Cardiac Investigations in Diagnosis and Management of Cardiac Sarcoidosis

Alexandros G. Mathioudakis MD1, Victoria Chatzimavridou-Grigoriadou MS1, Aggelos S. Aggelakas MD1, Georgios A. Mathioudakis MD, PhD2.

1Respiratory Assembly, Hellenic Society for the Advancement of Biomedical Research. 2Respiratory Department, IASO General Hospital, Athens, Greece

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Cite as: Mathioudakis AG, Chatzimavridou-Grigoriadou V, Aggelakas AS, Mathioudakis GA. Cardiac Investigations in Diagnosis and Management of Cardiac Sarcoidosis. Alveolus 2013 1(2):11-18

 

Introduction

Sarcoidosis is a multisystem disease characterized by a heightened type 1 helper T cell immune response at sites of disease activity and by the presence of non-caseating granulomas, the aetiology of which is not completely understood. It most commonly involves the lungs but can also affects the lymph nodes, liver, eyes, skin and virtually every organ. Sarcoidosis is usually a self-limited disorder, can be asymptomatic and rarely cause serious symptoms[1]. Sarcoidosis is more common among females and usually develops before the age of 50 years, with a peak incidence during third and fourth decades of life[1]. Although it is a universal disease, its incidence varies widely among different ethnic and racial groups. Northern European countries have the highest annual incidence of sarcoidosis (between 5 and 40 cases per 100,000), while Japan is at the other end (1-2/100,000)[2]. Furthermore, there is a fourfold difference in the incidence between the black (35.5-80/100,000) and white race (3-20/100,000)[3].

Only 5% of patients with sarcoidosis have clinically evident cardiac involvement[4.] However, cardiac granulomas are found in 27% of patients, in autopsy studies[4], and in 40% of patients, in imaging studies[5].

Cardiac Manifestations

Sarcoidosis is associated with a variety of clinical manifestations, which depend on the disease’s activity, the location and extent of cardiac granulomas. Congestive heart failure is the most common manifestation and a leading cause of mortality in these patients[6], followed by conduction abnormalities, ventricular and atrial arrhythmias, ventricular aneurysms, pericardial effusion and sudden cardiac death. Clinical suspicion of cardiac sarcoidosis should arise in patients with sustained monomorphic ventricular tachycardia, idiopathic dilated cardiomyopathy, in young patients with unexplained sustained second or third degree AV block and in patients with extracardiac sarcoidosis. The diagnosis of cardiac sarcoidosis is made in the co-existences of non-caseating granulomas on biopsies of cardiac or extra-cardiac tissues (after excluding other causes of  granulomatous inflammation) and cardiovascular abnormalities without any other possible causes.

Sarcoidosis has generally an excellent prognosis. Many patients are asymptomatic and 2/3 have a remission during the first decade after diagnosis, with minor or no remaining symptoms[7]. However, some patients may develop chronic progressive disease. The mortality of the disease is estimated between 1-6%. Patients older than 40 years at onset and coloured patients have a less favourable outcome[8]. Sudden cardiac death is a significant cause of mortality in patients with sarcoidosis. In their classic study, Roberts et al, showed that sudden cardiac death accounted for 67% of the deaths of patients with confirmed (at autopsy) cardiac sarcoidosis[9].

Investigations

Virtually all cardiac investigations may have findings in cardiac sarcoidosis. Electrocardiographic changes are common but not specific, while signal averaged ECG is more accurate (sensitivity 52%, specificity 82%)[10]. Left ventricular dilatation, shown by echocardiography is an independent predictor for mortality[6]. Diagnostically, echocardiography is also characterized by poor sensitivity and specificity. Electrophysiological studies are not diagnostic for cardiac sarcoidosis, but they should be considered in all patients with suspected cardiac involvement, because of the risk of sudden cardiac death (which can be the first cardiac manifestation).

Although endomyocardial biopsy is diagnostic, it has a lows sensitivity because cardiac involvement tend to be patchy. Furthermore, granulomas seem to be commoner in the left ventricle and not in the right, where the biopsies are usually performed[11]. Biopsies guided by imaging are more sensitive[12].

Myocardial perfusion imaging defects identified by thalium-201 and technetium-99 based SPECT are associated with AV blocks and arrhythmias[13]. Furthermore, the reverse redistribution phenomenon may indicate reversible microvascular constriction in areas around non-caseating granulomas[14]. Although reverse redistribution in SPECT is not specific for sarcoidosis, it has a positive correlation with the response of sarcoidosis to corticosteroids[15].

The property of gallium-67 to accumulate in areas of active inflammation is useful in the diagnosis of sarcoidosis and the assessment of the activity and distribution of the disease. Despite its poor sensitivity (less than 40%), gallium-67 has a sensitivity of almost 100%[16].

Fluorodeoxyglucose(FDG) PET can highlight active inflammatory lesions, since FDG, a glucose analogue, accumulates in areas with activated macrophages, which have higher metabolic rate and glucose utilization. Focal or focal on diffuse uptake of FDG is correlated with active cardiac sarcoidosis. The sensitivity and specificity are estimated 85% and 90% respectively[17]. Coronary artery disease can be differentiated by the concomitant study of myocardial perfusion imaging defects[18].

Cardiac MRI findings

In patients with cardiac sarcoidosis, cardiac MRI reveals zones characterized by disturbances in wall thickness, with associated wall motion abnormalities, increased T2 weighted signal indicative of oedema and late gadolinium enhancement pattern. Myocardial wall appears thickened during the acute inflammatory stage, while focal areas of myocardial thinning characterize the chronic stage with scarring. Delayed gadolinium enhancement (DLE) is characterized by a pattern which varies from linear to nodular with a patchy distribution, which is typically non-vascular in distribution. Increased signal is found in subepicardium or myocardium, or with a transmural distribution, but not in the endocardium[19,20]. It’s pattern varies from linear to nodular with a patchy distribution.

The sensitivity, specificity and accuracy of cardiac MRI in the diagnosis of cardiac sarcoidosis (using the Japanese Ministry of Health and Welfare guidelines as a reference) have been calculated to be 85%, 90% and 86,7% while the same percentages for Gallium scintigraphy were 15%, 80% and 42.8%[17].  A previous study, with the same criteria, estimated the sensitivity of cardiac MRI to be 100% and the specificity 78%[21].

A recent study suggested that the presence of DLE is associated with worse prognosis in patients with cardiac sarcoidosis. In particular, it was statistically significantly associated with lower left ventricular (LV) ejection fraction, larger both the systolic and diastolic dimensions of LV and with higher mortality[22]. Another study showed that transmural lesions of DLE are associated with a LV ejection fraction of 35% or lower[20]. Greulich et al, in a cohort of 155 patients with suspected cardiac sarcoidosis found that the presence of LGE is correlated to an increased Cox hazard ratio (31.6) for death, aborted sudden cardiac death or appropriate ICD discharge, with a poor correspondent predictive ability of clinical and functional parameters.

A recent study by Hamjeh et al. showed that cardiac MRI is now used in the routine workup of suspected cardiac sarcoidosis by 88% of phycisiancs caring for patients with sarcoidosis[24]. Consequently, the need for new diagnostic guidelines to be suggested that include cardiac MRI for the diagnosis of cardiac sarcoidosis is imperative.

Treatment

The treatment of sarcoidosis is restricted in cases where organ function is threatened. In cardiac sarcoidosis, a permanent pacemaker is suggested for patients with complete heart block. Moreover, the implantation of a cardioverter- defibrillator is suggested after an episode of ventricular fibrillation or ventricular tachycardia and also for patients with LV ejection fraction of less than 35%. The last category of patients may also be benefited by the administration of oral steroids. Arrhythmias secondary to cardiac sarcoidosis usually also receive the normal –for non sarcoid patients- antiarrhythmic treatment. Ablation is also an option for scar related ventricular tachycardias, while cardiac transplantation is only considered for younger patients with severe heart failure or resistant ventricular tachycardia[25].

The correlation between the presence of DLE and the prognosis of sarcoidosis, which is highlighted by several studies[20,22,23], indicates that cardiac MRI should be taken into consideration for deciding whether to administer steroids. Other studies shows that administration of corticosteroids leads to reduction of the size and intensity of DLE areas and associated clinical improvement of patients with sarcoidosis[26,27]. Although no randomized clinical trials have been performed yet, there is one which will start recruiting in the near future[28].

References

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[29] NCT01210677,  Cardiac Sarcoidosis Response To Steroids Trial (CASTOR)

 

Conflicts of Interest: None