What is the role of stem cell treatment of a heart attack: non-STEMI? Non-STEMI or Non-ST elevation Myocardial Infarction is the dominant presentation of acute coronary syndrome. This occurs when the blood supplied to the heart muscle is suddenly blocked. Other presentations include unstable angina and STEMI or ST-Elevation Myocardial Infarction. Patients presenting with symptoms of chest pain with or without accompanying symptoms of shortness of breath, profuse sweating, nausea or syncope, and have evidence of myocardial necrosis (elevation of cardiac enzyme: troponin) with absence of ST elevation are considered to have a Non-STEMI. ST segment depression, transient ST elevation or deep T-wave inversion on the electrocardiogram may be present but are not necessary. This was well described by my colleague Dr Mustafa Ahmed in the article on NSTEMI?
Stem cells in the treatment of a heart attack: What is the problem with a Non-STEMI?
Each year, it is estimated that almost 800,000 patients will experience an acute coronary syndrome of which 70% will have a Non-STEMI. Trends from the world data base of patients with acute coronary syndrome show that the percentage of patients with Non-STEMI is rising dramatically. Acute coronary syndrome is caused by plaque rupture or erosion with different degrees of superimposed thrombus or clot resulting in a decreased blood flow to the heart muscle. In most cases, the damage to the heart muscle is limited to the most inner layers of the myocardium and for this reason a Non-STEMI is called a minor or small heart attack. However, patients with Non-STEMI have more comorbidities, both cardiac and noncardiac. The patients are older (median age of 68), and they more often have had a previous MI, congestive heart failure, atrial fibrillation, diabetes and abnormal kidney function. The in-hospital mortality of Non-STEMI and STEMI is similar ( approx. 4%) but by 12 months, patients with Non-STEMI have an increased risk of myocardial infarction, death and recurrent instability. Early events are related to recurrent plaque rupture and thrombus and late events are closely related to left ventricular dysfunction and heart failure.
Stem cells in the treatment of a heart attack: What is the conventional treatment of a Non-STEMI?
Upon presentation, the clinical history, angina symptoms and equivalents, physical exam, ECG, renal function and cardiac troponin can be integrated into an estimation of the risk of death and complications of ischemic events. The patient with a high risk, continuing chest pain, hemodynamic instability (decrease in blood pressure or worsening heart failure) and uncontrolled arrhythmias (such as ventricular tachycardia) should be treated with anticoagulants, antiplatelets and treated with an invasive approach where the patient is taken to the cath lab for percutanous coronary intervention and coronary stenting if appropriate. Below is an example of a patient with Non-STEMI that was treated with coronary angioplasty and stenting of the circumflex artery. Notice that he had also a chronic occlusion of his right coronary artery with collaterals originating from the same circumflex artery. The area of ischemia was very significant.
Medications required in hospital for control of angina should be continued after hospital discharge. This may include nitrates, beta blockers, calcium antagonists and antiplatelets such as aspirin, clopidogrel, prasugrel or ticagrilor. Patients with heart failure should be treated with angiotensin converting enzyme inhibitors or angiotensin receptor blockers. These medications will help preserve the left ventricular function and prevent further decompensation of their heart failure. Patients should be treated with appropriate cholesterol management including statin, blood pressure control, smoking cessation and lifestyle changes.
Stem cells in the treatment of a heart attack: What is their role in a Non-STEMI?
During the Non-STEMI, prolonged ischemia causes myocardial cell death and progressive loss of heart muscle and contractile tissue. Cardiac cells possess minimal ability to regenerate themselves. The myocardial cells are replaced by scar tissue. Subsequently, these changes lead to left ventricular remodeling resulting in an enlargement of the heart and development of heart failure. The goal of stem cell therapy for subjects with a Non-STEMI is to improve cardiac function in an attempt to decrease the development and onset of congestive heart failure.
Multistem® is a multipotent adult progenitor cell product developped by Athersys, Inc. (Cleveland, Ohio). The stem cells are isolated from human bone marrow. The stem cell cultures can be expanded and used off the shelf for treatment of a variety of disease including myocardial infarction. Preclinical data of myocardial infarction demonstrated an improvement of left ventricular function 2-6 weeks post cell injection. Additionally, there was a significant increase in blood vessel around the infarct zone. In the phase 1 clinical trial, 19 patients were given a Multistem® intracoronary injection 2-3 days after their heart attack. All the patients studied had a STEMI. One of those patients was described in our previous article: “Surviving a heart attack: the big one“. Not only did he have an improvement of his heart function, but he had developed collaterals that prevented him from having further damage to his heart when his “widowmaker” proximal LAD reoccluded five years later. Patients that were treated with the higher dose of Multistem® had a 25% improvement of left ventricular function measured by echo at 4 months post treatment over baseline. These changes persisted at 1 year with an increase of 11% over baseline. Below is another example of a patient that underwent Multistem® injection in 2009. Fifty million stem cell dose were injected through the right coronary artery 3 days after presentation with an inferior STEMI and PCI with coronary stenting of his coronary artery (RCA).
Stem cells in the treatment of a heart attack: MRI to assess myocardial viability in a non-STEMI
MRI infarct size is an important predictor of mortality and major cardiovascular events. MRI spatial resolution allows for the detection of subendocardial infarcts. It correlates well with histology and PET scanning.
To perform MR imaging, we used a 1.5T whole body scanner (GE 450 Widebore at BBH Princeton) and a phase array body coil that is wrapped around the patient’s chest. Some of our patients are claustrophobic and for the study, one of our research nurses usually has to stay with the patients. The protocol starts with anatomical stack localizer scout imaging to determine the orientation of the left ventricle short axis imaging plane. For evaluation of the left ventricular function, cine MR imaging is performed using ECG modified gated gradient echo sequences and breath-holding technique. This results in dynamic images with high temporal resolution that allows for evaluation of the left ventricular wall motion and volume measurements. This is performed in collaboration with Dr Ricardo Bracer and our Radiology department. Below is an example of a patient with a non-STEMI involving a stenosis of the mid LAD that was treated with coronary stenting.
The MRI study performed immediately after coronary stenting and randomization into the Athersys protocol demonstrated significant anteroapical hypokinesis and LV dysfunction.
Six months later, the patient underwent repeat MRI showing significant improvement when compared to baseline. The patient is followed as part of the Athersys study. It is unknown at this time whether the patient received stem cell treatment versus control.
For imaging the myocardial infarct, the MRI protocol uses a special sequence called Inversion Recovery combined with a contrast agent called Gadolinium (Magnevist). Contrast agents do not accumulate in normal heart cells (e.g. myocytes) but rather accumulate in the extracellular space or into damaged, ruptured myocytes. Therefore, the presence of gadoliniumt can be used to assess infarcts of the myocardium and other myocardial disease. So, 10 minutes after bolus injection, delayed images are acquired using a sequential T1-weighted Inversion Recovery turboflash sequence, with a variable T1 delay adjusted for each patient. The optimized choice for Inversion Recovery time “nulls” the signal of the normal myocardium. This optimization also depends on the contrast dose which varies according to the patient’s weight and kidney function. The delayed enhancement images are then obtained 15 mins after intravenous injection with the patient holding their breath for 15 seconds. During that time a minimum of 12 slices covering the whole heart are acquired.
Stress myocardial perfusion imaging is performed using intravenous (iv) adenosine as a stress agent. Four minutes after starting the iv infusion of adenosine, iv gadolinium contrast is administered followed by acquisition of a spoiled gradient echo stress perfusion scan in the short and long axis of the heart before contrast reaches the left ventricular cavity. This allows us to assess the perfusion enhancement of the myocardium. Fifteen minutes after stopping adenosine, we acquire a rest perfusion scan using similar imaging technique. The infusion of adenosine can increase the myocardial blood flow up to 5 times normal in patients without coronary obstruction. The ratio of measured myocardial blood flow obtained with resting baseline and with maximal hyperemia (during adenosine infusion) provides an estimate of myocardial perfusion reserve. This can provide an assessment of the myocardium at jeopardy by identifying inducible ischemia and can predict recovery of myocardial function after myocardial infarction and revascularization with PCI. Below is an example of myocardial perfusion at rest.
Stem cells in the treatment of a heart attack: a patient with a non-STEMI
We are currently participating in a phase II prospective, randomized, double-blind, sham-controlled, multi-center clinical trial designed to assess the safety of AMI Multistem® in patients with Non-STEMI. Dr Farrell Mendelsohn is the principal investigator at BBH Princeton. Patients are randomized and treated no later than 3 days after their myocardial infarction. One of our patient had his first heart attack at the age of 26. Two years later he had his second heart attack. He had a lot of stress in his life, going through a divorce. Four months prior to his third heart attack, his ex-wife was killed in a car accident and he became solely responsible for the care and well-being of his seven year old daughter. He realized that he had to get better for his daughter. So when Dr Hutton Brantley, one of our investigators, approached him about participating in the AMI Multistem® trial, he did not hesitate! The AMI Multistem® trial is currently enrolling patients with Non-STEMI across the United States. If you would like more information, please refer to clinicaltrials.gov.
I had nstemie in March 2017. No doctors ever talked to me or explained anything. Thus with your fantastic articles, I’m learning. I have contacted a cardiologist with an upcoming appointment. Would you be able to review my medical record so I could have your expert advise on my steps forward.
Thank you for your interest in Myheart.net and I am glad our articles have helped you. We want to increase patient awareness and education in the matters of heart disease. I would recommend you follow through with your appointment with the cardiologist and discuss with him all the treatment options after he reviews your medical records and has the chance to take a good history and physical exam. He may want to do some other testing such as an echocardiogram and an exercise test. In the mean time, keep reading and stay informed. The patient is an important part of the team. When the patient understands and collaborates, it usually translates in better outcome!
My husband had two successful stents recently but a 3rd blockage was not a good vein to apply the stent … while in hospital he had a heart attack. He will begin cardio rehab in a week. He is taking an injection monthly called Repatha. Does he have a chance of making sufficient progress to live a good life… is there something else he should be doing?
Thank you for your interest in Myheart.net. This is a very good question. Stents are very useful for treating chest pain in patients with coronary artery disease including patients with non-stemi, but they are not required in everybody. Sometimes, the artery is not suitable for stenting; the artery is too small or too tortuous, or the artery has recanalized or reopened by itself. What is most important is the medical therapy that the doctor will prescribe and as a patient, to adhere to the treatment and adopt lifestyle changes that can prevent a recurrence of a non-stemi or the progression of the coronary artery disease.
Very good info
I had a NSTEMI MI, on June 3rd, blockage of 90% and 100% , no CHF, on June 6th $by pass surgery, and everything went well, discharged on the 10 th, just started Cardio Rehab.
my wife and I , switch to NO Processed food, eating not necessary low fat, but all organic, Grass fad, grassed finished beef, some game meet, pastured eggs, no carbs, except the Vegetable and some fruits.Nothing sugar , per say or glacemic foods,
I take good qual Omega 3, Vit K2 with Vit D3 and for Vit C i eat red bell pepper and Sauerkraut
I highly suggest everybody with a Cardiac event, to go for Cardiac Rehab, its a life saver
Thank you very much your interest in Myheart.net. Very glad that you are doing well post non-stemi and post cabg surgery. You are doing everything to speed your recovery and keep your bypass grafts opened! We wish we had more patients like you! These non-stemi heart attacks are a life changers, a wake up call. It is an adjustment to the new lifestyle, but it’s worth it!
Nice information, thanks for the resourceful blog really useful and informatic.
Thank you for your interest; we are planning to update with MRI images of patients with myocardial infarction in a follow up article. It is not an easy task to follow patients who have survived a heart attack and test whether a specific treatment, in this case stem cells, can reduce the damage caused by the heart attack. Stay tuned!
Great post.
thanks to share.i found it really helpful.
NSTEMI can lead to several complications.you can treat NSTEMI with Inhaled oxygen therapy or Bed rest with continuous monitoring by ECG.
Somewhatre on this website (wrong place probably), there is a reply that I wrote yesterday about an nstemi that I had 7 months ago. I am 78, workout at the gym 6-7x a week. I had what I thought were several “warning” signs over a period of several months-all in middle of night . (Ok – I wasn’t the sharpest knife in the drawer, I’ll admit.) Broad chest burning, cold, clammy sweats, and upper chest pain, upper arm burning – all intermittently. Each time, symptoms lasted 15-30 minutes and then I went back to sleep. I finally went to clinic to get their opinion and ended up quickly at nearby Univ. medical center. across the street. I wasn’t “typical” and I lay there for a couple hours until they could figure just what to do with me. I did have troponin of 5.7 that did not go down; depressed segments on ECG,; also had several cardiac markers (not diabetes). Finally they decided to do an angiogram at which time they did 3 stents (RCA 90%, 80% 70% ), plus LAD/D2 bifucation a week later. I think I flummoxed them initially but can’t really say. Anyway, I had superb IC who saved me from open heart surgery (per the somewhat irritated comment by of one of his colleagues. I had refused his suggestion of a stress test a few months before ). I’d be interested in your observations about my experience. Oh, I learned from my hospital record that someone had noted “great vessels.” At 78 yet!! However I do have not- so -good lipids and BP, and genetic factors. Yes, I know that I’m lucky.
Research in Japan show that high glucose (above 140) in the blood stream after eating (glucose spikes) causes damage to the blood vessels. Cumulative damage leads to heart attacks, stroke, diabetes and dementia. It takes a long time for the damage to appear, but glucose spike is the root cause of theses diseases. I do not or have read any recommendations from doctors of avoiding theses diseases by not eating foods that lead to glucose spikes or eating less of them during meals or snacks. How unfortunate.
thank you for your interest in Myheart.net. Studies showing repeated and abnormal spikes of blood sugar, hyperglycemia and poor diabetes control are related to micro- and macrovascular disease. This leads to atherosclerosis and myocardial infarction and stroke. Diabetes studies showed a significant 14% reduction in myocardial infarction for each 1% reduction in mean A1C. Even in the non diabetic, hyperglycemia is associated with an increased risk of cardiovascular disease. There was a linear relationship between cardiovascular events and the 2-h postprandial plasma glucose. This is a very important topic and we should devote more time on the subject in the future.
I had a NSEMI in March 2018 and now on the waiting list for a by pass possibly a double. What do you recommend by way of food selection and exercise in the meantime . Its likely to be a few months yet before I have the operation. I am 73 walk 2 miles minimum a day,weekend golf and still do an office job 4 days a week
Hi . I had a nstemi last year . Was put straight in the care of my gp , once discharged from the hospital a few days after the ha . I have terrible chest pains daily . I live in UK by the way . I go to my gp they don’t send me for tests nothing . I’m on few mads . I had a clot on my lung 19 year befor ha . I’m 54 and afraid every day . Why have I not been seen by a cardio Dr. All I was told was it’s not likely I will have another .
Happy New year from Ireland. I had 4 stents Dec 2018 and while an echo result is good my stress test leads to another angiogram Feb 2019. I don’t smoke eat well but work very hard as self employed in several business with a lot of people. Does stress (hidden stress) add to heart conditions?