Wellens syndrome

Image Source: https://www.ncbi.nlm.nih.gov/books/NBK482490/
 
Diagnostic criteria of Wellens syndrome:

• Presentation with acute, subacute, recent or stuttering chest pain (probable acute coronary syndrome)
• Biphasic (positive-negative) or deeply inverted, usually symmetrical T waves in leads V1-V4

• Isoelectric or minimally elevated (<1 mm) ST segments
• Preservation of precordial R-wave progression and no abnormal Q waves
• ECG pattern may be present in a pain-free state
• Normal or slightly elevated cardiac biomarkers

The patient was admitted to the interventional cardiology service. Cardiac catheterization revealed 99% stenosis of the left main coronary artery, 50% stenosis of the left anterior descending coronary artery and 100% occlusion of the previously stented left circumflex. The previously stented right coronary artery was patent.

Results of cardiac catheterization are shown below:

Interventions:
Due to the extent of stenoses, the patient had an intra-aortic balloon pump placed to reduce myocardial oxygen demand. The next day, he underwent multivessel coronary artery bypass grafting.
 
Socio-economic considerations:
This case highlights the importance of dual antiplatelet therapy and smoking cessation in patients with stent placement. It also demonstrates the challenges mental health and socioeconomic factors play in the patients’ ability to adhere to treatment plans.

There are 4 major types of high-risk acute coronary syndrome (ACS) where the ECG does not show diagnostic ST-segment elevation. These include:

• Posterolateral MI (old nomenclature: true posterior or high posterior MI). This diagnosis should be suspected in patients who present with typical ACS and the ECG shows ST depression in the anterior chest leads. The diagnosis can be confirmed by placing ECG leads to the back. This condition is a STEMI equivalent that warrants emergent cardiac catheterization and reperfusion.
• De Winter sign. This diagnosis should be suspected in patients who present with typical ACS and the ECG shows depression of the ST segment at the J point followed by tall, symmetrical upright T waves (“hyperacute T waves”). It usually signifies total or subtotal acute occlusion of the LAD. In my view, this too should be considered a STEMI equivalent and patients should undergo emergent cardiac catheterization and reperfusion. See the August 2020 ECG blog for details.
• aVR sign. This is characterized by acute chest pain, diffuse ST-segment elevation and ST elevation in aVR of ³ 1 mm. The aVR sign is strongly suggestive of severe and diffuse ischemia due to tight left main or multivessel coronary artery disease. However, it is not a STEMI equivalent. If other important causes such as proximal aortic dissection and hemorrhagic shock have been ruled out, the patients should undergo relatively urgent cardiac catheterization.
• Wellens syndrome. This is characterized by acute, subacute or stuttering chest pain, biphasic (positive-negative) and/or deep symmetrical T waves in the anterior chest leads and normal or slightly elevated troponins. The patients may be chest pain free on presentation.
  • Of the above listed 4 conditions, the Wellens syndrome is the “oldest” first described in 1982 and therefore, it is the best known among emergency medicine providers.
  • In my view, however, of the above listed conditions it is the least worrisome that usually does not require emergent intervention. In the original description of the Wellens syndrome, those patients who presented with ACS with the Wellens sign in the ECG and did not undergo bypass surgery (there was no PCI available at that time), had a significant likelihood of progressing to STEMI in the weeks or months after presentation. Also, medical management in the 1970s-1980s only included beta blocker and nitrates; we did not even use aspirin, heparin or statin.
  • In general, patients with ACS, ongoing chest pain and/or elevated troponin routinely undergo cardiac catheterization regardless of Wellens or not Wellens.
  • Those patients, however, who are pain free and have negative troponin and no Wellens sign usually first undergo noninvasive evaluation and then cardiac catheterization if the noninvasive test shows high-risk abnormalities.
  • In patients with ACS and the Wellens-type T-wave abnormalities, however, noninvasive testing should usually be avoided. Most patients should undergo cardiac catheterization even if they are pain free and have negative troponins.
  • Wellens-type T-wave changes are not completely specific for tight proximal LAD stenosis. They can be present in patients with massive pulmonary embolism, hypertensive urgency, acute or acute-on-chronic renal failure and severe hypertension. In questionable cases, adenosine Myoview, Lexiscan Myoview or CT coronary angiogram can be safely performed. Frank exercise testing and dobutamine studies, however, should not be done because they can provoke acute MI.​

Rate: 78/min
Rhythm: Normal sinus rhythm
Axis: Normal QRS axis
QRS: <120 msec; no abnormal Q waves
ST-T: ST depression at the J point (at the junction between the QRS complexes and ST segments) in the anterior/lateral leads, mostly upsloping ST segments and then, very tall peaked T waves (de Winter T waves). ST segment elevation in aVR.

The patient underwent emergent cardiac catheterization which found a 99% occlusion of the ostial LAD. The initial troponin-T was 4.78ng/mL and peaked at >50ng/mL (detection limit) later that day. It is important to remember that a positive troponin is not needed to make the diagnosis of STEMI or a STEMI equivalent.

Drs. Sabatini-Regueria and Fleming have beautifully summarized our current understanding of the de Winter sign, its prevalence, clinical significance, possible mechanism and the somewhat controversial guideline recommendations how to proceed when it is manifest. I have a few comments about the de Winter sign:

• The original description of the de Winter sign requires depression of the ST segment at the J point followed by very tall T waves. In my view, the ST depression part is not mandatory; very tall (“hyperacute”) T waves alone are equally diagnostic of proximal LAD occlusion (see example below).
• Unfortunately, there are no absolute diagnostic criteria what constitute hyperacute T waves, how tall the T waves need be. The clinical scenario is most important: if a patient has acute chest pain suggestive of acute MI, very tall T waves in the chest leads should warrant emergent catheterization and reperfusion.
• How can one distinguish tall T waves of hyperkalemia from tall T waves of de Winter? The clinical scenario is usually completely different. In a patient with sepsis, shock and renal failure, tall T waves almost certainly indicate hyperkalemia. In a patient who presents with acute chest pain, it is most likely the de Winter sign. Also, tall T waves of hyperkalemia are usually narrow based whereas the de Winter T waves are usually not.
• Although it is uncertain why 98% of patients with acute occlusion of the proximal LAD present with frank STEMI and 2% with the de Winter sign, the most compelling evidence suggests that the de Winter sign signifies subtotal occlusion of the proximal LAD, and STEMI signifies total occlusion. That is probably why most de Winter presentations are very early after the onset of chest pain and why, if not reperfused, the de Winter sign usually progresses to frank STEMI.
• In my view with a clinical presentation of acute chest pain, the de Winter sign should unequivocally be considered a STEMI equivalent mandating emergent cath and reperfusion. A lot is at stake!
• What is now known as the de Winter sign was originally described in 1947 by Dr. Dressler, the same cardiologist who described the Dressler syndrome. Although the de Winter group deserves huge credit for presenting more details about the de Winter sign and for popularizing it, in my view it should be renamed the Dressler – de Winter sign.
• Dr. de Winter is from the cardiology group in the Netherlands which used to be headed by Dr. Wellens. Both on the de Winter article and on the Wellens sign article, Dr. Wellens is the last author. They not only described these two syndromes, but also were one of the first to study the aVR sign. Dr. Wellens was a giant in electrocardiology and cardiac electrophysiology. He passed away a few months ago at age 85. The cardiology world is mourning his loss.

​

10.1056/NEJMc0804737
10.1016/0002-8703(47)90343-8
10.1016/j.jacc.2018.08.1038
10.1016/j.ajem.2013.09.037
10.12998/wjcc.v7.i20.3296
10.4103/HEARTVIEWS.HEARTVIEWS_90_19
10.1155/2018/6868204
10.21037/atm.2019.07.19
10.1016/j.jelectrocard.2017.08.024
10.1016/j.jacc.2020.07.015

Do not agree.
The ECG shows sinus rhythm with dextrocardia. The ST-T morphology cannot be reliably assessed. Repeat ECG with limb leads reversed, and place right-sided chest leads.

Note that the limb leads remained unchanged, but the QRS progression in the chest leads has normalized. One can now diagnose probable left ventricular hypertrophy (LVH) with secondary repolarization abnormality vs. anterolateral ischemia. As the repolarization abnormality was identical to that seen two years before, LVH was the more likely diagnosis. Possible abnormalities in the limb leads may have remained obscure.

(1) ECG showing dextrocardia – see above.
(2) Chest X-ray demonstrating a right-sided heart with the ventricular apex pointing to the right – below left.
(3) Abdominal CT showing the liver on the left and the spleen on the right – below right. The abdominal CT was recorded during a prior admission.

Two sets of high-sensitivity troponin measurements remained within normal limits. An echocardiogram showed new moderate biventricular dysfunction with left ventricular ejection fraction (LVEF) calculated at 35%, changed from echocardiogram three years prior in which biventricular function was normal and LVEF was 55%. Given a history that was concerning for ischemia and new biventricular dysfunction, the Cardiology service recommended cardiac catheterization which revealed calcification and minor luminal irregularities of all coronary vessels and a 50% stenosis of the mid left main coronary artery. No stents were placed, and medical management was recommended. The patient experienced several bouts of right sided chest pain reliably relieved by oral Tylenol. Her chest pain was felt to be musculoskeletal in nature. She was discharged in stable condition with follow-up appointments with both her primary care physician and Cardiology.

What is situs inversus, and what does it mean for our patient?
Situs solitus refers to the normal orientation/location of the thoracic and abdominal viscera. In situs solitus, we find a tri-lobed right lung, a bi-lobed left lung, and a heart on the left side with the apex facing left. The liver and gallbladder are on the right, the spleen is present on the left, the descending colon is on the right, the ascending colon on the left, and the inferior vena cava (IVC) runs to the right of the aorta in the abdomen, etc.

In 1 out of 10,000 people, the orientation of the thoracic and abdominal viscera is reversed - a heterotaxy syndrome called situs inversus. Of these patients, the vast majority have situs inversus totalis, in which the heart is in the right chest with the apex oriented toward the right (dextrocardia). The remainder of the thoracic and abdominal viscera are in positions exactly mirroring situs solitus. For example, the right lung is bi-lobed, the left lung is tri-lobed, the liver and gallbladder are on the left side, the spleen is on the right side, the ascending colon is on the left, the descending colon is on the right, the IVC runs to the left of aorta in the abdomen, etc. Approximately 2-5% of these patients will have congenital cardiac anomalies, but the vast majority will be asymptomatic with normal quality of life and life expectancy.

Approximately 1 in 22,000 people in the general population will have situs inversus with levocardia, meaning that, although the thoracic and abdominal viscera are in mirror/reverse position from situs solitus as in situs inversus totalis, the heart remains in levocardia (its normal orientation), located in the left chest with the apex oriented toward the left. Nearly 100% of these patients have congenital cardiac anomalies, usually of the cyanotic variety (i.e. transposition of the great vessels). These patients have a severely shortened life expectancy. In fact, only about 5-13% of patients with situs inversus with levocardia survive beyond 5 years of age.
Of patients with situs inversus totalis, 17-25% will have Kartagener syndrome characterized by chronic sinusitis, bronchiectasis and situs inversus. This syndrome is a result of dynein protein abnormalities causing impaired mucociliary clearance, known as primary ciliary dyskinesia. Interestingly, only 50% of patients with primary ciliary dyskinesia will have situs inversus, and thus only 50% will meet official criteria for Kartagener syndrome.

Based on radiographic, echocardiographic, and ECG evidence proving dextrocardia, CT angiography of the chest confirming a tri-lobed left lung and bi-lobed right lung, and CT abdomen obtained during previous hospital admission, our patient has situs inversus totalis without associated primary ciliary dyskinesia. She had no evidence of congenital cardiac abnormalities on her echocardiogram or catheterization. She had respiratory bronchiolitis associated interstitial lung disease and chronic obstructive pulmonary disease, both secondary to a greater than 25 pack-year history of cigarette smoking, rather than chronic sinusitis. This patient’s coronary disease did not seem to be related to her underlying situs inversus totalis, but rather due to the significant smoking history, diabetes, and hypertension.

If you order an ECG, please spend a couple of minutes to analyze it. The first steps include rate, regularity and rhythm. Then go left-to-right, starting with the P waves. The normal sinus P wave cannot be negative in lead I as the SA node is in the upper right atrium and therefore, atrial activation is right-to-left, going towards lead I. If the P wave is negative in lead I, follow the steps below:

Below is an example of right arm – left arm lead reversal. Note that the limb leads look essentially identical to what was seen in dextrocardia (everything negative in lead I, upright P, QRS and T in aVR and negative P, QRS and T in aVL), but in the chest leads, there is normal R-wave progression.

​Correct interpretation of the ECG
Atrial flutter with 2:1 AV conduction and frequent premature ventricular complexes

Hospital Course
The patient’s pre-hospital report of extreme tachycardia raised the possibility of 1:1 flutter and possibly syncope due to the dysrhythmia rather than seizure. Cardiology evaluated the patient and recognized the atrial flutter. The patient was given IV diltiazem which resulted in excellent rate control. It was felt that because of his brain injury and seizures, the patient was not a candidate for chronic anticoagulation. Catheter ablation was discussed but eventually rejected. Echocardiogram revealed right ventricular dilatation and hypokinesis, moderate tricuspid regurgitation, moderate pulmonary hypertension and marked right atrial dilatation.

Atrial flutter with 2:1 AV conduction (“2:1 flutter”) is one of the most commonly missed ECG diagnosis, both by the interpretation software and by providers. 2:1 flutter should always be entertained if the computer diagnoses “sinus tachycardia” but there is either an abnormal P-wave morphology and/or an abnormal PR interval. Consistent misreadings by the interpretation software include sinus tachycardia with first-degree AV block, sinus tachycardia with very short PR intervals, and ectopic atrial tachycardia. The most important factor in recognizing 2:1 flutter is to always consider this diagnosis in sick patients who present with a regular SVT. Once the diagnosis of 2:1 flutter is entertained, it is usually easy to prove it by using the “halving method”: recognizing negative P waves in the inferior leads whose distance is exactly half of the R-R intervals. If uncertain, the use of IV adenosine, by exposing the flutter waves, can be very helpful.
 
From the ED physician’s perspective, the most important job is to recognize the flutter and provide rate control. In patients who present repeatedly with atrial flutter, it is also prudent to suggest to the accepting team that curative treatment with catheter ablation should be entertained and discussed with cardiology.

Correct interpretation of the ECGs
ECG #1
- NSR with normal PR, normal QRS axis and RBBB 
- Sinus rate of 85/min with 1:1 AV conduction
 
ECG #2
- Regular bradycardia, still normal PR intervals and normal QRS axis, unchanged RBBB pattern 
- The sinus rate is now 90/min with 2:1 AV block; hence, the ventricular rate is 45/min
- Blue arrows below demonstrate twice as many sinus P waves as QRS complexes

​These ECG findings are consistent with right bundle-branch block and acceleration-dependent second-degree AV block where there is 1:1 AV conduction at slower sinus rates but 2:1 AV block at faster atrial rates. Acceleration- dependent AV block localizes the block to the His-Purkinje system, which is characterized by all-or-none conduction. At a critical sinus rate, only every other sinus impulse is able to conduct through the His-Purkinje system and every other P wave is blocked. On the conducted complexes, there is no change in the PR interval. The blocked P waves are almost never recognized by the interpretation software, which usually reads the rhythm as sinus bradycardia, a clinically trivial dysrhythmia. Therefore, the ECG must be carefully scrutinized in order to identify this ominous rhythm and the correct diagnosis.
 
- In this case, slowing down the sinus rate with carotid massage or IV beta-blocker can paradoxically improve AV conduction.
- Atropine, on the other hand, is contraindicated because it can worsen AV conduction by increasing the sinus rate.
- This finding is concerning for extensive distal conduction disease. Patients with bundle-branch block and acceleration-dependent AV block are at high risk of complete heart block at an anatomically distal level, which may result in asystole and cardiac arrest. 
- This finding requires urgent EP evaluation and is an absolute indication for dual-chamber (AV sequential) pacemaker implantation

​The patient was admitted directly from the outpatient EP office visit to Cardiology for permanent pacemaker implantation. He received a dual-chamber pacemaker. He continued to experience syncopal symptoms following his initial procedure due to intermittent loss of lead capture requiring revision and a brief admission to the cardiac ICU. The remainder of his hospitalization was uncomplicated, and he was discharged shortly thereafter with no recurrence of symptoms. During his first outpatient EP follow-up he was noted to be asymptomatic with no recurrence of syncope and a fairly low pacing burden. EP noted that they anticipate his pacing burden will increase over time.

​This patient had right bundle-branch block and an occult acceleration-dependent 2:1 AV block that was present but unrecognized on the ECGs during multiple prior ED visits for syncope. 
 
Bundle-branch block combined with acceleration dependent 2:1 AV block is indicative of extensive distal conduction system disease and requires urgent EP evaluation for pacemaker implantation to avoid degeneration to complete heart block and potentially, cardiac arrest. 
 
This rhythm is rarely detected by the interpretation software and will be missed on ECG review unless thoughtfully searched for. 

It is well known that patients with bifascicular block are at risk of developing complete heart block. This is especially true for patients with bifascicular block who experience syncope. It is less appreciated, but still well documented that patients with simple left or right bundle branch block and syncope too, as in the current case, are frequently found to have paroxysmal AV block and asystole.1 Based on these data it is recommended that patients with unexplained syncope who have any type of intraventricular block should undergo prolonged monitoring with an implanted loop recorder (class I recommendation).2 In this case, the patient had numerous previous workups by cardiologists and underwent a number of minimal value testing such as echocardiography and stress testing, but was never offered cardiac monitoring.
 
A second important lesson of the case is that 2:1 heart block is almost never recognized by interpretation softwares and is rarely recognized by providers. Most cases are interpreted as sinus bradycardia, which is usually a more benign dysrhythmia. Whenever a patient’s ECG appears to demonstrate regular sinus bradycardia, please carefully search for twice as many P waves than meets the eye by halving the interval between the conducted P waves. This “trick” only takes a few seconds to do. It is most important to search for 2:1 heart block in patients who have bundle-branch block and in patients who present with presyncope or syncope.