PET-detected Myocardial Inflammation is a Characteristic of Cardiac Sarcoid But Not of ARVC

PET-detected Myocardial Inflammation is a Characteristic of Cardiac Sarcoid But Not of ARVC - a Feasibility Study

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare condition in which the heart muscle cells especially of the main pumping chamber (the 'ventricle') is replaced by fat and scar tissue. Sarcoidosis is a condition that can affect many organs but when it affects the heart patches of inflammation can result in scarring, especially of the ventricles. Both conditions can cause dangerous heart rhythms and sudden death. Sarcoidosis can be treated with inflammation suppressing treatment (steroids), as well as pacemakers and implantable defibrillators which shock the heart back to normal rhythm. ARVC is usually treated with implantable defibrillators. The diagnosis of either condition can be difficult and indeed distinguishing the two can be extremely challenging. Increasingly nuclear scans (PET) are used to identify inflammation in the heart in patients suspected of having cardiac sarcoid. It is not known whether patients with ARVC have abnormal PET scans.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited condition characterised pathologically by fibro-fatty replacement of myocytes usually (but not exclusively) within the right ventricle. The clinical consequences of this process are usually re-entrant ventricular arrhythmias which may be fatal and ARVC consequently is the third most common cause of sudden cardiac death in the young. Diagnosis involves imaging, electrocardiography, myocardial biopsy and genetic testing. Task Force criteria for the diagnosis have been established. Nevertheless the condition can be difficult to diagnose (or exclude), especially in less advanced disease, a common scenario in individuals with a family member suffering from the condition. To complicate the situation further, we and others have published recent reports suggesting that other infiltrative conditions within the heart especially sarcoidosis, may fulfil Task Force criteria, leading to a false positive diagnosis. This is a particular concern since the natural history and treatment options for these conditions are very different.

Sarcoidosis is a granulomatous disorder of unknown cause, predominantly affecting the lungs, reticuloendothelial systems and skin. Cardiac involvement at autopsy is found in up to 25% of affected individuals although clinical manifestations are only present in approximately 5%. Isolated cardiac sarcoidosis, without manifestations in other systems is rare. The non-caseating granulomas frequently infiltrate left ventricular & septal myocardium although right ventricular involvement also occurs. Granulomas and resulting scar formation can cause conduction disturbances, cardiac failure and ventricular arrhythmias. Sudden death is not uncommon. Myocardial biopsy confirms the diagnosis but because of the patchy nature of the granulomatous process, the test is only positive in 50% of the affected individuals. Other investigations used to help make or support the diagnosis include echocardiography, MRI, electrocardiography, PET, and corroborating evidence from high resolution CT chest and skin biopsy. However, imaging findings may lack specificity for a precise aetiology. Cardiac MRI identifies areas of myocardial scar or fibrosis, which is the final step in the disease process. Although patterns of fibrosis have been well described in ARVC and cardiac sarcoidosis, significant overlap exists between these two diseases with regard to the exact location of fibrosis: for example ARVC can affect either or both ventricles. Typically, although affecting predominantly the RV, in advanced stages there is also a well described pattern of mid-wall patchy fibrosis in the basal infero-lateral wall of the left ventricle and sometimes in the inter-ventricular septum. Conversely, sarcoidosis typically affects the LV, and when fibrosis is found, the location is in the septal or infero-lateral territories. In sarcoid, RV enlargement can occur either due to granulomatous involvement within the RV myocardium, or secondary to the pulmonary hypertension associated with lung involvement. Cases of sarcoidosis where the RV is involved may be more difficult to diagnose: The RV enlargement and reduction in function overlap significantly with the Task Force Criteria for the CMR diagnosis of ARVC, furthermore, the pattern of late gadolinium enhancement is not sufficiently specific to guide the diagnosis to either ARVC or Cardiac Sarcoid with RV involvement.

Inclusion Criteria:

• Twenty patients from the age of 18-70 will be studied. We will include 10 patients with cardiac sarcoidosis diagnosed according to the Japanese Ministry of Health and Welfare criteria. All patients will have histologically proven sarcoidosis (cardiac biopsy not mandatory) and no other potential cardiac disease. They will have no family history of cardiomyopathy. We will also study 10 patients with ARVC diagnosed according to the Task Force criteria with in addition either a positive family history for the condition or harbour a known pathological mutation associated with it.

Exclusion Criteria:

• patients outside the age limit defined above and those who do not fulfil our inclusion criteria for either cardiac sarcoidosis or ARVC will be excluded.
• unwillingness to participate
• patients with any contraindication to MR scanning
• pregnant or breast feeding women
• diabetes