We Ordered Cardiac Biomarkers, Now What?
By Amanda Decimo, MSN, MPH, CRNA, from the IARS, AUA and SOCCA 2019 Annual Meetings*
In the IARS panel, Peri-Operative Myocardial Injury and Infarction: Pathophysiology, Prognosis and Treatment, Giora Landesberg, MD, DSc, MBA, Peter Nagele, MD, MSc, and Duminda Wijeysundera, MD, PhD, FRCPC, gave a thorough overview of the pathophysiology of injury and infarct.
They did not offer a simple solution for this complex clinical picture. Rather, they offered a sensitive evaluation of the complexities surrounding perioperative myocardial events. They emphasized that we need to consider how these cardiac biomarkers enhance our knowledge, yet it is still early in the process of deciding exactly what to do with this information.
Similar pathophysiology is involved in ST-elevated ischemia and non-ST elevated ischemia; however, there are major differences in treatment. ST depression indicates necrosis of cardiac muscle, whereas ST elevation indicates artery occlusion. Still, the prognosis for ST depression ischemia seems to be worse. A startling fact is that most cardiac ischemia is caused by relatively young, relatively non-occluding plaques.
In the 1990s, two essential developments occurred in cardiac medicine: troponin and continuous 12 lead ECG monitoring. It is clear that higher postoperative troponin levels indicate worse postoperative survival. Patients with elevated preoperative and postoperative troponins are at the highest risk. Multiple studies confirm these findings. Another important distinction is that troponins are only useful when GFR > 30.
What is the pathophysiology of myocardial infarction? Type 1 infarcts are STEMI, acute coronary syndromes (ACS), and they are relatively rare. Type 2 NSTEMIs are seen more commonly in the perioperative period. These infarcts are caused by stable coronary artery disease, stress-induced ischemia, tachycardia, and hypotension. Silent postoperative myocardial injury is 10-times more common than overt myocardial infarction.
Most ischemia is due to increased heart rate (HR), but how we define tachycardia should be considered. The traditional definition of a rate > 100 does not suffice. For example, if a patient’s baseline HR of 60 increases to 90, a 50% increase in HR can cause ischemia. A sustained increase in HR and sustained hypotension are clear contributors to the pathophysiology of ischemia.
Should we collect cardiac biomarkers before and after surgery? Dr. Nagele warns there are no clear answers, only pros and cons in this debate. The current best evidence is that if you have an elevated preoperative troponin, you have a 4-fold increased risk of short-term adverse outcomes.
Cardiac troponin (cTn) is an essential protein in the cardimyosin. It’s released into the bloodstream when cardiac cell injury occurs. We measure troponin C or troponin I. It is the gold standard for diagnosis of acute MI and has absolute myocardial tissue specificity. High sensitivity cardiac troponin (Hs-cTn) can detect minute baseline troponins that give more meaning to postoperative changes. Rapid MI diagnoses (within 1-2 hours) in the ED with Hs-cTN can speed time to treatment, where early treatment saves cardiac muscle.
Causes of chronic troponin elevation include ischemic heart disease, heart failure, chronic kidney disease, severe COPD, and cardiotoxic chemotherapy. If we do measure preoperative cTn levels, there is no accepted workup algorithm or intervention, based on the results.
Acute versus chronic troponin elevations are associated with different etiologies. Patients with severe ischemic heart disease, for example, would be expected to have high troponins and we may be measuring the obvious. For patients who arrive for elective procedures with unknown comorbidities, we can now identify unknown cardiac risk. But even cardiologists are unclear as to whether preoperative detection in these patients will improve care. It will be costly, but will it help?
Should we measure troponin after surgery? Causes of acute postoperative troponin elevations besides ischemia include new arrhythmias, renal failure, heart failure, and cardiac procedures. This elevation is a common signal for a multitude of events. New cTn release indicates myocardial necrosis, but not always ischemia.
A study of young, healthy athletes showed elevated cTn and Hs-Tn after intense treadmill exercise. The cause is unclear. Dr. Nagele speculates that perhaps cardiac remodeling occurs with stress to the heart, and this is part of healthy exercise-induced physiology.
Pros for collecting preoperative troponin include: improved patient care, a strong indicator of adverse outcomes, easy to obtain, and high-sensitivity for cardiac ischemia.
Cons include: expensive if used for all patients, etiology is poorly understood, and unclear relevance when clinical symptoms are absent.
Framework for Treatment
“There is always an easy solution to every problem — neat, plausible, and wrong.” -H.L. Mencken
Dr. Wijeysundera discussed treatment options. Myocardial infarction treatment is more straightforward than myocardial injury. We know that both postoperative infarct and injury (troponin elevation) are consistently associated with increased postoperative mortality. The solution is not as simple as a set of drugs, or one specific algorithm for every patient with biomarker elevation.
Myocardial infarct occurs when a patient has an elevated troponin and meets clinical criteria for infarct. Management of infarct involves acute treatment and secondary prevention, guided by pathophysiology. How do we clinically differentiate between Type 1 and Type 2 infarct?
Type 1 infarcts (approx. 25%) are rare, typically STEMI. The pathophysiology is plaque rupture with occlusive or non-occlusive thrombosis. Usually, these occur outside of the perioperative period. Treatment includes medical therapy and emergency cath lab admission.
Type 2 infarcts (75%) are the type we encounter more often perioperatively. Typically NSTEMI, with a fixed atherosclerotic lesion. But, it’s important to remember many cases of Type 2 infarcts are due to supply/demand imbalance, without underlying coronary disease. These cases include coronary vasospasm, major blood loss, and extreme hypertension without significant coronary artery occlusion. Type 2 infarcts are 3 to 5 times more likely postoperatively than Type 1 events.
The acute treatment goal with myocardial infarct is to consider it a Type 2 infarct and optimize supply/demand balance; if no response, consider Type 1 infarct. Imagine the weighted scale image with supply factors including optimizing blood pressure and hemoglobin concentration; demand factors include minimizing tachycardia, pain, and hypoxemia.
Secondary prevention involves reducing complications and preventing recurrent coronary events. Cardiologists and intensivists manage this after hospital discharge, but we need to be involved in the development of a system that ensures that patients receive follow-up. Three pillars of therapy include:
- vascular protection with antiplatelets, lipid-lowering medications, and ace inhibitors
- heart failure prevention with beta-blockers and assistive device, if needed
- risk factor management by optimizing patient risk factors (smoking, obesity, blood pressure and glucose control)
The MANAGE trial used dabigatran, a direct-acting anticoagulant (DAAC), for patients with postoperative myocardial injury (80%) and infarct (20%) after non-cardiac surgery. Dabigatran lowered venous and arterial complication rates significantly compared to the placebo control group. DAACs are appropriate and should be considered for inclusion in secondary prevention medication regimens.
How do we manage injury? Lots of uncertainty over this question remains. We have more sensitive biomarkers, but what do we do with this information? Dr. Wijeysundera says, ”Don’t treat biomarkers, treat disease.” We know postoperative troponin elevations are tied to bad outcomes, but the etiology is unclear with myocardial injury. We need to consider patient history and clinical context. Then ask, how likely is the cause cardiac?
Injury has many mechanisms outside of coronary etiology. Other causes of myocardial injury include critical illness and inflammation, tachycardia, atrial fibrillation, heart failure, pulmonary disease, and stress-induced cardiomyopathy. Pulmonary embolism is a relatively frequent cause for elevated troponin.
Transferring care after surgery and hospital discharge to ensure posthospital treatment continues is crucial with myocardial injury. Prevention needs to target why the patient has myocardial injury. Consider diagnostic testing and institute secondary prevention strategies targeted to the individual patient.
We need to consider our patients’ unique characteristics when deciding to collect cardiac biomarkers and when treating myocardial injury and infarct. A universal algorithm for all episodes of myocardial injury is unlikely — it’s not a one-size-fits-all solution.
*Coverage from the Peri-Operative Myocardial Injury and Infarction: Pathophysiology, Prognosis and Treatment Panel during the IARS 2019 Annual Meeting