Why is the angiogram normal?

Written by Willy Frick

A man in his 50s with a 15 pack-year smoking history presented to his primary care physician's office complaining of intermittent headache. He also complained of intermittent mild chest pain radiating into into both shoulders and his back, as well as occasional unexplained sweating. (Although radiation into the left arm is most classic for coronary ischemia, radiation into both arms is actually modestly more predictive). The primary care physician's note indicates low suspicion for cardiac ischemia, but "for completion, check troponin and ECG." If an ECG was obtained in the office, it was not saved. The patient had his blood drawn that morning, and troponin I was 6.496 ng/mL (ref. < 0.033). The PCP's office called the patient and advised him to present to the ER immediately. His ECG is shown.

ECG 1

Readers of this blog will have no trouble recognizing this as an OMI with some early reperfusion. Looking through the ECG in detail, we see:

• STE and HATW in II, III, aVF with terminal reperfusion TWI

• STD in aVL with overly upright T waves, reciprocal to inferior reperfusion

• ST flattening with subtle depression in V1 and probably V2, plus overly upright T waves suggestive of reperfused posterior occlusion

• Subtle coved STE in V6 with terminal TWI (and to a lesser extent V5) consistent with reperfused lateral occlusion

He underwent emergent angiography, which showed normal coronary arteries. His troponin peaked at 10.310 ng/mL and trended down.  (Smith: a typical peak troponin for an OMI is above 10 ng/mL)

What happened?

Answer: This is MINOCA -- Myocardial Infarction with Non-Obstructive Coronary Arteries. The name is self-explanatory. But MINOCA is more of an observation than a diagnosis, per se. The immediate next question is why? Possible etiologies (depending on your definition) include: plaque rupture with spontaneous recanalization, coronary artery vasospasm, spontaneous coronary artery dissection, or other rarer causes. Most sources exclude myocarditis.

When coronary artery vasospasm is suspected, it can be assessed in the cath lab with intracoronary acetylcholine. Comprehensive coronary evaluation (with testing for vasospasm and microvascular dysfunction) was shown in the randomized trial CorMicA to significantly improve angina, quality of life, and diagnostic accuracy. Unfortunately, this is not performed in most cath labs, and was not done in this case. The patient underwent cardiac MRI which demonstrated transmural infarction of the inferolateral wall as expected.

He was managed medically with aspirin, clopidogrel, and atorvastatin. In addition, his cardiologist suspected vasospastic angina and therefore started amlodipine. He had no further chest pain. Repeat ECG at follow up in clinic a few weeks later is shown. Clear inferior and posterior reperfusion.

ECG 2

Six years later: He presented to the ER with recurrence of his prior symptoms. He described mild substernal chest pain, again radiating into both shoulders with occasional sweating. He said the pain would come and go, sometimes lasting only a few seconds. In the ER, his symptoms had remitted. He stopped taking all his medications about a year prior. ECG is shown.

ECG 3

In isolation, this ECG is suggestive of possible reperfused inferoposterolateral OMI (inferior and lateral precordial TWI with ST flattening and overly upright T waves in V1-3 reciprocal to posterior leads). However, knowing that this patient had a prior infarct in this territory, it is unclear what these findings represent. (That is to say, this could be his baseline ECG.) Initial troponin I was 0.013 ng/mL (ref. < 0.033), repeat 2 hours later 0.016. At this point, the ER consulted cardiology who requested repeat ECG. The patient told the cardiologist that his symptoms had not returned since arriving at the hospital.

ECG 4

In the context of resolved chest pain, this was interpreted as confirmation of inferolateral reperfusion, and the patient was loaded with aspirin and clopidogrel and started on continuous heparin infusion with plan for catheterization. Serial cTnI values were 0.019 ng/mL and 0.027 ng/mL, rising but still within the reference range (< 0.033). The patient reported transient return of his pain, and repeat ECG was obtained.

ECG 5

Like ECG 3, this ECG could be mistaken for being non-specific. However, in this clinical context and especially following ECG 4, the current ECG actually represents re-occlusion! It is a snapshot of the T waves during their transition from deeply inverted reperfusion T waves to upright, hyperacute T waves. If the ECG had been recorded a few minutes later when the T waves were slightly more upright, it would have appeared pseudonormal. At this point, the patient went for angiography. The RCA is shown below.

Below is a still frame with a red arrow pointing to an area of focal vasospasm in the proximal RCA

Repeat angiogram after intracoronary nitro showing resolution of vasospasm:

The left coronary artery system was angiographically normal. The patient was restarted on amlodipine. Repeat cTnI remained within normal limits and trended down.

This finding at angiography explains both the present and prior presentations. In his index presentation years prior, he suffered type 2 MI secondary to vasospasm which was suspected but not confirmed at the time, and had resolved by the time angiography was performed. His symptoms were controlled by amlodipine for years, but he stopped taking it and his symptoms returned. At discharge, he was restarted on amlodipine and given a prescription for varenicline to help with smoking cessation. One final ECG was obtained 24 hours after symptoms had resolved.

ECG 6

This ECG confirms persistent reperfusion of the RCA. Some clinicians who see this ECG mistakenly believe it is worsened compared to ECG 5 since the T wave inversion is "worse." But readers of this blog understand the phenomenon of reperfusion, and recognize this change as reassuring evidence of adequate reperfusion.

Learning points:

• Vasospasm is one cause of MINOCA. It can be tested for, and CorMicA showed that doing so improves diagnostic accuracy and reduces angina.

• Calcium channel blockers and smoking cessation improve symptoms in patients with vasospastic angina.

• "Normal" cath does not rule out OMI, which is a clinical diagnosis.

• Vasospastic angina is commonly the worst in the morning and at night. Unlike classic angina pectoris, it does not always present as pain that is worse with exertion and improved by rest (since vasospasm can occur and resolve independent of activity and oxygen demand).