Wellens’ Syndrome was frequently mentioned this year at both conference and follow-up rounds, and my interest in this topic is as much about answering the questions raised by our discussions as it is about finding the historicity of this syndrome. All of the relevant literature is old, at times confusing, and not designed for relevance to emergency medicine; but I want to take you through it so you understand what we know about this acute coronary syndrome. I also make an attempt at calculating a rough NNT and explain why these ECG findings occur.
The original Wellens paper
H. J. Wellens was the corresponding author of a seminal publication in 1982 that first described this eponymous acute coronary syndrome. In this pre-troponin, pre-STEMI, pre-PCI, Q-wave MI era publication, the authors describe a subgroup of unstable angina (UA) patients whose natural history is that of an anterior wall myocardial infarction (MI). The authors describe that of 145 “consecutively admitted” patients with “impending infarction,” which they defined as what we would loosely call crescendo angina, 26 patients had abnormal ST changes and anterior T wave inversions (TWI) without a change in QRS complex. In this case series of 26 patients, 22 had TWIs anteriorly (defined here as mainly V2 and V3), and the remaining 4 had biphasic T waves in V2 and V3. Subsequent literature will refer to these ECG patterns as Wellens Type I and Type II, respectively. One half of these patients had these ECG findings on admission, and the other half developed them within 24 hours.
The first of this case series was described as an entire clinical course through which they unknowingly describe the future concept that acute MIs are due to plaque rupture and not progressive intraluminal stenosis. They report on a 45 year old male with 4 weeks of anginal pain who presented with a normal ECG on admission. His symptoms were controlled with nitro and beta blockers (the standard of care at the time in Holland), and he developed anterior TWIs at his routine 24 hour ECG. He subsequently went on to have a massive anterior STEMI on hospital day 9 leading to death secondary to “pump failure” only 12 hours later. His autopsy report showed a “fresh thrombus” in an already partially occluded proximal LAD.
The authors go on to describe the patients within the series as in one of two groups: those before they recognized the significance of the ECG patterns and those treated afterwards. The first 9 were part of the first group, and 8 of the 9 developed an MI. In the second group, the threshold to get these patients angiograms +/- subsequent CABG (the standard of care was for revascularization at the time) was significantly lower. All patients found to have CAD had >90% stenosis of the LAD, and all patients who underwent CABG had grafts to the LAD. Within the second group of 17 patients, 4 developed an MI. Of the total of 12 with MIs, 5 died within days. Sixteen patients in this series did not undergo catheterization or CABG, and 12 of these patients developed an anterior wall MI. None of the patients who underwent revascularization developed an MI. The authors conclude that the aforementioned ECG findings must represent a “subendocardial ischemia” which requires urgent angiography and revascularization.
The article concludes with a discussion via multiple commentators including Dr. Wellens, who says: “I believe that by using the ECG pattern, we can define a subset of people with a proximal LAD lesion, with a 75% chance of losing 35% of their myocardium within 2 weeks, and I believe that they should be distinguished from patients who develop ST segment elevations or depressions during pain. The pattern that I described develops after the pain, and it remains” (1).
The idea catches on
The following year, Haines et al. describe a series of 118 consecutively admitted unstable angina patients at an American center where 73 of these patients received coronary angiography. They reported a high specificity of anterior TWIs (defined here as I, aVL, and V2-V6) for LAD disease (2). Another small case series from the same year intending to report on the prognostic significance of ST elevations in “unstable angina” patients describes one patient who presented with an anterior STEMI. The patient, who was treated as unstable angina developed Wellens type II ECG findings after anginal control with nitro and beta blockers. The patient went on to develop another anterior STEMI and subsequently died prior to revascularization (3).
The second major paper on Wellens’ Syndrome
In 1989, Wellens was again the corresponding author of a larger case series of 180 patients admitted for unstable angina who had either Wellens syndrome at the time of presentation or after hospital admission. Sixty percent of these patients had either Wellens’ type I (75%) or type II (25%) EKG changes at the time of initial presentation, and the majority (almost 80%) of the remaining 40% developed Wellens’ ECG pattern within 24 hours. The authors continue with their strategy to “more urgently” get these patients catheterized (mean 3.3 days) to give us more meaningful data than their seminal 1982 publication.
Their strategy seems to have worked, because unlike their previous case series with a high rate of MI, they now report that only 8 of the 180 had a pre-revascularization MI. Fifty-six of these patients were treated medically due to a variety of reasons, and 26 eventually underwent revascularization as an outpatient (mean 8 months). Of the remaining 30, 8 died of an unknown cardiac event during their rather long follow-up period of 4 years. They contrast this to the group of patients (n=136) undergoing revascularization with survival to hospital discharge which had only one patient suffer a cardiac death during their follow-up period. Again, all these patients had LAD disease, and 83% were found to have a “culprit lesion” proximal to the second septal branch (4)
But what is the specificity of Wellens’ ECG pattern to detect a proximal LAD stenosis?
Neither of the original papers were designed to provide this data, but Kojuri et al conducted a retrospective study of 130 patients with known LAD stenosis and went back to look at the most specific ECG findings associated with disease of the LAD. They found the most specific predictors of proximal LAD lesions are inverted or biphasic T waves in the anterior leads. They determine the specificity of what we call either Wellens Type I or Type II to be 92% (5).
What about a number needed to treat (NNT) a Wellens’ ECG pattern in an unstable angina patient to prevent an MI?
Although there is no data on treating a Wellens’ Syndrome patient with dual anti-platelet therapy or heparin like we would in the ED today, it is possible to calculate a rough NNT to prevent an MI. Combining the data from both Wellens’ et al papers, 30 of the 55 medically treated patients developed an MI; and 9 of the 123 of the “experimental” early revascularization group developed an MI. MIs that occurred during revascularization were excluded. Using these numbers, the NNT (1/Absolute risk reduction; Absolute risk reduction = Control group event rate – Experimental event group rate) to prevent an MI is approximately 2. In other words, the number needed to admit a patient with Wellens’ Syndrome for urgent catheterization to prevent an MI is only 2.
Obviously, this is both an extrapolation of CABG data intended for PCI and an inexact representation, but it gives us some quantitative information that is convincing enough to highlight the importance that emergency physicians recognize this ECG pattern and relay this information to a cardiologist (who may be unaware of the significance).
Be careful not to mistake Wellens’ ECG pattern for something else
Anterior TWI is certainly not exclusive to ACS and can be from LVH, HOCM, acute pulmonary edema, or pulmonary embolism (see the previously posted article by Dr. Gruber and myself). Wellens’ syndrome should not have Q waves or QRS widening.
Wellens’ Syndrome is not a STEMI equivalent
Now that new onset LBBB has been removed from the AHA STEMI Guidelines, it no longer lists STEMI equivalents. Review literature suggests that LBBB meeting Sgarbossa or the Modified Sgarbossa criteria, de Winter ST/T waves, hyperacute T waves, and the ECG pattern representing left main coronary artery occlusion (LMCO) could be considered STEMI equivalents. Wellens’ ECG pattern, on the other hand, necessitates an urgent catheterization in house without stress testing (6).
Why does this pattern occur?
The Wellens ECG findings suggest a reperfusion pattern in all of the subsequent literature on the topic (7.8) and by the well-known FOAM educators Drs. Steve Smith of Hennepin and Amal Mattu of Maryland. There is no emergency medicine literature that gives any data (or even any references to data) to support this claim, so I wondered if cardiologists had noted that reperfused anterior STEMI patients often had new TWI after catheterization. I asked Steve Smith of hqmeded-ecg.blogspot.com this question, and he was kind enough to direct me to some older cardiology literature that nicely fills in this gap.
Two older cardiology papers report on continuous 12-lead ECG monitoring for patients getting thombolytics to treat acute MI. Although early ST-segment changes were the most common, terminal T-wave inversion was also common in patients who were given thrombolytics to yield a patent “culprit” vessel. Although their numbers are small, they report a positive LR of 10.6 for terminal t-wave inversion during thrombolysis to predict patency seen on the subsequent catheterization (9). The other paper included more patients and found that 60% of acute MI patients who are successfully thrombolysed show terminal T-wave inversions (10). There is also some new literature without large numbers suggesting that T wave inversions in the leads with the highest ST elevations are associated with a higher prevalence of STEMI-related artery patency before PCI. In other words, T wave inversions with concurrent STEMI may predict a spontaneous reperfusion (11). Having reviewed these articles, it is reasonable to assume that Wellens’ Syndrome ECG pattern represents the spontaneous reperfusion of an acute LAD occlusion.
Take home points:
– There is no modern data on the prognosis of Wellens’ Syndrome treated with dual anti-platelet therapy and heparin.
– The Wellens’ ECG pattern in patients admitted for unstable angina is specific for significant proximal LAD lesions.
– The pattern must be found when the patient is NOT having active chest pain, and the patient should report a story concerning for unstable angina.
– Be mindful of the differential of anterior TWI, and remember that Wellens’ Syndrome should not have Q waves or a widened QRS.
– Although not a STEMI equivalent, the Wellens’ pattern represents an impending MI within days to weeks.
– By identifying Wellens’ Syndrome, you have increased your pre-test probability that medical management will ultimately fail in preventing an MI.
– A very rough estimate of the NNT Wellens’ Syndrome patients with revascularization to prevent an MI is only 2.
– Wellens is likely a reperfusion pattern.
- de Zwaan C, Bär FW, Wellens HJ. Characteristic electrocardiographic pattern indicating a critical stenosis high in left anterior descending coronary artery in patients admitted because of impending myocardial infarction. Am Heart J. 1982 Apr;103(4 Pt 2):730-6.
- Haines DE, Raabe DS, Gundel WD, Wackers FJ. Anatomic and prognostic significance of new T-wave inversion in unstable angina. Am J Cardiol. 1983 Jul;52(1):14-8.
- Boden WE1, Gibson RS, Schechtman KB, Kleiger RE, Schwartz DJ, Capone RJ, Roberts R. ST segment shifts are poor predictors of subsequent Q wave evolution in acute myocardial infarction. A natural history study of early non-Q wave infarction. Circulation. 1989 Mar;79(3):537-48.
- de Zwaan C, Bär FW, Janssen JH, Cheriex EC, Dassen WR, Brugada P, Penn OC, Wellens HJ. Angiographic and clinical characteristics of patients with unstable angina showing an ECG pattern indicating critical narrowing of the proximal LAD coronary artery. Am Heart J. 1989 Mar;117(3):657-65.
- Kojuri J et al. Electrocardiographic Predictors of Proximal Left Anterior DescendingCoronary Artery Occlusion. Cent Eur J Med 2009 Sept; 3 (3): 294 – 99.
- Lawner BJ1, Nable JV, Mattu A. Novel patterns of ischemia and STEMI equivalents. Cardiol Clin. 2012 Nov;30(4):591-9.
- Rhinehardt J, Brady WJ, Perron AD, Mattu A. Electrocardiographic manifestations of Wellens’ syndrome. Am J Emerg Med. 2002 Nov;20(7):638-43.
- Tandy TK1, Bottomy DP, Lewis JG. Wellens’ syndrome. Ann Emerg Med. 1999 Mar;33(3):347-51.
- Doevendans PA1, Gorgels AP, van der Zee R, Partouns J, Bär FW, Wellens HJ. Electrocardiographic diagnosis of reperfusion during thrombolytic therapy in acute myocardial infarction. Am J Cardiol. 1995 Jun 15;75(17):1206-10.
- Wehrens XH1, Doevendans PA, Ophuis TJ, Wellens HJ. A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J. 2000 Mar;139(3):430-6.
- Alsaab A, Hira RS, Alam M, Elayda M, Wilson JM, Birnbaum Y. Usefulness of T wave inversion in leads with ST elevation on the presenting electrocardiogram to predict spontaneous reperfusion in patients with anterior ST elevation acute myocardial infarction. Am J Cardiol. 2014 Jan 15;113(2):270-4.