The Changing Paradigm of Hemodynamic Support Device Selection for High-Risk Percutaneous Coronary Interventions

Clinical Vignette

A 59-year-old man has 3 hours of chest pain and is transported to the emergency department. He is confused, combative, hypotensive (80/60), tachypneic, and tachycardic, with bilateral rales, hypoxia. The patient is intubated in the Emergency Department (P0₂ is 80% after intubation on 100% Fi0₂) and given fluids, bringing BP to 95/60. Electrocardiogram (ECG) shows 5 mm ST elevation inferiorly and 4 mm ST depression in V1-4. He is brought to the cath lab for emergent percutaneous coronary intervention (PCI). In the cath lab, left coronary angiography shows haziness at the distal left main, 80% ostial stenosis of the left anterior descending coronary artery (LAD) and small Ramus. Circumflex ostium has 60% stenosis. The RCA angiogram shows serial 90% mid stenoses with probable thrombus. Before beginning right coronary artery (RCA) PCI, the patient becomes more hypotensive and vasopressors are started along with insertion of an intra-aortic balloon pump (IABP). RCA PCI was performed; during each balloon occlusion for stenting, the patient had severe bradycardia and hypotension requiring addition of a second vasopressor. Should the mechanical hemodynamic support be changed?

The clinical vignette is meant to illustrate the dilemma faced in daily practice with the most difficult high-risk PCI patients. Hemodynamic support devices are designed to provide procedural (and post-procedural) stability with maintenance of cardiac output, mean arterial pressure, pulmonary venous pressure, and adequate oxygen perfusion.

The three most commonly used devices include the IABP, the Impella hemodynamic support system, and the Tandem Heart extracorporeal bypass system (Figures 1, 2, and 3 and Tables 1 and 2). Those patients with the highest risk and usually the lowest cardiac reserve were candidates for the most powerful support (e.g., left ventricular assist type devices [LVAD]). In some patients, the IABP has also been used in a prophylactic fashion and employed in a standby mode, inserting it and activating it only for hemodynamic collapse. Whether this is appropriate for the current clinical practice in high-risk PCI remains an open question.

In recent years, the development of a small, catheter-based LVAD device — the Impella system — permits use of more powerful hemodynamic support (relative to the IABP), which can be instituted earlier and with more facility than extracorporeal systems. Recent clinical outcome data across different scenarios support a shift in the paradigm of hemodynamic support device selection and implementation.¹

The motivation for using new devices in the cath lab was addressed in an editorial in Cath Lab Digest.² For the evaluation and ultimate selection, a new device or device application must satisfy most of the 8 questions that motivate change (Table 3).

The first question asked was “Does this device provide evident significant benefit?” Clearly, all three devices provide enhanced hemodynamic support to the high-risk PCI patient. The goals of hemodynamic support are achieved through different mechanisms, but optimal results should provide additional cardiac output, ventricular unloading, sustained and stable blood pressure, and reduction of myocardial ischemia to permit safe completion of the intervention. Among the many hemodynamic parameters, probably most strongly associated with survival in patients in cardiogenic shock is that of cardiac power output (CPO) measured in Watts (W), defined as mean arterial pressure multiplied by the cardiac output and divided by 451.³ The prognostic power of CPO to predict mortality indicates that a CPO <0.6 W predicts worsening heart failure in patients in a pre-shock state. CPO <0.53 W demonstrated significant mortality in cardiogenic shock.^3-5 It is logical that the cardiac assist device selected should be capable of maintaining the CPO above 0.6 W whenever possible under the existing critical conditions.

Cardiac assist devices may provide additional benefit through the modification of the oxygen supply and demand balance improving myocardial ischemia. The reduction in myocardial oxygen demand can be estimated using the pressure volume loop of cardiac function (Figures 4 and 5). The principal driving pressure of coronary blood flow is the aortic-left ventricular pressure gradient during diastole. Devices that can favorably alter the end-diastolic and end-systolic pressure-volume relationship can decrease myocardial work and provide myocardial protection from ischemia simultaneous with increased myocardial function.   

The basic mechanism of the IABP confers benefit through the 40-50 cc displacement of blood during diastole augmenting mean pressure, diastolic flow, and on deflation producing afterload reduction. All effects are modest at best relative to the Impella and Tandem Heart.

The Impella device provides benefit through active ventricular unloading and coronary flow augmentation well above that of IABP.^6,7 Impella has also been shown to immediately improve overall hemodynamics in cardiogenic shock,⁸ including cardiac power output⁹ and end-organ microcirculation;^9-12 both results appear to be favorable predictors of 30-day outcomes in acute myocardial infarction with shock.¹³

Both the Impella and Tandem Heart have the greatest impact on the pressure-volume loop of left ventricular function. The Tandem Heart unloads the left ventricle by drawing blood from the left atrium and infuses it back under pressure through the femoral artery, thus compromising to some degree the intrinsic myocardial work of contraction in overcoming the afterload of supplemented arterial pressure. Nonetheless, as a result of the unloading mechanisms, Impella and Tandem Heart have the greatest impact on cardiac function and hemodynamic stabilization.

The next question asked was, “Does this device make the procedure safer, shorter, and more comfortable for the patient?” In high-risk PCI or unstable patients or patients in cardiogenic shock, insertion of a hemodynamic support system early and quickly is often indicated. Further addressing the question, the safest device is that which has the fewest complications with  similar outcomes. The procedure will be shortened if the device can be inserted quickly. Ease of the procedure is balanced against the needed support of the patient. In terms of grading hemodynamic support, the weakest to strongest support devices are the IABP, Impella, and Tandem Heart. In terms of ease of insertion, the order is reversed. Compared to IABP, the Impella device provides stronger mechanical anti-ischemic therapy at the expense of a slightly more complex insertion and set-up. Although the Tandem Heart provides the largest cardiac output boost compared to both the IABP and Impella, it requires a complicated insertion method including a transseptal puncture with passage of a 21 Fr cannula to the left atrium. Arterial pressure is maintained by retrograde perfusion from the femoral artery via a 15 Fr cannula.

Intra-Aortic Balloon Pump (IABP)

An IABP is a 7 Fr catheter that is easily inserted using standard femoral puncture technique. IAB inflation at the onset of diastole increases diastolic pressure, which can increase coronary artery perfusion. Balloon deflation at the onset of systole decreases ventricular afterload and hence myocardial oxygen consumption (demand). Both diastolic augmentation and afterload reduction act to increase cardiac output approximately 0.2–0.4 L/min. A 20–30% increase in cardiac output in patients with low-output syndromes can be expected.^14,15 Direct measurement of coronary blood flow during IABP demonstrates augmentation in non-diseased and patent post-angioplasty vessels, but no increase in vessels with a significant stenosis.¹⁶

The indications and contraindications for hemodynamic support during high-risk PCI are shown in Table 4. The IABP requires maximal medical therapy to optimize hemodynamics and reduce myocardial ischemia. There is scant evidence that routine prophylactic IABP insertion reduces complications in patients having PCI for acute myocardial infarction (AMI) in the PAMI-II trial.¹⁷ In the BCIS-1 trial, 301 patients with low ejection fraction (<30%) and extensive myocardium at risk were randomized to routine or bailout IABP insertion (12% of patients), and no difference in MACE was seen.¹⁵

Routine IABP support after PCI is not indicated. In a prospective randomized study of 1100 patients with AMI (437 of which were high risk), Stone et al¹⁷ found that routine IABP support for 36–48 h after PCI did not improve the combined endpoint of death, reinfarction, infarct-related artery reocclusion, stroke, new-onset heart failure, or sustained hypotension compared to patients in the control arm. The ACC/AHA guidelines give IABP support a Class 1C recommendation for refractory cardiogenic shock.

Although the safety of IABP is very high, the most common complications of IABP are related to vascular access complications (2–14%). Prolonged intra-aortic balloon counterpulsation is also associated with hemolysis and platelet destruction. Despite the use of IABP during angioplasty in high-risk patients, there remains an in-hospital mortality of 6–19% (Figure 6).^14,15 In summary, IABP alone will not be sufficient to treat cardiogenic shock. The IABP will permit hemodynamic stabilization during pharmacotherapy until definitive reperfusion or more powerful support can be obtained.¹⁵

Impella LV Support Device   

The Impella LV support device is an alternative to IABP and full LV ‘extra-corporeal’ circulatory support (CPS or Tandem Heart). The Impella 2.5 is a 9–13 Fr, catheter-based, miniaturized ‘intra-corporeal’ LV pump that is placed across the aortic valve and directly unloads the LV, reduces myocardial workload and oxygen consumption, and increases cardiac output and coronary and end-organ perfusion.^18-21 The micro-axial Archimedes impeller draws blood from the LV through an inflow cannula and delivers non-pulsatile blood flow up to 2.5 L/min into the ascending aorta through an outflow port.

The Impella 2.5 is more complicated to insert than an IABP, but less than a Tandem Heart. The method uses a 6 Fr multipurpose catheter placed in the LV. A 0.018˝ stiff guidewire is introduced and the multipurpose catheter is exchanged for the Impella catheter and positioned across the aortic valve and into the LV. The Impella catheter’s pigtail tip facilitates safe positioning in the LV. Peripheral vascular disease and aortic valve disease are contraindications to the use of the Impella system.

Impella simultaneously unloads the LV while increasing aortic pressure.⁶ Increased aortic flow and pressure increases flow velocity and decreases coronary microvascular resistance. The Impella-induced increase in coronary flow probably results from both an increased perfusion pressure and a decreased LV pressure-volume relationship. The lower LV pressure facilitates reduced myocardial resistance to coronary flow and reduced end-organ damage.

Complications of the Impella have a similar incidence to IABP usually involving peripheral vascular compromise. Despite a slightly more difficult insertion, based on the higher level of circulatory support and improved markers of tissue perfusion, the Impella is an accepted important support device for high-risk PCI.

The Tandem Heart Pump System

The Tandem Heart (TH) percutaneous ventricular assist device is designed for short-term mechanical LV support. The TH involves the placement of a 21 Fr catheter inserted into the left atria from the femoral vein via a transseptal puncture.^22-25 Blood is withdrawn from the left atrium by an external centrifugal pump and infused into the femoral artery via a 15–17 Fr catheter. The TH can provide up to 4.5 L/min of cardiac support. Because of the large catheter diameter, iliac-femoral angiography must be performed prior to cannula insertion.

Compared with the IABP, the TH has been shown to improve hemodynamic parameters in two small trials.^26,27 However, there is a higher rate of complications with device use, including bleeding, tamponade, and vascular complications. The complexity of its insertion (>30 minutes in some cases) and a higher complication rate compared to Impella or IABP has limited the use of the TH in the high-risk PCI patient.

The final question is “Does this device make long-term outcome better?” The clinical studies on IABP over 3 decades supported the use of IABP in patients with refractory unstable angina, critical left main stenosis, severe 3-vessel coronary artery disease with impaired LV function, and patients in cardiogenic shock. IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in the National Registry of Myocardial Infarction. Barron et al28 reported on patients who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% versus 49%), but was not associated with any benefit in patients treated with primary angioplasty (45% versus 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72-0.93). Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy. Recent data on the outcome of IABP and infarct size in patients with acute anterior myocardial infarction without shock (The CRISP AMI Randomized Trial) demonstrated that among patients with acute anterior STEMI without shock, IABP plus primary PCI compared with PCI alone did not result in reduced infarct size.²⁹

The clinical studies on the Impella device also demonstrate benefit.³⁰ Long-term follow-up from the MACH II study demonstrated a larger increase in ejection fraction at 3 years in the Impella patient group versus standard of care.³¹

Safety and feasibility endpoints (incidence of 30-day adverse events and successful device function) were evaluated in the Europella registry of 144 consecutive patients who underwent a high-risk PCI.^32,33 The patients in this study were older (62% >70 years of age), 54% had a left ventricular ejection fraction (LVEF) ≤ 30%, and a high prevalence of co-morbid conditions. The mean European System for Cardiac Operative Risk Evaluation score (Euroscore) was 8.2 ± 3.4, and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of MI, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. The Impella 2.5 device use in high-risk PCI demonstrated safety, feasibility, and hemodynamic support with acceptable complication rates.

Most recently, the PROTECT II study compared the Impella to IABP.³⁴ Protect II was a prospective, multicenter, randomized trial in high-risk PCI patients requiring hemodynamic support. Patients had non-emergent high-risk PCI of an unprotected left main coronary or the last patent conduit, with an LVEF under 35% or three-vessel disease and a LVEF over 30%. The hypothesis was that the Impella system is superior to the IABP in preventing intra- and postprocedural major adverse events (MAE). The assumptions were 20% MAE rate for Impella and 30% for IABP, powered at 80%, alpha of 5% and totaling 654 patients. The outcome for the entire study cohort at 90 days showed a 21% reduction in major adverse events for Impella over the IABP (p = 0.029) (Figure 7). However, the benefits were different in patients where a Rotablator atherectomy device was used. In the pre-specified high-risk PCI patients without atherectomy (88% of study), Impella had a significant benefit over the IABP at both 30 and 90 days (p = 0.003) with a 29% reduction of MAE. In the prespecified atherectomy group (12% of study), there was no difference (p = 0.316) in MAE at 90 days. In this subgroup, the Impella arm demonstrated a significant increase in periprocedural CK-MB release (p = 0.030) and decreased repeat revascularization at 90 days (p = 0.006).

Because of the confounding variable of atherectomy usage in 12% of the study, event rates in the Impella group were similar to IABP at 30 days. Impella had a numerically lower MAE rate than the IABP at midpoint interim with a p-value of 0.4 at 30 days, triggering the stopping rule for futility based on the conditional power. However, at interim, the non-atherectomy arm, which comprised 88% of the interim patients, demonstrated a trend in favor of Impella (Impella MAE of 32% versus IABP MAE of 43%; p = 0.06). The final PROTECT II study includes 125 more patients that were not included at the interim analysis, and includes prespecified analysis of both non-atherectomy and atherectomy outcomes. The final study totaled 447 of the planned 654 patients. Impella patients had more atherectomy with more aggressive use documented, and had repeat revascularization rates that were significantly lower (3% Impella versus 30% IAB; p = 0.006) in the atherectomy arm at 90 days with no statistical difference on overall MAE. The secondary endpoint of Impella hemodynamic support effectiveness as defined by cardiac power output (CPO) was achieved (p = 0.001). Notwithstanding the controversy around this study, the results suggest that the patients undergoing the more complex interventions requiring rotational atherectomy benefited by the sustained support to complete their procedure with fewer complications. The Impella device provided a higher level of support with an equal or lower adverse cardiac event rate.

The clinical studies with the Tandem Heart were also favorable for the high-risk patients enrolled. Randomized multicenter clinical trial to evaluate safety and efficacy of TH versus conventional therapy with IABP in patients in cardiogenic shock is reported by Burkhoff et al.³⁵ Hemodynamic support between the TH and the IABP was compared in 42 patients from 12 centers within 24 hours of cardiogenic shock; cardiogenic shock due to MI in 70% of patients and decompensated heart failure in the remaining patients. Although mean support duration was 2.5 days, compared with the IABP, the TH achieved a significantly greater increase in cardiac index, mean arterial pressure, and greater decrease in pulmonary capillary wedge. No differences in 30-day survival or severe adverse cardiac events between the two groups were noted.

The TH was studied comparing results with IABP in two small studies^27,35 in AMI patients in cardiogenic shock. In a prospective, randomized study, 26 patients with cardiogenic shock were studied. The primary endpoint was the change of the cardiac index (CI) from baseline to 30 minutes after implantation. Secondary endpoints included lactic acidosis, hemolysis, and mortality after 30 days. Compared to the IABP, the TH demonstrated marked improvements in hemodynamic parameters, but increased bleeding complications ranging from 40–90%. There was no benefit on mortality between the 2 devices. The TH has been shown to be safe and feasible in one high-risk PCI study.²⁵ There have been no large multicenter randomized clinical trials comparing the TH with the Impella.

Hemodynamic Support Device Selection: The Paradigm

Applying the data to the device selection in our index patient, a decision must be made based on the clinical status and potential consequences of the intervention accounting for worst case scenario. At the time of the procedure in the middle of the night, the IABP was selected as the quickest way to obtain some degree of hemodynamic stabilization in the setting of AMI, pump failure during the institution of initial medical therapy. As the procedure progressed, continuing hemodynamic compromise occurred despite 2 vasopressors and the IABP. At this time, one should consider more powerful hemodynamic such as the Impella or TH. However, the team needed to institute the TH was not immediately available (0100 hours). In retrospect, it would have been advantageous to take time initially to achieve higher cardiac output by inserting the Impella at the beginning of the procedure and perhaps obviating peripheral and coronary vasoconstriction that accompany high-dose vasopressor therapy.³⁴ Ultimately, this patient was found to have a ruptured papillary muscle and in spite of being taken to surgery in the next 48 hours, he remained in critical condition in the surgical ICU.

Some of the advantages and disadvantages of the IABP, Impella and TH are listed on Table 5. From the CRISP study,²⁹ one can conclude that if powerful hemodynamic support is needed in the AMI patient, even before the patient requires multiple vasopressors, the insertion of the Impella device early in the procedure will permit successful completion of the procedure with a reduction of vasoconstrictors³⁶ and achieve an acceptable hospital survival.

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From the Chief of Cardiology LBVA and Associate Chief Cardiology, University of California – Orange CA and Long Beach, California.
Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Kern discloses that he has received an educational grant from Abiomed. He is a consultant to Merit Medical, and on the Speaker’s Bureau for Volcano Therapeutics and St. Jude Medical, Inc.
Manuscript submitted September 6, 2011, provisional acceptance given September 13, 2011, final version accepted September 19, 2011.
Address for correspondence: Morton J. Kern, MD, FSCAI, FAHA, FACC, Professor of Medicine,  Associate Chief Cardiology, University of California, Irvine Medical Center, Chief Cardiology, Long Beach Veterans Administration Hospital, 5901 E 7th Street, Bldg 126, Long Beach, CA 90807. Email: mkern@uci.edu