Syncope while on a treadmill

A 60-something ow healthy male had syncope while on treadmill.  911 was called and the patient was found by medics to be diaphoretic and hypotensive.

This strip was obtained:

Apparent Wide Complex Tachycardia at a rate of 280

What do you think?

What do you want to do?

Appropriately, the medics electrically cardioverted immediately. They did not feel they had time to sedate.

He cardioverted to sinus rhythm, and a 12-lead was obtained.

He was brought to the ED.

What is the diagnosis from the above rhythm strip?

To me, it was clearly atrial flutter with 1:1 conduction.   

The rate of 280 is just right for atrial flutter.  The waves look like atrial flutter waves, NOT like a wide ventricular complex.  There are little spikes (narrow complexes) at the top of every wave -- this is the narrow QRS complex on top of a flutter wave.

But how can the AV node conduct at a rate of 280?  Why such rapid AV conduction?  Because the patient was exercising, which increases sympathetic tone, facilitating AV conduction. 

Diagnosis: Atrial flutter with 1:1 conduction, with fast AV conduction made possible by sympathetic drive of exercise

On arrival, we obtained another 12-lead:

Unremarkable

Further history: One month history of shortness of breath on exertion, denies palpitations, chest pain, orthopnea, leg swelling. Recently diagnosed with intermittent paroxysmal atrial fibrillation but no EKGs available to confirm. 

Troponins 34>33>43, likely secondary to myocardial injury from tachycardia. 

Reverted to atrial fibrillation with RVR while in the hospital 3 times and needed cardioversion.

The patient was started on amiodarone, anticoagulation, and metoprolol, and scheduled for atrial flutter ablation.

He underwent ablation in the EP Lab.

At discharge

Continue amiodarone 400 mg PO BID x2 weeks then 200 mg daily until follow-up  

Continue Toprol XL 25 mg daily. 

Continue Eliquis 5mg BID, should be continued for 3 months

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MY Comment, by KEN GRAUER, MD (9/20/2024):  

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I found the following aspects of today's case of special interest. 

• Why did Dr. Smith immediately say the rhythm was AFlutter with 1:1 AV conduction?
• Why did today's patient develop AFlutter while exercising on a treadmill?
• Is longterm endurance-training a risk factor for AFib and AFlutter?

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Why is Today's Initial Rhythm AFlutter?

The KEY to determining the initial rhythm in today's case — depends on the heart rate. To illustrate this point — I've reproduced and labeled in Figure-1, a representative portion of today's initial rhythm (showing 3 simultaneously-recorded but unlabeled monitoring leads).

• As discussed often in Dr. Smith's ECG Blog — quick determination of heart rate often provides an important clue to the etiology of certain regular SVT (SupraVentricular Tachycardia) rhythms (See My Comment in the July 19, 2023 post, among others).
• Determining heart rate is easy when the rate is not overly fast. I favor simply dividing 300 by the number of large boxes in the R-R interval. (See my ADDENDUM below if you'd like a 3-minute refresher video on this approach).
• Quick and accurate estimation of heart rate is more challenging when the rhythm is fast and regular. I favor the Every-Other (or Every-3rd or 4th) Beat Method — that I've developed to facilitate rapid and accurate rate estimation. Find a QRS complex that begins on a heavy ECG grid line. In today's tracing — I chose the 10th beat in the top lead (See the 1st vertical RED line over this beat in Figure-1). 
• Because of how fast today's initial rhythm is — I looked at the R-R interval for every-4th-beat. Note in Figure-1 — that the amount of time it takes to record 4 beats (RED numbers in the top lead) is just over 4 large boxes (BLACK numbers in this Figure). Therefore — ONE FOURTH the rate is a little slower than 300/4 ~70/minute.
• The actual rate for the rhythm in ECG #1 is therefore ~70 X 4 ~280/minute.

How Does Knowing the Heart Rate Help?

As I've emphasized in My Comment in the October 25, 2022 post — and the March 6, 2020 post — determining IF the heart rate of a regular SVT rhythm is close to 150/minute (ie, ~130-to-170/minute range) provides a clue as to the need for considering each of the 4 Common Causes of a regular SVT in your differential diagnosis (ie, Sinus Tachycardia — Reentry SVTs [ = AVNRT; AVRT] — AFlutter — and ATach).

• A regular SVT rhythm significantly faster than ~170/minute is less likely to be sinus tachycardia in an adult — and unlikely to be AFlutter with 2:1 AV conduction.
• Exceptions to the above general rule of course exist (ie, Children may have sinus tach well over 200/minute — and an occasional adult with enhanced sympathetic tone may also have surprisingly fast sinus tachycardia) — but I find it helpful to be aware of these general rate limits.

BUT — Today's initial rhythm is much faster = about 280/minute!

• Athough we only see 3 of the 12 leads in Figure-1 — the QRS complex appears to be narrow and the rhythm is regular. Although there is some undulation in the baseline — clear sign of repetitive atrial activity is not seen. Best description of today's initial rhythm is therefore that of a regular SVT rhythm at ~280/minute, without clear sign of atrial activity.
• Sinus tachycardia does not go this fast.
• The 2015 ACC/AHA/HRS Guidelines on SVT (Page et al — Circulation 133(14):e506-e574, 2016) list the usual upper rate limit for ectopic ATach and AVNRT at ~250/minute — though other sources suggest occasional rates for these rhythms (and for AVRT in patients with an accessory pathway) that may attain up to 280/minute (StatPearls, 2023).
• The above said — it is unusual to encounter a regular SVT rhythm at a rate ≥280/minute. This finding should therefore suggest strong consideration of AFlutter with 1:1 AV conduction (Ectopic ATach and reentry SVTs could be possible — but are statistically less likely when the ventricular rate is as fast as it is in today's case). 
• 
  
• To Emphasize: Clinically — It will usually not matter what the precise etiology of a regular SVT at ≥280/minute is, since immediate cardioversion will usually be indicated regardless of what the specific etiology is (especially when the patient is acutely symptomatic — as in today's case).

Figure-1: The Every-Other-Beat Method (or in today's case — the Every-4th-Beat Method) for rapid estimation of heart rate. 

Does Exercise Induce Non-Sinus Tachyarrhythmias?

The answer to this question is fascinating — albeit extending beyond the scope of this ECG Blog. But some thoughts on this issue include the following:

• The answer regarding the effect of exercise on non-sinus tachyarrythmias is — It depends ... IF the patient is an adult of a certain age, who has underlying heart disease — then a high level of exercise becomes increasingly likely to precipitate non-sinus tachyarrhythmias, including potential to induce malignant ventricular arrhythmias. The KEY to determine is therefore — Does the patient have underlying heart disease?
• Details regarding the cardiac history for the 60-something man in today's case are limited to knowing he had dyspnea on exertion of uncertain cause over the preceding month — and that he was recently diagnosed with AFib (although it is unknown if the patient was in AFib prior to his syncopal episode on the treadmill). It is also unknown if this 60-something man had been regularly exercising over time vs being sedentary.
• 
  
• At the extreme — CPVT (Catecholamine Polymorphic Ventricular Tachycardia) is a rare but important entity to recognize because of its known association with exercise-induced arrhythmias despite a structurally normal heart! (See the February 6, 2015 post in Dr. Smith's ECG Blog - and - the Case Study of polymorphic VT induced by exercise, by Hoffmayer, Scheinman et al — Heart Rhythm 19:1214-1216, 2022).

The question that arises is — What effect (positive or negative) might regular endurance training have in adults without known heart disease (and without CPVT) — on the likelihood that vigorous exercise may precipitate a non-sinus tachyarrhythmia?

• Previous doctrine had been that regular performance of appropriate level exercise (including endurance training) provided important health benefits, as well as enhancing one's sense of well being.
• That said — recent evidence suggests that longterm endurance-training exercise may increase the risk of developing AFib (and AFlutter), especially as adults age (Opondo et al — Circ: Arrhythm & Electrophys 11(5), 2018) — (Calvo et al — Br J Sports Med 46(Suppl 1):i37-i43, 2012) — (Burkhart and Gerasimon — J Osteopath Med 118(5):337-340, 2018) — (Müssigbrodt, Mandrola et al — Scan J Med & Sci in Sports, 2017).
• "Moderate" exercise seems to have a protective effect with reduced risk of AFib — whereas "excessive" exercise has been shown to significantly increase the risk of developing AFib, especially as adults age. How much exercise is "moderate" vs "excessive" — is as yet unanswered (and appears to be highly variable depending on the individual).
• A series of potential mechanisms have been proposed for this increased incidence of AFib and AFlutter in otherwise healthy adults as they age. These include — inflammation of cardiac tissue from longterm endurance training — development of structural abnormalities from "athlete's heart" (remodeling; fibrosis of the atria; atrial and/or ventricular dilation or enlargement) — the effect of longterm increased vagal tone from athletic training — the effect of frequent sympathetic stimulation from endurance exercise — frequent PACs — and potentially other as yet undiscovered mechanisms.

BOTTOM Line: As per Dr. Smith — increased sympathetic tone from active treadmill exercise presumably precipitated the tachyarrhythmia-induced syncopal episode in today's patient (in similar fashion as sustained sinus tachycardia from peak exertion induced AFib in this Case Study by Faris et al — Cureus 14(2):e22577, 2022).

• How much of an effect underlying structural heart changes may have had in predisposing the 60-something man in today's case (who recently had AFib diagnosed) — is uncertain.
• As one who taught ETT (Exercise Treadmill Testing) locally and nationally to primary care residents and clinicians — I found being there during ETT to assess exercise capacity of healthy adults for the purpose of exercise prescription to be highly insightful for recommending safe exercise limits.
• What to advise hardcore endurance athletes regarding potential longterm effects of vigorous endurance-training exercise is another story. 

ADDENDUM: In this 3-minute video — I review a quick, user-friendly and accurate method for estimating heart rates (including the Every-Other-Beat Method — for rapid estimation of heart rate when the rate is very fast).

User-friendly estimation of heart rate (including when the rate is very fast).

 

Dynamic OMI ECG. Negative trops and negative angiogram does not rule out coronary ischemia or ACS.

By Smith, peer-reviewed by Interventional Cardiologist Emre Aslanger

Submitted by anonymous

A 53 y.o. male presents to the ED at 6:45 AM with left sided chest dull pressure that woke him up from sleep at 3am. The pain radiated to both shoulders. He arrived to the ED at around 6:45am, and stated the pain has persisted. He has had similar pain in recent weeks that has occurred at rest, but it typically goes away after about an hour. This time, did not go away. No other symptoms. He does have a recently diagnosed PE, and has not been taking his anticoagulation due to cost.

Here is his ED ECG at triage:

Obvious high lateral OMI that does not quite meet STEMI criteria.

He had a previous ECG on file:

Proving the findings are new

The cath lab was activated.

He was given aspirin and sublingual nitro and the pain resolved. He was started on nitro gtt. BP initially 160s/90s, O2 sats 95% on room air. Bedside cardiac ultrasound with no obvious wall motion abnormalities. The cardiology fellow agreed with plan for emergent cath and escorted the patient to the cath lab.   

 

Another ECG was recorded after the nitroglycerine and now without pain:

All findings are resolved.

This confirms that the pain was ischemia and is now resovled.

The initial hs troponin I returned < 3 ng/L.

6 hours trop was also < 3 ng/L.

Angiogram:

Mild coronary plaque

No significant obstructive coronary artery disease, ruptured plaque, or acute coronary occlusions to explain the patient's chest pain and EKG abnormalities

Echo:

The estimated left ventricular ejection fraction is 59%.

There is no left ventricular wall motion abnormality identified.

This is a quote from the chart: 

"In the setting of undetectable high-sensitivity troponin I greater than 3 hours after the initiation of chest discomfort, would consider noncardiac etiologies for the patient's symptoms.  Given the absence of objective evidence of myocardial injury and ischemia, it is very unlikely chest pain was due to cardiac etiology."

_________

I disagree with this, as does Dr. Aslanger.  Until proven otherwise with IVUS or OCT, this is a case of unstable angina in the era of high sensitivity troponin.

We wrote this article: Sandoval Y.  Apple FS.  Smith SW. High-sensitivity cardiac troponin assays and unstable angina.    Full text here.

Click here for cases of unstable angina in the era of hs trop, on this blog.

If the troponin had been elevated, with rise and/or fall, it would be myocardial infarction with non-obstructive coronary arteries (MINOCA).  As far as I can tell, there was no coronary provocation done to assess for spasm.  As for ruptured plaque, it is well known that most ruptured plaque happens in arteries that do NOT have any significant pre-existing obstruction.  I recently posted the below case by Willy Frick, which was obvious ACS but had minimal residual stenosis, and it engendered a very interesting Twitter discussion below.  Gregg Stone, a very famous interventional cardiology researcher, even weighed in.

Most plaque is EXTRALUMINAL!!  It cannot be seen on angiogram which is a lumenogram.  The best technique for assessing for ruptured plaque is intracoronary optical coherence tomography (OCT).  Intravascular ultrasound (IVUS) is also very useful.  As far as I can tell, neither IVUS nor OCT were done in this case.

The ECG and chest pain are clear: this was acute ischemia.  The combination of intensity and duration of ischemia was not great enough to result in elevated troponin.  Troponin studies make it clear that troponin is nearly 100% sensitive for ACS, but it is NOT 100% sensitive.  In fact, in nearly all troponin studies, a patient with an ECG like this would have been excluded.

Bottom line, Learning Points: 

1. A Negative Angiogram does not rule out Acute Coronary Syndrome

2. Undetectable troponins do not rule out Acute Coronary Syndrome

3. Unstable Angina still exists in the era of High sensitivity troponin

4.  You must follow up on diagnostic ECG findings.  Use IVUS or OCT.  (MRI would not have been positive without elevated trops)

5.  How important is it to find non-obstructive coronary disease?  Intervention is not the only treatment.  Medical therapy with statins and aspirin especially are important in a patient such as this.  (He did get a statin, but he did NOT get a diagnosis)

6. Do not ignore important ECG findings!!  They may be your only clue to pursue further investigation!!

Schematic: Extraluminal plaque is large without any intraluminal plaque

Normal angiogram, but IVUS shows significant plaque

See the below Twitter discussion, the exerpt from the classic Circulation paper, and the paper itself.  

This is Willy's case that began the discussion:

"The dye don't lie" ...except when it does. Angiogram Negative, or is it?

(See the full text and reference below)

How Big Are Coronary Atherosclerotic Plaques That Rupture?

https://www.ahajournals.org/doi/full/10.1161/01.CIR.94.10.2662

Plaque erosions (superficial intimal injury) and fissures (tears of variable depth) with overlying microscopic mural thrombosis are common abnormalities of the intimal surface of coronary atherosclerotic plaques. Davies et al1 found small plaque fissures in as many as 17% of patients who died of noncardiac causes. If no overlying obstructive luminal thrombus develops, these small plaque defects will cause no clinical events. Conversely, plaque rupture (disruption of the fibrous cap) that is complicated by occlusive thrombosis is clinically significant and is the underlying lesion in the majority of acute fatal coronary events: acute myocardial infarction and sudden death.2 3 4 5 6

Angiographic studies of coronary arteries before and after nonfatal myocardial infarction have frequently shown that at the site of the complete occlusion, the preexisting, underlying culprit lesion does not usually cause hemodynamically significant stenosis7 8 9 10 11 12 13 14 (Table 1). Several published studies have reported that nearly 50% of these lesions are at sites with <50% luminal diameter narrowing. Fewer than 20% of acute complete occlusions occur in lesions with antecedent angiographic diameter narrowing of >75%. Thus, it has recently become generally accepted that most plaque ruptures resulting in myocardial infarction occur in plaques that narrow the lumen diameter by <50%. This consensus has been expanded into the notion that nonstenotic, hemodynamically insignificant plaques may rupture, precipitating occlusive thrombosis, myocardial infarction, and/or death. This is a disheartening concept. It suggests that virtually all of the mature men and women of the industrialized world have a constant and unpredictable risk of a catastrophic coronary event.

Conversely, histopathological studies from patients with fatal coronary events have consistently shown that at the sites of plaque rupture with superimposed occlusive thrombosis, the underlying lesion is “severe” (Table 2, Fig 1). Studies in which planimetry was used to measure the plaque determined that the plaque occupied, on average, ≈90% of the cross-sectional area (68% diameter reduction).2 3 4 5 These studies did not use pressure fixation of the coronary arteries.

How does one reconcile two sets of consistent, reliable data that appear to be so different? Usually, when there is such consistent difference in opinion, it means that either everyone is wrong or everyone is partially correct. In this case, comparing angiography and pathology, the divergence arises because the two techniques are not measuring the same thing: the proverbial apples and oranges.

Both angiographic (Table 3) and pathological (Table 4) examinations are subject to limitations that can result in erroneous results that can lead to either overestimation or underestimation of the degree of luminal narrowing by plaque.15 16 17 18 19 20 21 22 23 24 25 Although these are important, it is our opinion that the most important factors responsible for the long-standing discordance between angiographic and pathological studies do not relate to poor technique or inaccurate interpretation but rather to two biological variables that make it illogical to even attempt to compare these two techniques.

The two factors most important in understanding angiographic/pathological discordance are (1) the diffuseness of coronary atherosclerosis and (2) vascular remodeling associated with the progression of atherosclerosis.

The diffuse nature of coronary atherosclerosis is well known to pathologists,26 27 28 29 30 angiographers,31 and more recently, coronary ultrasonographers,32 33 yet it seems to be ignored during standard evaluation of angiograms. In individuals with atherosclerotic coronary artery disease, it is virtually impossible to find a segment of the proximal coronary tree that is free of involvement by some degree of atherosclerosis. Thus, the concept of a focal stenosis due to a “plaque” is misleading. The observed plaque is not a discrete lesion but rather just a more severely involved region of a diffuse, widespread process.

The importance of vascular remodeling, elucidated primarily by the work of Glagov and associates34 and others,35 36 37 has only recently begun to be appreciated. This occurrence, now often called the Glagov phenomenon, consists of a progressive, compensatory increase in arterial cross-sectional area as atherosclerotic plaques enlarge. In effect, as the plaque grows, the lumen size remains the same. Thus, lumen size may remain normal despite occupation of ≈40% of the new arterial cross section by plaques. According to the Glagov concept, it is only when plaques enlarge further that the lumen size becomes compromised.

How then do the diffuseness of coronary atherosclerosis and vascular remodeling affect the angiographic and pathological quantification of coronary atherosclerosis? As shown in Fig 2, the degree of stenosis determined angiographically depends on a comparison of lumen diameter at the site of a stenosis with an adjacent site thought to be normal. Because there are no normal sites adjacent to stenotic regions in atherosclerotic coronary arteries, angiography will actually be comparing a severe stenosis with a mild or moderate stenosis and thus will underestimate the volume of disease at the site of stenosis, as shown recently by Mann and Davies.38 Because of compensatory enlargement, a segment of vessel with ≤40% involvement of the cross-sectional area by plaque may still have a lumen of normal size and shape. Therefore, by the time angiography detects a lesion, >40% of the arterial cross section may be involved by plaque. Thus, angiography may be fairly accurate in determining lumen size, but it will not detect the “volume” of atherosclerosis present. If the adjacent segment has some mild luminal narrowing, the amount of arterial luminal narrowing compared with a totally normal artery will also be underestimated.

Conversely, pathological evaluation, as shown in Fig 2, will correctly identify the percentage of cross-sectional area occupied by plaque. The pathologist may see a plaque that constitutes, for example, 50% of the cross-sectional area. However, because of the Glagov phenomenon, the artery may have enlarged 50% in cross-sectional area. Thus, the lumen observed may actually still be the same size as the original, normal lumen. Since the pathologist does not know the original cross-sectional area of the artery or the amount of compensatory enlargement of the artery from evaluation of a single cross section of the artery at a site of stenosis, the degree of luminal narrowing of that segment cannot be determined. Because the pathologist determines the degree of stenosis by dividing the lumen area by the total area, the degree of stenosis will be overestimated.

Thus, the angiographer determines the degree of stenosis by comparing lumens, assuming that one is normal, whereas the pathologist determines the degree of stenosis by comparing lumen to total plaque area. The angiographer uses a denominator that is too small, thereby underestimating the degree of stenosis. The pathologist uses a denominator that is too large, thereby overestimating the degree of stenosis. The latter sees the altered donut and the former sees only the hole, and both are attempting to relate their findings to the unseen pristine ring-shaped cake.

Furthermore, in studies reporting progression of insignificant lesions to total thrombotic occlusions, the mean interval between angiography and acute myocardial infarction is 2.5 years, with the interval as long as 12 or 18 years in some studies.7 8 9 10 11 12 13 14 These considerable time intervals could allow for growth of “small” lesions before acute occlusion. Studies such as those by Moise et al14 and Ellis et al39 have shown that the relative risk of developing an acute myocardial infarction in the territory supplied by an artery with a <50% angiographic stenosis is actually quite low. The reported high frequency of acute occlusions in such regions may be at least in part related to the fact that the vast majority of the coronary luminal surface area contains lesions that are relatively mild and only a small percentage of the arterial tree is involved by more severe lesions. Thus, on a statistical basis, even if a region were at low risk for an acute event, if the majority of the arterial tree were composed of such regions, they might appear to be overrepresented in terms of degree of risk of occlusion.

Wherein lies the truth? An accurate determination of the degree of atherosclerosis depends on knowledge of the lumen and plaque area at the site of stenosis and the lumen area at an adjacent normal site. Then, one could determine the degree of luminal narrowing and also the amount of plaque present at any given segment.

Intravascular ultrasound (IVUS) has the potential to provide all of this information (Fig 3). IVUS allows quantitative in vivo assessment of the arterial lumen and wall size and shape. It permits delineation of the intima, media, and adventitia and the presence of calcification, lipid pools, and fibrous regions. We used IVUS to study remodeling in coronary arteries with an angiographic diameter stenosis of >70%.40 We compared the stenosis site with a proximal reference site that had <25% diameter narrowing by angiography and <50% cross-sectional area stenosis by IVUS. Compensatory enlargement was defined as being present when the total coronary arterial cross-sectional area at the stenotic site was greater than that at the proximal nonstenotic site. We documented that the majority of stenotic lesions had compensatory enlargement and thus exhibited remodeling. Note, however, that in 26% of arteries there was “inadequate” remodeling in that the total cross-sectional area at the stenotic site was less than that in both the proximal and distal reference sites. Fig 3 shows IVUS images that provide in vivo verification of the remodeling phenomenon depicted in Fig 2. Unfortunately, vascular remodeling is variable and inconsistent. This is not a trivial finding, because it indicates that clinically significant coronary arterial narrowing by atherosclerosis may be a function of not only the amount of atherosclerosis but also the degree of remodeling present.41

What do the concepts discussed here indicate regarding the size of plaques that rupture with superimposed occlusive thrombus? Fig 1 shows typical examples of two such plaques. According to angiographic studies, we are to assume that in life, before rupture, these plaques were at sites with ≈50% diameter (75% area) stenoses. By planimetry, the cross-sectional area narrowings are 97% and 90%. These are typical findings at sites of plaque rupture.5 We are aware that the current consensus is that the propensity for plaques to rupture is independent of plaque size; however, in our opinion, the hypothesis that small atherosclerotic plaques are the most likely to rupture, with resulting occlusive thrombosis, is unproven. Furthermore, if this occurs at all, it is a rare event. It is not small but rather large plaques, which may not be producing significant stenosis, that undergo rupture with acute occlusive thrombosis, resulting in myocardial infarction and other ischemic events. Understanding of the angiographic, pathological, and ultrasonic images of atherosclerotic coronary arteries and awareness of their limitations should lead to a better understanding of the biology of coronary atherosclerosis and plaque rupture.

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MY Comment, by KEN GRAUER, MD (9/18/2024):

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I fully acknowledge that I am assessing today's case with limited knowledge of case details — and from the perspective of an "armchair quarterback" for whom "hindsight is always 100% in the retrospectoscope". That said — it's important to recognize the problems with this case.

• Even high-sensitivity troponin may be normal if the duration of coronary occlusion is brief (this said realizing that 2 hs-troponin assays done 6 hours apart were normal in today's case).
• The history is concerning (This patient was awakened from sleep by chest pain that persisted for several hours — on a background of intermittent CP in recent weeks).
• The ECG changes seen between the initial ECG and the repeat ECG after NTG — are undeniable!

BOTTOM Line in Today's CASE: 

Something potentially serious (and potentially life-threatening) is wrong! Additional evaluation is needed before attributing this patient's symptoms and the ECG changes after NTG to "noncardiac causes".

• Strictly speaking — this case does not at this time qualify as MINOCA — because the negative cath and 2 normal hs-troponins done 6 hours apart failed to document infarction. (For more on MINOCA — See My Comment in the November 16, 2023 post in Dr. Smith's ECG Blog).
• The above said — diagnostic considerations in today's case should include similar entities noted for patients who do qualify as having MINOCA (including the possibility of brief coronary occlusion = OMI — that simply was not picked up on cath and by the 2 troponin assays that were done).
• Among additional diagnostic tests to consider for this patient would be an Echo (ideally performed during an episode of chest pain!) — Cardiac MRI with LGE (as one of the KEY tests for identifying the etiology of MINOCA in a majority of patients) — and a simple, maximal-effort Exercise Treadmill Test (to better evaluate the effect of this patient's symptoms on every day activity — as well as to determine potential presence of ischemia with such activity).
• 
  
• P.S. — I would strongly consider the possibility of pure coronary spasm given the history, negative troponins and normal cath in light of the ECG changes seen below in Figure-1 (See My Comment in the June 5, 2024 post by Dr. Nossen).
• As was emphasized by Dr. Smith in this June 5, 2024 post (and in more detail above in today’s post) — "No intravascular ultrasound or OCT (Optical Coherence Tomography) were done — both of which could be used to find ruptured plaque that does not show up as stensosis on the angiogram (Giacoppo et al — Circulation 149(14), 2024). Nor was there a challenge to look for coronary spasm."  

Review of the 2 ECGs in today's case is insightful (Figure-1):

• The initial ECG shows sinus rhythm, LAHB and meets Peguero Criteria for LVH (See My Comment in the August 15, 2022 post of Dr. Smith's ECG Blog for more on LVH criteria).
• That said, in this patient awakened from sleep by severe CP — the hyperacute-looking ST elevation in leads I and aVL immediately caught my attention (within the RED rectangles). In this context — the Q waves that we see in these leads may be more than "normal septal q waves".
• The mirror-image opposite ST-T wave depression that we see in leads III and aVF — confirms that the ST elevation in leads I and aVL is not simply a repolarization variant! (within the BLUE rectangles in these leads). The fact that the 3rd inferior lead ( = Lead II) is also clearly abnormal (showing ST flattening with slight ST depression) — supports our assessment of clear abnormality in these limb leads until proven otherwise.
• In the context of the above limb lead changes — the loss of T wave amplitude in lead V5 — and especially the slight ST depression with shallow T wave inversion in lead V6 further support the likelihood of acute change until proven otherwise.

And then we see the repeat ECG obtained after NTG ( = ECG #2):

• There is marked improvement of the above-described ST-T wave changes in virtually all leads.
• Regardless of whether the change in R wave progression between ECG #1 and ECG #2 is the result of a lead placement error — there is no denying the dynamic ST-T wave changes in these limb leads between these 2 tracings.

My Conclusion: 

I repeat my "Bottom Line" from above: Something potentially serious (and potentially life-threatening) is wrong! Additional evaluation is needed before attributing this patient's symptoms and the ECG changes after NTG to "noncardiac causes".

Figure-1: To facilitate comparison — I've put the 2 ECGs in today's case together.