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Background: Cardiac sarcoidosis involves a significant but difficult-to-define risk of sudden cardiac death (SCD). Current guidelines recommend consideration of an implantable cardioverter defibrillator for patients with extensive or significant myocardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. However, extensive/significant LGE is not defined., Methods: A nationwide cardiac sarcoidosis registry was screened for patients entered before 2020 with cardiac magnetic resonance imaging done before or <3 months after diagnosis. Available studies were re-analyzed for LGE mass as a percentage of left ventricular (LV) mass and the number of LGE-positive LV segments in a 17-segment model. The occurrence of fatal or aborted SCD and ventricular tachycardia (VT) prompting therapy was recorded until the end of 2020 and subjected to cumulative incidence analyses, including competing events (LV assist device implantations, heart transplantations, and fatalities other than SCD). The predictors of SCD/VT were assessed using Fine and Gray modeling and time-dependent receiver operating characteristic analysis., Results: Altogether, 305 patients (66% women, median age 51) with clinically manifest, definite (45%) or probable cardiac sarcoidosis (55%) were analyzed. On follow-up (median, 4.0 years), 21 SCDs, 60 VTs, and 14 competing events were noted. Both LGE mass and the number of LGE segments predicted the composite of SCD/VT ( P <0.001), with receiver operating characteristic analyses identifying LGE mass ≥9.9% and ≥6 LGE segments as discriminative thresholds. At presentation, 70 patients were free of class I and class IIa implantable cardioverter defibrillator indications unrelated to LGE. Their 5-year rate of SCD/VT was 6.3% (0.0-14.8%) with LGE mass <9.9% versus 21.5% (6.5-36.6%) with higher LGE mass, and 6.9% (0.0-16.3%) with <6 LGE segments versus 20.5% (5.9-35.2%) with ≥6 segments., Conclusions: In cardiac sarcoidosis, myocardial LGE making up ≥9.9% of LV mass or affecting ≥6 LV segments may suggest prognostically significant LV involvement and a high risk of SCD. However, prospective validation of the thresholds is needed.

Aims: We set out to assess the utility of endomyocardial biopsy (EMB) in cardiac sarcoidosis (CS). Historically, EMB sensitivity in CS is only ≤25%, but comprehensive analyses of its current diagnostic performance are not available., Methods and Results: The data of 260 consecutive patients with CS (mean age 49 years, 60% female) meeting the Heart Rhythm Society diagnostic criteria were analysed retrospectively. Overall, 216 patients (83%) had undergone EMB, 47 with repeat procedures. EMB overall sensitivity was 38%, rising to 49% after repeat biopsies. On logistic regression analysis, positive EMB was predicted independently by presentation with ventricular tachyarrhythmia with an odds ratio (OR) of 3.8 (95% confidence interval [CI] 1.2-12.0, p = 0.021), left ventricular ejection fraction ≤45% (OR 3.7, 95% CI 1.5-9.1, p = 0.004), elevation of cardiac troponins (OR 2.7, 95% CI 1.1-6.4, p = 0.024), and presence of late gadolinium enhancement in left ventricular mid-apical septal segments on magnetic resonance imaging (OR 4.1, 95% CI 1.2-13.8, p = 0.024). EMB sensitivity, counting in repeats, was 16% in patients (n = 37) without any independent predictor versus 38%, 60%, 79%, and 88% in those with 1 (n = 76), 2 (n = 62), 3 (n = 33), and 4/4 (n = 8) predictors, respectively. The rate of serious complications was 0.7% without mortality or permanent harm. Positive EMB was not an independent predictor of prognosis., Conclusion: The sensitivity of EMB in CS depends on the extent, activity, and location of myocardial involvement, being the higher the more severe CS is. Its use should rely on weighing the pre-test likelihood and individual value of positive biopsy against the procedural risks., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy., Objectives: The authors studied temporal changes in the incidence, characteristics, and outcome of CS., Methods: A retrospective analysis was made of a 30-year nationwide cohort of CS., Results: The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P  < 0.001), left ventricular ejection fraction <50% (49%, 35%, and 31%; P  = 0.010), and elevation of natriuretic peptides (87%, 57%, and 49%; P  < 0.001). On magnetic resonance imaging, late gadolinium enhancement involved a median of 15% (IQR: 11%-22%) of left ventricular mass in studies of 1988 to 2009 (n = 16), 15% (IQR: 9%-22%) in studies of 2010 to 2014 (n = 87), and 11% (IQR: 5%-19%) in studies of 2015 to 2019 (n = 150) ( P  = 0.031). The respective 5-year incidences of the composite of death, heart transplantation, left ventricular-assisted device implantation, or ventricular tachyarrhythmia were 40% (95% CI: 29%-51%), 32% (95% CI: 25%-39%), and 23% (95% CI: 16%-30%) ( P  = 0.002). The prognostic trend disappeared after adjustment for differences in the presenting phenotype., Conclusions: Diagnoses of incident CS have increased exponentially in Finland. Concurrently, the phenotype has turned milder and prognosis better, suggesting detection of CS at an earlier stage of its course., Competing Interests: Dr Pöyhönen was supported by the 10.13039/501100003125Finnish Cultural Foundation (Helsinki, Finland), 10.13039/501100005633Finnish Foundation for Cardiovascular Research (Helsinki, Finland) and Finnish government grant for medical research (Helsinki, Finland). Dr Uusitalo has scientific collaboration with lecture fees with GE Healthcare; and has received lecture fee and advisory board activity with Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Competing Interests: Disclosures Dr Uusitalo reports advisory board activity with and lecture honoraria from GE Healthcare and Pfizer. Dr Lehtonen reports lecture honoraria from Pfizer. The other authors report no conflicts.

Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades., (© 2024. The Author(s).)

Background: Eosinophilic myocarditis (EM) is a life-threatening acute heart disease. Cardiac magnetic resonance (CMR) excels in the assessment of myocardial diseases but CMR studies of EM are limited. We aimed to describe CMR findings in histologically proven EM., Methods: Patients with histologically proven EM seen at an academic center from 2000 through 2020 were identified. Of the 28 patients ascertained, 15 had undergone CMR for diagnosis and constitute our study cohort., Results: The patients, aged 51 ± 17 years, presented with fever (53%), dyspnea (47%), chest pain (53%), heart block (20%), and blood eosinophilia (60%). On CMR, all 15 patients had myocardial edema with 10 of them (67%) having abnormally high left ventricular (LV) mass as well. LV ejection fraction measured < 50% in 11 patients (73%) and < 30% in 2 (13%), but only 6 (40%) had dilated LV size. Eight patients (53%) had pericardial effusion. LV late gadolinium enhancement (LGE) was found in all but one patient (13/14; 93%). LGE was always multifocal and subendocardial but could involve any myocardial layer. Patients with necrotizing EM by histopathology (n = 6) had higher LGE mass (32.1 ± 16.6% vs 14.5 ± 7.7%, p = 0.050) and more LV segments with LGE (15 ± 2 vs 9 ± 3 out of 17, p = 0.003) than patients (n = 9) without myocyte necrosis. Two patients had LV thrombosis accompanying widespread subendocardial LGE., Conclusions: In EM, CMR shows myocardial edema and LGE that is typically subendocardial but can involve any myocardial layer. The left ventricle is often non-dilated with moderate-to-severe systolic dysfunction. Pericardial effusion is common. Necrotizing EM presents with extensive myocardial LGE on CMR., (© 2023. The Author(s).)

Cardiac sarcoidosis (CS) results from epithelioid cell granulomas infiltrating the myocardium and predisposing to conduction disturbances, ventricular tachyarrhythmias, and heart failure. Manifest CS, however, constitutes only the top of an iceberg as advanced imaging uncovers cardiac involvement 4 to 5 times more commonly than what is clinically detectable. Definite diagnosis of CS requires myocardial biopsy and histopathology, but a sufficient diagnostic likelihood can be achieved by combining extracardiac histology of sarcoidosis with clinical manifestations and findings on cardiac imaging. CS can appear as the first or only organ manifestation of sarcoidosis or on top of pre-existing extracardiac disease. Due to the lack of controlled trials, the care of CS is based on observational evidence of low quality. Currently, the treatment involves corticosteroid-based, tiered immunosuppression to control myocardial inflammation with medical and device-based therapy for symptomatic atrioventricular block, ventricular tachyarrhythmias, and heart failure. Recent outcome data indicate 90% to 96% 5-year survival in manifest CS with the 10-year figures ranging from 80% to 90%. Major progress in the care of CS awaits the key to its molecular-genetic pathogenesis and large-scale controlled clinical trials., Competing Interests: Conflict of interest Lecture and/or advisory board fees from Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Takeda, Bayer, Amgen, Roche, and Aiforia technologies oy (M.I.M.). Lecture fee from Pfizer and research collaboration with GE healthcare (V.U.)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Giant cell myocarditis (GCM) is an inflammatory cardiomyopathy akin to cardiac sarcoidosis (CS). We decided to study the findings of GCM on cardiac magnetic resonance (CMR) imaging and to compare GCM with CS., Methods and Results: CMR studies of 18 GCM patients were analyzed and compared with 18 CS controls matched for age, sex, left ventricular (LV) ejection fraction and presenting cardiac manifestations. The analysts were blinded to clinical data. On admission, the duration of symptoms (median) was 0.2 months in GCM vs. 2.4 months in CS (P = 0.002), cardiac troponin T was elevated (>50 ng/L) in 16/17 patients with GCM and in 2/16 with CS (P < 0.001), their respective median plasma B-type natriuretic propeptides measuring 4488 ng/L and 1223 ng/L (P = 0.011). On CMR imaging, LV diastolic volume was smaller in GCM (177 ± 32 mL vs. 211 ± 58 mL, P = 0.014) without other volumetric or wall thickness measurements differing between the groups. Every GCM patient had multifocal late gadolinium enhancement (LGE) in a distribution indistinguishable from CS both longitudinally, circumferentially, and radially across the LV segments. LGE mass averaged 17.4 ± 6.3% of LV mass in GCM vs 25.0 ± 13.4% in CS (P = 0.037). Involvement of insertion points extending across the septum into the right ventricular wall, the "hook sign" of CS, was present in 53% of GCM and 50% of CS., Conclusion: In GCM, CMR findings are qualitatively indistinguishable from CS despite myocardial inflammation being clinically more acute and injurious. When matched for LV dysfunction and presenting features, LV size and LGE mass are smaller in GCM., Competing Interests: Conflict of interest: P.P. was supported by a Finnish government grant for medical research. J.L. was supported by Finnish Cardiac Society and a Finnish government grant for medical research. C.S. was supported by National Institutes of Health (NIH) grants K23HL132011 and R03HL15711. S.S. has received honoraria for lectures from Finnish Society of Chest Radiology, The Radiological Society of Finland and Society of Radiographers in Finland., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac sarcoidosis (CS) predisposes to sudden cardiac death (SCD). Guidelines for implantable cardioverter defibrillators (ICDs) in CS have been issued by the Heart Rhythm Society in 2014 and the American College of Cardiology/American Heart Association/Heart Rhythm Society consortium in 2017. How well they discriminate high from low risk remains unknown., Methods: We analyzed the data of 398 patients with CS detected in Finland from 1988 through 2017. All had clinical cardiac manifestations. Histological diagnosis was myocardial in 193 patients (definite CS) and extracardiac in 205 (probable CS). Patients with and without Class I or IIa ICD indications at presentation were identified, and subsequent occurrences of SCD (fatal or aborted) and sustained ventricular tachycardia were recorded, as were ICD indications emerging first on follow-up., Results: Over a median of 4.8 years, 41 patients (10.3%) had fatal (n=8) or aborted (n=33) SCD, and 98 (24.6%) experienced SCD or sustained ventricular tachycardia as the first event. By the Heart Rhythm Society guideline, Class I or IIa ICD indications were present in 339 patients (85%) and absent in 59 (15%), of whom 264 (78%) and 30 (51%), respectively, received an ICD. Cumulative 5-year incidence of SCD was 10.7% (95% CI, 7.4%-15.4%) in patients with ICD indications versus 4.8% (95% CI, 1.2%-19.1%) in those without (χ 2 =1.834, P =0.176). The corresponding rates of SCD were 13.8% (95% CI, 9.1%-21.0%) versus 6.3% (95% CI, 0.7%-54.0%; χ 2 =0.814, P =0.367) in definite CS and 7.6% (95% CI, 3.8%-15.1%) versus 3.3% (95% CI, 0.5%-22.9%; χ 2 =0.680, P =0.410) in probable CS. In multivariable regression analysis, SCD was predicted by definite histological diagnosis ( P =0.033) but not by Class I or IIa ICD indications ( P =0.210). In patients without ICD indications at presentation, 5-year incidence of SCD, sustained ventricular tachycardia, and emerging Class I or IIa indications was 53% (95% CI, 40%-71%). By the American College of Cardiology/American Heart Association/Heart Rhythm Society guideline, all patients with complete data (n=245) had Class I or IIa indications for ICD implantation., Conclusions: Current ICD guidelines fail to distinguish a truly low-risk group of patients with clinically manifest CS, the 5-year risk of SCD approaching 5% despite absent ICD indications. Further research is needed on prognostic factors, including the role of diagnostic histology. Meanwhile, all patients with CS presenting with clinical cardiac manifestations should be considered for an ICD implantation.

Background: In cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known., Objectives: The authors evaluated the incidence and characteristics of AF in newly diagnosed CS., Methods: The authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac 18 F-fluorodexoyglucose positron emission tomography ( 18 F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms., Results: Altogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial 18 F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF., Conclusions: In newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging., Competing Interests: Funding Support and Author Disclosures This study was supported by a Finnish government grant for medical research, the Aarne Koskelo Foundation, and the Finnish Foundation for Cardiovascular Research. Dr Uusitalo has received scientific collaboration with and a lecture fee from GE Healthcare; and has received a lecture fee and has advisory board activity with Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)