Intra-Aortic Balloon Pump Use and Outcomes with Current Therapies

ABSTRACT: Objectives. Our purpose was to describe the contemporary utilization, clinical outcomes and complication rates of intra-aortic balloon pump (IABP) therapy in this current age. Background. IABP use and outcomes, in the setting of modern antiplatelet therapy and primary percutaneous coronary intervention and the use of drug-eluting stents as we know them today, have not been clearly established. Methods. We performed a retrospective cohort study by collecting detailed clinical and device data from all 150 consecutive patients who received IABP therapy in our institution between 2004 and 2009. Results. Thrombocytopenia occurred in 50%, fever in 36%, bleeding in 27%, and vascular embolic events in 1%. Thrombocytopenia was the most common adverse event and was not significantly associated with the use of antiplatelet agents. The presence of diabetes mellitus, elevated white blood cells at presentation, and longer duration of IABP were significantly associated with the development of fever. Furthermore, those who developed fever had higher in-hospital mortality (31% versus 16%; p = 0.0487). Conclusions. In this contemporary cohort of IABP patients, complication rates of thrombocytopenia, fever and bleeding were relatively high but similar to prior studies, even in this current era of revascularization and antiplatelet medications. J INVASIVE CARDIOL 2011;23:116–119 ———————————————————— Intra-aortic balloon pump (IABP) counterpulsation reduces left ventricular afterload and myocardial work, improves diastolic coronary and systemic blood flow and increases cardiac output. Consequently, IABP use has grown significantly since its introduction in 1968 and is now the most commonly used form of mechanical circulatory assist, with 70,000 devices inserted annually in the United States. Despite this increased experience with and broadened indications for IABP use, the largest IABP registry to date was published before modern antiplatelet therapy or the establishment of primary percutaneous coronary intervention (PCI) protocols or the use of drug-eluting stents (DES), as we know them today.¹ The most common indication for IABP use remains cardiogenic shock due to acute myocardial infarction. Cardiogenic shock remains the leading cause of death among patients hospitalized for acute myocardial infarction. Prior studies suggest a trend toward reduced in-hospital 30-day mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock treated with IABP therapy and prompt revascularization compared to those treated with prompt revascularization alone.² The purpose of this study was to describe the contemporary utilization, clinical outcomes and complication rates of IABP therapy in this current age.

Methods

Patients. We performed a retrospective cohort study by collecting detailed clinical and device data from all 150 consecutive patients 18 years of age or older who received IABP therapy in our large, urban tertiary care center institution between 2004 and 2009. Paper and electronic charts were reviewed. Demographic variables, indications for and duration of IABP counterpulsation, baseline characteristics, clinical outcomes and complication rates were collected. All patients included in this cohort who presented with acute STEMI underwent urgent or emergent coronary angiography. The protocol for our institution during the time period of the study entailed that all STEMI patients receive a loading dose of aspirin of 162–325 mg, a loading dose of a thienopyridine, namely clopidogrel 300 mg or 600 mg, and an intravenous bolus of unfractionated heparin in the emergency room prior to arrival in the cardiac catheterization lab. The continuation of these medications and the use of glycoprotein IIb/IIIa inhibitors was left to the discretion of the physician, but depended on factors including thrombus and disease burden and the performance of PCI or the type of revascularization method. The protocol in our institution entails that patients referred for coronary artery bypass graft surgery (CABG) have thienopyridines held for 5–7 days prior to surgery. All IABP devices were inserted under fluoroscopy guidance in the setting of coronary angiography using standard techniques, most frequently sheathlessly. All patients received Fidelity, Linear or Sensation 7.5 French (Fr) or 8 Fr intra-aortic balloon catheters (34 cc or 40 cc Datascope; 30 cc or 40 cc Arrow). The protocol at our institution immediately after IABP placement is typically a 1:1 counterpulsation timing. The time of discontinuation is left to the discretion of the physician and depends on factors including hemodynamic stability, mechanical ventilation and timing of extubation, as well as complications such as fever, thrombocytopenia, limb or vascular complications, etc. At the time of discontinuation, afterload reducing medications are titrated up and the IABP counterpulsation timing is typically either progressively tapered from 1:1 to 1:2, 1:3, 1:4 or the patient is given a closely-monitored trial with the IABP device on standby, and the IABP is removed as these maneuvers are tolerated. Adverse events. All-cause in-hospital mortality was defined as mortality occurring from any cause during IABP use or after discontinuation of IABP within the index hospital admission. Thrombocytopenia was defined as the development of a platelet count less than 150 cells/L x 10⁹ or having > 50% decrease from the initial platelet count. Fever was defined as the development of body temperature greater than 100.4 °F. Major bleeding was defined according to the Global Strategies for Opening Occluded Coronary Arteries (GUSTO) definition for severe or life-threatening bleeding, i.e., either intracranial hemorrhage or bleeding that causes hemodynamic compromise or requires intervention. Minor bleeding was defined according to the GUSTO definition of moderate bleeding, i.e., bleeding that requires blood transfusion but does not result in hemodynamic compromise. Vascular complication was defined as the loss of a pulse or an abnormal limb temperature or pallor, requiring surgical evaluation or intervention. The protocol for limb assessment and monitoring in our institution in the setting of IABP placement is regular assessment performed by a physician immediately post-procedure, 6 hours post-procedure, and daily while the IABP remains inserted. Furthermore, the pulses are checked every hour by a nurse along with the vital signs in the Coronary Care Unit (CCU) while the IABP remains inserted. Statistics. Continuous variables are expressed as means ± standard deviation and discrete variables are presented as percentages. For the common complications, fever, thrombocytopenia, and bleeding, the patients with and without the complication were compared using Chi-square test and Fisher’s exact test. All tests were two-tailed, and a p-value Results Among the 150 patients included in this cohort, 95 (63%) were male and the mean age was 66 ± 13 years. The mean duration of IABP counterpulsation was 3.7 ± 2.2 days. Acute myocardial infarction was the diagnosis in 132 patients (88%), 49 (33%) of whom were in cardiogenic shock. The indications for IABP placement in our institution were high-risk coronary anatomy due to severe disease burden after or awaiting revascularization (36%), cardiogenic shock (33%), STEMI (26%), high-risk PCI (5%), and congestive heart failure (CHF) or mitral regurgitation (MR) (2%). Of our STEMI patients, 63 (81.2%) were revascularized, by PCI in 54 (70.1%), including 34 (63%) with drug-eluting stents, and by coronary artery bypass grafting (CABG) in 9 (11.7%). IABP therapy was discontinued in 67% of the patients after hemodynamic stabilization while the all-cause in-hospital mortality rate was 21%. Complication rates seen in this cohort included thrombocytopenia in 75 (50%), fever in 55 (36%), bleeding in 41 (27%), and vascular embolic events in 2 (1%). In our cohort, the overall prevalence of glycoprotein IIb/IIIa use was 50 patients (33%). Thrombocytopenia. Thrombocytopenia was the most common adverse event in our cohort. Regarding predictors of the development of thrombocytopenia, only a lower initial platelet count (216 cells/L x 10⁹ versus 308 cells/L x 10⁹; p = 0.0001) was found to significantly predispose patients to the development of thrombocytopenia, while the use of antiplatelet medications did not (Table 1). Thrombocytopenia was not associated with serious adverse consequences such as major bleeding or death. Fever. The presence of diabetes mellitus (DM) (60% versus 41%; p = 0.0386), elevated white blood cell count (WBC) at presentation (15.6 cells/L x 10⁹ versus 11.3 cells/L x 10⁹; p = 0.008), and longer duration of IABP therapy (4.8 days versus 3.0 days; p = 0.0001) were found to be significantly associated with the development of fever. Furthermore, those who developed fever had higher in-hospital mortality (31% versus 16%; p = 0.0487). Of those who developed fever, 16 (29.1%) had positive blood cultures, the only risk factor for which was longer duration of IABP therapy (6.1 days versus 4.3 days; p = 0.0182) (Table 2). Among patients with positive blood cultures, the most common pathogen was coagulase-negative staphylococcus. Bleeding. Of those who developed bleeding (41 patients, 27%), only 19 (13%) were related to IABP use or the angiogram/PCI procedure and only 4 (3%) had major bleeding as defined previously. Among the patients with major bleeding related to IABP use or the angiogram/PCI procedure (3%), all received aspirin and heparin, 6 (75%) received clopidogrel, and 2 (50%) received glycoprotein IIb/IIIa inhibitors. Major bleeding due to IABP use or procedure-related was not significantly associated with antiplatelet medications, PCI or duration of IABP use.

Discussion

The main findings of this study are the following: 1) In this contemporary cohort of patients treated with IABP, the incidences of thrombocytopenia, fever and bleeding were similar to prior studies even in the setting of current antiplatelet medications and revascularization strategies; 2) thrombocytopenia was the most common adverse event, and was seen more frequently in patients who had lower initial platelet counts, but was not associated with antiplatelet therapy use; and 3) fever predicted higher in-hospital mortality. In the largest IABP registry to date, the Benchmark Counterpulsation Outcomes Registry, Stone et al¹ reported that of the subset with acute myocardial infarction (AMI) consisting of 5,495 patients (24%) between 1996 and 2001, all-cause in-hospital mortality varied significantly, with the performance of early coronary revascularization, with the highest mortality in those who were not revascularized. Although early revascularization was performed in almost 82%, their registry preceded full establishment of modern primary PCI protocols, modern antiplatelet therapy and use of DES as we know them today. Stone et al reported an in-hospital mortality rate of 20%, a total complication rate of 8.1% (which only included major and minor bleeding, major and minor limb ischemia, stroke and other embolic phenomena, and IABP failure) and a major complication rate (consisting of severe limb ischemia, severe bleeding, balloon leak or death due to IABP insertion or failure) of only 2.7%.¹ Multiple studies reported highly variable total complication rates,^3–5 including Kumbasar et al, who reported a total complication rate of 18.7%, consisting of lower extremity ischemia in 7.7%, major bleeding in 8.8% and IABP rupture in 4.4%.⁵ Prior studies reported total complication rates as high as 29%, consisting of primarily lower extremity ischemia and bleeding as well.^6–8 Not only did many of these studies vary in the complication rates they reported but also in their definitions and types of complications, as specified above. Of our STEMI patients, 63 (81.2%) were revascularized either by PCI in 54 (70.1%), including 34 (63%) of those with DES, or by CABG in 9 (11.7%) and the majority (67%) stabilized hemodynamically. All-cause in-house mortality occurred in this cohort in 32 (21%), none of which were attributed to the IABP itself. Other complication rates seen in this cohort included thrombocytopenia in 75 (50%), fever in 55 (36%), bleeding in 41 (27%), and vascular embolic events in 2 (1%). These complication rates are relatively high, but similar compared to most of the prior studies despite modern revascularization techniques, antiplatelet therapy and DES. Cardiogenic shock due to acute STEMI remains the most common indication for IABP placement as well as the leading cause of death among patients hospitalized for acute myocardial infarction. In the SHOCK registry, Sanborn et al reported an incremental improvement in in-hospital mortality in STEMI patients with cardiogenic shock who received prompt thrombolysis and IABP therapy compared to those who received thrombolysis alone (47% versus 63%, respectively).² This is similar to findings of small retrospective studies and the National Registry of Myocardial Infarction study, and the GUSTO thrombolytic trials, which similarly suggested intra-aortic balloon counterpulsation (IABP) was beneficial.^14,15 This is in contrast, however, to the TACTICS trial, which only showed a mortality benefit from IABP in the patients with the most severe cardiogenic shock, those with Killip Class III or IV.¹⁶ Furthermore, in the prospective, randomized PAMI-II trial, in which STEMI patients were randomized to IABP versus traditional care after percutaneous transluminal coronary angioplasty (PTCA), IABP did not significantly improve reinfarction or mortality.¹⁷ However, the PAMI-II trial preceded modern primary PCI protocols for STEMI, modern antiplatelet therapy and the use of drug-eluting stents as we know them today. Although thrombocytopenia is a commonly accepted complication of IABP therapy, there are few studies that quantify the actual prevalence of thrombocytopenia in IABP use or assess factors that predispose to its development. In a retrospective cohort study of 107 patients, Bream-Rouwenhorst et al reported an incidence of IABP-associated thrombocytopenia of 57.9% and heparin-induced thrombocytopenia of 2.8%.⁹ The authors further found no apparent difference with or without the use of thienopyridines and glycoprotein IIb/IIIa inhibitors in the rates of thrombocytopenia.⁹ In our cohort, using the definition given above, the incidence of thrombocytopenia was 50%, similar to the aforementioned study. When a less conservative definition for thrombocytopenia of platelet counts less than 100 cells/L x 10⁹ is used, the prevalence in our cohort is 15 patients (10%). We found that only lower initial platelet count (216 cells/L x 10⁹ versus 308 cells/L x 10⁹; p = 0.0001) was found to significantly predispose patients to the development of thrombocytopenia while none of the antiplatelet therapies, including thienopyridines and glycoprotein IIb/IIIa inhibitors, predisposed patients to thrombocytopenia. Additionally, patients without thrombocytopenia had significantly more PCI performed than those with thrombocytopenia, which may merely represent that patients with thrombocytopenia were more likely to be selected for a less invasive strategy with less bleeding risk. Fever and sepsis are common after acute myocardial infarction complicated by cardiogenic shock, especially with prolonged IABP use.^10,11 The clinical significance of fever in IABP patients remains unknown. However, prior studies suggest fever after acute myocardial infarction is associated with worse clinical outcomes and infarct expansion.¹² Kohsaka et al reported that of the 297 patients enrolled in the SHOCK trial, clinically significant signs of sepsis were seen in 54 (18%), most commonly fever (94%) and leukocytosis (72%).¹⁰ Of these, most but not all (74%) had positive blood cultures.¹⁰ While the increased risk of infection of these critically-ill patients who are also often undergoing numerous invasive procedures cannot be overstated, it is well accepted that these patients are also in a state of markedly increased inflammation with stimulated release of pro-inflammatory cytokines as well. Furthermore, Hochman postulates that an inflammatory process leading to inappropriate nitric-oxide mediated vasodilation plays a strong role in the development and persistence of cardiogenic shock in patients with acute coronary syndrome.¹³ Supporting this was a significantly lower systemic vascular resistance observed in the patients with signs of sepsis and positive blood cultures in the aforementioned substudy of the SHOCK trial.¹⁰ In our study, 55 patients (36%) developed fever, leading to discontinuation of IABP in 17 (11%). When those who developed fever were compared to those who did not, the presence of DM (60% versus 41%; p = 0.0386), elevated WBC at presentation (15.6 cells/L x 10⁹ versus 11.3 cells/L x 10⁹; p = 0.008), and longer duration of IABP therapy (4.8 days versus 3.0 days; p = 0.0001) were found to significantly predispose patients to the development of fever. Those who developed fever had significantly higher in-hospital mortality (31% versus 16%; p = 0.0487). Of those who developed fever, 16 (29.1%) had positive blood cultures, which was predicted only by longer duration of IABP therapy (6.1 days versus 4.3 days; p = 0.0182). This suggests that in addition to being a marker of infection and often sepsis, fever is also likely a marker of increased inflammation and pro-inflammatory cytokines in the setting of cardiogenic shock in acute myocardial infarction. This suggests the likely mechanism for the increased mortality associated with fever seen in this study. Lending further support to this concept that fever in this population is a significant marker of inflammation, those who received PCI, especially with DES, were less likely to develop fever. Accordingly, prompt PCI and revascularization lead to an attenuated inflammatory response in these patients. Study limitations. The limitations of our study include the non-randomized, retrospective design.

Conclusion

In this contemporary cohort of IABP patients, complication rates of thrombocytopenia, fever, and bleeding were relatively high but similar to prior studies, even in this current era of revascularization and antiplatelet therapies. Lower initial platelet counts predisposed to the development of thrombocytopenia, while treatment with antiplatelet agents and glycoprotein IIb/IIIa inhibitors did not. Fever predicted higher in-hospital mortality. DM, elevated WBC at presentation, and longer IABP duration predisposed to the development of fever.

References

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———————————————————— From the ^*Division of Cardiology, ^§Department of Medicine, Beth Israel Medical Center, New York, New York. The authors report no conflicts of interest regarding the content herein. Manuscript submitted June 24, 2010, provisional acceptance given July 27, 2010, final version accepted November 29, 2010. Address for correspondence: Lori Vales, MD, Beth Israel Medical Center, The Heart Institute, 1st Avenue at 16th Street, Baird Hall – 5th Floor, New York, NY 10003. E-mail: lvalesmd@gmail.com.