Early Detection of Acute Myocardial Infarction Using Microfluidics

A healthy person—a non-smoker regularly working out in the gym, eating a healthy diet, with a good physique—died of a heart attack. While another person—having a non-healthy lifestyle, a smoker—felt chest pain, fainted, and survived a heart attack thanks to the quick response of the emergency medical team who arrived on time and resuscitated him.

A heart attack, technically referred to as an acute myocardial infarction (MI), is a form of cardiovascular disease (CVD) and one of the leading causes of death globally. In fact, the World Health Organization (WHO) estimates 17.9 million people die of cardiovascular disease each year. CVDs include a variety of conditions, including coronary heart diseases, cerebrovascular disease, rheumatic heart disease, and others but heart attacks and strokes are responsible for roughly 85% of CVD¹ deaths.

Of course, the scariest aspect of heart attacks and strokes is they are sudden and often fatal, so timely medical intervention is crucial to prevent a catastrophic health issue, or worse, death. Heart attacks and strokes are mainly caused by the blockage of an artery, typically from the buildup of fatty deposits on the inner walls of the blood vessel, that prevents blood from flowing to the heart or brain. These fatty deposits can impair the blood flow directly, or rupture and form a clot that blocks blood flow downstream. Strokes can also be caused by bleeding from a blood vessel in the brain.

Early symptoms of a heart attack may include pain or discomfort in the center of the chest and/or pain or discomfort in the arms, the left shoulder, elbows, jaw, or back. Also, the person may have trouble breathing or shortness of breath; nausea or vomiting; light-headedness or faintness; a cold sweat; and turning pale.² Although these symptoms can indicate a heart attack or stroke, they can also indicate other events including panic attacks, heartburn, indigestion, respiratory issues, flu-like illness, etc., and therefore, are not perfect predictors. Since time is crucial in determining heart attacks and strokes, it is critically important to have a way to quantify or predict that such an event will happen.

Microfluidic devices have been used for early detection in several disease diagnostics tools. The question: Is it possible to use the same technology to detect heart attack or stroke early on?

Understanding Acute Myocardial Infarctions

Electrocardiography (ECG or EKG) is the simplest diagnostic tool for detecting MI; however, typically used during or after the event,6 this method tends to be insufficient and isn’t sensitive enough for early detection. In the ECG chart, when the ST-segment changes in appearance and is elevated above the baseline (ST elevation), it usually indicates blockage of the involved coronary artery and that the heart muscle is currently dying. While the non-ST elevation myocardial infarction (non-STEMI) typically involves an artery with partial blockage, it generally does not cause as much heart muscle damage.

In the emergency room, echocardiography is another tool that enables physicians to diagnose myocardial infarction. This method looks for any abnormality in the heart’s structure via ultrasound imaging. Also, a blood sample is drawn from the patient for analysis to confirm the findings. The excess creatine kinase and other biomarkers, such as myoglobin and troponin, are signs of myocardial necrosis (death of tissues), but the increase is delayed by a few hours after the coronary occlusion.²

According to the Joint Taskforce,³ myocardial infarction is classified based on five patient types of categories.

• Type 1: Spontaneous infarction presenting ischemia due to a previous coronary event like plaque erosion and/or plaque rupture (ST or no-ST elevation infarction). 
• Type 2: Infarction related to ischemia caused by oxygen (increased demand or decreased supply), embolism, arrhythmia, and hyper or hypotension.
• Type 3: Sudden infarction with cardiac death occurring before tests can be performed or before cardiac biomarkers appear in the blood.
• Type 4: Infarction related to percutaneous coronary interventions associated with the intervention itself and stent thrombosis.
• Type 5: Infarction related to coronary artery bypass grafting.

Microfluidics as a Potential Tool for Early MI Detection

The observable symptoms or ECG as the predictor of the potential occurrence of heart attacks are unreliable and, in most cases, misleading. Cardiac biomarkers were used as detection means for many years and are subject to numerous studies. These include enzymatic [creatine kinase (CK), glycogen phosphorylase isoenzyme BB (GPBB)], proteins such as heart-type fatty acid binding protein (hFABP), troponins (cTn, TnC, TnI, TnT), and peptides (copeptin and irisin).⁴

One approach for early detection could be to combine several detection modalities to identify the potential for a future MI event. This would involve synthesizing key data from a variety of sources including standard detection methods, biomarkers, risk factors, and patient history.

Because the sensitivity and specificity of ECG are low in diagnosing a heart attack, European Society of Cardiology (ESC) and the American College of Cardiology (ACC) decided on the following detection criteria: The patient must have at least two of the following: (1) typical symptoms, (2) a characteristic elevation, (3) a decreasing pattern in cardiac markers (e.g., CK-MB isoenzymes), preferably serum troponins (cTnI or cTnT), or (4) a typical ECG trace with Q waves that indicate a diagnosis of MI.⁴

For cardiac biomarkers, serum troponins (Tnl) remain the gold standard for the diagnosis of AMI with ECG and echocardiography. However, these are used during, and several hours after, the MI event. Evaluating troponins requires time to get the result and is challenging to implement on-site, since this requires laboratory work, proper equipment, and a trained medical practitioner.

If we can find the ideal biomarker suitable for MI early detection, biosensors⁵ integrated into a microfluidic device⁶ can potentially be used to detect these biomarkers. Ideally, the microfluidic device would be disposable, small, and that body fluid sample (blood, saliva, urine) could be injected into the device, and all the required laboratory processes would be completed within the device in minutes. Imagine with this type of device, a person could determine with certainty if their symptoms are the result of a heart attack or something less serious, practically anywhere—like a sports venue, the office, at home, or even at a doctor’s clinic or hospital.

Microfluidic devices could also be implemented on a wearable such as a patch or a new type of cardiac holster that could be linked to the patient’s mobile phone or smartwatch to provide continuous monitoring for all the patient categories mentioned, especially type 3 where the event is sudden and fatal.

Takeaways

While a heart attack or an acute myocardial infarction is often fatal, there is no commercial device available that can detect a heart attack before it happens. Instead, we’re left to diagnose the disease in retrospect. But the possibility for such a device still exists. Cardiac biomarkers and biosensors are the most promising avenues for early detection, together with risk assessment and other diagnostic tools such as ECG, imaging, and ultrasound to determine the heart’s health condition.

Microfluidic devices with a biosensor can potentially detect specific biomarkers to determine an impending heart attack event when only one or two symptoms appear. The devices could also be used as a screening test for whether it will be a potential heart attack.

However, there is still a lot of work ahead to determine the most accurate biomarker as well as the biosensor that will determine with certainty that the collected data is accurate to detect a possible heart attack. Until then, CVDs, particularly heart attacks and strokes, will remain one of the top causes of death in the world. Let’s hope that our scientists and engineers can accelerate the development of an early-detection device and someday prevent this disease from claiming the lives of millions in the future. 

References

1. bit.ly/mpo0423des1
2. bit.ly/mpo0423des2
3. go.nature.com/3Fsjlod
4. Aydin S, Ugur K, Aydin S, Sahin ?, Yardim M. Biomarkers in acute myocardial infarction: current perspectives. Vasc Health Risk Manag. 2019 Jan 17;15:1-10.  doi: 10.2147/VHRM.S166157. PMID: 30697054; PMCID: PMC6340361.
5. bit.ly/mpo0423des3
6. Lim WY, Thevarajah TM, Goh BT, Khor SM. Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection. Biosens Bioelectron. 2019 Mar 1;128:176-185. doi: 10.1016/j.bios.2018.12.049. Epub 2019 Jan 9. Erratum in: Biosens Bioelectron. 2019 Mar 15;129:299. PMID: 30685097.

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Lorenzo Gutierrez has over 30 years of product development experience in semiconductor, consumer electronics, and medical devices. He started working with microfluidics at the University of Tokyo in Japan in 1999, and continued developing microfluidic systems at University of Toronto in 2011. Lorenzo has developed new fabrication techniques, materials, processes, and methods in commercializing cartridges and instruments. His microfluidic applications include cell-based, immuno and molecular assays. Lorenzo specializes in overall system design, hardware engineering, integration, and translation of assay workflow to consumable cartridges. At StarFish Medical, Lorenzo manages the microfluidic cartridge development team.