Heart Attack and Stroke: Same Disease, Different Organs?

I’m spending the last month of internal medicine residency on a neurology rotation.  I suppose that’s fair; my wife, a neurology resident, had to do a whole year of medicine.  To me, the most interesting part of neurology is the parallel between stroke and acute myocardial infarction (AMI).  Conceptually these are two manifestations of a common underlying disease process.  Yet, there are glaring differences in their management, and I can’t help but wonder why.

For instance, neurologists and cardiologists use different protocols for anticoagulation and thrombolysis.  Tissue plasminogen activator (tPA) is a first line therapy for ischemic stroke unless there are contraindications, including recent use of anticoagulation.  Thrombolytic therapy is also used to treat STEMI when percutaneous coronary intervention (PCI) is not immediately available.  In contrast to stroke, STEMI thrombolysis calls for higher doses of tPA as well as concurrent infusion of heparin to prevent recurrent thrombosis.1  Perhaps thrombolysis after stroke is a more cautious affair due to the risk of reperfusion injury and hemorrhagic conversion.

For decades STEMI PCI has largely replaced tPA, yet endovascular therapy for stroke is a relatively recent innovation and its utility is limited to proximal large vessel occlusions.  While PCI relies on balloon expandable stents designed to prevent restenosis, stenting is perhaps a less attractive option in stroke due to the tortuous anatomy of intracranial vessels and the bleeding risk associated with dual antiplatelet therapy.2 Instead, neurologists perform mechanical thrombectomy using stent retrievers and aspiration catheters.  While routine thrombectomy during STEMI PCI is generally not beneficial,3 aspiration and rheolytic catheters can be used selectively in the event of large thrombus burden.

Finally, evidence does not support facilitated PCI (i.e. pretreatment with tPA prior to PCI).4-5  Interestingly, it is common practice among neurologists to pretreat with tPA prior to mechanical thrombectomy.  Theoretically pretreatment may facilitate clot extraction, but does this strategy outweigh the additional bleeding risk?6

Heart attack and stroke are similar diseases occurring in different organs.  With widespread adoption of mechanical thrombectomy for acute stroke, the fields of neurology and cardiology increasingly share similar practices.  Still, there are striking differences in stroke and AMI management—no doubt a constant source of cognitive dissonance as I complete my neurology rotation and start cardiology fellowship.



  1. Kijpaisalratana N, Chutinet A, Suwanwela N. Hyperacute simultaneous cardiocerebral infarction: Rescuing the brain or the heart first? Frontiers in Neurology 2017;8:664.
  2. Gralla J, Brekenfeld C, Mordasini P, Schroth G. Mechanical thrombolysis and stenting in acute ischemic stroke. Stroke 2012;43:280-285.
  3. Jolly SS, James S, Dzavik V, et al. Thrombus aspiration in ST-segment elevation myocardial infarction. An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration. Circulation. 2016;135:143–152.
  4. The ASSENT-4 PCI Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI). Lancet. 2006;367:569–578.
  5. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205–17.
  6. Kasemacher J, Mordasini P, Arnold M, et al. Direct mechanical thrombectomy in tPA-ineligible and -eligible patients versus the bridging approach: a meta-analysis. J Neurointerv Surg. 2019;11:20-27.

Why I Study Cardioprotection

That question.

It’s always looming. It comes from the tenured professor at the back of the room during my annual progress report to the department. It comes from the clinician from another field who pauses in front of my AHA Sessions poster. Heck, it even comes from my mother as I chat about my day in the lab. It reliably resurfaces with uncanny punctuality every time I talk about my research.

“So… if you can’t predict a heart attack, why does this matter?”

My dissertation project focuses on cardioprotection. That is, the phenomenon that a nonlethal stimulus applied prior to a heart attack can protect the heart against the insult.

Cardioprotection was first investigated in the context of acute myocardial infarction (MI). In the 1980s, it was discovered that brief, nonlethal bouts of ischemia and reperfusion (I/R) to the heart prior to a subsequent ischemic challenge can reduce the size of the infarct in a canine model, termed ischemic preconditioning1. This study was seminal because it demonstrated the existence of an endogenous cardioprotective network that might be harnessed for therapeutic benefit. In later studies, researchers found that ischemia and reperfusion at a remote vascular bed, organ, or limb can bring also protect the heart via remote preconditioning2, 3. Remote preconditioning is even more clinically translational and relevant; it’s far less challenging to slip a blood pressure cuff on a patient’s bicep than, say, occlude an artery.

But still. These studies looked at interventions applied before the heart attack.

If you can’t predict a heart attack, is this important?

My answer is a well-rehearsed and resounding YES. Let me summarize and consolidate, quick and dirty, the vast amount of info I’ve learned during my PhD about the value of preconditioning and cardioprotection. Here are three reasons why preconditioning and cardioprotection are important:

1. Some of the pathways invoked by preconditioning might also be useful during or after reperfusion. Basic scientists uncovering the complex signaling and mechanism of cardioprotection have revealed a number of therapeutic targets that could lead to the development of drugs or therapeutics that activate these pathways when most needed4. In other words, we believe that advancements developed within the preconditioning models might also be useful for perconditioning (during reperfusion) or postconditioning (after reperfusion). This gives us hope that we can intervene during the ambulance ride, at the time of stenting, or throughout recovery and still benefit the patient.

2. Cardioprotection can be reframed outside of acute myocardial infarction. There is a need for myocardial salvage in clinical scenarios where a high risk of ischemia and reperfusion injury is expected. These situations include cardiac surgery and coronary artery bypass graft surgery, organ transplantation, where situations of I/R adversely affect the organ’s lifespan, and elective percutaneous coronary intervention (PCI). PCI alone is performed on millions of patients annually, and perioperational MI occurs in at least 10% of those patients, depending on how you measure it5. In such cases, strategies to preserve myocardia can reduce susceptibility to perioperative injury in situations where MI can be reliably predicted.

3. The jackpot— any evidence that cardioprotective interventions might work in man. A slew of clinical trials have suggested that cardioprotection, whether based in ischemic techniques or pharmacological strategies, can be effective in humans6. The caveat is that these clinical studies are inconsistent and vary widely in the exact methodology and measured outcome (such as biomarkers, imaging, or major adverse cardiovascular and cerebrovascular events). We still don’t have an approved cardioprotective therapy, but this seems encouraging!

As an early career investigator, routinely and enthusiastically defending my work has led to some challenging conversations. Those difficult, engaging discussions have given me guts as a grad student and awareness as a scientist.

Now I can focus on that next big question: “When are you going to graduate?”

  1. Murry, C.E., R.B. Jennings, and K.A. Reimer, Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986. 74(5): p. 1124-36.
  2. Przyklenk, K., et al., Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation, 1993. 87(3): p. 893-9.
  3. Kharbanda, R.K., et al., Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation, 2002. 106(23): p. 2881-3.
  4. Hausenloy, D.J., Cardioprotection techniques: preconditioning, postconditioning and remote conditioning (basic science). Curr Pharm Des, 2013. 19(25): p. 4544-63.
  5. Lansky, A.J. and G.W. Stone, Periprocedural myocardial infarction: prevalence, prognosis, and prevention. Circ Cardiovasc Interv, 2010. 3(6): p. 602-10.
  6. Heusch, G., Cardioprotection: chances and challenges of its translation to the clinic. Lancet, 2013. 381(9861): p. 166-75.

Annie Roessler Headshot

Annie Roessler is a PhD Candidate at Loyola University in Chicago, IL. Her research focuses on the neurobiology and molecular mechanisms of electrically-induced cardioprotection. She tweets @ThePilotStudy and blogs at flaskhalffull.com