Search Results (82)

Cardiac sarcoidosis (CS) is a critical and frequently underdiagnosed phenotype of sarcoidosis, characterized by non-caseating granulomatous infiltration of the myocardium. This review synthesizes current knowledge regarding the pathogenesis, diagnosis, and management of CS. The disease manifests with a heterogeneous clinical spectrum ranging from asymptomatic conduction abnormalities to life-threatening ventricular arrhythmias and heart failure. Diagnosis remains challenging due to the patchy distribution of granulomas, which limits the sensitivity of endomyocardial biopsy. Consequently, a multimodal diagnostic approach is essential, integrating advanced imaging modalities such as cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). These tools not only facilitate detection but also enable the differentiation of active inflammation from chronic fibrosis. Histopathological assessment, supported by specific immunophenotyping and electron microscopy, remains the gold standard for confirming diagnosis and excluding mimics like giant cell myocarditis or infectious granulomatous diseases. Management requires a multidisciplinary strategy combining immunosuppressive therapy, primarily corticosteroids and steroid-sparing agents, with guideline-directed cardiac care, including implantable cardioverter-defibrillators for arrhythmia risk stratification. Emerging biomarkers and artificial intelligence-driven imaging analysis promise to further refine risk stratification and therapeutic monitoring, advancing precision medicine in this complex disorder. Full article

Myocarditis and inflammatory cardiomyopathy are inflammatory diseases of the heart muscle that can have both infectious and non-infectious causes. They can be caused by an unresolved viral infection or other infection, or they can be autoimmune, toxic, or allergic in nature. The specific identification of the pathogen and/or confirmation of inflammation can only be achieved through direct tissue analysis using endomyocardial biopsy (EMB), as neither detection of the virus nor assessment of the quality and intensity of the inflammation is possible using non-invasive methods. Accordingly, the removal and analysis of an EMB is considered the diagnostic gold standard in international guidelines and statements. The sudden onset of atypical angina pectoris and initially exertion-dependent dyspnea, as well as arrhythmias, pericardial effusion, and progressive symptoms of heart failure, indicate an acute inflammatory process of the myocardium. In addition, nonspecific symptoms such as fatigue and reduced physical performance may also occur. Diagnostic evaluation includes an electrocardiogram (ECG), cardiac imaging, and laboratory tests. The analysis of the EMB is crucial for a definitive diagnosis and thus for the initiation of an etiology-based, specific and personalized therapy. This includes histological and immunohistochemical inflammation diagnostics as well as molecular virological diagnostics. These enable both the detection of viruses and the assessment of transcriptional virus activity. New analyses using metagenomic next generation sequencing (NGS) techniques provide insights of enormous diagnostic and therapeutic relevance. This applies both to the spectrum of detectable pathogens and to the possibility of confirming transcriptional viral activity. In addition, gene expression profiling enables the differentiation of specific forms of myocardial inflammation (e.g., giant cell myocarditis, cardiac sarcoidosis, and eosinophilic myocarditis) and reduces the influence of “sampling errors” in focal inflammatory processes. The treatment of heart failure or ventricular arrhythmias is always symptomatic according to general evidence-based guidelines. In severe cases, mechanical circulatory support or even a heart transplant may be necessary. Patients with histologically confirmed myocardial inflammation or intramyocardial viral infection can be offered specific, causal, and personalized therapy. These patients can be successfully treated with immunosuppressive or antiviral therapy, which significantly improves the prognosis of the disease. Full article

Cardiac magnetic resonance (CMR) has revolutionized the diagnosis and risk stratification of myocarditis. Beyond its capacity in detecting functional abnormalities, CMR is now capable of tissue characterization with high sensitivity and specificity, allowing for the identification of myocardial edema, hyperemia, and necrosis/fibrosis. The introduction of the Lake Louise Criteria (LLC), updated in 2018 with the integration of parametric mapping techniques, has significantly improved diagnostic sensitivity and specificity. This review details the definition, stages, and etiologies of myocarditis, exploring the diagnostic journey from early techniques to the modern multiparametric approach. It underscores the prognostic value of CMR findings and highlights challenging scenarios such as genetic cardiomyopathies that mimic myocarditis. It then discusses CMR patterns in specific conditions like cardiac sarcoidosis, amyloidosis, and immune checkpoint inhibitor-induced myocarditis. Finally, future perspectives for CMR in myocarditis are addressed. Full article

Background: Speckle-tracking echocardiography (STE) has been increasingly used to uncover subtle cardiac dysfunction in patients with extracardiac sarcoidosis (ECS) who show no clinical evidence of heart disease. However, prior investigations were mostly retrospective, methodologically heterogeneous, and focused primarily on left ventricular (LV) function. We conducted a prospective study to provide a broader evaluation of myocardial deformation across both ventricles and atria in ECS without fibrotic pulmonary involvement. Methods: Forty-one patients with ECS (mean age 57.4 ± 10.2 years; 58.5% male) and 30 age- and sex-matched controls without ECS and without known structural heart disease (58.5 ± 11.1 years; 53.3% male) were enrolled. All participants underwent conventional transthoracic echocardiography (TTE) supplemented by comprehensive STE analysis of ventricular and atrial function. Subclinical myocardial dysfunction was defined as LV global longitudinal strain (GLS) less negative than −20%, and potential predictors were analyzed. Results: Standard TTE did not show echocardiographic features suggestive of overt infiltrative cardiomyopathy but revealed higher E/average e′ ratios in the ECS group, suggesting subtle diastolic dysfunction. While traditional indices of biventricular systolic function remained preserved, STE demonstrated significant reductions in LV-GLS, LV global circumferential strain, right ventricular-GLS, and both left and right atrial reservoir strain. Multivariate analysis identified disease duration as the sole independent determinant of LV-GLS impairment (OR 2.26, 95%CI 1.10–4.65; p = 0.03). A disease duration of ≥4.5 years predicted abnormal GLS with 88% sensitivity and 75% specificity (AUC 0.89; 95%CI 0.76–1.00). Conclusions: ECS without fibrotic pulmonary involvement is associated with early impairment of biventricular and biatrial strain despite preserved conventional function. The extent of dysfunction correlates strongly with disease duration, underscoring the value of STE for early detection and monitoring. Full article

Background: Cardiac sarcoidosis (CS) is associated with potentially serious complications, including heart failure and life-threatening arrhythmias. The diagnosis and management of CS is multifaceted, requiring a multi-disciplinary team (MDT)-based approach. A new regional CS clinical service was established in Sussex County (UK) in January 2025. This service is based on a core of cardiologists working with a wider MDT, including specialists in pulmonary sarcoidosis, nuclear medicine and cardiac electrophysiology. This study assessed the clinical performance of this new service. Methods: Patients with suspected CS referred to the Sussex CS Service between January and December 2025 were included, as compared to a control cohort of patients referred for CS assessment before the service was conceived. Results: Of the 51 CS service referrals, 13 patients fulfilled the Heart Rhythm Society (HRS) criteria, all of whom were correctly diagnosed with CS, whilst only two out of seven HRS-positive control patients were correctly diagnosed. In the 38 HRS-negative CS service referrals, 8 patients (21%) were still given a clinical CS diagnosis compared to none in the HRS-negative controls. Of the 21 patients diagnosed with CS, 7 (33%) had active myocardial inflammation and 8 (38%) had LV systolic dysfunction. Where indicated, immunosuppressive and heart failure therapies were initiated in all patients. Eight CS patients (38%) underwent implantable cardioverter defibrillator implantation. No deaths or heart failure hospitalisations occurred within the first 11 months. Conclusions: An MDT-based CS service model can provide multi-faceted care to patients, without major short-term adverse outcomes. The service model replicability and long-term outcomes require further assessment. Full article

Background/Objectives: It is unclear whether assessment of phasic atrial function could improve risk stratification for new-onset atrial fibrillation (AF) in patients with newly diagnosed cardiac sarcoidosis (CS). We aimed to investigate the prognostic value of left atrial (LA) phasic dysfunction by cardiac magnetic resonance (CMR) for new-onset AF in newly diagnosed patients with CS. Methods: 78 patients with CS, without a prior history of AF, were studied using CMR feature tracking. Over a 4-year follow-up period, AF was documented by Holter monitoring and interrogation of intracardiac devices. Clinically silent CS was defined as CS in patients with biopsy-proven extracardiac sarcoidosis, with no cardiac symptoms, but with abnormalities on CMR or positron emission tomography consistent with CS. Results: Patients with clinically manifest CS were younger (mean age 56 vs. 51 years, p = 0.018), had poorer ventricular function, higher extent of atrial late gadolinium enhancement and significantly lower LA reservoir, conduit and booster function compared to patients with clinically silent CS. Over a 4-year follow-up period, 39% of patients with clinically manifest CS and 29.7% of patients with clinically silent CS developed AF. LA reservoir strain was a strong predictor of AF in the entire cohort. In subgroup analysis, age (HR 1.30, 95% CI 1.02–1.65, p = 0.030) and LA reservoir strain (HR 0.63, 95% CI 0.44–0.90, p = 0.011) were independent predictors of AF in patients with clinically silent CS, whereas baseline NT-proBNP (HR 1.003, 95% CI 1.001–1.006, p = 0.017) predicted AF in patients with clinically manifest CS. Conclusions: Reduced LA reservoir strain on CMR predicts new-onset AF in patients with newly diagnosed CS. The predictive value of LA reservoir strain is strongest in clinically silent CS and decreases with disease progression in clinically manifest CS. Full article

Background/Objectives: Cardiac sarcoidosis (CS) is a challenging diagnosis due to its subclinical progression and the limitations of existing screening tools. Cardiac magnetic resonance (CMR) and PET/CT imaging have improved diagnosis and detection. Aldosterone, a hormone with known profibrotic effects, may offer additional diagnostic value. We therefore aimed to determine whether plasma aldosterone level is associated with myocardial fibrosis, independent of active inflammation, in CS. Methods: This observational study included 541 patients with biopsy-proven sarcoidosis and preserved left ventricular ejection fraction (LVEF ≥ 50%). All underwent CMR with extracellular volume (ECV) mapping and 18F-FDG PET/CT to assess myocardial fibrosis and inflammation, respectively. Plasma aldosterone levels were also measured. Results: Plasma aldosterone levels were significantly higher in patients with cardiac sarcoidosis (172 [IQR 106–235] pg/mL) compared to those without cardiac involvement (143 [100–205] pg/mL, p = 0.02). Aldosterone was independently associated with the presence of late gadolinium enhancement (LGE) on CMR (OR 1.002 per 1 pg/mL increase; 95% CI 1.001–1.004, p = 0.04) and with higher ECV values (β = 0.008 per 1 pg/mL, p = 0.001). Regression analysis showed that aldosterone is associated with ECV (b-0.009, CI: 0.002–0.016, p = 0.009) and there was no interaction according to LGE status indicating a relationship with diffuse myocardial fibrosis even in the absence of visible scarring. No association was observed with T1-, T2-, or PET/CT-defined inflammation. Conclusions: Plasma aldosterone is a robust marker of myocardial fibrosis in sarcoidosis, particularly in early or subclinical stages. Its correlation with ECV—but not with inflammatory imaging markers—suggests its link with myocardial diffuse fibrotic remodeling before, and independently of, overt scarring or inflammation. Full article

T1 mapping and extracellular volume (ECV) calculations in cardiac magnetic resonance (CMR) have the potential to identify early fibrosis that is not yet visible using late gadolinium enhancement; however, the need for same-day blood draws due to the temporal variations in hematocrit (Hct) limits the use of ECV. We aimed to determine the reproducibility of synthetic Hct and ECV using different published models among groups of subjects. Healthy subjects and those with diagnosed cardiac amyloidosis, sarcoidosis, and hypertrophic cardiomyopathy (HCM) scanned using a 1.5T scanner with native and post-contrast T1 maps and same-day Hct were included. Among 148 subjects, there was excellent reproducibility (all ICCs ~0.98) between synthetic and measured ECV across the six formulas, despite only modest reproducibility of synthetic/measured Hct (ICCs 0.52–0.66). The levels of accuracy predicting abnormal measured ECV were consistently excellent among the different synthetic ECV models. The difference in the CMR vendor used to generate models did not seem to affect the results of the comparisons. We conclude that synthetic ECV yielded excellent reproducibility compared with ECV calculated using measured hematocrit, possibly obviating the need for blood extraction in cardiac MRI settings without point-of-care Hct. Full article

Introduction: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening manifestation of systemic sarcoidosis, often leading to arrhythmias, conduction abnormalities, or heart failure. Diagnosis is challenging due to nonspecific symptoms and the need for advanced imaging or biopsy. Case Presentation: We describe a 49-year-old man admitted with severe decompensated heart failure (NYHA IV). He had a history of complete heart block treated with pacemaker implantation and subsequent CRT-D upgrade. On admission, echocardiography revealed biventricular dysfunction with severe mitral and tricuspid regurgitation. Cardiac MRI demonstrated extensive non-ischemic late gadolinium enhancement. Blood cultures grew methicillin-sensitive Staphylococcus aureus (MSSA) and intravenous antibiotics were initiated. Despite diuretics and inotropes, his condition deteriorated. Corticosteroid therapy was started due to high suspicion of sarcoidosis. Endomyocardial biopsy confirmed CS. The patient developed neuropsychiatric complications and, despite urgent listing for heart transplantation, died during hospitalization. Conclusions: This case highlights the diagnostic and therapeutic challenges of CS, the limitations of corticosteroid therapy in advanced disease, and the importance of early recognition with advanced imaging modalities. Full article

Restrictive cardiomyopathy (RCM) poses a significant challenge in diagnosis, is frequently identified in advanced stages, and has limited therapeutic options, which may lead to adverse cardiovascular outcomes. This narrative review examines the application of artificial intelligence (AI) across key diagnostic modalities and delineates priorities for translational advancement. The discussed diagnostic tools include echocardiography, cardiac magnetic resonance (CMR), electrocardiography (ECG), and electronic health records (EHR). A targeted, non-systematic search of PubMed and Scopus was performed to identify studies focused on model development, validation, or diagnostic accuracy concerning RCM and related infiltrative disorders. The findings suggest that AI can enable earlier detection, standardize imaging protocols, and enhance phenotype-driven management of RCM. Nonetheless, several challenges exist, including limited data access, the absence of external validation, variability across imaging devices and locations, and the imperative for transparent, explainable systems. Key priorities for successful implementation encompass establishing multi-center collaborations, detecting and correcting bias, clinician involvement in deployment, and integrating multimodal data, including imaging, signal data, and -omics. If effectively integrated into clinical practice, AI has the potential to redefine the management of RCM from a condition recognized primarily in its later stages to one characterized by early detection, dynamic risk assessment, and personalized treatment strategies. Full article

Background: Cardiac involvement, one of the most life-threatening complications of sarcoidosis, remains under-recognized due to its oligo-symptomatic presentation in some patients. This retrospective study aimed to evaluate the utility of various clinical predictors of cardiac sarcoidosis (CS) development. Methods: The study included patients with pulmonary sarcoidosis diagnosed according to the recent ATS guidelines between January 2020 and July 2024 who underwent cardiac magnetic resonance (CMR) due to clinical suspicion of CS. The original Lake Louise criteria were used to identify active myocarditis. Results: Out of 393 patients diagnosed with pulmonary sarcoidosis, CMR was performed in 92 patients. Cardiac sarcoidosis was confirmed in 48 patients (52%, CS+), and excluded in 44 patients (48%, CS−). CS(+) patients demonstrated significantly more frequent Holter ECG abnormalities and liver/spleen sarcoidosis compared to CS(−) patients. Stage IV pulmonary disease, ECG abnormalities, and hypercalcemia were more common in CS(+) than in CS(−) patients; however, these differences did not reach statistical significance. Multivariate analysis identified Holter ECG abnormalities and liver/spleen involvement as significant predictive factors for CS, increasing the risk of cardiac involvement by approximately 4- and 6-fold, respectively. An AI-assisted simple scoring system based on five parameters: ECG abnormalities, Holter ECG abnormalities, liver/spleen involvement, gender, and stage of sarcoidosis predicted CS with a sensitivity of 76% and specificity of 74%, using an optimal cut-off value of ≥7.6 points. Conclusions: In patients with pulmonary sarcoidosis, an AI-assisted scoring algorithm derived from L1-regularized logistic regression results accurately predicted cardiac involvement on CMR with high specificity and sensitivity. Prospective validation of this algorithm is necessary to confirm its clinical utility in predicting cardiac sarcoidosis. Full article

Background/Objectives: Sarcoidosis is a systemic inflammatory disease that can cause cardiac autonomic dysfunction (SCAD), often underrecognized despite its clinical importance. While [¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) and cardiac magnetic resonance imaging (CMR) assess cardiac involvement, [¹²³I]-meta-iodinebenzylguanidine ([¹²³I]MIBG) scintigraphy evaluates cardiac sympathetic innervation, offering complementary insights to potentially improve SCAD detection and management. This retrospective study explores the role of [¹²³I] MIBG scintigraphy in detecting SCAD among patients with unexplained cardiac symptoms. It focuses on its potential to provide complementary diagnostic information in patients where established imaging techniques, such as [¹⁸F]FDG PET/CT and CMR, fail to detect cardiac sarcoidosis. Methods: Sarcoidosis patients referred to the St. Antonius Hospital (2017–2024) who underwent [¹²³I]MIBG scintigraphy were included. Collected data encompassed demographics, SCAD symptoms, cardiac imaging findings, and carvedilol treatment outcomes. [¹²³I] MIBG abnormalities were defined as a heart-to-mediastinal ratio ≤1.6 or a washout rate ≥20%. Results: Among the final cohort of 40 sarcoidosis patients with unexplained cardiac symptoms and normal [¹⁸F]FDG PET/CT and CMR findings, 19 patients (48%) showed abnormal [¹²³I] MIBG scintigraphy results suggestive of SCAD. No significant differences were observed in clinical characteristics between patients with normal and abnormal [¹²³I]MIBG findings. Of the 16 patients treated with carvedilol, 88% reported symptom improvement, although 50% experienced side effects. Conclusions: [¹²³I]MIBG scintigraphy revealed abnormalities in a substantial number of sarcoidosis patients with unexplained cardiac symptoms despite normal [¹⁸F]FDG PET/CT and CMR. These findings indicate a potential role for [¹²³I]MIBG in detecting SCAD, but prospective studies are needed to confirm their clinical significance. Full article

Background/Objectives: Cardiac sarcoidosis (CS) is a granulomatous inflammatory cardiomyopathy with heterogeneous presentations, from palpitations to heart failure and sudden cardiac arrest. Despite advances in imaging and immunosuppressive (IS) therapy, relapse patterns and long-term outcomes remain poorly defined. This study aimed to characterize relapse and identify predictors of relapse and major adverse cardiac events (MACE) in a real-world CS cohort. Methods: This retrospective single-center study included 25 adults diagnosed with CS at Geneva University Hospitals between 2016 and 2024, classified per the 2024 American Heart Association diagnostic criteria. Relapse was defined as clinical, arrhythmic, or imaging deterioration requiring treatment escalation. MACE included cardiovascular hospitalization, device therapy, left ventricular assist device, heart transplant, or death. Statistical methods included Kaplan–Meier analysis with log-rank tests and multivariable Cox regression adjusted for age and sex. Results: Relapse occurred in 13 patients (56%), frequently subclinical (61.5%) and detected incidentally on routine PET-CT during IS tapering. In the multivariate model, predictors of relapse included right ventricular FDG uptake (aHR 13.1; 95% CI 1.3–133.7; p = 0.03) and second-line immunosuppression duration ≤24 months (aHR 20.1; 95% CI 1.1–363.8; p = 0.04). Relapse-free patients were more often maintained on dual or triple IS therapy (71.4% vs. 15.4%; p = 0.02) and low-dose prednisone (<10 mg/day) (57.1% vs. 7.7%; p = 0.03). Conclusions: Relapse is common in CS, often subclinical, and associated with PET-CT findings and premature IS tapering. Maintenance therapy may reduce risk. Multimodal imaging remains critical for disease monitoring, though tracers with higher specificity are needed. Further research should refine relapse definitions and support personalized treatment strategies. Full article

Background/Objectives: Cardiac amyloidosis (CA) and cardiac sarcoidosis (CS) are two distinct infiltrative cardiomyopathies that can present with overlapping clinical features, including heart failure and arrhythmias. However, they arise from fundamentally different pathophysiological mechanisms: amyloid protein deposition in CA versus granulomatous inflammation in CS. These differing pathophysiologies result in divergent imaging patterns, clinical trajectories, and treatment strategies. This study aims to compare the clinical presentations, imaging characteristics, and outcomes of patients with CA and CS to identify key differentiating factors that can improve diagnostic precision and guide therapy. Methods: This single-center, retrospective, cross-sectional study analyzed electronic medical records of patients diagnosed with CA (limited to transthyretin CA) or CS at Mount Sinai Morningside system from January 2017 until October 2023. Patients were identified using diagnostic codes and confirmed by histology or disease-specific imaging criteria. Clinical data, transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR) imaging, pyrophosphate scintigraphy (PYP), and fluorodeoxyglucose positron emission tomography (FDG-PET) findings were collected. Statistical comparisons between groups were performed using chi-square tests and independent t-tests, with p < 0.05 considered statistically significant. Results: A total of 16,834 patients were screened and 216 patients were included in the analysis (125 CA, 92 CS). CA patients were older (78.2 vs. 62.0 years, p = 0.01), had greater interventricular septal thickness (1.57 vs. 1.10 cm, p = 0.01), and exhibited diffuse late gadolinium enhancement (LGE) and elevated extracellular volume (ECV) on CMR. CS patients had higher rates of ventricular tachycardia (53.3% vs. 10.7%, p = 0.01), increased myocardial fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) (90%), and more frequent implantable cardioverter-defibrillator (ICD) placement (66.3% vs. 13.0%, p = 0.01). Conclusions: CA and CS demonstrate distinct imaging profiles, arrhythmic risks, and treatment patterns. Early differentiation using advanced imaging is crucial for implementing disease-modifying therapies in CA and for immunosuppression and ICD implantation in CS, thereby improving patient outcomes. Full article

Background/Objectives: Cardiac sarcoidosis (CS) is an inflammatory cardiomyopathy with a strong clinical impact on patients affected by the disease and a challenging diagnosis. Methods: This comprehensive narrative review evaluates the role of [18F]fluorodesoxyglucose ([18F]FDG) positron emission tomography (PET)-based radiomics and machine learning (ML) analyses in the assessment of CS. Results: The value of [18F]FDG PET-based radiomics and ML has been investigated for the clinical settings of diagnosis and prognosis of patients affected by CS. Even though different radiomics features and ML models have proved their clinical role in these settings in different cohorts, the clear superiority and added value of one of them across different studies has not been demonstrated. In particular, textural analysis and ML showed high diagnostic value for the diagnosis of CS in some papers, but had controversial results in other works, and may potentially provide prognostic information and predict adverse clinical events. When comparing these analyses with the classic semiquantitative evaluation, a conclusion about which method best suits the final objective cannot be drawn with the available references. Different methodological issues are present when comparing different papers, such as image segmentation and feature extraction differences that are more evident. Furthermore, the intrinsic limitations of radiomics analysis and ML need to be overcome with future research developed in multicentric settings with protocol harmonization. Conclusions: [18F]FDG PET-based radiomics and ML show preliminary promising results for CS evaluation, but remain investigational tools since the current evidence is insufficient for clinical adoption due to methodological heterogeneity, small sample sizes, and lack of standardization. Full article