Patients with suspected chronic coronary syndrome: initial clinical management and diagnostic probability assessment

4 Mar, 2025

Scientific

Coronary Artery Disease (Chronic)

Doctor Alexander Kharlamov

FESC

Chronic coronary syndrome represents a broad spectrum of stable coronary artery disease, requiring an accurate initial assessment for effective management. The pre-test probability assessment guides the diagnostic pathway, incorporating clinical risk factors, symptoms, and patient characteristics. The ESC and AHA/ACC guidelines advocate for a structured approach using non-invasive imaging, including coronary computed tomography angiography, myocardial perfusion imaging, and cardiac magnetic resonance imaging, tailored to individual risk profiles. A multimodality imaging strategy enhances diagnostic accuracy while minimising unnecessary invasive procedures. Clinicians should integrate risk assessment tools with patient-centred care to optimise early management, improve outcomes, and ensure efficient healthcare resource utilisation. Topic(s): Coronary Artery Disease (Chronic)

Keywords

chronic coronary syndrome, diagnostic pathways, non-invasive imaging, pre-test probability, risk stratification

Abbreviation list:

AHA/ACC: American Heart Association/American College of Cardiology

CAD: coronary artery disease

CCTA: coronary computed tomography angiography

CMR: cardiac magnetic resonance

CCS: chronic coronary syndrome

ECG: electrocardiogram

ESC: European Society of Cardiology

MPI: myocardial perfusion imaging

PTP: pre-test probability

Take-home messages

Pre-test probability (PTP) assessment is essential in guiding diagnostic decisions for suspected CCS, reducing unnecessary testing.
A patient-centred approach integrating symptoms, risk factors, and imaging results enhances clinical decision-making.
Non-invasive imaging modalities, such as CCTA, MPI, and CMR, are pivotal in diagnosing and risk stratifying patients.
Future advancements, including artificial intelligence and novel biomarkers, may refine diagnostic accuracy and personalised CCS management.

Impact on practice

Accurate risk stratification and pre-test probability assessment are fundamental in the initial evaluation of suspected chronic coronary syndrome. Incorporating a multimodality imaging approach helps tailor diagnostic strategies, reducing unnecessary invasive procedures while ensuring timely intervention in high-risk patients. Clinicians must balance guideline recommendations with individual patient profiles to optimise care. Understanding the strengths and limitations of different diagnostic tools can enhance early disease detection, improve clinical outcomes, and refine healthcare resource allocation.

Patient-oriented message

Patients experiencing symptoms like chest discomfort, shortness of breath, or fatigue may require an evaluation for CCS—a condition related to reduced blood flow to the heart. To begin, you and your physician may have a detailed discussion about symptoms, medical history, and risk factors like high blood pressure, diabetes, or smoking. Based on this, your physician will estimate the likelihood of significant heart artery disease using a pre-test probability (PTP) assessment, which helps guide the next steps. Lifestyle changes and regular monitoring may be recommended if your risk is low. If your risk level is higher, further tests—such as heart scans or stress tests—may be needed to assess blood flow to the heart. The goal is to ensure that patients receive the proper care while avoiding unnecessary tests and procedures.

Introduction

Chronic coronary syndrome (CCS) poses a significant public health challenge, encompassing a range of clinical manifestations associated with coronary artery disease (CAD). The latest guidelines from the European Society of Cardiology (ESC) have reshaped the diagnostic and management strategies for CCS, highlighting the necessity of precise risk stratification and individualised treatment approaches [1]. This article seeks to consolidate current insights on the initial clinical evaluation and diagnostic probability assessment of suspected CCS cases, focusing on the most recent evidence-based guidelines and diagnostic techniques.

Understanding chronic coronary syndrome

CCS includes a range of clinical presentations of CAD, such as stable angina and silent ischemia, which, if not properly managed, can result in substantial morbidity and mortality [2]. The ESC guidelines have transitioned from using the term "stable CAD" to "chronic coronary syndrome" to highlight the continuous risk of adverse cardiovascular events in these patients [3]. This revision reinforces the need for thorough assessment and personalised management strategies tailored to each patient's profile.

Initial clinical assessment

The initial evaluation of patients with suspected CCS starts with a detailed discussion with the patient about the symptoms, medical history, risk factors, the identification of potential comorbidities and physical examination [4]. CCS symptoms can vary widely, contributing to underdiagnosis or misdiagnosis if not thoroughly assessed [2]. A comprehensive understanding of the patient's clinical presentation, including atypical manifestations, is essential for accurate diagnosis and effective management. Based on this, the doctor will estimate the likelihood of significant heart artery disease using a pre-test probability (PTP) assessment, which guides the next steps [4].

Risk stratification and diagnostic probability assessment

The ESC guidelines advocate using a PTP assessment to classify patients based on their likelihood of having obstructive CAD [3]. This approach considers clinical factors such as age, sex, and symptom characteristics to inform subsequent diagnostic decisions. For example, patients with a high PTP may require invasive testing, whereas those with a low PTP may be managed conservatively [5].

Recent studies have validated the updated PTP models, confirming their effectiveness in clinical practice [3]. Additionally, coronary artery calcium scoring (CACS) has been proposed as a valuable tool for risk stratification, especially in asymptomatic individuals with CAD risk factors [6]. However, current guidelines do not universally endorse CACS for all patients, emphasising the importance of individualised assessment based on clinical context [6].

Pre-test probability

Understanding PTP

In the context of CCS, PTP plays a vital role in guiding the appropriate diagnostic approach [7]. Based on clinical factors such as age, sex, symptom presentation, and risk factors, the ESC guidelines classify PTP into three categories: low (<5%), intermediate (5–15%), and high (>15%) [7]. Note that the 2019 ESC guidelines revised the PTP thresholds, with low risk from 15% to 5% [7]. Additionally, the updated guidelines highlight the importance of combining clinical judgment with validated scoring models, such as the Diamond-Forrester model, to improve the accuracy of PTP assessment [8].

Clinical factors influencing PTP assessment

Age and sex are among the strongest predictors of CCS, as CAD prevalence rises with age and differs between sexes [8]. For example, younger women often present with atypical symptoms, which can contribute to underdiagnosis, whereas older men are more likely to experience classic angina symptoms [2].

Symptom presentation is another key determinant, with patients exhibiting typical angina having a higher PTP compared to those with atypical symptoms [9]. Additionally, traditional risk factors such as hypertension, diabetes, hyperlipidaemia, and smoking further increase the probability of CAD [2]. Incorporating these factors into PTP assessment enables a more individualised approach to diagnosis and management.

Diagnostic testing based on PTP assessment

The ESC guidelines recommend a stepwise approach to diagnostic testing based on the PTP assessment. For patients with low PTP, non-invasive testing may not be necessary, and clinicians can consider a conservative management approach [9]. In contrast, an intermediate or high PTP, should lead to further diagnostic evaluation to confirm or exclude the presence of obstructive CAD.

Non-invasive imaging modalities, such as coronary computed tomography angiography (CCTA) and functional imaging tests (e.g., stress echocardiography and myocardial perfusion imaging), are recommended for patients with intermediate to high PTP [10]. These tests provide valuable information regarding the presence and extent of coronary artery disease, guiding subsequent management decisions.

Role of non-invasive imaging in PTP assessment

Non-invasive imaging is crucial in evaluating patients with suspected CCS, especially those with intermediate PTP. CCTA has become a first-line diagnostic tool due to its high sensitivity and specificity in detecting obstructive CAD, allowing for effective risk stratification [10].

Functional imaging tests, such as stress echocardiography and myocardial perfusion imaging, are valuable for assessing myocardial ischaemia [10]. These modalities help evaluate the functional significance of coronary lesions, which is essential for guiding treatment strategies.

Impact of comorbidities on PTP assessment

Conditions such as diabetes, chronic kidney disease, and peripheral artery disease are linked to a higher risk of adverse cardiovascular events [2]. These comorbidities require a more thorough evaluation of the patient's overall cardiovascular risk profile, which can influence the interpretation of PTP and the choice of subsequent diagnostic tests.

For example, patients with chronic kidney disease often have elevated troponin levels, which can complicate the assessment of myocardial injury and require careful interpretation of diagnostic findings [9]. Likewise, diabetes can modify the typical presentation of angina, increasing the risk of underdiagnosing CAD in this population [2].

Challenges in PTP assessment

Despite advancements in PTP assessment, several challenges persist. Variability in clinical practice, differences in patient populations, and the subjective nature of clinical judgment can contribute to inconsistencies in PTP evaluations [9]. Additionally, relying solely on traditional risk factors may not fully account for the complexity of CAD, particularly in women and younger patients [8].

Incorporating novel biomarkers and advanced imaging techniques can improve the accuracy of PTP assessments and enhance risk stratification in these challenging cases [9]. Further research is necessary to validate these approaches and develop standardised protocols for PTP assessment across diverse patient populations.

Future directions in PTP assessment

Future research should aim to refine PTP assessment methods and investigate the potential of emerging diagnostic technologies. Integrating artificial intelligence and machine learning algorithms into risk stratification models may enhance the precision of PTP assessments and support personalised treatment approaches [7].

Developing comprehensive risk assessment tools that combine clinical, imaging, and biomarker data could offer a more holistic evaluation of a patient’s cardiovascular risk profile [9]. and empower clinicians to make well-informed decisions regarding diagnostic testing.

Finally, the pre-test probability assessment plays a key role in guiding clinical decisions and management strategies. The ESC guidelines offer a comprehensive framework for PTP assessment, highlighting the need to incorporate clinical factors, validated scoring models, and non-invasive imaging techniques.

Diagnostic modalities

The choice of diagnostic modality is critical in the management of suspected CCS (Figure 1). The ESC guidelines advocate non-invasive imaging techniques, such as CCTA and functional imaging, as first-line diagnostic tests [11]. CCTA has gained prominence due to its high sensitivity and specificity for detecting obstructive CAD, making it a valuable tool in the diagnostic workup of CCS [12].

Figure 1. Stepwise approach to the initial evaluation and management of patients with suspected chronic coronary syndrome. Reproduced with permission from [13].

^a In selected patients. ^b Consider also coronary spasm or microvascular dysfunction. ANOCA: angina with non-obstructive coronary arteries; CAD: coronary artery disease; CCTA: coronary computed tomography angiography; ECG: electrocardiogram; ED: emergency department; GDMT: guideline-directed medical therapy; INOCA: ischaemia with non-obstructive coronary arteries.

In addition to CCTA, other non-invasive modalities, such as stress cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT), are also recommended for assessing cardiac function and perfusion and identifying patients who may benefit from revascularisation [14].

Overview of imaging modalities in CCS

A stepwise approach is recommended in order to accurately diagnose CAD, evaluate the severity of the disease, and guide treatment decisions.

The primary imaging modalities include:

CCTA
Cardiac magnetic resonance imaging (CMR)
Myocardial perfusion imaging (MPI)
Echocardiography

Each modality has unique strengths and limitations, which clinicians must consider when selecting the appropriate imaging technique for individual patients.

CCTA

CCTA has become a first-line non-invasive imaging modality for evaluating CAD, particularly in patients with low to intermediate pre-test probability [15]. The ESC guidelines designate CCTA as a Class I recommendation for the initial assessment of patients with suspected CCS [11], based on its high sensitivity and specificity for detecting obstructive CAD, [16].

Beyond detecting obstructive CAD, CCTA also offers insights into coronary artery morphology and the presence of non-obstructive plaques, which may have clinical significance [17]. However, CCTA has certain limitations. The procedure involves exposure to ionising radiation, raising concerns about long-term risks, especially in younger patients [16]. Additionally, CCTA may be less suitable for individuals with high heart rates or significant arrhythmias, as these factors can compromise image quality [11]. Moreover, extensive coronary calcification can create artefacts that may interfere with accurate result interpretation.

CMR

CMR is a valuable imaging modality for evaluating myocardial perfusion, cardiac function, and tissue characterisation [18, 19]. The ESC guidelines classify CMR as a Class I recommendation for patients with suspected CAD, especially when other imaging techniques yield inconclusive results [5].

One of CMR's key advantages is its ability to provide comprehensive cardiac structural and functional information without exposing patients to ionising radiation. It can assess myocardial perfusion during stress testing, facilitating the detection of functionally significant coronary artery lesions [20]. Additionally, CMR can evaluate myocardial viability using late gadolinium enhancement (LGE), essential for determining the suitability of revascularisation procedures [18].

However, CMR has some limitations, including limited availability, high costs, and the need for specialised personnel for image acquisition and interpretation [18, 19]. Furthermore, specific patient contraindications, such as implanted medical devices or severe claustrophobia, may restrict its use [5].

MPI

MPI is a non-invasive imaging technique used to evaluate myocardial blood flow and is widely utilised in assessing patients with suspected CAD [20]. The ESC guidelines recognise MPI as an essential risk stratification and diagnosis tool in patients with CCS [10]. By providing crucial insights into myocardial perfusion, MPI can detect areas of ischaemia that may not be apparent on anatomical imaging [21].

This technique is particularly beneficial for patients with atypical symptoms or a high likelihood of balanced ischaemia, where anatomical imaging alone may be inconclusive [21]. Additionally, MPI can be performed using various radiotracers, offering flexibility in clinical practice. However, MPI has certain limitations, including exposure to ionising radiation and the risk of false-positive results due to attenuation artifacts or patient motion [21]. Moreover, as MPI does not provide detailed anatomical information, additional imaging modalities may be required for a comprehensive assessment.

Echocardiography

The ESC guidelines recommend echocardiography for evaluating patients with suspected CCS [22] and assessing cardiac structure and function, particularly in individuals with heart failure or valvular disease [23].

However, echocardiography has some limitations, including operator dependency and potential challenges in image quality due to factors such as obesity or lung disease [23]. Furthermore, it fails to reveal coronary artery anatomy, requiring supplementary imaging modalities for a more comprehensive evaluation.

Multimodality imaging approach

The ESC guidelines emphasise a multimodality imaging approach for assessing CCS, recognising that combining different imaging techniques can provide a more comprehensive evaluation [24]. For instance, integrating CCTA with functional imaging modalities such as MPI or CMR enhances diagnostic accuracy and improves risk stratification. This approach enables clinicians to capitalise on the strengths of each imaging method while minimising their limitations. CCTA offers detailed anatomical insights, whereas MPI assesses the functional significance of coronary lesions, leading to more informed treatment decisions [24]. Such an integrated strategy is particularly valuable in complex cases where conventional imaging alone may not provide definitive results.

Despite its advantages, adopting a multimodality imaging strategy presents challenges, including higher costs, logistical difficulties, and the need for coordinated care across multiple specialties [24]. Additionally, interpreting findings from various imaging techniques requires significant expertise, which may not be readily available in all clinical settings.

Anatomical vs functional diagnostic approaches

Overview of imaging modalities in CCS

The ESC guidelines recommend a multimodal approach to imaging in patients with suspected CCS, incorporating anatomical and functional assessments to evaluate coronary artery health comprehensively. The primary imaging modalities include:

Anatomical imaging: primarily represented by CCTA, which provides detailed images of coronary artery anatomy.
Functional imaging: includes modalities such as MPI, CMR, and stress echocardiography, which assess myocardial perfusion and function.

Comparison of anatomical and functional imaging approaches

The choice between anatomical and functional imaging approaches in CCS depends on various factors, including the clinical scenario, patient characteristics, and the specific information required for diagnosis and management.

Clinical scenarios favouring anatomical imaging

Anatomical imaging, particularly CCTA, is often preferred in the following scenarios:

Low to intermediate pre-test probability: CCTA effectively rules out CAD in patients with low to intermediate pre-test probability, providing reassurance and potentially avoiding unnecessary invasive procedures [11].
Assessment of coronary anatomy: CCTA is the gold standard for visualising coronary artery anatomy, making it ideal for patients with known CAD who require information on disease progression or further evaluation of coronary anatomy before revascularisation [11].

Clinical scenarios favouring functional imaging

Functional imaging is favoured in the following scenarios:

Assessment of myocardial ischaemia: MPI and CMR are beneficial for assessing myocardial ischaemia, especially in patients with atypical symptoms or a high likelihood of balanced ischaemia [18].
Risk stratification: functional imaging provides valuable prognostic information regarding the likelihood of future cardiovascular events, helping to guide treatment decisions [19].

Challenges in implementation

Although comprehensive guidelines are available, challenges persist in implementing the recommended practices for CCS management. Factors such as disparities in healthcare systems, limited access to advanced imaging modalities, and variations in clinician expertise can influence the quality of care for patients with suspected CCS [11]. Furthermore, the integration of emerging diagnostic technologies, including artificial intelligence for CCTA interpretation, offers promising advancements and practical challenges for clinical practice [12].

Role of biomarkers

Recent research has underscored the potential of biomarkers in diagnosing and managing CCS. Circulating exosomal circRNAs have emerged as promising diagnostic markers, distinguishing CCS patients from those with non-cardiac chest pain [25]. Moreover, traditional biomarkers such as troponins may offer valuable prognostic insights, especially in patients with comorbidities like chronic kidney disease [26].

Future directions

Future research should focus on refining diagnostic algorithms and exploring novel therapeutic approaches for CCS. The ongoing development of advanced imaging techniques and biomarkers holds promise for enhancing diagnostic accuracy and personalising treatment strategies [27]. Furthermore, large-scale studies are needed to evaluate the long-term outcomes of patients managed according to the latest guidelines, ensuring that evidence-based practices are effectively translated into clinical care.

Conclusion

The management of patients with suspected chronic coronary syndrome requires a comprehensive approach that integrates clinical assessment, risk stratification, and appropriate diagnostic testing. The ESC guidelines provide a robust framework for clinicians to navigate the complexities of CCS management, emphasising the importance of personalised care. As research continues to evolve, integrating innovative diagnostic modalities and therapeutic strategies will be essential in improving outcomes for patients with CCS.

Note to editors

Authors:

Alexander Kharlamov, MD, FESC, FACC, FEACVI

Affiliation:

De Haar Research Task Force, Rotterdam, the Netherlands

Address for correspondence:

Dr Alexander Kharlamov, DHRF, Keurenplein 41, 1069CD Amsterdam, the Netherlands

E-mail

X: @drskharlamov

Author disclosures:

The author declares no conflict of interest.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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