Imaging Favored Cardiac Sarcoidosis, But Tissue Told a Different Story
A 43-year-old woman with biopsy-proven systemic sarcoidosis and dilated cardiomyopathy entered care with recurrent decompensated heart failure and a diagnostic question that can dominate inflammatory cardiomyopathy practice: was this cardiac sarcoidosis, active myocarditis, or both? Fluorodeoxyglucose positron emission tomography-computed tomography showed diffuse myocardial uptake and was interpreted as probable cardiac sarcoidosis. On paper, the imaging fit a familiar inflammatory pattern. At the bedside, the trajectory did not cooperate.
Despite guideline-directed heart failure therapy and immunosuppression, her clinical course moved in the wrong direction. Progressive heart failure was followed by renal failure and refractory shock, and she died. The post-mortem myocardial biopsy shifted the center of gravity of the case: active non-granulomatous myocarditis was present, but granulomas were absent. Rare viral inclusion-like structures consistent with cytomegalovirus were identified in lung tissue, while immunohistochemistry remained negative.
Why Probable Cardiac Sarcoidosis Can Overreach the Data
Cardiac sarcoidosis is notoriously difficult to diagnose when tissue is scarce, patchy, or inaccessible. In practice, clinicians often rely on a composite of extracardiac sarcoidosis, imaging abnormalities, arrhythmic burden, ventricular dysfunction, and treatment response. FDG uptake strengthens suspicion because activated inflammatory cells consume glucose avidly, but uptake alone cannot prove granulomatous infiltration. Diffuse myocardial signal can also appear in other inflammatory cardiomyopathies, including active non-granulomatous myocarditis, where cellular inflammation alters myocardial metabolism without the histologic hallmark of sarcoid granulomas.
This case illustrates the hazard of equating metabolic activity with a single disease mechanism. A positive PET scan may justify urgent treatment, but it does not settle pathology. When the myocardium is inflamed, the heart can look deceptively similar across distinct etiologies, and the therapeutic consequences diverge sharply once immunosuppression enters the picture.
A diffuse FDG pattern is not a pathology report.
Progressive Deterioration Under Immunosuppression Raises the Stakes
The worsening course despite treatment mattered because it forced the team to confront the possibility that the initial working diagnosis was incomplete. Steroid resistance is described as uncommon in cardiac sarcoidosis, so continued decline after immunosuppression should trigger a second diagnostic pass rather than simple escalation. In inflammatory cardiomyopathy, persistent hemodynamic collapse can reflect inadequate disease control, misclassified disease, superimposed infection, or a second process entirely. Renal failure and refractory shock narrowed the margin for error quickly.
The case also raises a difficult bedside issue: immunosuppression can be life-saving when granulomatous inflammation is truly driving myocardial injury, but it can be harmful if the dominant process is infectious or if the tissue diagnosis is wrong. Cytomegalovirus entered the differential because of the inclusion-like structures seen in lung tissue and the elevated cytomegalovirus titres, even though immunohistochemistry was negative. Those findings did not establish active viral myocarditis, but they reinforced how wide the differential becomes when a patient with systemic inflammatory disease deteriorates under treatment.
Post-Mortem Biopsy Reframed the Final Diagnosis
The autopsy biopsy documented active non-granulomatous myocarditis without granulomas. That distinction matters because it separates a granulomatous cardiomyopathy from a different inflammatory pattern that may require a different infectious, autoimmune, or supportive approach. The absence of granulomas does not automatically exclude sarcoidosis everywhere in the heart, however, because myocardial involvement in sarcoidosis is famously patchy. Sampling error remains a real limitation even with tissue confirmation, and the post-mortem setting cannot reconstruct the full burden of disease across the living myocardium.
So the diagnosis did not collapse into certainty; it became more precise and more constrained. Active myocarditis was real. Granulomatous inflammation was not demonstrated. Co-existing cardiac sarcoidosis could not be definitively ruled out because tissue sampling after death cannot sample every diseased region in a patchy myocardial process.
Tissue Reassessment Should Not Wait for Collapse
The clinical message is straightforward for teams managing inflammatory cardiomyopathy: when the course worsens despite 2 to 4 weeks of intensive therapy, the threshold for myocardial tissue reassessment should fall. Imaging remains essential, but imaging should not monopolize decision-making when hemodynamics deteriorate, renal function fails, or shock emerges. A multidisciplinary framework is not a formality here; it is the only way to integrate heart failure management, imaging interpretation, pathology, and infectious evaluation before a narrow therapeutic window closes.
This case also exposes the limits of therapeutic momentum. Once probable cardiac sarcoidosis is named, subsequent treatment decisions can drift toward confirmation bias, especially when extracardiac sarcoidosis is already proven. Yet myocardial inflammation is not a single entity. Granulomatous sarcoid infiltration, non-granulomatous myocarditis, and infectious mimics can all produce decompensation, but they do not carry identical implications for immunosuppression.
What This Grand Round Case Changes at the Bedside
For clinicians, the practical lesson is not that FDG PET-CT is unreliable. It is that FDG PET-CT is incomplete when used alone to define the biology of a failing heart. In a patient with known systemic sarcoidosis, diffuse myocardial uptake can strongly suggest cardiac sarcoidosis, but persistent decline after treatment should reopen the differential rather than narrow it. Histology remains the only direct route to granulomas, and even histology can miss the disease if the sample is not representative.
The strongest warning in this case comes from the mismatch between the presumed mechanism and the fatal clinical course. Imaging suggested one inflammatory phenotype, treatment followed that assumption, and tissue later identified a different myocardial injury pattern. In inflammatory cardiomyopathy, that gap can decide whether clinicians continue immunosuppression, search for infection, or reconsider the entire diagnosis.
The authors close a difficult diagnostic loop, but one uncertainty remains embedded in the pathology itself: post-mortem sampling cannot fully exclude co-existing cardiac sarcoidosis in a patchy myocardial disease. That limitation defines the case’s clinical value more than any single scan result ever could.