I just returned from the Scottsdale Interventional Forum (SIF2017), where a wide-ranging discussion of mechanical left ventricular (LV) support for patients with high-risk percutaneous coronary intervention (PCI), ST-elevation myocardial infarction (STEMI), and patients in shock ensued. The issues surrounding the implementation, management, timing, adjunct pharmacologic treatment, and effectiveness of different types of LV support devices were presented and debated. Several pressing questions arose that I believe are the beginning of a new treatment paradigm.
Let’s start with conventional wisdom [CW] regarding shock patients. (Remember CW is what we think is true, but in reality, may not be). Challenges to CW are not “alternative facts” as someone in Washington, D.C. suggested, but are more accurate or up-to-date information.
CW Fact 1. All “shock” patients are similar. This CW fact is certainly not true, given the different types and timing of STEMI patients presenting to the emergency department (ED) and cardiac cath labs. The assumption that all shock patients are similar begs for better definitions (see below).
CW Fact 2. The mortality ceiling of shock patients will never be below 50%. While this fact is true for the moment based on the results of the numerous shocks studies over the last 25 years, it is hoped that more focused and better stratified patient selections (e.g., early vs late arrivals) will improve the survival statistics, showing us those that are likely to benefit by treatment and those in whom treatment will likely be futile. Combining different types of patients with variable presentations, pre-shock, or late shock currently produces results wherein none of the interventions can lower the 50% shock mortality ceiling. In addition, part of our acute myocardial infarction (AMI) shock treatment algorithm emphasizes the importance of reperfusion over restoring hemodynamics and systemic perfusion with LV support. Should the impact of the early restoration of physiology (i.e., first LV support) show some reduction in morality, it would turn the door-to-balloon time (D2B) paradigm on its head.
CW Fact 3. LV support devices have the same outcomes in shock patients. This fact is also not true, because of CW Facts 1 and 2. The difference between devices — for example, the intra-aortic balloon pump (IABP) and Impella (Abiomed) are obscured in studies with small data sets, mixing different patient types with different definitions of shock, variable time to institution of LV support, and the duration of the shock state before treatment. Among the most recent studies, the IMPRESS study1 also showed no difference between IABP and Impella, mostly due to weak study design and other factors discussed below. Such studies do not move our understanding of device differences forward.
How Should We Define Shock?
Shock is the physiologic state of hypoperfusion of the body’s vital organs. Shock has different presentations depending on the cause (cardiogenic, hypovolemic, septic, toxic, etc.). For the cath lab, we’ll focus only on cardiogenic “shock” patients. Typically, they have poor perfusion due to low cardiac output, hypotension, peripheral vasoconstriction, cool extremities, reduced urine output, reduced cerebral perfusion (often with confusion or obtundation), and/or respiratory failure, all of which culminate in cardiac instability and death. Not every sign or symptom above must be present for the patient to be considered to be in shock. As with many clinical syndromes, the shock presentation is part of a continuum, beginning with reversible early or pre-shock with marginal blood pressure, but without profound hypoperfusion, and ultimately evolving into irreversible shock with a variable time line. The exact point where reversible shock crosses over to irreversible shock is not well defined. Irreversible shock is associated with the need for intensive pharmacologic, respiratory, and hemodynamic support, despite which profound metabolic derangements (e.g., severe acidosis, high lactate levels, hyperkalemia, etc.) as well as multisystem organ failure (e.g., hypoxic encephalopathy, hepato-renal syndrome, DIC and other coagulation abnormalities, etc.) occur.
The S2S (Shock to Support) Time and the “Golden Hour” of Trauma Survival
Doug Drachman, MD, an interventional cardiologists from Boston, Mass., presented a talk at SIF2017 on why we should favor use of higher (e.g., Impella catheter pump, TandemHeart, and extracorporeal membrane oxygenation [ECMO]) than lower (IABP) LV support devices for patients in shock and why early LV support implementation is critically important. He reviewed the fact that no study has shown any intervention has reduced the shock mortality below 50% and that even after surviving the initial shock episode, there are increased late adverse events, including death, seen over the next year. For example, several studies comparing patient outcomes with and without IABP in AMI cardiogenic shock showed no hemodynamic or survival benefit of IABP.2,3
Recently, however, Basir et al4 showed that inserting an Impella LV support device early before PCI reduced peri-procedural and 30-day mortality rates significantly, compared to insertion of LV support during or after a PCI problem (Figure 1). Moreover, the benefit was a time-dependent phenomenon. The Impella Implantation in Acute MI with Shock cVAD Registry4 showed an improved survival from 26% to 66% if the Impella was implanted in <1.25 hours compared to >4.5 hours (Figure 2).
The finding of improved survival with rapid restoration of hemodynamics and attempts to normalize the patient’s physiology/circulation is highly consistent with the dictum of the U.S. Army Trauma teams that restoring systemic physiology first (and quickly) is the most important aspect of saving the patient’s life. The term “Golden Hour”, first described by R Adams Cowley, MD, at the University of Maryland Medical Center in Baltimore5, is the critical period in which life-saving support must be instituted to have success. While the D2B is important for STEMI patients not in shock, restoring blood pressure and systemic physiology in shock patients appears to be as or more important than immediately opening an occluded vessel. It should not be expected that coronary reperfusion alone would restore the myocardial function quickly enough to prevent irreversible shock, as the heart must take time to recover from the stunned and post ischemic state. Basir et al4 showed us that earlier initiation of LV support was associated with higher survival rate. From these data and the concept of the Golden Hour, we should be thinking about instituting LV support early, as Dr. Drachman said, coining the term “S2S” (the “shock to support” time), making all attempts to shorten our S2S as much or more than the pressure to shorten the D2B time, thus giving the patient a chance to break through the shock mortality ceiling.
An identical concept to S2S, specifically addressing earlier mechanical support with Impella, called the “door to unloading (DTU)” time has been described by William O’Neill, MD, medical director of the Center for Structural Heart Disease at Henry Ford Hospital in Detroit. Its practical application is being investigated prospectively in cardiogenic shock by a collaboration of southeastern Michigan hospital systems using a single protocol for early identification of cardiogenic shock in STEMI, in the Detroit Cardiogenic Shock Initiative (Detroit CSI). The key elements of this prospective registry include the early identification of cardiogenic shock, early use of Impella support (before PCI), avoidance or early termination of pressor and inotropic support, guidance of recovery, or need for escalation using invasive hemodynamics with right heart catheterization. Preliminary data is expected by this time next year (ACC 2018). Under a uniform protocol, shock study centers will have better stratification of the study population, which will permit more meaningful interpretation of their results.
One of the greatest and most difficult remaining questions is whether we can triage shock patients to those who can and cannot be saved, instituting early support therapy for those who can and holding back on ineffective and/or expensive therapies for those who cannot. This ethically charged issue will have to be addressed as our treatment paradigm shifts toward early S2S.
Are There LV Support Device Differences? The IMPRESS Trial (IABP vs Impella in AMI Shock Patients)
As noted above, IABP trials in shock showed little or no benefit.2,3 The studies providing comparisons of devices (IABP vs Impella, Impella vs Tandemheart, Tandemheart vs ECMO) in shock patients are understandably but unfortunately small or non-existent. The most recent comparative trial is the IMPRESS Trial (Impella CP versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock).1 The IMPRESS study randomized 48 patients with severe cardiogenic shock due to AMI to Impella CP (n=24) or IABP (n=24). Cardiogenic shock was defined as systolic blood pressure <90 mmHg or the need for inotropic or vasoactive medication and the requirement for mechanical ventilation. The investigators found mortality at 30 days in patients treated with either IABP or Impella CP was similar (50% and 46%, respectively, P=NS) and at 6 months, mortality rates for both Impella CP and IABP were 50%, concluding that in this “explorative” randomized, controlled trial showed no mortality difference between IABP and Impella. What does this small and “explorative” trial really tell us about these devices in the shock patient?
It is recognized that patient selection is always challenging. Cardiac arrest was present prior to randomization in 100% of the Impella-treated group and 83% of the IABP-treated group. Therefore, there were many patients who had post-anoxic neurologic death. These patients could not have been expected to derive any benefit from any form of hemodynamic support. Patients with anoxic encephalopathy or refractory shock (38% of the enrolled patients) had a 100% mortality, while the remaining patients (62% of enrollment) had 80% survival rate (i.e., mortality rate of 20%) something never seen before in any cardiogenic shock trial. Some enrolled patients had trauma as part of their presentation. The trauma subgroup had a high mortality rate that was maldistributed (21% in the Impella group with an 80% death rate, and 8% in the IABP group with a 50% mortality). The inclusion of trauma as part of the cardiogenic shock syndrome mortality should be questioned. Finally, the statistical assumptions to achieve a meaningful mortality difference between IABP and Impella could not be achieved with only 48 patients. Other detracting factors included the intention-to-treat design with some patients not receiving the intended support device or who had crossed over to higher support, 98% of the patients having cardiac arrest, skewing typical outcomes, and the variable and unknown timing of the institution of mechanical LV support. In summary, this study was small, lacked statistical power to be clinically relevant, and unable to say anything conclusive about the differences or impact of the two support devices.
The Bottom Line
For patients in cardiogenic shock, LV mechanical support, depending on the hemodynamic profile of the device, can restore and support the systemic circulation, an especially beneficial effect if instituted early, an action that may improve shock mortality. Studies demonstrating that a short S2S or DTU time before coronary reperfusion would reduce mortality are in progress. Studies that show no differences among LV support devices with regard to reduction in mortality must be taken with a grain of salt, especially those with small sample sizes (i.e., low statistical power/accuracy), poorly defined inclusion criteria (e.g., early <6 hours vs late shock presentation), and weak study designs (crossovers or patients not receiving the intended treatment). For our patients presenting in shock, we should start thinking of shortening the S2S and DTU, as we did with shortening the D2B time, for best outcomes.
- Ouweneel DM, Eriksen E, Sjauw KD, et al. Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol. 2017; 69(3): 278-287.
- 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 multi-organ dysfunction syndrome. Crit Care Med. 2010; 38: 152-160.
- Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012; 367(14): 1287e1296.
- Basir MB, Schreiber TL, Grines CL, Dixon SR, Moses JW, Maini BS, et al. Effect of early initiation of mechanical circulatory support on survival in cardiogenic shock. Am J Cardiol. 2017; 119: 845-851.
- Cowley RA. A total emergency medical system for the State of Maryland. Md State Med J. 1975 Jul; 24(7): 37-45.
Disclosure: Dr. Kern is a consultant for Abiomed, Merit Medical, Abbott Vascular, Philips Volcano, ACIST Medical, Opsens Inc., and Heartflow Inc.