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Education in Heart
Systemic disorders in heart disease
Cardiac sarcoidosis: applications of imaging in diagnosis and directing treatment
  1. George Youssef1,
  2. Rob S B Beanlands1,
  3. David H Birnie2,
  4. Pablo B Nery2
  1. 1Molecular Function and Imaging Program, The National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  2. 2Cardiac Electrophysiology Service, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  1. Correspondence to Professor Rob Beanlands, National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada; rbeanlands{at}ottawaheart.ca

https://doi.org/10.1136/hrt.2011.226076

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    Epidemiology

    Sarcoidosis has been reported to have a particular predilection for adults under the age of 40 years.w1 The incidence of sarcoidosis varies greatly by ethnicity and region, occurring in 3 to 20 per 100 000 for whites and 35.5 to 80 per 100 000 for blacks.1 Scandinavian populations have been reported as having a higher prevalence than other Caucasian regions.w2

    The incidence of cardiac sarcoidosis (CS) also varies by the type of study performed, whether clinical or autopsy study, with clinical and autopsy reports ranging from 5–10% up to 27%, respectively.2 w3 Recently, Mehta et al observed almost 40% of patients with sarcoidosis had CS on advanced imaging (cardiac MRI or positron emission tomography (PET)).3

    Pathogenesis of cardiac sarcoidosis

    The aetiology of sarcoidosis remains unclear. Genetic, environmental, infectious, and immune dysregulation aetiologies have all been postulated.w4 Data from ACCESS (A Case-Control Etiologic Study of Sarcoidosis)4 indicated a relative risk of 4.7 for parents and siblings of sarcoid patients. While several genes or polymorphisms have been suggested,w5–w7 it is unlikely that sarcoidosis is a purely genetic disease. Rather, it may be a final common pathway of granulomatous disease caused by a heterogeneous group of agents in a genetically susceptible patient. The American Thoracic Society, the European Respiratory Society, and the World Association of Sarcoidosis and Other Granulomatous Disorders5 define sarcoidosis as a multisystem disorder of unknown cause.

    The cardiovascular system is the third most frequently involved organ system in patients with sarcoidosis.w8 All parts of the heart can be affected, with the left ventricular free wall being the most common location (figure 1).6 The cardiac conduction systemw9 is also commonly affected. The hallmark of sarcoidosis is the presence of non-caseating, non-necrotising, granulomas (figure 2).7 w10 w11

    Figure 1
    Figure 1

    Heart of a patient who underwent transplantation showing advanced tan to yellow-white fibrotic areas in the endocardium, myocardium, and epicardium, with a gradient of involvement, more severe towards the base of the heart. Note the heavy involvement of the epicardium in the anterior left ventricle (upper right of the picture) and endocardium of the right ventricle (lower left of the picture). Reproduced with permission from the College of American Pathologists: Lagana SM, Parwani AV, Nichols LC. Cardiac sarcoidosis: a pathology-focused review. Arch Pathol Lab Med 2010;134:1039–46.w45

    Figure 2
    Figure 2

    Non-caseating, multinucleated granuloma on histologic specimen from the pericardium of a patient with sarcoidosis (haematoxylin and eosin, 40× original magnification.) Reproduced from Ayyala US, Nair AP, Padilla ML. Cardiac sarcoidosis. Clin Chest Med 2008;29:493–508, with permission from Elsevier.13

    Clinical manifestations

    Clinical manifestations of CS are dependent on the location, extent and activity of disease, and range from clinically silent disease to sudden cardiac death (SCD). Conduction abnormalities, ventricular arrhythmias, and heart failure may occur. Clinical clues to the diagnosis are listed in box 1.

    Box 1

    When cardiac sarcoidosis should be considered

    1. Unexplained sustained second or third degree atrioventricular block in young adults (age <55 years)

    2. Sustained monomorphic ventricular tachycardia and idiopathic dilated cardiomyopathy

    3. Patients with extracardiac sarcoidosis.

    Conduction abnormalities

    Conduction abnormalities occur due to involvement of the basal interventricular septum, and range from second to third degree atrioventricular (AV) block and bundle branch block (right more common than left). Third degree AV block (or complete heart block (CHB)) is the most common abnormality and has been reported in 23–30% of CS patients. Patients presenting with CHB secondary to CS tend to be younger than those with idiopathic heart block.8 Kandolin et al showed that CS is more common than previously thought in adults aged <55 years presenting with unexplained AV block.8 In this subgroup, CS was diagnosed in 19% of patients, with two thirds of the cases reported as sarcoidosis with isolated cardiac involvement.

    Ventricular arrhythmias

    Ventricular tachycardia (VT) is the second most common manifestation of CS and has been reported in 23% of CS patients.9 Areas of resolving inflammation usually evolve to myocardial scar, providing the substrate for re-entry. Monomorphic VT is most commonly observed; however, polymorphic VT can also occur in patients with CS.w12

    Atrial arrhythmias

    Atrial arrhythmias due to left atrial dilatation or inflammatory atrial foci are possible but less common, with an estimated incidence of 19%.2 They may also occur due to left atrial scarring.

    Sudden death

    SCD, due to either ventricular arrhythmia or complete heart block, is the most feared complication and can be the first manifestation of CS. In a series of patients with confirmed CS at autopsy, the terminal event was sudden death in 67% of the patients.6

    Congestive heart failure

    Heart failure is becoming the leading cause of death in patients with CS—responsible for 73% of deaths in a prospective Japanese study by Yazaki et al.10 Systolic or diastolic heart failure can occur and is often associated with conduction system disease and ventricular arrhythmias, and less frequently with mitral valve dysfunction secondary to papillary muscle infiltration or rupture.

    Diagnostic tests

    The diagnosis of CS is challenging. A high index of suspicion is essential. In 2006, the Japanese Society of Sarcoidosis and Granulomatous Disorders revised the former 1993 guidelines for the diagnosis of CS (box 2).11 The role of these guidelines has not been truly validated. Table 1 shows13 the advantages and disadvantages of different diagnostic modalities. A stepwise approach to diagnosis is depicted in figure 3.

    Box 2

    Guidelines for the diagnosis of cardiac sarcoidosis1112

    Histological diagnosis group

    Cardiac sarcoidosis is confirmed when endomyocardial biopsy specimens demonstrate non-caseating epithelioid cell granulomas with histological or clinical diagnosis of extracardiac sarcoidosis.

    Clinical diagnosis group

    Although endomyocardial biopsy specimens do not demonstrate non-caseating epithelioid granulomas, extracardiac sarcoidosis is diagnosed histologically or clinically and satisfies the following conditions and more than one in six basic diagnostic criteria:

    1. Two or more of the four major criteria are satisfied

    2. One in four of the major criteria and two or more of the five minor criteria are satisfied

    Major criteria

    1. Advanced atrioventricular block

    2. Basal thinning of the interventricular septum

    3. Positive gallium-67 uptake in the heart

    4. Depressed ejection fraction of the left ventricle (<50%)

    Minor criteria

    1. Abnormal ECG findings: ventricular arrhythmias (VT, multifocal or frequent PVCs), complete RBBB, axis deviation or abnormal Q wave

    2. Abnormal echocardiography: regional abnormal wall motion or morphological abnormality (ventricular aneurysm, wall thickening)

    3. Nuclear medicine: perfusion defect detected by thallium-201 or technetium-99 m myocardial scintigraphy

    4. Gadolinium enhanced CMR imaging: delayed enhancement of myocardium

    5. Endomyocardial biopsy: interstitial fibrosis or monocyte infiltration of moderate grade

    CMR, cardiac magnetic resonance; CS, cardiac sarcoidosis; PVC, premature ventricular contraction; RBBB, right bundle branch block; VT, ventricular tachycardia.

    View this table:
    Table 1

    Imaging modalities in the diagnosis of cardiac sarcoidosis; utility, advantages and disadvantages

    Figure 3
    Figure 3

    Proposed diagnostic algorithm for cardiac sarcoidosis. The scheme is proposed as a means to integrate the role of advanced imaging in the diagnostic algorithm for cardiac sarcoidosis. Diagnostic approach differs according to clinical presentation; conduction system disease and/or ventricular arrhythmia (A) or biopsy proven extracardiac sarcoidosis (B). *In the absence of CAD; #defined as more than 1000 PVCs/24 h; &Gallium-67 scintigraphy or technetium based MPI are reasonable alternatives if FDG-PET or CMR not available. AV, atrioventricular; CMR, cardiac magnetic resonance; EMB, endomyocardial biopsy; FDG PET, fluorodeoxyglucose positron emission tomography; LVEF, left ventricular ejection fraction; PVC, premature ventricular contraction; RWMA, regional wall motion abnormality; VT, ventricular tachycardia.

    Electrocardiography/signal averaged ECG

    ECG abnormalities are common, including conduction abnormalities or arrhythmias, but there is a low level of accuracy making it difficult to determine the extent of cardiac infiltration. The presence of sustained VT has independent prognostic value for predicting mortality in patients with CS.10 Signal averaged ECG can be a useful diagnostic tool in the evaluation of cardiac involvement, with a sensitivity of 52% and a specificity of 82%.w13

    24 h Holter monitoring

    Holter monitoring in patients with suspected or confirmed CS may be considered, having a sensitivity and specificity of 67% and 80%, respectively.w14 w15 However, abnormalities are usually non-specific (premature ventricular contractions, non-sustained VT). Although not diagnostic, these findings can increase the clinical suspicion for CS, especially in patients with extracardiac sarcoidosis.

    Echocardiography

    Echocardiographic abnormalities have been reported in 14–56% of patients with sarcoidosis.14 w16 There are no specific changes but common abnormalities include abnormal septal wall thickness (thinning or thickening), wall motion abnormalities often in a non-coronary distribution, as well as systolic and diastolic dysfunctions. Early, mild or focal disease may not be present. However, echocardiography can define left ventricular (LV) dilatation which is a strong independent predictor of mortality10 (figure 4). Novel technologies for early detection include cycle dependent variation of myocardial integrated backscatter analysis, which can differentiate damaged and normal myocardium by measuring myocardial acoustic properties.w17

    Figure 4
    Figure 4

    Granuloma present in right ventricle (arrow) in a patient with known cardiac sarcoidosis. Positron emission tomography imaging demonstrated increased uptake in the same area confirming active sarcoidosis. Reproduced from Ayyala US, Nair AP, Padilla ML. Cardiac sarcoidosis. Clin Chest Med 2008;29:493–508, with permission from Elsevier.13

    Cardiac MRI

    Cardiac magnetic resonance (CMR) results depend on the age of the pathological process. In the acute inflammatory stage, the following are observed: (1) myocardial thickening with wall motion abnormalities; (2) increased T2 weighted signal, indicative of oedema; and (3) late enhancement pattern. In the chronic stage with scarring, focal areas of myocardial thinning with delayed enhancement are apparent typically in the basal septum. The latter can be linear in the subepicardium, transmural, or nodular with patchy distribution. Enhancement is typically non-vascular in distributionw18 w19 (figure 5). However, Patel et al15 showed a variable pattern of involvement, with 48% of hyperenhanced regions classified as coronary artery disease (CAD) type, while 86% of affected patients (18/21) had at least one region with hyperenhancement in a non-CAD type pattern. The CMR diagnostic accuracy was studied by Smedma et al in a series of 58 patients with suspected CS against the older Japanese Ministry of Health and Welfare (JMHW) guidelines with a sensitivity and specificity of 100% and 78%, respectively.16 In studies by Ohira and Mehta et al, CMR was shown to have a better specificity but lower sensitivity than fluorodeoxyglucose (FDG) PET.3 w20 CMR was included as a diagnostic criterion in the most recent update of the JMHW guidelines in 2006.11

    Figure 5
    Figure 5

    Middle aged patient with biopsy proven systemic sarcoidosis, presenting with ventricular tachycardia. Echocardiography showed posterior wall motion abnormality with ejection fraction of 35–40%. Cardiac catheterisation was normal. Cardiac magnetic resonance shows dense, epicardial based delayed enhancement in both the inferolateral and anteroseptal walls, typical of cardiac sarcoidosis. Image provided with permission from James White, Robarts Research Institute, University of Western Ontario, Canada.

    An advantage of CMR is that it does not expose patients to ionising radiation. Important limitations include CMR's inability to study patients with pacemakers/defibrillators and the risk of nephrogenic systemic fibrosis with gadolinium in patients with renal impairment.

    Radionuclide examinations

    Nuclear imaging modalities in CS include thallium-201 and technetium-99 m based myocardial single photon emission CT (SPECT), gallium-67 (Ga-67) scintigraphy, and FDG PET. Myocardial perfusion imaging (MPI) defects in the LV may correlate with atrioventricular block and arrhythmias. Changes in the right ventricle (RV) may be associated with ventricular tachyarrhythmias of RV origin.w21

    Thallium-201 and technetium-99 m based SPECT

    In addition to identifying MPI defects, the phenomenon of ‘reverse redistribution’ has been described on both thallium-201 and technetium-99 m imaging, where resting focal perfusion defects decrease in size or disappear during stress imaging.w22 w23 This is likely due to focal reversible microvascular constriction in coronary arterioles surrounding the sarcoid granulomas.w24–w26 Reverse distribution is not specific for CS as it can also occur in CAD. In serial studies the amount of reverse distribution correlated with the degree of improvement with corticosteroids.w27

    Gallium-67

    Ga-67 accumulates in areas of active inflammation, and has been used to diagnose and assess disease activity in pulmonary and extrapulmonary sarcoidosis. Though its specificity is nearly 100%, its sensitivity is much lower than other radionuclide tests, ranging from 0–36.4%w28–w31 (figure 6).

    Figure 6
    Figure 6

    (Left) Posteroanterior chest radiograph demonstrating a borderline enlarged cardiac silhouette in a patient with cardiac sarcoidosis. (Right) Gallium-67 scan showing increased update of 67-Ga in the cardiac apex, consistent with active granulomatous inflammation. Reproduced with permission from Deng JC, Baughman RP, Lynch JP 3rd. Cardiac involvement in sarcoidosis. Semin Respir Crit Care Med 2002;23:513–27.w46

    PET

    FDG is a glucose analogue that is useful for differentiating between normal and active inflammatory lesions where the activated macrophages show a higher metabolic rate and glucose utilisation.w32 While no individual clinical finding is pathognomonic for the diagnosis, FDG PET has gained interest in functional imaging of inflammatory disease activity to assess fibrogranulomatous disease in the myocardium.

    Focal or focal on diffuse FDG uptake patterns suggest active CS. Concomitant use of PET perfusion tracers can help exclude significant obstructive CAD (figure 7).

    Figure 7
    Figure 7

    An elderly patient presenting with ventricular tachycardia. Positron emission tomography (PET) scan (panels A and B) shows reduced Rb-82 perfusion (upper row) together with focal increased fluorodeoxyglucose (FDG) uptake (lower row) in the basal anterior and anteroseptal walls. This is confirmed in the whole body FDG PET/CT scan (C), denoting a mixture of active granulomatous inflammation and scarring. Whole body FDG scan also showed evidence of pulmonary sarcoidosis with bilateral hypermetabolic pulmonary lesions and enlarged hilar lymph nodes.

    Several small Japanese studies have demonstrated the high diagnostic accuracy of fasting FDG PET when compared to the JMHW guidelines.

    Recently, Langah et al performed a retrospective study of 30 patients with systemic sarcoidosis and suspected CS referred for FDG PET.17 Sensitivity and specificity were 85% and 90%, respectively. This was significantly higher than Ga-67 (sensitivity and specificity of 15% and 80%, respectively). In another recent study by Ohira et al, the sensitivity of FDG was similarly high (88%) while specificity was not as high as previously shown (38%). The latter was explained on the basis of the potential ability of FDG to detect early subclinical lesions even in patients who do not meet the JMHW guidelines.w20

    FDG PET sensitivity was shown to be superior to Tc-99 m based SPECT MPI (30–40%).w29 w31 Interestingly, Mehta et al3 used FDG PET as the gold standard in order to test the JMHW guidelines. The latter showed a sensitivity of 33% (CI 16% to 55%) and specificity of 97% (CI 86% to 99%) compared to FDG.

    A meta-analysis studying the diagnostic accuracy of FDG PET in 164 patients from six studies, against the Japanese guidelines, showed the sensitivity to be consistently high with a pooled value of 89%; the pooled specificity was 78%.18

    Recently Tahara et al, using the coefficient of variation (COV), showed that FDG uptake was distinctly heterogeneous in CS patients with greater COV compared to controls, sarcoidosis patients without cardiac involvement or dilated cardiomyopathy patients. Following corticosteroid treatment in CS patients, the COV was significantly decreased and became similar to the other groups.12

    Endomyocardial biopsy

    Endomyocardial biopsy (EMB) can provide a definitive diagnosis of CS. Unless EMB is guided by imaging, it has low sensitivity due to the patchy distribution of granulomas, revealing non-caseating granulomas in <25% of patients with CS.w33 w34 In patients with extracardiac sarcoidosis, histological confirmation by lymph node or lung biopsy should be targeted first due to higher diagnostic yield and lower procedural risk. If this approach is not feasible or isolated CS is suspected, EMB should be performed, ideally guided by imaging to increase diagnostic yield.19

    Although EMB is not routinely performed in the evaluation of heart failure, it should be strongly considered in selected cases. Consensus recommendations for the evaluation of idiopathic cardiomyopathy support the use of EMB in patients with heart failure of recent onset and ventricular arrhythmias that are refractory to treatment.w34 The same applies to recent onset HF associated with new conduction system disease—that is, AV block or bundle branch block.

    Electrophysiology study

    The role of programmed ventricular stimulation through an electrophysiology study (EPS) has been debated over the years.w35 Even though an EPS is not used to diagnose CS, it may be valuable in the risk stratification of patients. Mehta et al studied a cohort of 76 patients with biopsy proven systemic sarcoidosis but without cardiac symptoms who had CS diagnosed by advanced cardiac imaging, and showed that 11% of patients had inducible sustained ventricular arrhythmias.20 Over a median follow-up of 5 years, six of eight patients with a positive EPS had ventricular arrhythmias or died, compared with one death (non-cardiac) in the negative EPS group (p<0.0001). Importantly, patients with a negative EPS had a benign course. This is the largest study to date, providing evidence that a positive EPS can help identify patients at risk for ventricular arrhythmias and may be useful in the risk stratification of patients without documented heart block or VT. Whether imaging can similarly define such risk requires additional study.

    In summary, EPS should be considered in patients with biopsy proven systemic sarcoidosis and asymptomatic CS diagnosed by advanced imaging. Inducible sustained ventricular arrhythmias warrant placement of an implantable cardioverter-defibrillator (ICD).

    Prognosis

    Overall, the presence of cardiac involvement in patients with sarcoidosis is associated with adverse outcomes. The presence of heart failure carries a poor prognosis, with 3 and 5 year survival when compared with patients with idiopathic dilated cardiomyopathy and a similar degree of LV dysfunction.w36 In patients with unexplained dilated cardiomyopathy, EMB verified sarcoidosis predicts poor prognosis.w33

    Patients presenting with ventricular arrhythmias or AV block are at risk for major adverse cardiac events. Kandolin et al showed that patients aged <55 years with AV block had >10-fold increase in the risk of adverse cardiac outcomes in 2 years when compared with patients without CS.8

    A recent study by Patel et al15 showed that even subclinical CS is associated with SCD. In 81 patients with biopsy proven extracardiac sarcoidosis, myocardial involvement was confirmed by CMR in 26%, and five of 21(19%) patients died over a follow-up period of 21 months.

    Differential diagnosis

    Alternative clinical diagnoses include CAD, arrhythmogenic right ventricular cardiomyopathy (ARVC), idiopathic dilated cardiomyopathy, and giant cell myocarditis (GCM). Criteria favouring CAD include distribution of wall motion/thinning in specific vascular territory, subendocardial late enhancement on CMR, and reversal of stress defects on nuclear MPI. ARVC has a predilection for the RV. The incidence of CS was 15% in patients with suspected ARVC when studied by RV biopsy.w37GCM is a granulomatous disease that is also characterised by recurrent ventricular arrhythmias and is generally associated with more rapid cardiac deterioration than CS. EMB is recommended to confirm diagnosis and should be performed early if GCM is suspected.

    Management

    Medical treatment

    Corticosteroids/immunotherapy

    There are no published clinical consensus guidelines on the treatment of CS. Corticosteroid treatment is advocated by some experts.13 The mechanism of action is still debated, but it is believed that steroid agents can slow disease progression by re-establishing a normal T helper 1/T helper 2 (Th1/Th2) balance, reducing inflammation and, possibly, granuloma formation.

    This is based on very modest data from small retrospective observational studies showing variable clinical responses (table 2). Yodogawa et al suggested that patients may benefit from this therapy in the absence of severe LV dysfunction when the LV ejection fraction is >35%.w38 The effects of corticosteroid treatment on the clinical course of CS have not been studied in any randomised, prospective trials.

    View this table:
    Table 2

    Retrospective observational studies on cardiac sarcoidosis treatment

    Although retrospective data support corticosteroid treatment, the timing, dose and duration of treatment remain uncertain. Doses from 30–60 mg of prednisone daily are usually prescribed. The starting dose of 30 mg/day appears sufficient to improve prognosis.10 Patients should be reassessed in 2–3 months, and if responding, doses should be tapered to 10–15 mg/day over a period of 6 months. If periodic evaluations reveal controlled disease, prednisone should be tapered further and ultimately discontinued. Corticosteroid taper or withdrawal may only be pursued in cases of absent disease activity documented with SPECT, PET or CMR. Alternative agents, including methotrexate, infliximab, cyclophosphamide, antimalarials, and thalidomide, have been used with reported success in sarcoidosis. However, data to support their use in CS are extremely limited.

    Antiarrhythmic drug treatment

    Antiarrhythmic drug (AAD) treatment is often required in patients with CS. However, there have been no prospective studies evaluating the impact of these agents in this population. Thoughtful clinical judgement is needed to weigh the benefits versus the risks of these agents. As this subgroup is at risk for SCD, AADs should be used in association with ICD placement. Currently, the use of AADs is reserved for the treatment of ventricular arrhythmias resulting in recurrent ICD shocks in patients with prior ICD insertion.

    Device therapy

    Among patients with CS, sudden death due to ventricular tachyarrhythmias or AV block account for 30–65% of deaths.6 These observations constitute the rationale for the use of pacemakers and ICDs. Documented sustained VT and aborted VT/ventricular fibrillation arrest warrant ICD placement.

    There are no randomised data to support the utilisation of ICD for primary prevention of SCD in patients with CS presenting with advanced conduction system disease—for example, second or third degree AV block, but no documented sustained ventricular arrhythmia. However, expert opinion advocates ICD placement instead of a pacemaker, as this subgroup of patients is at risk for ventricular arrhythmia and SCD in the long term. In support of this recommendation, the 2008 American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines for device therapy have listed CS as a reasonable indication for ICD implantation with a class IIa recommendation.w39 As such, ICD placement is recommended.

    Cardiac transplantation

    Cardiac transplantation for CS is rare. It should be considered, however, in young patients with end stage heart failure or individuals with recurrent ventricular arrhythmias not amenable or refractory to catheter ablation. It should be noted that recurrent CS in the transplanted heart has been reported.w40

    Current trials on cardiac sarcoidosis treatment

    Currently, there are two planned or ongoing trials in CS therapy. The CArdiac Sarcoidosis response TO steRoids (CASTOR) trial is a prospective, double blind, placebo controlled, randomised trial evaluating the use of corticosteroid treatment in patients with CS (NCT01210677). This study will also assess the clinical and imaging predictors of response to treatment with corticosteroids as well as the utility of FDG PET and CMR imaging in the management of CS.

    The Implantable Defibrillator for the Prevention of Sudden Death in Patients in Cardiac Sarcoidosis trial (NCT01013311) is a retrospective study assessing the use of ICD for primary prevention of SCD in patients.

    Imaging to direct treatment

    The role of imaging in directing treatment and follow-up of CS patients is controversial. Ga-67 accumulation may be predictive of response to corticosteroid treatment.w26 Studies have also shown that Ga-67 accumulation was more common in CS patients presenting with CHB and VT than those without, with resolution of arrhythmias in most patients after corticosteroid treatment.9 w41 Similar findings were demonstrated for FDG PET. In a study of 17 patients with biopsy proven CS, most patients demonstrated a significant decrease in FDG uptake, whereas 13NH3 defects exhibited no significant change after steroid treatment.w31 The role of CMR in following the medical treatment response is still unclear. While some patients showed unchanged or slightly decreased enhancement in the study by Matoh et al,w42 Vignaux et alw43 reported an excellent clinical correlation. Whether imaging directed treatment improves outcome remains to be determined and is the subject of ongoing studies.

    Because of the risk for SCD in CS, a diagnosis of CS made on imaging may be particularly valuable in directing device therapy decisions in patients who have not presented with syncope, heart block or VT (figure 8).

    Figure 8
    Figure 8

    Algorithm for device therapy in cardiac sarcoidosis, based on best available data. AV, atrioventricular; F/U, follow-up; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction.

    Several questions concerning the diagnosis and treatment of CS remain unanswered and there is a clear need for prospective registries and randomised controlled studies in the field. Since most centres diagnose a relatively small number of cases per year, a logical approach would be through a multicentre collaboration. This approach has been successful for a number of conditions—for example, infective endocarditis.w44

    Conclusions

    Sarcoidosis remains an enigma with an uncertain aetiology and a challenging diagnosis. CS is of importance because it is a common manifestation of sarcoidosis that carries potentially serious adverse outcomes. Imaging has been useful in the assessment of CS. More recently, the increased accuracy of advanced imaging, particularly PET and MRI, appears to add to the diagnostic capabilities, but their true impact requires further study. We have presented an approach to diagnosis and management based on the best currently available evidence. Treatments for CS, including steroids, while often accepted by some, have not been tested in a randomised controlled trial. Likewise, the role of imaging in identifying those at risk for events and the response to treatment requires further study. Whether or not this can lead to treatment decisions that impact outcome is a focus of ongoing research.

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    Acknowledgments

    The authors thank Dr James White for providing the CMR image and Carrie Barlow for her assistance in preparing the manuscript.

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    Footnotes

    • Funding GY is a clinical research fellow supported by the University of Ottawa International Fellowship, the Division of Cardiology and the Molecular Function and Imaging Program (HSFO program grant PRG6242) and IMAGE HF Team Grant Program supported by Canadian Institutes for Health Research (CIHR) and TEKES Finland (grant CIF99470). RSB is a Career Investigator supported by the Heart and Stroke Foundation of Ontario.

    • Competing interests In compliance with EBAC/EACCME guidelines, all authors participating in Education in Heart have disclosed potential conflicts of interest that might cause a bias in the article. Professor Beanlands has undertaken research contracts for Lantheus Medical Imaging, GE Healthcare, and MDS Nordion, and consulting for Lantheus Medical Imaging and Jubilant DraxImage. All the other authors have no competing interests.

    • Provenance and peer review Commissioned; internally peer reviewed.