Chest pain is a common symptom in both emergency and outpatient settings, with a broad differential diagnosis that includes acute coronary syndrome (ACS) and pulmonary embolism (PE) (1). Correctly distinguishing between these conditions is critical, as misdiagnosis can lead to inappropriate management and poor patient outcomes (2). ACS and PE often present with overlapping symptoms such as chest pain and dyspnea, complicating the diagnostic process (3).

Acute coronary syndrome refers to a spectrum of conditions like unstable angina and myocardial infarction caused by acute myocardial ischemia, diagnosed through clinical assessment, electrocardiogram (ECG), and cardiac biomarkers (4). In contrast, PE results from obstruction of the pulmonary arteries, typically due to thrombi from deep vein thrombosis, and is diagnosed using imaging such as computed tomography pulmonary angiography (CTPA) (5, 6). This case report underscores the diagnostic challenges between ACS and PE, emphasizing the need for a thorough approach to ensure accurate and timely treatment.

PE and ACS share overlapping symptoms, such as chest pain and dyspnea, which can lead to misdiagnosis. Both conditions can present with non-specific signs, and elevated markers of myocardial injury may also occur in PE due to right ventricular strain. In ACS, sustained troponin elevation reflects left ventricular myocardial necrosis, whereas in PE, transient troponin rise is linked to right ventricular microinfarction. Similarly, NT-proBNP elevation in PE correlates with right ventricular strain, contrasting with its association with left heart failure in ACS. The predictive value of these biomarkers is supported by studies showing that a hsTnT cutoff ≥14 pg/mL in PE predicts adverse outcomes (OR = 4.97; 95% CI = 1.71–14.43; P = 0.003) (9), while elevated NT-proBNP strongly predicts right ventricular dysfunction (P < 0.001) and higher risks of in-hospital complications (OR = 6.8; 95% CI = 4.4–10) (10).

This challenge is heightened in patients with risk factors for both thromboembolic and cardiovascular diseases. In this case, the patient’s smoking, hypertension, and chronic kidney disease complicated the distinction between ACS and PE. Initial ECG changes and elevated troponins, usually linked to myocardial ischemia, suggested an acute cardiac event. CAG was promptly performed to rule out life-threatening causes, but the absence of significant coronary artery stenosis redirected the diagnostic focus to PE.

The diagnosis of PE often requires heightened clinical suspicion, especially when initial evaluations like CAG do not reveal cardiac causes of symptoms. The Wells and Geneva scores are widely used to assess PE probability and guide further testing (11). While the Wells score has high sensitivity, it has lower specificity, leading to more false positives in low-risk patients (12). The Geneva score, though less subjective, offers similar utility but may be slightly less sensitive in certain populations (13). It’s important to note that these tools are just part of the diagnostic process. In this case, although the patient had a low pretest probability based on both scores, the Pulmonary Embolism Rule-Out Criteria (PERC) couldn’t exclude PE, as the patient was over 50 years old (14). This illustrates the need for further diagnostic work-up even with low scores and highlights the importance of combining clinical judgment with comprehensive evaluation to avoid missing a PE diagnosis.

D-dimer is a fibrin degradation product often elevated in conditions involving significant clot formation and breakdown (15). Elevated D-dimer levels can occur in various conditions, including ACS, infections, malignancies, and trauma, reducing its utility as a standalone diagnostic marker (16). However, D-dimer is crucial in diagnosing PE, especially when combined with clinical pretest probability (C-PTP) assessments. A study indicated that among patients with low C-PTP and D-dimer levels below 1000 ng/mL, or moderate C-PTP with levels below 500 ng/mL, none of the 1,325 patients had thromboembolic complications during follow-up (17). This approach increased the percentage of patients avoiding chest imaging from 48.1 to 65.7%, representing a 33.9% relative reduction. These findings highlight that a normal D-dimer level can effectively rule out PE in low-to moderate-risk patients, while elevated levels require further investigation. In this case, the patient’s significantly elevated D-dimer raised suspicion of thromboembolism, confirmed by imaging showing DVT and PE. Thus, D-dimer testing should be routinely considered in patients with clinical ambiguity or thromboembolic risk factors to avoid missed PE diagnoses, especially when symptoms overlap with ACS.

The management strategies for PE and ACS differ significantly, particularly regarding antithrombotic therapy. While ACS treatment primarily relies on antiplatelet agents and reperfusion therapies (18), the cornerstone of PE treatment is anticoagulation, which prevents further clot formation and aids in resolving existing thrombi (11). When a clear diagnosis is uncertain, balancing the risks of bleeding against the benefits of preventing thromboembolic events is crucial. In patients with low bleeding risk, early anticoagulation initiation can be considered, especially if PE is strongly suspected. In this case, anticoagulation therapy was promptly started after CAG ruled out ACS, given the ongoing suspicion of PE. This early intervention is critical in reducing mortality and complications associated with PE.

This study provides novel insights into two critical challenges in cardiopulmonary medicine: (1) distinguishing low-risk PE from high-risk ACS and (2) refining therapeutic strategies for borderline-risk patients. First, we demonstrate that biomarker elevations (troponin and D-dimer) combined with echocardiographic evidence of right ventricular strain (moderate tricuspid regurgitation, Increased pulmonary artery pressure) may indicate clinically significant thrombotic burden in low-risk PE patients (PESI class I)—challenging sole reliance on clinical prediction scores. Second, we validate the role of aggressive mechanical interventions (dual thrombectomy + IVC filter) in patients with DVT, where anticoagulation monotherapy fails to address recurrent embolic risks. Third, we emphasizes a multidisciplinary approach for optimizing patient outcomes (19), especially in complex cases like this one. These findings underscore the necessity of physiologic risk assessment over static scoring systems and redefine therapeutic strategy for ostensibly “low-risk” PE patients to improve outcomes (20).

Both PE and ACS are life-threatening conditions that require prompt diagnosis and treatment to prevent serious complications. This case report highlights the challenges in distinguishing between these two conditions, emphasizing the importance of thorough clinical evaluation when symptoms overlap. Clinicians should maintain a high index of suspicion for PE in patients presenting with ACS-like symptoms, particularly when initial cardiac investigations fail to reveal a clear ischemic cause. Timely recognition and appropriate management are essential to improve patient outcomes.