MINOCA SYNDROME

By Paulina Maldonado
Universidad De Durango, Chihuahua, Mexico
Houston, Texas.
Amin H. Karim MD
Baylor College of Medicine and
Methodist Institute of Academic Medicine, Houston, Texas

A 65 year old patient presented, disabled from old cerebro vascular accident causing flaccid left sided hemiplegia with contractures, admitted to hospital for change of mental status; he developed hypotension; EKG showed ST elevation in II, III and aVF as well as V3V4V5 diagnostic of inferior wall myocardial infarction with lateral extension.

He was rushed to the cath lab where cardiac catheterization showed what looked like “normal coronary arteries”.

His high sensitivity peaked at 1200. He was treated with intravenous heparin and beta blockers; he remained hemodynamically stable and was discharged.

Myocardial Infarction with nonobstructive coronary atherosclerosis

Although the occurrence was initially reported about 80 years ago a very small number of patients are found to have MINOCA.  

The term MINOCA is reserved for patients with elevated troponin associated with myocardial ischemia at presentation and should not include disorders with non ischemic elevated troponin. 

It is important to mention and reiterate that MINOCA should not be considered a final diagnosis but rather a working one that requires further testing. 

Epidemiology

The incidence of MINOCA varied from 1% to 15% and roughly 6% of all Acute Myocardial Infarction cases. 

  1. Younger (18-55)
  2. Female
  3. lower prevalence of hyperlipidemia
  4. ⅓ presented with ST segment elevation of myocardial infarction

Pathogenesis:

MINOCA is heterogenous and can be divided into coronary, cardiac and extra cardiac causes. Ischemia happens during a temporary suspension of blood flow to the myocardium and it takes place in the epicardial arteries or the microvasculature. 

CoronaryCardiacExtra cardiac 
plaque rupture or erosionMyocarditisstroke
coronary spasmTakotsubo syndromepulmonary embolism
spontaneous coronary artery dissectioncardiomyopathiessepsis
coronary embolizationcardiac traumarenal failure
coronary microvascular disorderstachyarrhythmiashypoxemia

Risk factors:

  • Associated with Long term major adverse cardiovascular events after MINOCA including ST segment elevation on a presenting Electrocardiogram
  • older age
  • reduced left ventricular ejection fraction
  • diabetes mellitus
  • hypertension
  • tobacco use
  • prior Myocardial infarction
  • Stroke
  • peripheral artery disease
  • chronic obstructive pulmonary disease
  • chronic kidney disease
  • lower total cholesterol
  • Peak troponin
  • Depression at the time of MINOCA 

Signs and Symptoms:

  • Chest pain/chest pressure / chest heaviness
  • Nausea
  • jaw, neck or upper back pain
  • pain or pressure in the lower chest or upper abdomen
  • shortness of breath
  • fainting
  • indigestion
  • fatigue

Diagnostics:

Requires a comprehensive diagnostic workup. Is the first line diagnostic tool to detect non obstructive epicardial coronary arteries (less than 50% stenosis) in the setting of an Myocardial Infarction.

Imagining modalities are vital in diagnosing and identifying the underlying mechanisms of MINOCA.

Coronary intravascular imaging

With Intravascular Ultrasound 40% cases and Optical Coherence Tomography 50% cases  is essential to diagnose plaque disruption.

It should be performed at the time of coronary angiography for Acute Myocardial Infarction in all 3 major epicardial arteries. 

Cardiac Imaging

Transthoracic echocardiography used in the assessment of cardiac function after a MINOCA. It can be used in the diagnosis of Takotsubo cardiomyopathy and non ischemic cardiomyopathy specifically to demonstrate recovery of left ventricular function.

Transesophageal echocardiography can be used when coronary embolism is suspected.

Cardiac Magnetic Resonance Imagining (CMRI) provides a diagnosis in 74-87% of all MINOCA patients. 

  • Subendocardial (or transmural) pattern of myocardial edema, inflammation or fibrosis is suggested of ischemic Myocardial Infarction.
  • Epicardial pattern is suggestive of non ischemic Myocardial Infarction.

Echocardiogram can be used to diagnose Takotsubo  cardiomyopathy and non ischemic cardiomyopathy, but CMRI can only be used to detect myocarditis.

Myocardial perfusion quantification with adenosine or regadenoson can be used to diagnose coronary microvascular dysfunction non invasively.

The timing to perform a CMRI is important; it should be completed as close to the acute myocardial infarction as possible. CMRI carries not only diagnostic value but prognostic value as well. 

Multimodality approach

OCT and CMRI together resulted in a diagnosis in 85% of the cases whereas Optical Coherence Tomography alone was only 46% and Cardiac Magnetic Resonance Imagining 74%. 

Treatment

It should me customized to the underlying diagnosis:

MedsUnderlying diagnosis
Aspirin and High intensity statinsPlaque disruption
dual antiplatelet therapy by adding ticagrelor for less than 1 monthPlaque disruption not undergoing stenting
Beta blocker and renin angiotensin system inhibitorsleft ventricular dysfunction
Long acting calcium channel antagonist (dihydropyridine and nondihydropyridine)MINOCA patients secondary to epicardial coronary vasospasm
nitrates can be added to calcium channel antagonistsrefractory variant angina
antithrombotic agents coronary embolism or thrombosis
targeted therapiesunderlying thrombophilia
conservative management (avoiding increased risk of complications with intervention)spontaneous coronary artery dissection
Percutaneous coronary interventionSTEMI, cardiogenic shock, ongoing ischemia
aspirin, beta blocker, statin and renin angiotensin system spontaneous coronary artery dissection (should be assessed based on individual risk factors
antianginal treatment with b blockers, calcium, channel antagonists and ranolazineChest pain
MINOCA mimickersHeart failure
mechanical circulatory supportprogressive circulatory failure
resolves in most patients within 2-4 weeksMyocarditis, but if they develop arrhythmia and persistent cardiac dysfunction medical therapy should be administered.
antivirals and immunosuppressivesunderlying etiologies

Prognosis:

Short and long term mortality

At 1 year follow up, MINOCA mortality is 2 to 5%.

Among individuals 65 and older the risk of adverse outcomes is higher 12%

Possible Reinfarction

only occurs in 1.3 to 2.6% of patients at 1 year and 7.1% at 4 years.

Quality of life

Identified factors that increase the risk of Major advance cardiac event:

  • older age
  • hypertension
  • smoking
  • reduced ejection fraction
  • chronic obstructive pulmonary disease
  • elevated creatinine 
  • cancer 
  • elevated CRP

Requires further investigation that may require longer hospitalizations. It is commonly found that Myocardial Infarctions is missed in women due to non classic presentations such as shortness of breath, dizziness, nausea or unusual fatigue. Patients with MINOCA do present with recurrent chest pains without myocardial infarction.

Literature Cited: 

To Treat or Not to Treat

A Panel Discussion Between Practicing and Experienced Cardiologists
on How to Tackle Risk Assessment in Asymptomatic People .

The case presentation and the comments that follow were interchanged on our WhatsApp groups APCNATeam in November 2024. This discussion presents an example of how experienced practicing cardiologist, faced with real life patients, navigate the findings on trials and papers and come to conclusion of what to tell the patient and how to proceed with the next preventive or therapeutic step. Please excuse any errors or omissions and will be happy to correct since the readers are themselves the Editorial Board. (Amin H. Karim MD)

Dr. Bashir Hanif
Need opinion on a 45 year old with positive family history of premature CAD. Asymptomatic. Very active, brisk walk n jog 45 minutes 6 days a week without symptoms.
CAC n Lipids are given below. What would you do next? Cath? Stress test? Or just Aspirin n high dose statins?

Abdul Hakeem
Where is the bulk of the calcium? If it’s a prognostically imp territory then I would get exercise MPS for further risk stratification. Agree with HD statin bring LDL<50 perhaps EPA
Salman Arain
I had the same question @Dr.Basheer Hanif – what is the distribution of calcium? 550 distributed over three vessels is less concerning than 350+ in the LM and proximal LAD. In the latter case, I may offer a stress test. Also, if the patient has a family history of premature CAD, then it may be reasonable to do a stress test.

Maryam Moten

Hussain Khwaja
I would do ASA and high dose statin to bring LDL between 25-50
Question is what we are going to do if stress test comes abnormal ?
Basheer Hanif
That was my problem too as this was the only report apparently they gave which doesn’t give distribution of calcium. He is completely asymptomatic despite heavy exertion.
Abdul Hakeem
So how does calcium scoring help in a very active asymptomatic person? Just creates a very pesky conundrum
Khurram Nasir
Preventive Management my friend, think beyond stenosis and intervention
Muhammad Saad
it can help to emphasize use of statins in asymptomatic patients
Khurram Nasir
Ldl below 55
Check Lpa if high family screening
ASA
SBP below 130
GLP1RA if diab pre diab
Further emphasize on diet and lifestyle
Abdul Hakeem
I have heard that and I’m sure there is some piece of evidence that it modifies human behavior but the consternation it causes seems to be its overwhelming impact!
Khurram Nasir
Few thoughts :
Make sure they’re not capturing any MAC

⁠ paradoxically the more number of vessels involved the more risk (prognostically) vs the more rationale thinking that if higher in one vessel possibly higher risk of stenosis or future risk

⁠ the relationship of high cac is not correlated with the stenosis in the same vessel, actually u may find often in the other with less score

⁠the issue is more distributive cac more turbulence in flow and more risk beyond plaque burden and rupture risk

⁠despite higher risk, majority don’t have event so no good way to assess who specifically is more at risk

⁠stress test not a bad idea in these uncertain cases
⁠hopefully pak Sehat with cac and CCTA in young Pakistanis will tell us what it means so kudos to bashir on leading the way

There is now huge body of evidence, actually, there is a meta-analysis from our group and JCC imaging that higher cac modifies, patient lifestyle, behavior, and attendance, and as well as physician behavior on prescription patterns

Also, as thought, from rationale thinking that it may increase anxiety and concerns, apart from few anecdotal cases, actually the evidence suggest otherwise

I see these patients all the time, it is how you message to them, that is great that you found out this,rather than waiting for an event to happen, and we have simpler an easier way to significantly modify the risk

Abdul Hakeem
Calcium score (in hugely asymptomatic)= demaagh me keera. The pt will find himself a Cardiol who will be more than happy to cath and stent him ( to prevent events
Khurram Nasir
I believe you; Well, just because there are bad practices, and some of these arguments have been made by long-term skeptics like David Brown even in the US, doesn’t mean that we stop doing the right thing

it means we start educating not only the patients, but also Cardiology community on what the best practices are

This is like saying we should stop screening for hypertension, because most of cardiologist will start on clonidine and may cause more harm

The same argument it’s gonna be made for anything
For deemagh me keera means more patient discussion and education and that means spending more time at the patient, unfortunately, that doesn’t exist much in most place even beyond Pakistan, and maybe that’s what we need to do, so we have more patient centric approach and care..
And btw asymptomatic doesn’t mean the person is not high risk for MI not only long term but also short term
Can’t think of any good rationale why the pt and pts physician wouldn’t want to know about so actually one can mitigate this totally preventable catastrophic complications and downstream issues like revascularization
Abdul Hakeem
I can’t agree more. I’m just saying unless we have solid evidence that “screening ca scores” in healthy asymptomatic individuals alters long term outcomes incrementally to usual practice we should be selectively doing calcium scores particularly in prevention rebellious pts
Khurram Nasir
First of all, this is old school, and things have changed: Let me help, explain,⁠ also, we need to put yourself in the patient’s shoes and ask ourselves whether we are better off in making a guess or knowing the actual risk and personalizing management accordinglyly

Cac test is no longer a screening test but more of a decision aid to guide risk and management, screening means that you do it for a person who is not candidate for a therapy, you find disease, intervene, and see if it improves. Here cac is also used for a lot of individuals who are already candidates for therapy, is to guide whether they need it or not and what intensity, so completely different philosophy.

⁠well proven to outperform any guesstimation approaches that you and Ion and others use in the clinic, and by the way, none of them have been tested in any randomized trial that using them improves outcome.. also by the way that I said I would be in a study that seeing a cardiologist improves outcome so maybe we can take everything with a grain of salt

⁠ as far as a pure screening approach and outcomes this concert there is a large study in Denmark, which is ongoing, and in the interim analysis has shhkwn 11% reduction in MI and stroke in the entire population, and three specified analysis, almost 11% all cosmetology reduction, and younger individuals
Abdul Hakeem
Thanks for the insightful comments khurram bhai. Always very scholarly and encyclopedic!
Syed Iqbal Rahmatullah
Repeat CAC to know the distribution or get the scan film to review.
High dose statin (goal LDL 30 to 40)
Aspirin
Lp a
Stress echo regardless of distribution
Life style adjustment. (Particularly dietary, HbA1c, BMI)

I had a similar patient yesterday, asymptomatic, played squash 5 days a week, and had very low LDL,
CAC 350, pakistani recently retired anesthesiologist, age 62, visiting his son here. No other risk factors.
SE showed anterior and inf wall hk, Rest echo 65%ef, post exercise 45%.
LHC showed discrete lesions but diffuse 3 vessel disease, extensive but good targets. Scheduled for cabg next week.
Farhan Katchi
I’ll just add that i use cac, as informed largely by Khurram’s body of work, and it has strengthened patient trust, buy in, compliance, and in my 7 years IMO better outcomes. My patients are more motivated to lose weight, eat better, exercise, and engage in escalating up medical preventative therapy when they know and understand the cac score concept (I show them the images in clinic on the screen so it’s concrete and not abstract). I have started to use LP(a) and ApoB in the same way that I use cac scores for risk adjudication, especially in women and the young where a cac of 0 may not tell the full longer term preventative story.
Bashir Hanif:


Syed Fazal:
Great discussion!
Now at the end of discussion, looks to like need one stent in type A lesion in mid cir, and all the above recommendations, for secondary treatment! Now he will need more anti platelets med for stent!
Bashir Hanif:
So who will put a stent and who would treat it medically. He is completely asymptomatic. It’s not a prognostic lesion!
Syed Arman Raza
Academic answer (in my view): no stent. Medical mgmt. Real world: stent + medical mgmt
Sabha Bhatti
Has he had functional testing ?If there’s ischemia in that territory you could consider stenting
Bashir Hanif:
You know functional study is going to be low risk and we are not going to change his prognosis/ risk of MI or mortality by putting a stent!!
Sabha Bhatti:
Yes but … Potentially that’s the bridge between academic and real world answer .. you have another justification for not stenting if there’s no ischemia
Bashir Hanif:
There will be ischemia. I can tell you what functional test is going to show. He jogs for 45 mins without symptoms. So it’s probably going to be medium size mild intensity ischemia at high work load. Will you send him to Hakim for stenting with this report?
Sabha Bhatti:
No one can do 45 min on a Bruce . Infact 16 min and few sec is the max I’ve seen . It helps to see symptoms , ECG and ofcourse vitals with exercise. No stent for now . Avoid oculostenotic reflex
Bashir Hanif:
I didn’t say 45 mins Bruce. I said jogs n brisk walk for 45 mins.
I advised him medical treatment. No stent
Ata Qureshi
This is a non prognostic, low risk lesion and I would manage it medically.
Syed Iqbal Rahmatullah
Bashir, was FFR done on left circ lesion? What was the rationale for doing cath, to begin with?
Bashir Hanif:
My point is it’s a non prognostic lesion pt is asymptomatic. Even if it had shown some ischemia or FFR was positive, in asymptomatic pt , would stenting change the risk of future MI or mortality??
I believe in CCS but if pt is symptomatic on GDMT or it’s a LM or may be Ostial LAD I would go for invasive approach and revasc. options. I don’t know about you and Hakeem but I had to relearn medical management of CCS when I moved back as lot of patients refuse to go for Revasc ( even LM n 3 VD ) and they are doing fine on medical management for years now. So as you said we need to resist oculostenotic reflex as much as possible!!( Disclaimer: I am an Interventionalist)
My 20 years of experience in Pakistan tells me Medical management can do wonders if done appropriately with belief!!
Abdul Hakeem
One our fellow intv cardiologist has classified this very well. Reasons for PCI in SIHD
if I can’t do it then GDMT
If I don’t do it someone else will
medical therapy until I return from vacation
Syed Fazal
I think most of us IC do lot more stents without evidence of mortality benefit.
Definitely there are regional differences for many other obvious reasons in different countries.
And as I said there is no consensus in this type A lesion.
Definitely in board exam don’t even think about stenting at this lesion!
Farhan Katchi
In cases of high cac, if I suspect LM or 3VD, I will Cath or CCTA to define anatomy for cabg referral. EXCEL and NOBLE and guidelines support revasc of this disease with cabg on account of its survival benefit even in asymptomatic patients. Now the ven diagram of asymptomatic and severe LM and significant 3VD is probably tiny especially if you consider 3V ischemic rather than anatomic disease and verify “asymptomatic” status on a treadmill
Haris Riaz:
I haven’t had a chance to follow this interesting discussion but ISCHEMIA trial frequently gets cited [sometimes even by people who haven’t actually read the full text or gone through the supplementary materials from nejm]. It might be interesting to note that:
One fifth patients in the conservative arm underwent revascularization
There are many other important limitations that need to be kept in mind before applicability. The trial [like COURAGE] reaffirms that medical management is effective in stable patients with stable symptoms compliant with GDMT.
Approximately one third of patients in ISCHEMIA had no angina in the last month before enrolment.
15% patients in ISCHEMIA had no objective evidence of ischemia on core lab assessment
One fifth patients in the invasive arm didn’t undergo revascularization


STEMI on the Forehead !

Amin H. Karim MD
Institute for Academic Medicine
Houston, Texas

Today a 65 year old patient showed up in the office. He had not seen me for last 5 years for whatever reason and now needed a surgical clearance. He worked as a RN at a Houston Hospital and subsequently at the VA Hospital;

I did a routine EKG as follows:

It was unchanged from his previous EKGs from years ago. When he was following with me, he had a cardiac workup including imaging tests showing normal coronaries.

On taking his interval history, I found some interesting facts. While working at the VA he had some atypical chest pain. He went to the ER and had an EKG and was seen by a cardiologist stat. He was rushed to the catheterization lab and had a diagnostic cardiac catheterization which showed normal coronaries. A few months later he had similar chest pain and again went to the ER at a premier hospital in town for evaluation. An EKG was done and STEMI was called immediately. He protested to the cardiologist that he had cardiac catheterization a few months ago and that it was normal! The cardiologist was insistent that he have another one since his EKG showed that he was having a heart attack and could die. His protests were to no avail and he was rushed to the lab and had another diagnostic cardiac study which of course showed normal coronaries. The cardiologist came and apologised to him for not listening to him.

Now it was my turn to beat him on the head and tell him: ” You have STEMI written on your forehead. Wherever, you go you will be treated with emergency response and the STEMI will be summoned and you will be rushed in an elevator with a security guard holding it! Once in the cath lab you will be surrounded by a frantic team counting minutes!

So this is what you are going to do. You will take a copy of your EKG, go to Office Depot and have it reduced and laminated; then carry it with you in your wallet and if you land in the ER and before they wheel you away to the cath lab, show them the EKG and tell them that your EKG is always abnormal and that they should compare to see if there are any changes. Otherwise you will someday end up with a clot in your hand or leg or some other complication!

I think he got the message.

No offence meant and take it in the lighter vein, but I am sure every interventional cardiologist taking emergency calls faces these alarms and the 90 minutes door to balloon time does not allow much margin to hunt for old EKGs!

Amin H. Karim MD
September 27 2024