Saturday, November 19, 2016

Diffuse Subendocardial Ischemia on the ECG. Left main? 3-vessel disease? No!

This was contributed by some folks at Wake Forest:
Jason Stopyra, Shannon Mumma, Sean O'Rourke, and Brian Hiestand.
It was edited by Smith

A 52-year-old male with a past medical history of hypertension and COPD summoned EMS with complaints of chest pain, weakness and nausea. The paramedic’s initial impression of the patient was that he was critically ill. The patient’s mental status was altered and his skin was pale and dusky. The initial blood pressure was 80/palp with a heart rate of 104, respirations 20, oxygen saturations of 94% and a finger stick blood glucose of 268. Exam was otherwise notable for audible wheezes, sluggish cap refill, confusion, and difficulty following commands and answering questions.

An immediate 12-lead EKG was obtained:
There is ST elevation in leads aVR and V1, with marked ST depression in I, II, III, aVF, V3-V6.
What should be done?  
Should the cath lab be activated?

Smith comment:
This patient did not have a bedside ultrasound.    Had one been done, it would have shown a feature that is apparent on this ultrasound (however, this patient's LV function would not be as good as in this clip):

This is recorded with the LV on the right.

Look at the aortic outflow tract.  What do you see?  Answer below in the still shot.

Clinical Course

The paramedic activated a “Code STEMI” alert and transported the patient nearly 50 miles to the closest tertiary medical center. En route, EMS administered aspirin 325mg by mouth, but withheld nitroglycerin due to initial hypotension. In addition, the patient received 750 mL of fluid resuscitation with transient improvement of blood pressure.

The patient was brought directly to the cardiac catheterization lab for PCI, bypassing the ED. In the cath lab, the patient’s blood pressure remained low. The diagnostic coronary angiogram identified only minimal coronary artery disease, but there was a severely calcified, ‘immobile’ aortic valve. Aortic angiogram did not reveal aortic dissection. During the procedure, the patient had an increasing oxygen requirement and was intubated for airway protection and oxygenation. A transthoracic echocardiogram showed an LV EF of less than 15%, critically severe aortic stenosis, severe LVH, and a small LV cavity. The patient was transported to the CCU for further medical optimization where a pulmonary artery catheter was placed.

Here is the still shot of the ultrasound above:
This still shot shows the area of interest:
There is a hyperechoic area at the aortic valve
This is aortic sclerosis and is highly associated with aortic stenosis.
If you see this, you should Doppler the valve.
The aortic valve in this example also had critical stenosis by Doppler

The patient continued to be hemodynamically unstable with poor cardiac output and very high LV filling pressures. Despite the use of multiple high dose vasopressors, he continued to be hypotensive. The following day, the patient underwent balloon aortic valvuloplasty for severe symptomatic aortic stenosis with hypotension and NYHA class IV symptoms. Post-valvuloplasty, the patient’s pressure gradient improved, but was still substantial. Patient was continued on maximal pressors, but remained hypotensive. Approximately seven hours after he returned from valvuloplasty he went into asystolic arrest.

The 12-lead EKG EMS initially obtained for this patient showed severe ischemia, with profound "infero-lateral" ST depression and reciprocal ST elevation in lead aVR.  Although this is considered a "STEMI equivalent" and the ACC/AHA guidelines even approve of thrombolytics for ACS with this ECG, the usual criteria used to alert the cath lab team of an inbound Code STEMI are not met by this ECG.

Smith comment:
Remember, ST depression does not localize to the area of ischemia, so "infero-lateral" does not tell you where the ischemia is - in fact, it is diffuse subendocardial ischemia.  ST elevation in lead aVR is reciprocal to this ST depression of diffuse subendocardial ischemia; the ST depression vector is towards II and V5 and thus the ST elevation vector is towards aVR.

Author continued:
STE in aVR is often due to left main coronary artery obstruction (OR 4.72), and is associated with in-hospital cardiovascular mortality (OR 5.58).1 ST elevation of 1 millimeter or greater has been shown to be 80% sensitive and 90% specific for severe left main coronary artery and/or 3-vessel disease that may require coronary artery bypass grafting, in some series.2 The astute paramedic recognized this possibility and announced a CODE STEMI.

Smith comment:
I would change the above statement to: "In the setting of ACS, STE in aVR is often due to left main or 3-vessel obstruction...."  The ECG cannot diagnose the etiology of ischemia; it only the presence of ischemia, from whatever etiology.  Diffuse subendocardial ischemia is more often due to supply/demand mismatch in the absence of ACS than it is due to ACS.  Common etiologies of supply/demand mismatch are hypoxia, tachydysrhythmias,  hypotension (from whatever cause), anemia, coronary artery stenosis without ACS, or (intraventricular) hypertension.

--Oxygen supply is determined by: 1) oxygen carrying capacity, 2) O2 saturation, and 3) Coronary flow.   Thus, in the absence of athero-thrombotic mechanism (ACS), myocardial ischemia can be brought on by:
1) Hypotension (diastolic hypotension, as all coronary flow happens during diastole because intramyocardial pressure during systole stops blood flow).  Hypotension may of course be a result of a brady- or tachydysrhythmia.
2) Hypoxia, including poisons of oxidative phosphorylation such as HS, CO, CN.
3) Anemia, or poisons of hemoglobin such as methemoglobin or CO
4) Fixed coronary stenosis that limits flow.

--Oxygen demand is determined by:
1)  Afterload (high resistance to LV outflow), which is increased by elevated blood pressure or by aortic stenosis
2)  Heart rate: sinus tachycardia

--This patient has both decreased supply (hypotension) and increased demand from 1) high afterload (LV pressures are very high because of the aortic stenosis outflow resistance) and 2) high heart rate.

--This demonstrates that there may be some value to heart auscultation, to listen for an aortic murmur.  In fact, bedside ultrasound might even find severe aortic stenosis.  If you can use Doppler, then you can diagnose it.

Authors' commentary: Cardiogenic shock in the setting of severe aortic stenosis.
As I met the paramedics and cath team in the lab, I was ready to see severe coronary disease (CAD), but the vessels were non-obstructive. This patient’s severe aortic stenosis (AS) and associated severe cardiogenic shock likely created the ECG pattern, resulting in a very difficult challenge for our inpatient team.

Fundamentally, cardiogenic shock is an issue of decreased cardiac output. This may be secondary to multiple factors, including decreased cardiac contractility (ie. myocardial infarction), arrhythmias, valvular pathology, shunts, or outflow obstructions.

As with other cases of shock, initial fluid resuscitation may be considered. In cardiogenic shock, fluid may worsen the pulmonary edema associated with acute heart failure, but may still be required to support the hemodynamic status of the patient.

Guidelines from the American Heart Association have been unchanged for decades with recommendations for positive inotropes, such as dobutamine and dopamine, in cases of cardiogenic shock.3 There is evidence to show that using sub-maximal doses of both dobutamine and dopamine in conjunction, rather than using a single agent, provides benefit for the patient. Benefits include improvement in the patient’s MAP and cardiac output, while minimizing the amount of myocardial oxygen used with the increased cardiac output (CO).4 This is crucial, as these patients may have already had some degree of cardiac ischemia. This was particularly important for the patient presented above, given the baseline increase in oxygen consumption seen in AS due to the outflow obstruction.

Smith comment: 
In a large randomized trial of dopamine vs. norepinephrine (11) for shock which was published after the above-mentioned recommendations, dopamine had more adverse events (especially severe dysrhythmias, and especially atrial fibrillation).  In the subgroup of patients with cardiogenic shock, dopamine had a 33% statistically significant elevated mortality over norepinephrine.   Thus, norepinephrine is a better choice in cardiogenic shock (as in this patient) than dopamine or dobutamine.  Dobutamine may be preferred in patients without severe hypotension who have high vascular resistance.
--De Backer D et al.  Comparison of Dopamine and Norepinephrine in the Treatment of Shock.  NEJM 362(9):779; March 4, 2009. 

Author continued: 
Another positive inotrope to consider would be milrinone as it decreases SVR and increases cardiac output; however, one must proceed with caution as the pharmacological mechanism of milrinone can cause vasodilation and worsen hypotension.

When pressors are not able to sustain blood pressure, balloon valvuloplasty may be considered. This is a procedure whereby a catheter is introduced through the femoral artery, and advanced to the have the tip distal to the left subclavian artery. A balloon is then threaded over the catheter, and is inflated and deflated with diastole and systole, respectively. It has been recommended as a bridge to surgery in those that are not candidates for surgery.5 Unfortunately, availability is generally limited to major medical centers.6,7 Surgical repair of AS, by either TAVR or SAVR, is the definitive treatment for this condition. It should be noted, though, that emergent surgical intervention in unstable AS patients is associated with significant mortality, with rates between 30-50%.8

Vasodilator therapy for critical AS

Although not applicable to the case above given the patient’s hypotension, nitroprusside may be appropriate for patients with pulmonary edema in the setting of acute heart failure secondary to AS. Though long thought to be contraindicated in AS due to the condition’s preload-dependent state, there has been some evidence to indicate nitroprusside is beneficial to these patients. In one important uncontrolled study, nitroprusside used in patients with critical AS and heart failure with reduced ejection fraction (mean EF of 21%, mean MAP of 81 mm Hg) had significant improvement of cardiac index, without any episodes of hypotension, ischemic EKG changes, arrhythmias, or dyspnea.9  The only criterion for exclusion from this study was hypotension, defined as either the need for intravenous inotropic or pressor agents (dobutamine, dopamine, epinephrine, milrinone, norepinephrine, or phenylephrine) or a mean systemic arterial pressure below 60 mm Hg. The mean MAP for these patients was 81 +/- 13.

Furthermore, a study compared patients with AS to patients without AS in acute pulmonary edema who received nitrates. There was no significant difference between the percentage of patients in each group who developed hypotension after starting therapy. However, there was note that once these patients did develop hypotension, patients with moderate and severe AS were more likely to have sustained hypotension despite interventions.10

The 2014 ACC/AHA guidelines for the Management of Patients with Valvular Heart Disease, referencing this article, gives this recommendation:

"CLASS IIb 1. Vasodilator therapy may be reasonable if used with invasive hemodynamic monitoring in the acute management of patients with severe decompensated AS (stage D) with NYHA class IV HF symptoms. (Level of Evidence: C) In patients who present with severe AS and NYHA class IV HF, afterload reduction may be used in an effort to stabilize the patient before urgent AVR. Invasive monitoring of LV filling pressures, cardiac output, and systemic vascular resistance is essential because of the tenuous hemodynamic status of these patients, in whom a sudden decline in systemic vascular resistance might result in an acute decline in cardiac output across the obstructed aortic valve. However, some patients do benefit with an increase in cardiac output as systemic vascular resistance is slowly adjusted downward due to the reduction in total LV afterload. AVR should be performed as soon as feasible in these patients."

The variables that interplay in cases of severe aortic stenosis are what cause these patients to be so difficult to manage, and specific therapies targeted to fix one issue often worsen the effects of another issue. If someone is in respiratory distress, their airway and breathing needs to be secured, either through non-invasive or invasive means. Next, the patient’s blood pressure needs to be stabilized. Oftentimes the most appropriate agent will be a positive inotrope, with consideration of a vasoactive agent in persistent hypotension. Once a patient is stabilized, determining the extent of damage to their myocardium and a plan for definitive management can then be determined.

Smith comment:

Supportive care is often overlooked in the management of cardiogenic shock.  The work of breathing demands significant cardiac output and thus puts demands on the heart.  Mechanical ventilation with paralysis removes up to 50% oxygen demand and can put the heart to rest.  I would immediately intubate a patient who is this ill.

As for other invasive therapies, intra-aortic balloon counterpulsation (12, 13) appears to work well in non-randomized studies, and this would also make sense: the balloon in the aorta inflates in diastole, increasing diastolic pressure and thus coronary flow. It also deflates during systole, which normally would reduce afterload; however, in the setting of aortic stenosis, the afterload is determined mostly by the valve, not by post-valve resistance.

Smith Final Comment:It is uncertain what initiated this patient's instability.  Any alteration in physiology can change "compensated" AS to "decompensated" AS.  For instance: sepsis, bleeding, dehydration, hypoxia, and mild ACS.  This patient had a small LV cavity which is unusual for someone with AS, poor LV function, and high filling pressures, but is probably due to severe LVH.  As LV filling pressures were found to be high, this small LV cavity would not be a result of volume depletion.  In any case, once AS becomes decompensated, for whatever reason, it is extremely difficult to manage because of the low coronary perfusion pressure and high oxygen demand.

1.   Taglieri N, Marzocchi A, Saia F, et al. Short- and long-term prognostic significance of ST-segment elevation in lead aVR in patients with non-ST-segment elevation acute coronary syndrome. Am J Cardiol 2011;108:21-8.
2.   Kosuge M, Ebina T, Hibi K, et al. An early and simple predictor of severe left main and/or three-vessel disease in patients with non-ST-segment elevation acute coronary syndrome. Am J Cardiol 2011;107:495-500.
3.      Overgaard, Christopher; Dzavik, Vladimir. Contemporary Reviews in Cardiovascular Medicine. Inotropes and Vasopressors: Review of Physiology and Clinical Use in Cardiovascular Medicine. Circulation. 2008;118:1047-1056.
4.      Richard, C; et al. Combined Hemodynamic Effects of Dopamine and Dobutamine in Cardiogenic Shock. Circulation 67, No. 3, 1983.
5.      Safian RD, Berman AD, Diver DJ, et al. Balloon aortic valvuloplasty in 170 consecutive patients. N Engl J Med 1988;319:125-30
6.      Rahimtoola SH. Catheter balloon valvuloplasty for severe calcific aortic stenosis: a limited role. J Am Coll Cardiol 1994;23:1076-1078
7.      Moreno PR, Jang IK, Newell JB, Block PC, Palacios IF. The role of percutaneous aortic balloon valvuloplasty in patients with cardiogenic shock and critical aortic stenosis. J Am Coll Cardiol 1994;23:1071-1075
8.      Hutter AM Jr, De Sanctis RW, Nathan MJ, et al. Aortic valve surgery as an emergency procedure. Circulation 1970;41:623-627
9.      Umesh N. Khot, MD; et al. Nitroprusside in Critically Ill Patients with Left Ventricular Dysfunction and Aortic Stenosis. N Engl J Med 2003; 348:1756-1763, 5/1/2013.
10.  Claveau, D; et al. Complications Associated with Nitrate Use in Patients Presenting with Acute Pulmonary Edema and Concomitant Moderate or Severe Aortic Stenosis. Annals of Emergency Medicine. 2015 Oct; 66(4):355-362.
11.  De Backer D et al.  Comparison of Dopamine and Norepinephrine in the Treatment of Shock.  NEJM 362(9):779; March 4, 2009. 
12.  Folland ED, et al.  Intraaortic Balloon Counterpulsation as a temporary support measure in decompensated critical aortic stenosis.  J Am Coll Cardiol. 1985;5(3):711-716.
13.  Olcay A. et al.  Cardiogenic shock in the setting of severe aortic stenosis: role of intra-aortic balloon pump support.  Heart 97:838-843
14.  Nishimura RA and Otto CM, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease.  Journal of the American College of Cardiology 63(22):e57-e185; June 10, 2014.


  1. Just a note, you comment on the patient having a balloon valvuloplasty but in the description it describes an inter-aortic balloon pump.

    1. This patient had balloon valvuloplasty. Balloon pump might have been useful as well.

  2. But EF seems to be normal in the above performed echo. Where is the EF of less than 15%??

    1. You have to read everything, not skim. Look at what it says:
      Smith comment:
      This patient did not have a bedside ultrasound. Had one been done, it would have shown a feature that is apparent on this ultrasound (however, this patient's LV function would not be as good as in this clip):

  3. Hi Dr. Smith:

    I am a first year medical student, and I have been studying ECGs on my own. In this scenario, would it have been possible to suspect LVH in the patient based on the ECG alone? The voltage criteria are not entirely met, but there seems to be ST depression and T wave inversion in the lateral leads. Or would the right axis deviation counter-indicate LVH? My knowledge is still very limited, so I apologize if there is a very obvious answer to this question.

    1. There is no evidence of LVH and the ST-T abnormalities are nothing like what is seen in LVH.
      Onc you've seen a lot more ECGs, you'll see what I mean.
      Steve Smith

  4. Dr. Smith, thanks as always for your great posts. Regarding your comment under "Oxygen" - 'all coronary flow happens during diastole because intramyocardial pressure during systole stops blood flow' - I thought the left heart coronaries only perfused during systole but the right heart coronaries perfused during systole and diastole because the right heart chamber pressure was lower. Is this not correct?

    1. No. When the LV is contracting, it has to have higher pressure than the LV chamber in order to pump that blood. And the LV chamber must be higher than the aortic pressure for there to be a gradient to pump. therefore, the systolic intramyocardial pressure is higher than arterial pressure and there is no flow during systole. In the RV, there is flow during both systole and diastole.

    2. And that explains why tachycardia is bad for the blood/oxygen supply to the myocardium - with increasing heart rate the systole duration still remains more or less constant, it's the duration of the diastole which decreases. So the duration of blood flow to the myocardium (diastolic) decreases with increasing heart rate. Correct?

  5. Dr. Smith, thanks as always for your great posts. Under the section 'Oxygen Supply' you write that all coronary blood flow happens during diastole. But I though right heart perfusion occurred during systole as well as diastole because the right heart chamber pressures in systole are much lower than left heart chamber pressures during systole. Is this not correct? Thanks, Ken

    1. Ken,
      That sounds correct, but I'm not totally certain that the duration of systole does not shorten in tachycardia (again, it sounds correct, but I don't know of any data on it -- do you?)


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