Background

• Wellens syndrome, also known as Wellens’ sign or LAD coronary T-wave syndrome, is an electrocardiographic (ECG) pattern that indicates critical stenosis of the left anterior descending artery (LAD), one of the major coronary arteries supplying blood to the heart. It was first described by Hein J.J. Wellens and his colleagues in 1982. 
• Wellens syndrome is typically observed in patients with unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). Specific changes in the T-wave morphology on the ECG characterize it. The classic pattern in Wellens syndrome is biphasic or deeply inverted T-waves in leads V2 and V3, which may appear symmetrical or asymmetrical. The T-wave changes are often accompanied by little to no elevation or depression of the ST segment. 
• The presence of Wellens syndrome on an ECG is of great clinical significance as it signifies a high-risk condition. It indicates a critical narrowing of the LAD, most commonly caused by an occlusive lesion in the proximal segment of the artery. If left untreated, this lesion can block blood flow in the LAD, resulting in a large anterior wall myocardial infarction (heart attack). 
• The characteristic T-wave changes in Wellens syndrome are typically transient and may quickly return to normal or progress to significant ST-segment elevation. Therefore, prompt ECG pattern recognition and appropriate management are crucial to prevent a significant cardiac event. 
• Patients with Wellens syndrome are at a high risk of imminent anterior wall myocardial infarction. The recommended treatment for these patients involves urgent coronary angiography to identify and treat the critical stenosis causing the ECG changes. Percutaneous coronary intervention (PCI), such as balloon angioplasty or stent placement, is often performed to restore blood flow to the affected coronary artery and prevent further myocardial damage. 
• In summary, Wellens syndrome is an ECG pattern characterized by biphasic or deeply inverted T-waves in leads V2 and V3, indicating critical stenosis of the LAD. It is associated with a high anterior wall myocardial infarction risk and requires prompt recognition and intervention to prevent a significant cardiac event. 

Epidemiology

• The distinctive ECG (electrocardiogram) pattern of Wellens syndrome is relatively prevalent among individuals exhibiting symptoms congruent with unstable angina. Among patients admitted with unstable angina, the ECG pattern can be observed in approximately 14-18% of cases. 
• Wellens syndrome signifies severe proximal LAD (left anterior descending) disease; consequently, its inherent advancement culminates in an anterior wall myocardial infarction. This progression is highly probable, to the extent that relying solely on medical management is insufficient to halt the natural course. The transition to an anterior wall MI occurs swiftly, with an average duration of 8.5 days from the onset of Wellens syndrome to the occurrence of infarction. 
• In the event of an anterior wall myocardial infarction, there exists a significant risk of pronounced morbidity or mortality. Therefore, it is crucial to promptly identify this pattern to prioritize timely intervention and care. 

Anatomy

Pathophysiology

• The pathophysiology of Wellens syndrome is closely related to the underlying coronary artery disease and the specific changes in blood flow within the left anterior descending artery (LAD). 
• The primary cause of Wellens syndrome is a critical stenosis or narrowing of the LAD, one of the major coronary arteries responsible for supplying blood to the heart’s anterior wall. This stenosis is often caused by atherosclerosis, characterized by the buildup of fatty plaques and cholesterol deposits in the arterial walls. 
• The pathophysiological process begins with developing an atherosclerotic plaque within the LAD. As the plaque progresses, it can become unstable and vulnerable to rupture or erosion. If a rupture occurs, platelets and clotting factors aggregate at the site, forming a thrombus or blood clot. 
• The thrombus partially or entirely obstructs the lumen of the LAD, reducing blood flow downstream. However, in the case of Wellens syndrome, the stenosis is often not severe enough to cause a complete occlusion. Instead, critical stenosis allows blood flow to continue, albeit at a reduced rate. 
• The characteristic ECG findings in Wellens syndrome, namely biphasic or deeply inverted T-waves in leads V2 and V3, are thought to result from transient episodes of reperfusion of the ischemic myocardium. During these episodes, blood flow to the affected area improves temporarily, leading to normalization or inversion of the T-waves. 
• However, this improvement in blood flow is often short-lived. The critical stenosis in the LAD persists, and the blood flow to the affected region becomes compromised again. If left untreated, the stenosis can progress, causing complete occlusion and a large anterior wall myocardial infarction. 
• It is important to note that the pathophysiology of Wellens syndrome is distinct from that of ST-segment elevation myocardial infarction (STEMI). In STEMI, complete occlusion of the coronary artery results in prolonged ischemia and myocardial damage. In Wellens syndrome, intermittent blood flow allows for transient improvement and the potential for salvage of the myocardium if timely intervention is performed. 
• Overall, Wellens syndrome’s pathophysiology involves critical LAD stenosis, intermittent blood flow to the affected area, and transient reperfusion episodes leading to characteristic ECG changes. Timely recognition and intervention are crucial to prevent progression to a major cardiac event and minimize myocardial damage. 

Etiology

The primary etiology of Wellens syndrome is a specific type of coronary artery disease, namely critical stenosis of left anterior descending artery (LAD). The stenosis is most commonly caused by atherosclerosis, a progressive disease characterized by the buildup of fatty plaques and cholesterol deposits within the arterial walls. 

Atherosclerosis develops over time due to various risk factors, including: 

• Hypertension: High blood pressure can lead to endothelial dysfunction, causing damage to the inner lining of the arteries and promoting plaque formation. 
• Dyslipidemia: Elevated levels of LDL cholesterol (low-density lipoprotein) and reduced levels of HDL cholesterol (high-density lipoprotein) contribute to the development of atherosclerosis. 
• Smoking: Cigarette smoking damages the arterial walls and accelerates the progression of atherosclerotic plaques. 
• Diabetes Mellitus: Individuals with diabetes have an enhanced risk of atherosclerosis due to metabolic abnormalities and associated conditions such as insulin resistance and hyperglycemia. 
• Family history: Atherosclerosis development involves a genetic element, and individuals with a familial coronary artery disease background face an elevated risk. 
• Age and gender: Advanced age and male gender are associated with a higher prevalence of atherosclerosis and subsequent coronary artery disease. 

Genetics

Prognostic Factors

The prognosis of Wellens syndrome is influenced by several factors that can help predict the likelihood of future cardiac events and guide appropriate management. These prognostic factors include: 

• ECG Findings: The specific ECG pattern seen in Wellens syndrome, with biphasic or deeply inverted T-waves in leads V2 and V3, strongly predicts future major cardiac events. Patients with this pattern risk developing a large anterior wall myocardial infarction if left untreated. 
• Degree of Stenosis: In the LAD (left anterior descending artery), the severity of stenosis is an important prognostic factor. Critical stenosis, particularly in the proximal segment of the LAD, is associated with a higher risk of myocardial infarction and adverse cardiac outcomes. 
• Dynamic Changes in ECG: Wellens syndrome is characterized by dynamic changes in the T-wave morphology, with the ECG findings alternating between biphasic or inverted T-waves and normal or minimally elevated ST segments. Dynamic changes indicate ongoing ischemic episodes and a higher risk of acute coronary events. 
• Recurrent Symptoms: The recurrence of chest pain or angina despite medical management is a concerning prognostic factor. It suggests ongoing ischemia and a higher likelihood of subsequent cardiac events. 
• Response to Treatment: The response to coronary intervention, such as percutaneous coronary intervention (PCI) with balloon angioplasty or stent placement, can provide prognostic information. Successful intervention with restoring blood flow in the LAD is associated with a better prognosis than incomplete revascularization or persistent stenosis. 
• Left Ventricular Function: It is assessed by echocardiography or other imaging modalities, impaired left ventricular function indicates a higher risk of adverse cardiac events. Reduced ejection fraction and impaired myocardial contractility are associated with worse outcomes. 
• Comorbidities: Other cardiovascular risk factors and comorbidities, such as diabetes, hypertension, renal dysfunction, or prior history of cardiovascular events, can impact the prognosis of Wellens syndrome. These factors contribute to the overall cardiovascular risk profile and influence the likelihood of future cardiac events. 

Clinical History

• The clinical presentation of  Wellens syndrome can vary but typically includes certain characteristic features. The age group, associated comorbidity or activity, and acuity of the presentation can provide additional context. Here’s a breakdown of these aspects: 
• Age Group: Wellens syndrome commonly affects individuals in their middle to older age group. It is frequently observed in patients over 40, although it can also occur in younger individuals. 

Physical Examination

The physical examination findings in Wellens syndrome are generally non-specific and may not reveal significant abnormalities. However, certain features may be present and provide some clues to the underlying cardiac condition. It is key to note that the diagnosis of Wellens syndrome primarily relies on the characteristic electrocardiographic (ECG) findings rather than physical examination. Here are some aspects that may be noted during the physical examination: 

• Vital Signs: The vital signs, including blood pressure, heart rate, and respiratory rate, are typically within the normal range. However, in some cases, patients might have an elevated heart rate due to ongoing myocardial ischemia or anxiety related to chest pain. 
• Cardiac Auscultation: The cardiac examination may reveal normal or non-specific findings. The presence of a regular rhythm and absence of murmurs, gallops, or abnormal heart sounds are commonly observed. Sometimes, a soft or distant S1 sound may be heard if left ventricular dysfunction is associated. 
• Signs of Heart Failure: Patients with Wellens syndrome may exhibit signs of heart failure in more severe cases. These can include elevated jugular venous pressure, pulmonary rales or crackles on lung auscultation, peripheral edema, or signs of fluid overload. However, these signs are not specific to Wellens syndrome and can occur in various cardiac conditions. 
• Chest Examination: The chest examination may be unremarkable, with no significant abnormalities noted on inspection or palpation. In some cases, patients may have tenderness or discomfort upon chest wall palpation due to ongoing chest pain. 

It is key to remember that the diagnosis of Wellens syndrome primarily relies on the characteristic ECG findings, specifically biphasic or deeply inverted T-waves in leads V2 and V3, rather than physical examination. However, a thorough physical examination is still essential to assess overall cardiovascular status, identify signs of heart failure, and rule out other potential causes of chest pain. 

Age group

Associated comorbidity

• Wellens syndrome is often seen in patients with a history of angina or known coronary artery disease. Many individuals with Wellens syndrome may have a prior history of unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI). They may have risk factors such as hypertension, dyslipidemia, smoking, diabetes mellitus, or a family history of coronary artery disease. 
• The acute presentation of Wellens syndrome is usually associated with chest pain or angina. The chest pain may be described as substernal, pressure-like, or squeezing. The pain is often precipitated by physical exertion or emotional stress and may be relieved with rest or nitroglycerin. Some patients may present with anginal symptoms at rest or with minimal exertion. 

Associated activity

Acuity of presentation

• Wellens syndrome is considered an urgent or even emergent condition. The acuity of presentation can vary. Some patients may have ongoing chest pain or angina during evaluation, indicating an acute event. Others may present a recent history of chest pain that has resolved by the time of evaluation, but the ECG findings of Wellens syndrome are still present. In such cases, the ECG changes are a warning sign of an impending major cardiac event if left untreated. 
• It is key to note that some patients with Wellens syndrome may have a relatively stable presentation, whereas others may have more severe symptoms. The severity of symptoms does not necessarily correlate with the degree of stenosis in the LAD or the risk of future cardiac events. Regardless of the acuity of presentation, prompt recognition and appropriate management are crucial to prevent further myocardial damage and significant cardiac events. 

Differential Diagnoses

The differential diagnosis of Wellens syndrome involves considering other conditions that can cause similar ECG changes or present with similar clinical features. It is essential to differentiate Wellens syndrome from other cardiac conditions as the management and prognosis can vary significantly.

Some critical conditions to consider in the differential diagnosis of  Wellens syndrome include: 

• Acute Coronary Syndrome (ACS): Wellens syndrome is a specific form of ACS characterized by critical stenosis of the left anterior descending artery (LAD). However, other types of ACS, such as unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI), can also present with similar symptoms and ECG changes. It is vital to evaluate for other signs and symptoms of ACS, such as elevated cardiac enzymes and dynamic ST-segment changes. 
• Prinzmetal’s Angina: Prinzmetal’s angina, also known as variant angina, is caused by transient coronary artery spasms that can lead to myocardial ischemia. The ECG findings in Prinzmetal’s angina can mimic Wellens syndrome with ST-segment elevation during angina episodes. However, the underlying mechanism is different, and coronary artery spasm rather than fixed stenosis is responsible. Coronary artery spasms can be evaluated by performing provocative tests such as ergonovine or acetylcholine provocation during coronary angiography. 

• Ventricular Hypertrophy: Left ventricular hypertrophy (LVH) due to hypertension or aortic stenosis can cause repolarization abnormalities and T-wave changes on the ECG. Differentiating LVH from Wellens syndrome can be challenging, but biphasic or deeply inverted T-waves in leads V2 and V3, along with a clinical suspicion of ACS, favors Wellens syndrome. 
• Electrolyte Imbalance: Electrolyte abnormalities, particularly potassium and calcium imbalances, can lead to ECG changes resembling Wellens syndrome. Hypokalemia or hypocalcemia can cause T-wave abnormalities, but the specific inverted T-wave pattern in leads V2 and V3 seen in Wellens syndrome is less typical in electrolyte imbalances. 
• Early Repolarization: Early repolarization is a benign ECG finding characterized by J-point elevation and upward concavity of the ST segment, often with notching or slurring. In some cases, the ECG changes of early repolarization may overlap with Wellens syndrome, particularly in leads V2 and V3. However, the absence of profoundly inverted or biphasic T-waves and J-point elevation throughout the precordial leads suggest early repolarization rather than Wellens syndrome. 
• Pulmonary Embolism: Pulmonary embolism, especially in massive or sub-massive cases, can cause right ventricular strain and ECG changes that may resemble anterior wall ischemia. The differentiation can be challenging, and additional clinical features, such as respiratory symptoms, can aid in distinguishing pulmonary embolism from Wellens syndrome. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• The treatment of Wellens syndrome involves various approaches to stabilizing the patient’s condition, preventing further myocardial damage, and reducing the risk of major cardiac events.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

• Bed rest: Patients with Wellens syndrome are generally advised to maintain bed rest or limit physical activity to reduce myocardial oxygen demand and minimize the risk of ischemia. 
• Continuous cardiac monitoring: Patients should be closely monitored using continuous cardiac telemetry to detect any changes in rhythm or new ECG abnormalities. 
• Pain relief: Adequate pain relief, typically achieved with sublingual nitroglycerin, should be provided to alleviate anginal symptoms. 

• Antiplatelet therapy: Aspirin is commonly prescribed to reduce the risk of further thrombus formation and potential coronary artery occlusion. Dual antiplatelet therapy with aspirin and P2Y12 inhibitor may be considered in selected cases. 
• Heparin or anticoagulation: Unfractionated heparin or low molecular weight heparin may be administered to prevent clot formation and progression in the coronary arteries. Anticoagulation is essential if the patient is considered for an invasive procedure. 
• Nitroglycerin: Nitroglycerin is used for symptom relief and to promote coronary vasodilation, which can improve myocardial blood flow. It is typically administered sublingually or intravenously as needed to control anginal symptoms. 

• Coronary angiography: Urgent coronary angiography is essential to identify the critical stenosis in the left anterior descending artery (LAD) responsible for Wellens syndrome. It helps determine the extent and severity of the stenosis and guides further management decisions. 
• Percutaneous Coronary Intervention (PCI): PCI is the preferred treatment option if critical stenosis is confirmed. This procedure involves balloon angioplasty and stent placement to restore blood flow in the LAD and alleviate myocardial ischemia. 
• Coronary Artery Bypass Graft (CABG) surgery: In some cases where PCI is not feasible or if there are multiple significant coronary artery lesions, CABG surgery may be considered an alternative revascularization option. 

• Acute phase: During the acute phase, immediate stabilization, including pain relief, antiplatelet therapy, and continuous cardiac monitoring, is crucial. Prompt referral for coronary angiography and consideration for revascularization are vital steps. 
• Subacute and long-term management: Patients typically undergo a comprehensive evaluation of their coronary artery disease and associated risk factors after the acute phase. This includes risk factor modification (e.g., smoking cessation, blood pressure control, lipid management), initiation of guideline-directed medical therapy (e.g., beta-blockers, statins), and participation in cardiac rehabilitation programs. 

Medication

Future Trends

Media Gallary

References

• Wellens Syndrome: Wellens Syndrome – StatPearls – NCBI Bookshelf (nih.gov)