Valvulitis and aortitis associated with ankylosing spondylitis: early detection and monitoring response to therapy using cardiac magnetic resonance imaging

Dear Editor, A 44-year-old Pacific Islander with a 10-year history of ankylosing spondylitis (AS) presented with chest heaviness at rest and shortness of breath in addition to inflammatory back pain and secondary osteoarthritis of the right hip. An electrocardiogram (ECG) showed first-degree atrioventricular (AV) block with a PR (transit time from sinus node to exit of the AV node) interval of 300 ms. An electrocardiogram in 2003 was normal. Serial troponin I levels were borderline elevated (maximum 0.04 μg/L, normal < 0.04μg/L). Inflammatory markers were elevated (erythrocyte sedimentation rate of 22 and C-reactive protein 61 mg/L) in keeping with an acute exacerbation of AS. Contrast-enhanced cardiovascular magnetic resonance (CE-CMR) was performed to investigate the possibility of myocarditis. This demonstrated striking late enhancement of both aortic and mitral valve annuli, associated with significant soft tissue thickening. (Fig. 1a,b). There was also thickening of the aortic and mitral leaflets, associated with mild mitral regurgitation. The images were consistent with mitral and aortic valvulitis, a non-rheumatic manifestation of acute AS. Four-chamber (a) and three-chamber (b) views on magnetic resonance imaging showing delayed hyper-enhancement of both aortic and mitral annuli, associated with significant soft tissue thickening (arrows). Repeat cardiovascular magnetic resonance at 3 months (c,d) showed no change in the perivalvular soft tissue thickening, but the late enhancement was now absent (arrows). LA, left atrium; LV, left ventricle; Ao, aorta. Treatment with adalimumab 40 mg subcutaneously fortnightly was commenced and the inflammatory markers returned to normal within 2 weeks. No other treatment was started. A repeat ECG showed a decrease in PR interval. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improved from 7.87 to 4.1. Follow-up CE-CMR 3 months later showed no change in the perivalvular soft tissue thickening, but the late enhancement was absent (Fig. 1c,d). Furthermore, there was no evidence of myocardial edema on T2 short T1 (tau) inversion recovery (STIR) sequence. Ankylosing spondylitis is a chronic inflammatory disease mainly affecting the axial skeleton and sacroiliac joints. Cardiac complications, in particular aortic root/valvular heart disease (VHD) and conduction disturbances, have been estimated to occur in approximately 10% with a sizeable asymptomatic group.1,2 Aortitis, which involves the aortic root and the ascending aorta, leads to valvular insufficiency which rarely occurs in the first decade of disease. Aortitis and valvulitis are rare events and the prevalence is unknown. Valvular changes in AS have been described as fibrotic, thickened and retracted cusps with rolled edges. These changes lead to aortic insufficiency.3 Histopathological findings of the aortic wall consist of proliferation of the intima cells, focal inflammation of the media with destruction of elastic tissue, fibrosis and fibrous thickening of the adventitia.3,4 Treatment of aortitis and valvulitis has not been tested in clinical trials. The tumor necrosis factor alpha (TNF-α) inhibitors are effective for the treatment of musculoskeletal manifestations. Immunosuppressive agents, primarily prednisone and cyclophosphamide, have been used with anecdotal benefit. Recently infliximab has been reported to be effective.5 Adalimumab was effective in suppressing the aortitis and valvulitis in our case. Valve replacement is necessary if the inflammation of the aortic valve annulus and root is not controlled. A recently reported case of a young man who presented with a complicated course of recurrent prosthetic valve dehiscence secondary to aortitis illustrates the problem.6 The ability to characterise pathophysiologic changes in cardiac tissue is an important diagnostic and prognostic strength of CMR. Late enhancement following the administration of intravenous contrast reflects the retention of gadolinium in areas where its volume of distribution is increased. This imaging sequence uses an inversion pulse to null the signal response from normal myocardial tissue, thereby highlighting areas with increased accumulation of gadolinium as bright regions. In early stages of inflammation the volume of distribution of gadolinium is increased due both to its entry into acutely permeable cell membranes, and the degree of interstitial edema. Later replacement of necrotic areas by collagen-rich scarring may also result in an increased volume of distribution, generating an alternative mechanism of gadolinium retention. T2-weighted imaging detects tissue edema with the long T2 of water-bound protons as the contrast-generating mechanism, resulting in a high signal intensity of edematous tissue.7 In our patient the follow-up imaging using a T2-weighted sequence confirmed a lack of edema. It is of particular interest in this case that there appears to be resolution of the late gadolinium enhancement following pharmacotherapy, suggesting that transient interstitial edema may be an important mechanism of gadolinium retention in valvulitis and annulitis. This is in distinction to myocardial inflammatory injury such as myocarditis, where late enhancement specifically reflects irreversible myocardial injury (i.e. necrosis and fibrosis).7 CMR is a useful imaging modality for detection and quantification of vasculitis in patients with AS. In particular, CMR has greater ability to detect earlier changes of vasculitis.8 Moreover, identification of vessel and myocardial wall edema with STIR and fat-suppressed T2-weighted sequences is potentially important. In this case, CMR proved valuable in diagnosing annulitis and valvulitis; it facilitated the prompt institution of medical therapy and also confirmed the response to therapy. The conduction disturbance improved but was not abolished. To the best of our knowledge this is the first reported case that describes the benefit of adalimumab in the treatment of aortitis and valvulitis in AS.