Decoding Complexity: A Multimodal Approach in the Diagnosis of Isolated Cardiac Sarcoidosis

Abstract

Sarcoidosis is a chronic inflammatory condition of uncertain origins, affecting multiple organs and characterized by the formation of granulomas. Cardiac involvement, known as cardiac sarcoidosis (CS), occurs in 5%–10% of cases and can lead to heart failure, arrhythmias, and sudden death. Distinguishing CS from other heart conditions poses a significant challenge. However, improved diagnostic techniques such as cardiac magnetic resonance (CMR) and positron emission tomography combined with computed tomography (CT) have enhanced recognition rates, replacing invasive procedures like endomyocardial biopsy. Clinical guidelines have further facilitated diagnosis. This case report underscores the diagnostic complexity of CS and highlights the emerging role of contrast-enhanced cardiac CT as a viable alternative to CMR, particularly in patients with contraindications to CMR.

INTRODUCTION

Cardiac sarcoidosis (CS) is a significant cause of mortality in sarcoidosis patients worldwide, particularly among Japanese patients.[1] It typically presents with ventricular arrhythmias, high-grade blockages, or symptoms of heart failure (HF).[2] Clinically manifest CS occurs in 3%–10% of patients with sarcoidosis in America and Europe, although its prevalence from certain autopsy studies is estimated to be up to 25%.[3] Diagnosing CS remains challenging, but advancements in imaging techniques, along with clinical guidelines, have improved detection rates.[4] This clinical case is of particular interest as it not only describes complex cardiomyopathy but also demonstrates the utility of computed tomography (CT) as an additional diagnostic tool in facilitating the final diagnosis.[5]

CASE REPORT

A 76-year-old man with a medical history of hypertension, type 2 diabetes, and subclinical hyperthyroidism was admitted to our hospital center due to acute HF. At the age of 49, he underwent permanent dual-chamber pacemaker implantation for advanced atrioventricular block, both leads were not compatible with cardiac magnetic resonance (CMR). Unfortunately, the patient didn’t undergo further diagnostic evaluation beyond transthoracic echocardiography (TTE), which revealed preserved biventricular function without regional wall motion abnormalities. Despite his relatively young age, no additional diagnostic tests were conducted to investigate the underlying cause of the conduction disorder. He received regular cardiology follow-up until 2023, when he experienced sustained ventricular tachycardia with a right bundle branch block morphology, prompting medication adjustments and pacemaker upgrade to an intracavitary defibrillator.

Despite optimized antiarrhythmic therapy, the patient was readmitted for recurrent ventricular tachycardia, leading to an increase in antiarrhythmic medication and scheduling for electrophysiological study and potential ablation. During his most recent admission, he presented with worsening dyspnea and palpitations but was asymptomatic at rest upon admission to the cardiology department. Physical examination revealed mild signs of peripheral and central congestion, which resolved rapidly with diuretic therapy. Laboratory tests showed elevated N-terminal probrain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels. Chest X-ray revealed initial pulmonary congestion, whereas the electrocardiogram showed a paced atrioventricular rhythm [Figure 3]. Defibrillator interrogation revealed no major arrhythmias or recent device interventions.

Figure 3.

12-lead electrocardiogram showing a pacing-induced atrioventricular rhythm

Subsequent TTE revealed severe left ventricular enllargement with significantly reduced ejection fraction (EF), global longitudinal strain abnormalities, and regional wall motion abnormalities [Figure 4]. Although recent coronary angiography showed no significant lesions, the deterioration in ventricular function raised suspicion of inflammatory cardiomyopathy. Further investigations for CS included specific blood tests and assessment for extracardiac manifestations, all yielding inconclusive results. In particular calciuria, angiotensin-converting enzyme and interleukin-2 receptor resulted negative, whereas beta2 microglobulin resulted slightly increased. The fundus oculi excluded ocular involvement.

Figure 4.

Transthoracic echocardiography four-chamber view showing severe left ventricular enlargement and hypertrophy

To evaluate myocardial fibrosis, due to contraindications for CMR, we performed contrast-enhanced cardiac CT (CT-LE) that revealed late enhancement (LE) in the basal lateral wall of the left ventricle [Figure 1].

Figure 1.

Cardiac computed tomography late enhancement short axis in a 76-year-old male with cardiac sarcoidosis, showing late gadolinium enhancement extending almost through all the thickness of the basal lateral wall of the left ventricle (LV)

Whole-body ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) combined with CT demonstrated hypermetabolism in the basal and lateral segments of the left ventricle, matching the perfusion defect observed on CT-LE. This “mismatch pattern” is highly suggestive of CS and a predictor of cardiac events. In addition, 18F-FDG-PET excluded the involvement of other organs [Figure 2].

Figure 2.

Whole-body 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography short axis view in a 76-year-old male with cardiac sarcoidosis, showing hypermetabolism at the basal and lateral segments of the left ventricle

Based on these findings and in accordance with Japanese Circulation Society (JCS) criteria,[6] a clinical diagnosis of isolated CS was established, bypassing the need for endomyocardial biopsy (three major criteria were satisfied: [1] high-grade atrioventricular block; [2] left ventricular contractile dysfunction or focal ventricular wall asynergy; and [3] F-FDG PET reveals abnormally high tracer accumulation in the heart). Endomyocardial biopsy was not performed as the risk–benefit ratio was considered too high; indeed, the patient was not in an advanced disease state such as cardiogenic shock or arrhythmic storm and the late gadolinium enhancement (LGE) was localized to the left ventricle only. Immunosuppressive therapy with prednisone was initiated, along with standard HF treatment for reduced EF. After 3 months of therapy, significant reductions in NT-proBNP and hs-cTnT levels were observed, along with improvements in functional capacity and a reduction in major ventricular arrhythmias. Subsequent thoracic 18F-FDG-PET/CT demonstrated no cardiac uptake, indicating a successful treatment response. Corticosteroid therapy was gradually tapered, and a semiannual cardiology follow-up was scheduled given the favorable response to treatment and clinical improvement [Table 1].

Table 1.

Key events and findings in the patient’s timeline from admission to outcome

Time point		Event
Admission		Admitted to the emergency department for dyspnea and asthenia
Medical history		He had a pacemaker implanted and a few years later a defibrillator upgrade due to ventricular tachycardia
Initial diagnosis		Initially diagnosed with acute HF decompensation. The ischemic cause was ruled out thanks to a negative invasive coronary angiography
Blood test		Increased markers of myocardiocytolysis (hs-cTnT) and NT-proBNP
Imaging		Chest X-ray showed initial pulmonary congestion without pleural effusion
		TTE showed severely reduced EJ due to wall motion abnormalities
Further imaging		Whole-body 18F-fluorodeoxyglucose positron emission tomography revealed hypermetabolism at the basal and lateral segments of the left ventricle with no extra-cardiac uptake
CT findings		Contrast-enhanced cardiac compute tomography demonstrates LE extending almost through all the thickness of the basal lateral wall of the LV
Treatment		Prednisone titrated down every 4 weeks in decrements of 5–10 mg/day and first-line therapy for HF with reduced EJ
Outcomes		Significant reduction levels of NT-proBNP and hs-cTnT. Improvement of functional capacity in his daily activities and no further major ventricular arrhythmias

CT=Computed tomography, hs-cTnT=High-sensitivity cardiac troponin T, NT-proBNP=N-terminal probrain natriuretic peptide, HF=Heart failure, TTE=Transthoracic echocardiography, EJ=Ejection fraction, LE=Late enhancement

DISCUSSION

This case report emphasizes the importance of investigating the etiology of certain clinical manifestations, especially when suspected, through second-level techniques that are becoming increasingly widespread today, such as CMR and CT, confirming the importance of a multimodal imaging approach, especially in the context of such complex and rare cardiomyopathies. In particular, we highlighted the advances toward which cardiac CT is heading. LGE-CMR is considered the gold standard for the assessment of myocardial scar and fibrosis in many cardiomyopathy guidelines.[7]

CMR can accurately quantify the extent and distribution of hypertrophy, assess the presence and severity of myocardial fibrosis, and detect associated abnormalities. Finally, CMR is useful for distinguishing cardiac amyloidosis (CA) from other cardiomyopathies, such as hypertrophic cardiomyopathy, CA, Anderson–Fabry disease, and mitochondrial cardiomyopathies.[8] Although LGE-CMR remains the preferred modality, CT-LE is emerging as a viable alternative to CMR, particularly in patients with non-CMR compatible external devices.[9] When CT-LE is performed with a customized and optimized protocol, it achieves high quality, maintaining an appropriate radiation dose and offering a superior spatial and temporal resolution compared with that of CMR.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.