Case-Based Learning on Discordant Imaging and Biomarker Findings in Early Cardiac Dysfunction

Abstract

Discordant findings between cardiac imaging and biomarker assays present a diagnostic challenge in the early detection and management of cardiac dysfunction. This review explores the epidemiology, pathophysiology, clinical implications, and management strategies for patients exhibiting early cardiac dysfunction with discordant results, using a case-based learning approach. Emphasis is placed on integrating traditional and advanced modalities, understanding underlying mechanisms, and applying recent evidence and guideline-based recommendations to optimize patient care.

Introduction

Early recognition of cardiac dysfunction is critical for preventing progression to overt heart failure and improving patient outcomes. Clinicians increasingly rely on both cardiac imaging modalities, such as echocardiography and cardiac MRI, and circulating biomarkers like B-type natriuretic peptide (BNP) and high-sensitivity troponin. However, clinical scenarios often arise where imaging and biomarker findings are discordant, complicating diagnosis and management. This article provides a comprehensive review of such discordances, their clinical significance, and guidance for evidence-based decision-making in daily practice.

Epidemiology / Disease Burden

Cardiac dysfunction affects millions worldwide and is a leading cause of morbidity and mortality. Early-stage disease, often subclinical, is increasingly detected due to widespread use of sensitive biomarkers and advanced imaging. However, up to 20% of patients evaluated for suspected heart failure may exhibit discordant findings—normal imaging with elevated biomarkers, or vice versa—posing unique diagnostic and therapeutic dilemmas. Understanding the prevalence and burden of these discordances is essential for targeted screening and risk stratification strategies.

Pathophysiology

Cardiac dysfunction arises from complex interactions between myocardial injury, neurohormonal activation, hemodynamic stress, and structural remodeling. Biomarkers such as BNP reflect wall stress and neurohormonal activation, while high-sensitivity troponin indicates myocyte injury. Imaging detects structural and functional changes, including left ventricular ejection fraction, wall motion abnormalities, and diastolic dysfunction. Discordance can result from temporal disparities (e.g., biomarkers rise before structural changes become apparent), comorbid conditions (e.g., renal impairment elevating BNP), or technical and interpretive limitations in imaging. Understanding these mechanisms is critical for accurate interpretation and clinical decision-making.

Risk Factors

Patients at risk of discordant findings often have comorbidities such as chronic kidney disease, obesity, atrial fibrillation, or advanced age, which can independently alter biomarker levels or imaging results. For instance, obesity may attenuate natriuretic peptide levels despite structural heart disease, while chronic kidney disease may elevate BNP in the absence of overt dysfunction. Additionally, early cardiomyopathies (e.g., chemotherapy-induced or infiltrative diseases) may manifest with subtle or regionally confined abnormalities not captured by standard imaging, leading to discordant findings. Identifying these risk factors enables tailored diagnostic approaches and avoids misclassification of disease status.

Clinical Features

Patients with early cardiac dysfunction frequently present with nonspecific symptoms such as exertional dyspnea, fatigue, or mild edema. In discordant cases, symptoms may be absent or out of proportion to objective findings, challenging clinical assessment. Physical examination may reveal signs of volume overload or subtle arrhythmias. A high index of suspicion, particularly in high-risk populations, is necessary to prompt appropriate diagnostic evaluation. Case-based learning highlights the importance of integrating patient history, examination, and targeted investigations to elucidate the true extent and significance of underlying cardiac dysfunction.

Diagnosis

Diagnosis involves a combination of biomarkers (BNP, NT-proBNP, high-sensitivity troponin), imaging modalities (transthoracic echocardiography, cardiac MRI, and increasingly, strain imaging), and clinical assessment. Discordant findings may necessitate advanced investigations, including serial biomarker measurements, stress testing, or tissue characterization by cardiac MRI. Emerging data support the use of global longitudinal strain (GLS) assessment, which can detect subclinical myocardial dysfunction even when ejection fraction is preserved. Multidisciplinary team discussion and, in selected cases, endomyocardial biopsy or genetic testing may provide clarity in complex scenarios. Diagnostic algorithms increasingly emphasize the integration of multimodal data to guide management.

Treatment & Management

Management strategies should be individualized, considering the totality of clinical, imaging, and biomarker data. In patients with discordant findings, clinicians must balance the risk of under- or overtreatment. For those with elevated biomarkers and normal imaging, close monitoring, risk factor modification, and initiation of guideline-directed medical therapy (GDMT) for heart failure may be warranted. In cases with abnormal imaging but normal biomarkers, further evaluation for alternative etiologies and periodic reassessment are recommended. Patient education, lifestyle modification, and comorbidity management remain cornerstones of care, ensuring optimal outcomes regardless of initial diagnostic ambiguity.

Recent Advances / Emerging Therapies

Recent advances include the application of artificial intelligence and machine learning algorithms to integrate and interpret complex multimodal data, improving diagnostic accuracy in discordant cases. Novel biomarkers, such as galectin-3 and soluble ST2, offer additional prognostic information and may help resolve diagnostic uncertainty. Strain imaging and tissue characterization by cardiac MRI have become invaluable for early detection of subclinical dysfunction. Pharmacologic advances include the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and angiotensin receptor-neprilysin inhibitors (ARNIs), which have demonstrated benefit even in patients with preserved ejection fraction and may be considered in selected discordant cases based on emerging evidence.

Guideline Recommendations

Major guidelines from the American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) emphasize a patient-centered, multimodal approach to the evaluation of cardiac dysfunction. In the setting of discordant findings, guidelines recommend repeated assessment, consideration of comorbid conditions affecting test interpretation, and shared decision-making with patients regarding management. Multidisciplinary heart teams are encouraged to guide complex cases, ensuring that diagnostic and therapeutic decisions are tailored to the individual patient's risk profile and clinical context. Ongoing research is expected to refine guidance for managing discordance in the diagnostic workup.

Conclusion

Discordant imaging and biomarker findings in early cardiac dysfunction are common and pose significant challenges for clinicians. A systematic, mechanism-based, and patient-specific approach integrating clinical, biomarker, and imaging data is essential. Advances in diagnostic modalities and therapeutics continue to improve our ability to detect and manage early disease. Ongoing research and guideline evolution will further enhance the care of patients with discordant findings, ultimately reducing the burden of cardiac dysfunction and improving outcomes.