The War on Shock: Is Industry Leading the Charge?

Jaya Mallidi, MD, MHS

2:00 AM on call. I wake up to the sound of my phone ringing. The emergency room (ER) physician is calling to evaluate a 93-year-old man, Mr Smith,* with ongoing chest pain. His ECG shows diffuse ST-segment depressions. His systolic blood pressure is low, at 80 mm Hg on pressor support. I hear this information and think cardiogenic shock (CS) and probable left main or multivessel coronary artery disease.

I walk toward the ER clutching my jacket closely in the chilly December night. My thoughts drift to the recent controversies in the management of patients with CS, specifically the use of the Impella (Abiomed; Danvers, MA)—the US Food and Drug Administration-approved, temporary, percutaneous mechanical circulatory support (MCS) device.

A few months earlier, I had attended a national conference on the management of CS. The mortality rate for this high-acuity, low cardiac output state often associated with multiorgan dysfunction has remained high, at about 40%-50% over the past several years. The conference focused on an algorithmic approach of early identification, activation of the cath lab for hemodynamic assessment, and early use of MCS, specifically Impella, before percutaneous coronary intervention (PCI). Implementation of these protocols led to survival rates as high as 72% to 77%, according to observational analyses. I myself presented a similar, case-based CS algorithm at a conference last year.

#waronshock and Rising Impella Use

The concept of a "war on shock" was introduced by Alexander G. Truesdell, MD, a cardiologist and former Army physician, as a call for the cardiovascular community to build a multidisciplinary healthcare system to improve outcomes in patients with CS. This metamorphosed on Twitter into the hashtag #waronshock, tagged to case presentations of patients with CS who underwent Impella-assisted PCI. Such tweets are retweeted exponentially with felicitations and thumbs-up emojis. At CS conferences and in the Twittersphere, Impella is the hero of the #waronshock—a war that we are winning.

The enthusiastic efforts of thought leaders and, more important, the unconditional support of Abiomed with training mobile vans and apps, has resulted in the rapid dissemination of Impella over the past few years. Contrary to the success stories on Twitter and at CS conferences, a recent independent analysis of a large healthcare data base involving almost 50,000 patients, half of whom had CS, presented last month at the American Heart Association Scientific Sessions saw a signal of potential harm—an increased risk for bleeding and death among patients treated with Impella compared with an intra-aortic balloon pump (IABP). Abiomed made a public announcement critiquing the analysis as flawed and biased, stating that patients in the Impella group were sicker. A twitter debate broke out, with some physicians challenging Abiomed’s interpretation and arguing that patients in the IABP group were sicker.

Heterogeneity Among Patients With CS

Mr Smith is not a data point. He is a real patient with CS. His demographics may or may not be captured in datasets. He may or may not be like the patients enrolled in clinical studies. His story is not glamorous enough to share on Twitter or at CS conferences, especially if he does not make it. But he exists in a tremendously real way for me right now, and this real world of CS has the following salient feature: heterogeneity. The clinical presentation of CS falls into five different stages only recently defined by the Society for Cardiovascular Angiography and Interventions cardiogenic shock classification schema. There is also significant heterogeneity among institutions and in the clinical decision-making of physicians treating patients with CS. Our experience, skill set, and core value system (conservative versus aggressive) are not uniform.

In this heterogeneous world of CS we can go around in circles debating the confounding factors in the observational and registry studies without coming to any definitive conclusion. The more important question we need to ask ourselves: How did we get to this juncture? Why are we faced with a stark discrepancy between claimed benefit versus harm in different analyses of the Impella device? Did we, as a medical community, allow the industry to lead the charge in the war on shock?

Arbitrary Use of MCS Without High-Quality Evidence

Approval for use of the Impella device in CS comes from two small randomized controlled trials (RCTs) with hemodynamic end points, and observational and registry data. There are no RCTs to date showing a definite mortality benefit for Impella use in patients with CS. The DanGer Shock trial, a multicenter RCT being done in Denmark and Germany to evaluate the benefit of Impella in patients with acute coronary syndrome complicated by CS, is not yet completed.

An RCT is essential to overcome selection bias and direct the use of Impella in terms of timing and which subset of the CS population, if any, would or would not benefit from its use. Before allowing widespread use, we as a community of cardiovascular physicians should have led the charge and done the RCT, despite the practical challenges of conducting clinical trials in acute settings. But we did not. Instead, we allowed Abiomed's cardiogenic shock protocol to come into existence. Collaboration between the medical community and industry is necessary, predominantly for financial support of ongoing research. In the world of CS, I wonder if this collaboration morphed into abdication of our leadership role.

The war on shock needs be fought on many fronts. Impella as one of the war tools is distributed widely into a space rife with heterogeneity. As the soldiers in the war, we are now using the war tool arbitrarily, and when battles are lost, we start to wonder why.

Palliative Care and Noble Intentions

The scientific statement on contemporary management of cardiogenic shock by the American Heart Association embraced the concept of palliative care alongside other treatments as part of the multidisciplinary team approach to CS. The writers recognized the need to discuss advanced goals of care and to promote patient-centered supportive decision-making. The protocol in this document recommends consideration of palliative care at every step along the continuum of care of patients with CS. However, palliative care utilization in CS is very low. Popular CS algorithms used in observational studies demonstrating high survival rates either relegate palliative care to the very last step after several days of Impella support or do not mention it at all. The Abiomed cardiogenic shock protocol mentions escalation of care and not palliation.

The intention to reduce mortality in patients with CS is noble. The Abiomed motto—"Recovering Hearts; Saving Lives"—is noble. However the vagaries of the medical-industrial complex, much described in the literature, invariably erode this nobility. Financial incentives and conflicts of interest unconsciously erode this nobility.

John Ioannidis, the physician scientist who pioneered the field of meta-research, said, "Science is a noble endeavor, but it's also a low-yield endeavor. I'm not sure that more than a very small percentage of medical research is ever likely to lead to major improvements in clinical outcome. We should be very comfortable with that fact." As physicians, dealing with life and death on a daily basis, we understand this. The medical-industrial complex, on the other hand, cannot be comfortable with that fact. Unless we are vigilant, this discomfort of the medical industrial complex will unconsciously taint the clinical decision-making in everyday practice.

With these thoughts, I walk into the ER. The bright, white, artificial light suddenly feels cold and harsh. I clutch my jacket even closer and enter Mr. Smith's room.

*Some details have been changed to protect the patient's identity.

Jaya Mallidi is an interventional cardiologist in Santa Rosa, California. An ardent patient advocate, she writes opinion pieces using patient stories as context to highlight problems in the practice of modern-day medicine. In addition, she enjoys digital sketching and playing tennis.

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