heart disease, and acute coronary syndrome. The search was restricted to human studies and clinical trials or RCTs only. In addition, we also manually searched bibliographies of identified studies if needed.

All RCTs were published before November 2014 on the treatment of AMI with IABP in either intensive care unit or coronary care unit settings. Studies were excluded if they were in abstract form only, not RCT, not on AMI patients, IABP in surgery or when other cardiac support devices, such as a left ventricular assist device (LVAD) or an extracorporeal membrane oxygenator, were used. Information on the surname of the first author, year of publication, average patient age, sample size, mean or medium IABP duration, inclusion criteria, exclusion criteria, and outcomes were extracted. Data from each study were collected in intention-to-treat categories rather than per-protocol categories to avoid bias towards excluding patient dropped-out, withdrew, or incompliance to the treatment. For assessment of the risk of bias, Cochrane risk of bias tool11 was used. Two authors independently collected information from all studies to obtained information on sequence generation, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other sources of bias. We assigned “unclear” to an item with insufficient information.

All analyses were conducted using STATA 12.0 (StataCorp LP, College Station, TX). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for each study. Relative weights were assigned according to the contribution of each study to each analysis. Publication bias was assessed graphically using a funnel plot. Statistical significance was set as 0.05 on the basis of 2-way z tests and χ2 tests.


Literature Search

Potentially relevant references were identified by the above stratagem. A total of 3026 references were identified (Pubmed: n = 1962, Embase: n = 1049, 15 records identified from other sources). Seventeen relevant studies with 3226 participants8,9,12–26 were enrolled after in-depth review. The selection strategy of our study is shown in Figure 1.

Flowchart of the selection process in our study. IABP = intra-aortic balloon pump, RCT = randomized controlled trial.

Study Characteristics

The baseline characteristics of the 17 studies included in the meta-analysis are summarized in Supplemental Digital Content-Table 1, The risks of bias in all studies (measured by Cochrane risk of bias tool) are presented in Figures 2 and 3. The mean (or medium) duration of IABP support in the selected RCTs ranged from 24 hours to 11 days. All the patients in the trials received optimal medical therapy based on guidelines. We analyzed the impact of IABP management on short-term mortality in 14 trials (n = 2354), long-term mortality in 9 trials (n = 1743), risks of hemorrhage in 8 trials (n = 1296), reinfarction in 8 trials (n = 1371), recurrent ischemia in 4 trials (n = 964), and stroke in 4 trials (n = 684) during the study periods.

The results of evaluation using Cochrane collaboration's tool for assessing risk of bias. Each risk of bias item presented as percentages across all included studies.
Summary of the risk of bias for 17 RCTs assessed using Cochrane Collaboration's tool. Green colored symbol corresponds to low risk of bias, the yellow corresponds to unclear risk of bias, and the red corresponds to high risk of bias.

IABP Failed to Improve the Short- and Long-Term Mortality

The short-term mortality was analyzed in 14 studies involving 2354 patients (5 trials in AMI with cardiogenic shock and 9 trials in AMI without cardiogenic shock). As shown in Figure 4, there was no significant difference on short-term mortality (<30-day mortality) between IABP on AMI patients with cardiogenic shock and control group (RR, 0.91; 95% CI, 0.77–1.08; P = 0.293). Similar result was also observed in AMI patients without cardiogenic shock (RR, 0.88; 95% CI, 0.60–1.29; P = 0.279). Taken together, our meta-analysis indicates that short-term mortality of patients with AMI with and without cardiogenic shock does not differ between IABP and control group (RR, 0.90; 95% CI, 0.77–1.06; P = 0.214).

Forest plot of short-term mortality in acute myocardial infarction with or without cardiogenic shock. Solid lines denote CIs of effect size (ES) estimate for individual studies, boxes denote the study weighting, dashed line denotes the combined ES, and the diamonds denote the CI for the overall effect size. CI = confidence interval, RR = relative risk.

Interestingly, further analysis of 2 subgroups in 9 studies (4 AMI trials with cardiogenic shock and 5 without cardiogenic shock) also demonstrated that IABP therapy was not associated with a significantly reduced risk of long-term mortality (6- and 12-month mortality) rate (RR, 0.91; 95% CI, 0.79–1.04; P = 0.155). This analysis covers 1743 patients, 866 patients in the IABP group and 877 in the control group. Moreover, the results remained the same when the analysis was performed on studies only either on patients with cardiogenic shock (RR, 0.95; 95% CI, 0.83–1.10; P = 0.492) or without cardiogenic shock (RR, 0.73; 95% CI, 0.49–1.09; P = 0.122) (Figure 5).

Forest plot of long-term mortality in myocardial infarction with or without cardiogenic shock. CI = confidence interval, RR = relative risk.

IABP May Increase the Risks of Hemorrhage and Recurrent Ischemia for AMI Patients During Mechanical Support

Furthermore, incidences of hemorrhage, reinfarction, recurrent ischemia, and stroke within IABP group and control group were also analyzed. We observed no significant differences in the risks of reinfarction (RR, 1.01, 95% CI 0.64–1.59; P = 0.954) and stroke (RR, 2.95, 95% CI 0.97–9.0; P = 0.057) between IABP and control groups. However, as shown in Figure 6, amongst 1296 patients (644 patients in the IABP group and 652 in the control group) in the investigation, the risk of hemorrhage was significantly higher in IABP group than control group (RR, 1.49; 95% CI, 1.09–2.04; P = 0.013). In addition, we also found that IABP treatment was associated with an increased risk for recurrent ischemia events (RR, 0.54, 95% CI 0.37–0.79; P = 0.002) among 4 reports13,15–17 analyzed.

(A) Risk of hemorrhage, (B) re-infarction, (C) stroke, and (D) recurrent ischemia in myocardial infarction with or without cardiogenic shock. CI = confidence interval, RR = relative risk.


The aim of AMI management is to reduce the mortality by improving or restoring the coronary circulation. Thus far, even with rapidly emerging medical options available, mechanical circulatory support devices are still necessary to provide hemodynamic support when required. IABP has been shown to improve the outcomes of AMI patients with cardiogenic shock by increasing diastolic peak pressure and reducing afterload in the pre-PCI era.27 In addition, IABP was reported to maintain the hemodynamic stability in selective high-risk AMI individuals under going PCI during short term.28 The prophylactic IABP support in high-risk patients during selective PCI has also been thoroughly evaluated in a study with a total of 106 patients, suggesting IABP could reduce the level of C-reactive protein and short-term mortality following PCI.24

However, there has been ongoing controversy on IABP application on AMI patients with or without cardiac shock since the 1990s. Although IABP results in a hemodynamic benefit on afterload reduction and coronary perfusion improvement, the effects on cardiac output are modest and not sufficient to reduce mortality.29,30 As shown in a recent meta-analysis, preoperative insertion of IABP reduced mortality in selective high-risk coronary artery bypass graft patients.31 IABP may play a role as a bridge or transition in short term but not on increasing long-term survival rate, which are also affected by subsequent physiopathologic progression and treatment following AMI. Before the IABP-Shock II Trial, which did not find improved 30-day, 6-month, or 12-month survival rate after the implantation of IABP,8,9 Prondzinsky et al23 showed that IABP support could reduce afterload, as measured by a significant reduction in BNP in 2010. However, they also revealed that mechanical support, such as IABP, failed to prevent the initiation and development of systemic inflammatory response syndrome (SIRS) and multi-organ dysfunction syndrome (MODS), which lead to the high mortality of AMI patients with cardiogenic shock as assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II score.23 There was a meta-analysis from Bahekar et al32 supporting Prondzinsky et al in the importance of prognosis assessment in patients with AMI complicated with cardiogenic shock. Although APACHE II score was not applied in the meta-analysis, it reported a significant reduction of in-hospital mortality in AMI with cardiogenic shock, while AMI patients with high-risk and cardiogenic shock may not benefit from the use of IABP in terms of in-hospital mortality, rate of reinfarction, and recurrent angina.32 Nevertheless, this study might be inherent biased due to the combined analysis of RCTs, prospective and retrospective observational studies.

Most of current meta-analyses and recommendations for IABP application were mainly based on nonrandomized data due to the difficulties in conducting a randomized clinical trial in the emergency setting of AMI. According to the absence of meta-analysis on prospective randomized studies, it is of great value to reassess the therapeutic effectiveness of IABP for circulatory support in AMI. Therefore, we carried out the current updated meta-analysis but failed to reveal a substantial benefit from IABP therapy on reducing the short- and long-term mortality, in AMI with or without cardiac shock. The potential limitation of our study is that IABP-SHOCK II trial may have relatively larger weight. Although there was no significant difference on the short-term mortality regardless of whether IABP-SHOCK II trial was included or not, the long-term mortality was improved without IABP-SHOCK II trial. However, our results are consistent with another recently published meta-analysis, which also showed that IABP was not found to improve 30-day mortality among patients with AMI in RCTs, no matter patients had cardiogenic shock or not.33 As we know, cardiogenic shock is commonly rapidly progressive and usually fatal. Despite of the advances in coronary revascularization, cardiogenic shock as a complication of AMI still remains as a huge clinical challenge with high mortality. It eventually results in SIRS and MODS due to peripheral hypoperfusion with microcirculatory dysfunction of ischemia sensitive tissues and organs. This would happen in various percentage of patients with mild, moderate, or severe cardiogenic shock, which could preclude the statistical processing.34–36 Therefore, further studies should include hemodynamic measurements or laboratory inflammatory markers within a scoring system to divide AMI patients into more accurate subgroups.

In addition, safety is another important issue in consideration of IABP application. Although the sheathless catheter insertion technique and catheters with smaller profiles were developed, the use of IABP may produce a high rate of complications, such as hemorrhage, recurrent ischemia, stroke, and reinfarction. Although no differences regarding hemorrhage were observed in IABP-Shock II Trial,8 conflicting conclusions were reported in a meta-analysis, in which IABP was found to significantly increase the risk of moderate-to-severe bleeding.32 In our meta-analysis, we also found IABP was associated with an increased rate of bleeding, possibly associated with the use of multiple antithrombotic agents with aggressive anticoagulation regimen in acutely MI patients.37,38 Besides, the use of IABP was also the strongest independent predictor for major bleeding due to femoral artery cannulation, prolonged duration of IABP support, IABP-related thrombocytopenia and renal impairment, which were consistently demonstrated by other study populations, especially in patients who had developed or were anticipated to develop cardiogenic shock.39,40 Davidavicius et al further pointed out that IABP insertion in the urgent setting in response to intraprocedural hemodynamic instability confers a higher risk of bleeding compared with selective insertion for stable patients.41 In terms of other safety issues, we observed significantly increased risk for recurrent ischemia in IABP group than in the control group. Although it seems more closely related to the premorbid status of patients, our findings may add additional support on a more conservative strategy for using IABP in acute phase of MI with or without cardiogenic shock.

As mentioned earlier, AMI is not only associated with compromised cardiac contractile function, especially in patients with cardiogenic shock. Therefore, other than mortality, more comprehensive assessment of hemodynamic changes and inflammatory markers of patients with AMI may serve as better end point for IABP application. In addition, there were <10% of patients in control group accepting IABP or LVAD support in IABP-SHOCK II trial, which might interfere the analysis of mortality in our study.42,43 In terms of the timing of IABP insertion, it was too difficult to control in real clinical settings and to be included for analysis in most studies. Future RCTs with larger numbers of patients and rigorous design are required in the future.

In conclusion, the findings of this study suggest that IABP use in AMI patients with or without cardiogenic shock may not reduce the short-term and long-term mortality, and potentially promote the recurrent ischemia and hemorrhage events.


We feel grateful for the support from the National Natural Science Foundation of China (No. 81300116), the Research Fund for the Young Scholars of the Higher Education Doctoral Program of China (No. 20120201120083), and the Fundamental Research Funds for the Central Universities of China (No. XJJ2013062).


1. Thiele H, Allam B, Chatellier G, et al. Shock in acute myocardial infarction: the Cape Horn for trials? Eur Heart J 2010; 31:1828–1835.
2. Aissaoui N, Puymirat E, Tabone X, et al. Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French nationwide registries. Eur Heart J 2012; 33:2535–2543.
3. Khera R, Cram P, Lu X, et al. Trends in the use of percutaneous ventricular assist devices: analysis of National Inpatient Sample data, 2007 through 2012 [published online ahead of print March 30, 2015]. JAMA Intern Med 2015; doi: 10.1001/jamainternmed.2014.7856.
4. Bergh N, Angeras O, Albertsson P, et al. Does the timing of treatment with intra-aortic balloon counterpulsation in cardiogenic shock due to ST-elevation myocardial infarction affect survival? Acute Card Care 2014; 16:57–62.
5. Sjauw KD, Engstrom AE, Vis MM, et al. A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines? Eur Heart J 2009; 30:459–468.
6. Romeo F, Acconcia MC, Sergi D, et al. The outcome of intra-aortic balloon pump support in acute myocardial infarction complicated by cardiogenic shock according to the type of revascularization: a comprehensive meta-analysis. Am Heart J 2013; 165:679–692.
7. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv 2013; 82:E266–E355.
8. Thiele H, Zeymer U, Neumann FJ, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. New Engl J Med 2012; 367:1287–1296.
9. Thiele H, Zeymer U, Neumann FJ, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. Lancet 2013; 382:1638–1645.
10. Kolh P, Windecker S, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur J Cardiothorac Surg 2014; 46:517–592.
11. Higgins JP, Altman DG, Gotzsche PC, et al. The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed.) 2011; 343:d5928.
12. O’Rourke MF, Norris RM, Campbell TJ, et al. Randomized controlled trial of intraaortic balloon counterpulsation in early myocardial infarction with acute heart failure. Am J Cardiol 1981; 47:815–820.
13. Flaherty JT, Becker LC, Weiss JL, et al. Results of a randomized prospective trial of intraaortic balloon counterpulsation and intravenous nitroglycerin in patients with acute myocardial infarction. J Am Coll Cardiol 1985; 6:434–446.
14. Waksman R, Weiss AT, Gotsman MS, et al. Intra-aortic balloon counterpulsation improves survival in cardiogenic shock complicating acute myocardial infarction. Eur Heart J 1993; 14:71–74.
15. Ohman EM, George BS, White CJ, et al. Use of aortic counterpulsation to improve sustained coronary artery patency during acute myocardial infarction. Results of a randomized trial. The Randomized IABP Study Group. Circulation 1994; 90:792–799.
16. Kono T, Morita H, Nishina T, et al. Aortic counterpulsation may improve late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy. J Am Coll Cardiol 1996; 28:876–881.
17. Stone GW, Marsalese D, Brodie BR, et al. A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty. J Am Coll Cardiol 1997; 29:1459–1467.
18. van’t Hof AW, Liem AL, de Boer MJ, et al. A randomized comparison of intra-aortic balloon pumping after primary coronary angioplasty in high risk patients with acute myocardial infarction. Eur Heart J 1999; 20:659–665.
19. Ohman EM, Nanas J, Stomel RJ, et al. Thrombolysis and counterpulsation to improve survival in myocardial infarction complicated by hypotension and suspected cardiogenic shock or heart failure: results of the TACTICS Trial. J Thromb Thrombolysis 2005; 19:33–39.
20. Li JL, Xue H, Wang BS, et al. Effect of prolonged intra-aortic balloon pumping in patients with cardiogenic shock following acute myocardial infarction. Med Sci Monit 2007; 13:CR270–CR274.
21. Vijayalakshmi K, Kunadian B, Whittaker VJ, et al. Intra-aortic counterpulsation does not improve coronary flow early after PCI in a high-risk group of patients: observations from a randomized trial to explore its mode of action. J Invasive Cardiol 2007; 19:339–346.
22. Perera D, Stables R, Thomas M, et al. Elective intra-aortic balloon counterpulsation during high-risk percutaneous coronary intervention: a randomized controlled trial. JAMA 2010; 304:867–874.
23. Prondzinsky R, Lemm H, Swyter M, et al. Intra-aortic balloon counterpulsation in patients with acute myocardial infarction complicated by cardiogenic shock: the prospective, randomized IABP SHOCK Trial for attenuation of multiorgan dysfunction syndrome. Crit Care Med 2010; 38:152–160.
24. Gu J, Hu W, Xiao H, et al. Prophylactic intra-aortic balloon pump reduces C-reactive protein levels and early mortality in high-risk patients undergoing percutaneous coronary intervention. Acta Cardiol 2011; 66:499–504.
25. Patel MR, Smalling RW, Thiele H, et al. Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial. JAMA 2011; 306:1329–1337.
26. Wu K, He S, Ye S. Primary evaluation to safety and value of IABP in patients with acute coronary syndrome complicated with pump failure. China Prac Med 2011; 6:6–9.
27. Kern MJ, Aguirre F, Bach R, et al. Augmentation of coronary blood flow by intra-aortic balloon pumping in patients after coronary angioplasty. Circulation 1993; 87:500–511.
28. Yan B, Peng L, Zhao X, et al. Nesiritide fails to reduce the mortality of patients with acute decompensated heart failure: an updated systematic review and cumulative meta-analysis. Int J Cardiol 2014; 177:505–509.
29. Trost JC, Hillis LD. Intra-aortic balloon counterpulsation. Am J Cardiol 2006; 97:1391–1398.
30. Unverzagt S, Buerke M, de Waha A, et al. Intra-aortic balloon pump counterpulsation (IABP) for myocardial infarction complicated by cardiogenic shock [published online ahead of print March 27, 2015]. Cochrane Database Syst Rev 2015; doi: 10.1002/14651858.CD007398.pub3.
31. Zangrillo A, Pappalardo F, Dossi R, et al. Preoperative intra aortic balloon pump to reduce mortality in coronary artery bypass graft: a meta-analysis of randomized controlled trials. Crit Care 2015; 19:10.
32. Bahekar A, Singh M, Singh S, et al. Cardiovascular outcomes using intra-aortic balloon pump in high-risk acute myocardial infarction with or without cardiogenic shock: a meta-analysis. J Cardiovasc Pharmacol Ther 2012; 17:44–56.
33. Ahmad Y, Sen S, Shun-Shin MJ, et al. Intra-aortic balloon pump therapy for acute myocardial infarction: a meta-analysis [published online ahead of print March 30, 2015]. JAMA Intern Med 2015; doi: 10.1001/jamainternmed.2015.0569.
34. Babaev A, Frederick PD, Pasta DJ, et al. Trends in management and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock. JAMA 2005; 294:448–454.
35. Goldberg RJ, Spencer FA, Gore JM, et al. Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: a population-based perspective. Circulation 2009; 119:1211–1219.
36. Alexander JH, Reynolds HR, Stebbins AL, et al. Effect of tilarginine acetate in patients with acute myocardial infarction and cardiogenic shock: the TRIUMPH randomized controlled trial. JAMA 2007; 297:1657–1666.
37. Spencer FA, Moscucci M, Granger CB, et al. Does comorbidity account for the excess mortality in patients with major bleeding in acute myocardial infarction? Circulation 2007; 116:2793–2801.
38. Kadakia MB, Desai NR, Alexander KP, et al. Use of anticoagulant agents and risk of bleeding among patients admitted with myocardial infarction: a report from the NCDR ACTION Registry – GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry – Get With the Guidelines). JACC Cardiovasc Interv 2010; 3:1166–1177.
39. Loh JP, Pendyala LK, Torguson R, et al. Incidence and correlates of major bleeding after percutaneous coronary intervention across different clinical presentations. Am Heart J 2014; 168:248–255.
40. de Waha S, Desch S, Eitel I, et al. Intra-aortic balloon counterpulsation – basic principles and clinical evidence. Vascul Pharmacol 2014; 60:52–56.
41. Davidavicius G, Godino C, Shannon J, et al. Incidence of overall bleeding in patients treated with intra-aortic balloon pump during percutaneous coronary intervention: 12-year Milan experience. JACC Cardiovasc Interv 2012; 5:350–357.
42. Khashan MY, Pinsky MR. Does intra-aortic balloon support for myocardial infarction with cardiogenic shock improve outcome? Crit Care 2013; 17:307.
43. Thiele H, Schuler G, Neumann FJ, et al. Intraaortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock: Design and rationale of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial. Am Heart J 2015; 169:e7–8.

Supplemental Digital Content

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.