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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 1  |  Issue : 3  |  Page : 252-261

Acute arrhythmia or ventricular dysfunction - when is it sarcoid? Indian perspective


1 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Cardiac Radiology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Cardiac Pathology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India

Date of Web Publication23-Feb-2016

Correspondence Address:
Raghav Bansal
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2395-5414.177239

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  Abstract 

Background: Sarcoidosis is a granulomatous disease of unknown cause with multi-organ system involvement. It is important to keep a high index of suspicion to diagnose cardiac sarcoidosis in patients presenting with recent onset ventricular dysfunction and arrhythmias. Methods: We profile a series of our patients to show how different patients of cardiac sarcoid can present. Results: In the seven cases we reported, all patients had presented with arrhythmias and left ventricular (LV) dysfunction, a common theme which may help in identifying the patients with cardiac sarcoidosis. They were all investigated by magnetic resonance imaging (MRI), positron emission tomography (PET), Mantoux, computed tomography (CT) scan, and single photon emission CT, with an endomyocardial biopsy and a biopsy of any accessible lymph node. Treatment was with steroids, antituberculosis treatment (ATT) with automatic implanted cardioverter-defibrillators (AICDs), and pacemakers as per need. Conclusion: All patients with recent onset LV dysfunction, recent onset of unexplained tachy- or brady-arrhythmias with ventricular dysfunction, and ventricular arrhythmias of recent onset of unexplained origin should undergo an MRI. If the MRI raises a suspicion of sarcoidosis, then Mantoux, PET, CT scans, endomyocardial catheter biopsies, and biopsy from any other accessible site should be considered. Further therapy with ATT and steroids, AICD and pacemakers, and antiarrhythmics is based on the patient profile.

Keywords: Cardiac sarcoidosis, arrhythmias, congestive heart failure and sudden death


How to cite this article:
Bansal R, Parakh N, Naik N, Jagia P, Gulati G, Juneja R, Ray R, Mohan A, Seth S. Acute arrhythmia or ventricular dysfunction - when is it sarcoid? Indian perspective. J Pract Cardiovasc Sci 2015;1:252-61

How to cite this URL:
Bansal R, Parakh N, Naik N, Jagia P, Gulati G, Juneja R, Ray R, Mohan A, Seth S. Acute arrhythmia or ventricular dysfunction - when is it sarcoid? Indian perspective. J Pract Cardiovasc Sci [serial online] 2015 [cited 2019 Jul 20];1:252-61. Available from: http://www.j-pcs.org/text.asp?2015/1/3/252/177239


  Introduction Top


Sarcoidosis is a granulomatous disease of unknown cause with multi-organ system involvement. Sarcoidosis commonly involves lymph nodes, skin, lungs, eyes, and central nervous system. According to Indian estimates from VP Chest Institute, Delhi, sarcoidosis is diagnosed in 61.2/100,000 new cases. [1] Sarcoidosis is a disease of the young- and middle-aged and affects females more than males. Cardiac involvement is clinically uncommon and presents only in 5% of the cases and when present portends a poor prognosis. However, on autopsy series, cardiac involvement has been estimated up to 20-30% cases. [2],[3] Cardiac involvement may occur in up to 58% of the cases and is responsible for mortality in 85% of cases in Japan.

The most common presentations of cardiac sarcoidosis are arrhythmias, congestive heart failure, and sudden death. It is important to keep a high index of suspicion to diagnose cardiac sarcoidosis in patients presenting with recent onset ventricular dysfunction and arrhythmias. Cardiac sarcoidosis has a poor prognosis but remains responsive to immunosuppression if started early. We profile a series of our patients to show how different patients of cardiac sarcoid can present.


  Methods Top


Most of the patients in this series had presented with either arrhythmias and were then found to have sarcoidosis or had left ventricular (LV) dysfunction with some pulmonary finding and further evaluation revealed evidence of sarcoid or they came to a pulmonologist with pulmonary sarcoid, and evidence of cardiac involvement was found. The data of 7 such patients is presented.


  Results Top


Seven patients of cardiac sarcoid are presented [Table 1] to show how such patients can present and how they can be diagnosed with the current available diagnostic modalities.
Table 1: Detailed profile of seven patients with cardiac sarcoid

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Case 1

A 40-year-old male, known diabetic since 2 years on oral hypoglycemic agents (HbA1c - 8.0 g%), presented with recurrent palpitations with presyncope and one episode of syncope while driving. He also had dyspnea on exertion New York Heart Association Class II since last 2-3 months. This time, he presented with persistent palpitations. His electrocardiogram (ECG) showed monomorphic ventricular tachycardia (VT) with alternating bundle branch block type morphology, and he was pharmacologically cardioverted with amiodarone. He had the first-degree heart block on baseline sinus rhythm. Echocardiogram showed severe LV dysfunction with ejection fraction (EF) of 20-25%. Contrast enhanced computed tomography (CECT) chest showed multiple enlarged mediastinal lymph nodes and multiple micronodules in peripheral lung fields with centrilobular nodules in the left upper lobe. Cardiac magnetic resonance imaging (MRI) was suggestive of transmural septal enhancement of anterior, anteroseptal, and inferoseptal segments of LV and right ventricular (RV) with global hypokinesia. Technetium-99 (Tc-99m) sestamibi perfusion single photon emission computed tomography (SPECT) scans at rest were suggestive of a dilated LV cavity with normal perfusion. Coronary angiography was also done and showed normal coronaries. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed a focal area of increased uptake in the mid and the proximal anteroseptal wall with complete suppression of FDG uptake in the rest of the myocardium. The serum angiotensin-converting enzyme (ACE) level was 10 IU/ml. Bronchoalveolar fluid analysis, transbronchial lymph node biopsy, and endomyocardial biopsy (EMBx) were inconclusive for sarcoidosis. The patient was started on steroids and also underwent a single chamber automatic implanted cardioverter-defibrillator (AICD) implantation. The patient had recurrent shocks 7 days after AICD implantation and was started on amiodarone. The patient is doing fine on follow-up and has improved significantly.

Case 2

A 46-year-old male, a known case of hypertension and diabetes since 2 years, presented with worsening dyspnea since 1 year. He had bradycardia and hepatosplenomegaly on abdominal examination. The ECG showed complete heart block with narrow complex escape rhythm. Echocardiogram was suggestive of global hypokinesis with an EF of 35%. Cardiac MRI mid-ventricular interventricular septum akinesia delayed enhancement suggestive of cardiac sarcoidosis. EMBx was also done which showed myocytes with hypertrophy and nuclear enlargement. The areas of focal interstitial fibrosis were also noted. However, there were no granulomas found. The patient was started on steroids, standard treatment for heart failure, and underwent a single chamber permanent pacemaker implantation. The patient improved and was discharged for follow-up.

Case 3

A 30-year-old female presented with recurrent palpitations lasting a few seconds of rest since last 20 days. There was no history of dyspnea on exertion or angina on exertion. The examination was normal. Ventricular function was normal. Holter monitoring showed frequent ventricular premature contractions (VPCs) and recurrent nonsustained ventricular tachycardia [Figure 1]a and b. Cardiac sarcoidosis was suspected. CECT chest showed enlarged pretracheal, paratracheal, subcarinal, and parahilar nodes with central necrosis and peripheral enhancing rim. There was diffuse myocardial involvement with evidence of focal perfusion defects along with inferior and inferolateral wall thinning in mid-ventricular to apical segments on SPECT [Figure 2]. Late gadolinium enhancement (LGE) images showed multiple areas of linear/patchy mid-myocardial enhancement in interventricular septum and inferolateral region. FDG-PET showed no abnormal FDG uptake in myocardium with mild FDG uptake in multiple mediastinal lymph nodes. Transbronchial needle aspiration was done from mediastinal lymph nodes, which showed epithelioid granulomas with no necrosis and negative staining for acid-fast bacillus. EMBx was also done, which was negative for granulomatous inflammation. The patient was started on steroids and the patient improved at follow-up.
Figure 1: (a) Electrocardiogram showing frequent ventricular premature contractions. (b) Holter record showing run of nonsustained ventricular tachycardia.

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Figure 2: Technetium-99 single photon emission computed tomography showing evidence of focal perfusion defects along with inferior and inferolateral wall thinning in mid-ventricular to apical segments.

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Case 4

A 57-year-old female presented with dyspnea on exertion Class II and recurrent episodes of palpitations lasting 30 min to 1 h associated with presyncope, not related to exertion. Cardiac examination was unremarkable. Echocardiogram showed moderate LV dysfunction with an EF of around 35-40%. Holter showed episodes of VT. She had already been diagnosed to have cardiac sarcoidosis on the basis of endomyocardial Bx, which showed epithelioid granulomas [Figure 3] and was started on steroids. She continued to have persistent palpitations despite steroids. The patient underwent VT ablation under CARTO. However, recurrent episode of VT persisted. The patient underwent AICD implantation. In the post-AICD period, she received recurrent shocks for recurrent VT, for which sotalol was started. She was started on amiodarone and flecainide. However, VT could not be controlled and was refractory. The patient was taken up for bilateral cervicothoracic sympathectomy. After sympathectomy, VT was controlled. The patient was admitted again with easy fatiguability and Class III dyspnea. On evaluation, she was found to have severe anemia with normal ferritin levels suggestive of anemia of chronic disease. She was given a blood transfusion and was managed conservatively. To look for persistent activity, PET scan was done which showed a dilated LV cavity and perfusion defects and increased FDG uptake in the mid and proximal septum. The patient was started on methotrexate and steroids were continued. The patient improved at follow-up.
Figure 3: EMCB (case 4, epithelioid granulomas).

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Case 5

A 30-year-old male presented with recurrent episodes of cerebrovascular accident. He underwent Holter monitoring for evaluation. Holter showed frequent VPCs of right bundle branch block (RBBB) morphology. Echocardiogram evaluation was normal. There were no cardiac symptoms or abnormalities on examination. Cardiac MRI was suggestive of abnormal myocardial enhancement. Cardiac sarcoidosis was suspected on cardiac MRI findings.

Case 6

A 44-year-old male, presented with dyspnoea on exertion Class II with no history of chest pain and pedal edema. Chest X-ray was suggestive of mediastinal lymphadenopathy. CECT was suggestive of right paratracheal and lower paraesophageal lymphadenopathy. Echocardiogram showed global hypokinesia with EF of 20%. Coronary angiography showed normal coronaries. EMBx was done, which was suggestive of noncaseating epithelioid granulomas. Mantoux test was borderline positive. The patient was started on antituberculosis treatment (ATT) and steroids, and the patient subsequently improved at follow-up.

Case 7

A 48-year-old male presented with recent onset dyspnea since 15 days. On evaluation, he was found to have a severe LV dysfunction with LV ejection fraction (LVEF) 10-15%. Holter monitoring showed recurrent, stable VT (RBBB morphology with superior axis). CECT chest [Figure 4] was suggestive of type 3 pulmonary sarcoidosis with parenchymal interstitial septal thickening with peribronchovascular nodularity and mediastinal and hilar lymphadenopathy. Cardiac MRI showed a dilated LV cavity with global hypokinesia. LGE images showed mid-myocardial enhancement [Figure 5] in anterior, anterolateral, anteroseptal, and inferoseptal segments of the basal and mid-cavity regions. LGE was also seen in posteromedial papillary muscle. Mantoux test was negative and serum ACE levels were 37 IU/L (normal: 8-65). The patient was advised an AICD. He was also started on amiodarone and steroids. He improved at follow-up, and there was documented improvement in LVEF.
Figure 4: (Case 7, CT scan showing lung fields with interstitial thickening).

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Figure 5: MRI (case 7, myocardial late enhancement suggestive of sarcoidosis).

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  Discussion and Review of Literature Top


In the 7 cases we reported, all patients had presented with arrhythmias and LV dysfunction, a common theme which may help in identifying the patients with cardiac sarcoidosis.

On the basis of our experience, we present the algorithm [Figure 6]. All patients with recent onset LV dysfunction, recent onset of unexplained tachy- or brady-arrhythmias with ventricular dysfunction, and ventricular arrhythmias of recent onset of unexplained origin should undergo an MRI. If the MRI raises a suspicion of sarcoidosis, then Mantoux, PET, computed tomography (CT) scans, endomyocardial catheter biopsies, and biopsy from any other accessible site should be considered. Further therapy with ATT and steroids, AICD and pacemakers, and antiarrhythmics is based on the patient profile.
Figure 6: Algorithm for diagnosis of Cardiac Sarcoid.

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A look at cardiac sarcoid as a disease

Sarcoidosis is a granulomatous disorder with a good prognosis. However, this prognosis changes drastically for the poor with cardiac involvement.

Etiopathogenesis

The etiology of sarcoidosis is unknown. Many environmental and infectious causes have been hypothesized, but none has been proved definitively. The most accepted theory is that it occurs in genetically susceptible individuals with specific exposures. Agricultural employment and exposure to insecticides have been shown to risk factors in a multicenter, case-controlled study. [4] Many microorganisms have been implicated as possible etiologies. These include mycobacteria, Mycoplasma, Corynebacterium, Propionibacteria, Borrelia, Rickettsia, and Herpes virus. [5] However, their role is still to be proven. The precipitating event in the form of antigenic exposure evokes a nonspecific cell-mediated immunity in the host which led to the formation of noncaseating granulomas involving various organs. These granulomas, characteristic of sarcoidosis, consist of well-differentiated mononuclear phagocytes and lymphocytes. In the early stage, CD4 positive T-cells predominate with a T-helper type 1 response, secreting interleukin-2 and interferon-γ. This shifts to a T-helper type 2 response at a later stage during the fibroblastic stage of the granuloma and results in tissue scarring. Maintenance of inflammation is thought to be mediated through interleukin-6. [6],[7]

Noncaseating granulomas in cardiac sarcoidosis may involve the LV free wall, basal ventricular septum, right ventricle, papillary muscles, right and left atria. [8] The clinical manifestations depend on the site and extent of these granulomas. Edema, granuloma formation and fibrosis with scarring are the three histologic stages.

According to a case-controlled etiologic sarcoidosis study, the first degree relatives have 5 times relative risk of sarcoidosis that of control subjects. [9] The genetic factors determine the risk, the pattern of disease, its severity, and also the prognosis. Monozygotic twins are more commonly affected as compared to dizygotic twins. The incidence of sarcoidosis is different in different populations, being the highest in the Scandinavian and Japanese populations. Studies have identified associations with major histocompatibility complex antigens. In Japanese female patients, cardiac sarcoidosis has been associated with HLA-DQB1*0601 and the allele Tumor necrosis factor allele (TNFa2). [10],[11]

Clinical features

Sarcoidosis presents with a range of possibilities from asymptomatic to involve organ failure. Respiratory complaints are the most common presenting symptoms and include cough and dyspnea. Cutaneous and ocular manifestations are the next two most common manifestations. However, due to nonspecific and insidious nature of the symptoms and signs, the diagnosis is often delayed. Constitutional symptoms include fatigue, low-grade fever, night sweats, and weight loss, with fatigue being the most common. The prevalence of involvement of various organ systems is given in [Table 2].
Table 2: Prevalence of organ system involvement at presentation of disease

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The frequency of cardiac involvement is influenced by race. Asymptomatic cardiac involvement varies from 20 to 27% in the United States to as high as 58% in Japan. [12] Symptomatic cardiac disease is uncommon and occurs in about 2-5% cases in the United States and Europe. However, in Japanese patients, symptomatic involvement occurs in over 25% cases. It may be easier to reach a diagnosis of cardiac sarcoidosis when it occurs in the setting of multisystem involvement as compared to the patients with isolated cardiac involvement, in whom the diagnosis is hardly ever suspected. [13] It is important to keep a high index of suspicion to make an early diagnosis as treatment improves the diagnosis. The rate of various cardiac manifestations is given in [Table 3]. [14]
Table 3: Prevalence of cardiac findings in cardiac sarcoidosis

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Complete heart block and bundle branch block

When complete heart block occurs in younger patients, the diagnosis of cardiac sarcoidosis should be entertained. Moreover, when associated with LV dysfunction, the diagnosis becomes even more likely. Sudden death may be a direct manifestation of complete heart block. Heart block occurs by involvement of basal septum by granulomas and scar tissue. Complete heart block deserves evaluation with Holter monitoring and appropriate imaging.

Ventricular arrhythmias

These are the most common arrhythmias seen in cardiac sarcoidosis. A study demonstrated an incidence of 23%. [15] Abnormal automaticity may originate from foci of myocardial involvement with granulomas. Active inflammation and even scarring can lead to dispersion of waveform of ventricular activation and recovery, leading to re-entry phenomenon. Inflammation can play a role in exacerbation of electrical storm. Therefore, corticosteroid can play an integral role in arrhythmia suppression. Atrial arrhythmias are less common and usually occur secondary to atrial dilatation and pulmonary involvement rather than atrial granulomas. [8] Pleomorphism and cycle length variation should always be looked for. These features help in distinguishing idiopathic VT from VT due to cardiac sarcoidosis. [16]

Congestive heart failure

Extensive infiltration of myocardium with noncaseating granulomas can lead to systolic or diastolic dysfunction and heart failure. Progressive heart failure is the cause of cardiac death in 25-75% cases. [17] It is often difficult to differentiate LV dysfunction in cardiac sarcoidosis from idiopathic dilated cardiomyopathy. As shown by Yazaki et al., as compared to idiopathic dilated cardiomyopathy, cardiac sarcoidosis has a higher incidence of complete heart block (67% vs. 0%), right bundle branch block (57% vs. 17%), and abnormal LV free wall thickness (73% vs. 17%). [18]

In spite of extensive myocardial involvement, pericardial involvement is uncommon and asymptomatic. Small pericardial effusions were seen in 19% of the cases with the help of echocardiography. [19] Valvular involvement is also rare and occurs in fewer than 3% of the cases. However, mitral regurgitation can occur secondary to papillary muscle dysfunction and LV dilatation in up to 68% of patients. [20] Ventricular aneurysms commonly in the anterior and septal wall segments occur in 10% of the patients. These aneurysms can be further arrhythmogenic. Although leading to healing of granulomas with fibrous tissue, steroid therapy is associated with aneurysm formation. [21] However still, this should never be a deterrent to start steroid therapy where indicated as aneurysms may occur with active myocardial involvement.

Pulmonary hypertension and cor pulmonale

The frequency of pulmonary hypertension has been reported to be 73.8% in 363 cases listed for a lung transplant by Shorr et al. [22] Pulmonary hypertension in sarcoidosis can occur due to multiple mechanisms. It can be secondary to pulmonary venous hypertension due to LV failure. It also occurs with extensive lung involvement with vascular changes occurring secondary to alveolar hypoxia. There may also be an intrinsic sarcoid vasculopathy involving the pulmonary vasculature. Compression of pulmonary vasculature by mediastinal lymph nodes is a rare cause. Due to multiple causes, pulmonary hypertension requires a complete and careful workup. It is important to recognize this entity as it is a marker of poor prognosis in sarcoidosis.

Diagnosis

The diagnosis of cardiac sarcoidosis is challenging due to lack of sensitive and specific tests. There is no gold standard diagnostic test. The 2006 revised Japanese society of sarcoidosis and other granulomatous disorders guidelines proposes histological and clinical criteria [Table 4]. [23] However, the diagnosis can only be made in the presence of confirmed extra-cardiac sarcoidosis. Diagnosis of isolated cardiac sarcoidosis remains an enigma.
Table 4: Revised guidelines for diagnosing cardiac sarcoidosis (Japan Society of Sarcoidosis and Other Granulomatous Disorders)

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Endomyocardial biopsy

The yield of EMBx is typically limited up to 20% due to the patchy involvement of the myocardium. [24] Furthermore, the granulomas are most commonly located in the LV free wall and or basal septum, whereas the transvenous biopsies are obtained from the RV free wall. Multiple biopsies should be taken to increase the yield and decrease the sampling error. In spite of its low yield, EMBx can be considered while entertaining the diagnosis of cardiac sarcoidosis as it can help in ruling out other disorders and help confirm the diagnosis in the presence of noncaseating granulomas. The differential diagnosis includes rheumatoid arthritis, Lyme disease, dermatomyositis, cardiac amyloidosis, and alcohol-related cardiomyopathy. These disorders can usually be distinguished on clinical grounds.

Electrocardiogram and Holter monitoring

An ECG should be a part of an investigation in every case. Prevalence of ECG abnormalities is related to the severity of disease. In a study by Silverman et al., ECG abnormalities were found in 15% of the cases with no cardiac involvement at autopsy, in 42% of the patients with mild involvement, and in 75% of the patients with severe involvement. However, ECG remains nonspecific and nondiagnostic. [3] Holter monitoring and stress ECG can be considered to screen asymptomatic patients and to document rhythm abnormalities missed on baseline ECG. Suzuki et al. reported a sensitivity of 67% and specificity of 62% with 24 h Holter monitoring, when there were >100 ventricular premature complexes per day. [25] QT dispersion may be a marker of sudden cardiac death.

Echocardiography

The abnormalities which may be seen on echocardiography in cardiac sarcoidosis include depressed EF, segmental or global hypokinesia or dyskinesia, ventricular enlargement or hypertrophy, diastolic dysfunction, ventricular aneurysms, valvular regurgitation, mitral valve prolapse due to papillary muscle dysfunction and pericardial effusion. [21] Even in the absence of ECG changes and symptoms, echocardiographic abnormalities may be seen in up to 40% of the patients. [26],[27] The areas with myocardial granulomas or scarring appear hyperechoic on echocardiography. [27] However, echocardiography does not detect microscopic granulomas and cannot make or exclude the diagnosis of sarcoidosis with certainty. A new technique, cycle-dependent variation of myocardial integrated backscatter may be abnormally decreased in the basal septum even in the absence of two-dimensional echocardiographic abnormalities. In future, this may be used as a technique to detect early myocardial involvement in patients with sarcoidosis.

Radionuclide imaging

Thallium-201 imaging can be used to detect myocardial involvement in sarcoidosis. Thallium-201 is absorbed by living myocardial cells. Hence, areas appearing as "cold spots" are suggestive of scar, necrosis, ischemia, or inflammation. Thus, the fibro-granulomatous replacement of myocardium is seen as areas of decreased thallium-201 uptake in the ventricular myocardium. [28] The presence of these cold spots at rest imaging is seen more commonly in coronary artery disease. These can be differentiated by the phenomenon of "reverse distribution" (the imaging defect at rest increases with exertion in coronary artery disease, and decreases in cardiac sarcoidosis). [29] However, this finding is also not specific for cardiac sarcoidosis and may be seen in other cardiomyopathies. The response to treatment may be monitored by the progression and resolution of these perfusion defects. [30]

Tc-99m sestamibi has higher radioactivity than thallium-201 and gallium-67 and may be more sensitive in detecting the myocardial involvement in sarcoidosis. Combined use of thallium-201 and gallium-67 may also improve detection rates. [31] Okayama et al. showed in a small series of patients that gallium-67 avid lesions on scintigraphy may be helpful in predicting response to steroids. [32] These radionuclide imaging tests should not be used for screening of cardiac sarcoidosis as these are usually nonspecific. Appropriate use entails testing only in cases which are suspected to have the disease on echocardiographic imaging and ECG findings.

Cardiac magnetic resonance imaging

Cardiac MRI is a highly sensitive noninvasive tool for detecting cardiac inflammation and scarring. T2-weighted imaging picks up edema associated with inflammation and granuloma formation, and LGE imaging is helpful in determining scarred regions. LGE is the dominant sequence of MRI used for detection of cardiac sarcoidosis. [33] MRI imaging can also predict prognosis in cardiac sarcoidosis and may be helpful in predicting the response to corticosteroid therapy. [34],[35]

Positron emission tomography

18 F-FDG is a glucose analog which helps in detecting active inflammatory lesions, and this imaging modality is more sensitive than thallium-21, gallium-67, and technetium-99 single photon emission CT. [36] A low specificity occurs with diffuse uptake by the entire myocardium. The specificity can be improved with a low carbohydrate and high-fat diet before the procedure and with intravenous heparin injection. Exercise should also be avoided for 24 h before the procedure. There is a heterogeneous pattern of uptake in cardiac sarcoidosis as compared to patients with dilated cardiomyopathy and controls. [37] The patients treated with steroids show decreased uptake indicative of regression of inflammation suggesting response to therapy. FDG-PET seems promising as an imaging modality to diagnose cardiac sarcoidosis and also to monitor response to therapy.

Coronary angiography

Sarcoidosis rarely involves coronary arteries. [38] The role of coronary angiography is in excluding coronary artery disease and significant atherosclerosis.

Serum markers

Serum ACE levels, which is a useful biomarker for systemic sarcoidosis, have failed to show adequate sensitivity for cardiac sarcoidosis. [39] Soluble form of interleukin-2 receptor has been proposed as a useful biomarker for cardiac sarcoidosis. However, the data are still insufficient to bring it to clinical use. [40]

Isolated cardiac sarcoidosis

According to the JSSOG 2006 criteria, it is a must to have secure diagnosis of extra-cardiac diagnosis before diagnosing cardiac sarcoidosis. [23] Thus, it becomes impossible to have a confirmed diagnosis of isolated cardiac sarcoidosis. However, it is important to make the diagnosis early due to the poor prognosis associated with the cardiac involvement. Takaya et al. have reported that isolated cardiac sarcoidosis may have a poorer prognosis than systemic sarcoidosis with cardiac involvement. [39] Isobe and Tezuka have recently proposed an algorithm for diagnosing isolated cardiac sarcoidosis. [41] It involves keeping a high index of suspicion, and if any suspected features are found on echocardiography or electrocardiography, then multimodality imaging and EMBx should be done. If these are suggestive, then the diagnosis of isolated cardiac sarcoidosis can be made after ruling out extra-cardiac granulomas in the eye, lung, skin, and musculoskeletal system with careful screening. The main problem is of the low sensitivity of EMBx.

Management

The inflammation associated with sarcoidosis responds to corticosteroids in 60-80% of the cases. Corticosteroids render symptomatic relief and improved imaging findings and normalization of blood test results (serum ACE levels), making them the first line agents in the treatment of sarcoidosis. However, there are no randomized control trials regarding the use and dosage of steroids. The data supporting their use are limited to small case series and anecdotal reports. In a study, 75 patients treated with steroids were compared to twenty patients not receiving steroids. [42] The outcome in the form of 5 years survival was much better in the steroid arm (75% vs. 10%). In addition, outcomes were better with earlier initiation of therapy when LV EF was ≥50%. This observation underscores the importance of earlier initiation of treatment to prevent deterioration of cardiac function. The optimal dose of steroids is not known. [43] The usual starting dose is at 60-80 mg/day and is gradually tapered over 6 months to 10 mg/day. If the disease remains dormant, the steroids can be further tapered and stopped. However, at any sign of recurrence of activity, steroids should be restarted at initial dose and gain tapered.

Other immunosuppressive agents may be used when steroids are contraindicated or when the response to therapy is inadequate or to reduce the side effects of steroids. The agents which have been used include methotrexate, azathioprine, cyclosporine, leflunomide, mycophenolate mofetil, and anti-tumor necrosis factor-α (TNF-α) agents including infliximab. The experience with these agents is limited. In cardiac sarcoidosis, the combination of weekly methotrexate (6 mg/week) and low dose prednisolone (5-15 mg/day) has been shown to stabilize the cardiac function in a report. [44] Other agents lack sufficient data for their use.

The response of arrhythmias to steroid therapy is variable. Ventricular arrhythmias usually do not respond to steroids. Class I antiarrhythmics should not be used due to their proarrhythmic action in the presence of myocardial involvement in the form of granulomas and scarring. If antiarrhythmic therapy is contemplated, then β-blockers, sotalol, and amiodarone must be selected. Amiodarone use is complicated by the presence of pulmonary involvement and one should carefully monitor for pulmonary toxicity. If antiarrhythmics fail at controlling these arrhythmias, then catheter ablation must be considered. [45] After the occurrence of lethal arrhythmias, implantable cardioverter defibrillator (ICD) implantation for secondary prophylaxis is indicated. [46] Frequent shocks after ICD implantation are common and may reduce the quality of life. There is no consensus regarding the use of ICDs for primary prophylaxis in cardiac sarcoidosis. [47]

Bradyarrhythmias including complete heart block usually have a better response to steroid therapy. However, most cases will require permanent pacemaker due to the fear of sudden cardiac death with intermittent complete heart block.

Cardiac transplantation should be considered for young patients not responding adequately to immunosuppressive therapy. However, no consensus is available regarding indications of transplantation in cardiac sarcoidosis. The prognosis after cardiac transplantation seems to be reasonable as compared to other diseases. Zaidi et al. have shown a better 1 year survival after orthotopic cardiac transplant in sarcoid patients as compared to nonsarcoid patients (88% vs. 85%). [48]

Indian data on cardiac sarcoid

Sharma's data showed five out of 164 patients with pulmonary sarcoid had cardiac involvement with DCM, pericardial effusion, complete heart block, pulmonary hypertension, or PET positivity. In another series of 210 pulmonary cases, 15 had cardiac involvement [Table 5]. Both series show that occurrence of arrhythmias was common. The series by Ajit and Narasimhan [Table 5] again show the common occurrence of arrhythmias in cardiac sarcoidosis.

Cardiac sarcoid is one manifestation of a multisystem disease. It can be suspected in patients with ventricular dysfunction with rhythm disturbances of recent onset in an appropriate setting. Treatment involves immunosuppressives with antiarrhythmic therapy. Though thought rare in India, with MRI, PET, and biopsies, more cases are seen and treated in India.
Table 5: Indian Data on cardiac sarcoid

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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.[51]

 
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