13.4Valvular Abnormalities

Valvular abnormalities such as mild aortic or mitral regurgitation have been described with a greater frequency in asymptomatic patients with pSS than in healthy, age-matched controls [7]. Since these abnormalities were associated with low C4 values, the authors of the study [7] postulated that immune complexes and the activated classical complement pathway might be involved in the pathogenesis of these abnormalities. In most patients, these abnormalities have no clinical significance.

13.5Diastolic Dysfunction

A relatively high prevalence of left ventricular diastolic dysfunction and increased left ventricular mass has been reported by echocardiographic studies in pSS patients [3, 7, 8]. Because these patients had no cardiac symptoms, the etiology and clinical significance of these findings remain unknown at present [3, 7, 8].

13.6Atrioventricular Block

Complete heart block has been described in two patients with pSS and anti-SS-A/ anti-SS-B antibodies [15, 16]. Another ECG study [17] reported a prevalence of first degree atrioventricular block of about 10% in pSS patients. The finding of firstdegree heart block was associated with disease activity and anti-SSB antibodies [17]. In contrast to the neonatal heart, which is susceptible to conduction abnormalities such as congenital heart block caused by maternal anti-SS-A/anti-SS-B autoantibodies, the adult atrioventricular node is generally thought to be resistant to the damaging effects of anti-SSA/anti-SSB antibodies.

13.7Subclinical Atherosclerosis

Although mortality data in pSS show no excess in cardiovascular mortality [18, 19], the possibility of accelerated atherosclerosis in these patients has recently been raised [20–22]. Premature atherosclerosis is known to occur in rheumatoid arthritis and systemic lupus erythematosus. Although the precise etiology of accelerated atherosclerosis in rheumatologic diseases has not been elucidated completely, there is evidence that inflammation plays a pivotal role in the atherosclerotic process [23]. In a small cohort of patients with pSS, Vaudo et al. described greater intima-media thickness of the carotid and femoral arteries in women with pSS than in healthy controls [22]. Furthermore, the association of

artery thickening with anti-SSA antibodies and leucopenia raises the possibility that immune dysregulation contributes to early atheromatosis [22]. Greater frequencies of hypercholesterolemia, hypertriglyceridemia, diabetes mellitus, and hyperuricemia have recently been described in patients with pSS compared to healthy controls [20, 24, 25]. The question of premature atherosclerosis in pSS requires further investigation.

13.8Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) occurs rarely in pSS, which contrasts with the relatively high prevalence of PAH in SSc, MCTD, or SLE [6, 26–28]. Although various studies based exclusively on Doppler echocardiography have reported a relatively high frequency of pulmonary hypertension in pSS [3, 7], the only study that used hemodynamic measurements to establish the diagnosis of PAH in patients with pSS is by Launey et al. [6]. These authors described nine cases of pSS associated PAH with a complete clinical assessment including hemodynamic evaluation, type of PAH as well as outcome.

Based on findings of nine pSS patients with PAH and a review of additional 19 cases of PAH reported in the literature, it has been suggested [6] that there is a true cause and effect relationship between PAH and pSS. This is supported by the data of Launey et al., who showed that PAH occurs in pSS patients with laboratory markers of intense B-cell activation, such as antinuclear antibodies, anti-Ro/SSA or antiRNP antibodies, and hypergammaglobulinemia [6]. In addition, immunofluorescence studies have revealed deposits by immunoglobulin and complement in the pulmonary arterial walls of pSS patients with PAH. In the nine pSS patients reported by Lanuey et al. [6], Raynaud’s phenomenon occurred in 67%, cutaneous vasculitis in 33%, and interstitial lung disease in 44%. Thromboembolic lung disease was the underlying cause of PAH in two patients [6]. Additional risk factors for development of PAH in pSS such as portal hypertension and interstitial lung disease are present in some patients [6].

The pathogenesis of PAH in pSS is unknown. The higher frequency of Raynaud’s phenomenon, cutaneous vasculitis, and various antibodies detected in these patients, points towards a pulmonary vasculopathy and B-cell activation playing a role in the pathophysiology of PAH [6]. The efficacy of standard PAH and immunosuppressive therapy lends further support to the notion of an underlying vasculopathy [6].

In most cases, the PAH was severe at presentation, with the mean pulmonary artery pressure being 47 mmHg (±10 mmHg). Exertional dyspnea was the initial symptom in the majority of patients whereas a delay in diagnosis of more than a year was also common. The reported survival in the cohort reviewed by Launey et al. was overall poor, being 73% and 66% at 1 and 3 years, respectively [6].