The main findings of the current study can be summarized as follows: 1) in a large multicenter cohort, SSc patients with impaired left atrium function, defined as ƐR ≤ 30% showed lower survival at 10-year follow-up as compared to patients with ƐR > 30%; 2) ƐR was independently associated with all-cause mortality.
Cardiac involvement in SSc patients
Cardiac involvement in SSc is a challenging diagnosis which however is an important determinant of adverse prognosis [1, 20]. In particular, myocardial dysfunction in these patients is caused by inflammation, ischemia, and fibrosis but it cannot be easily detected [21].
Therefore, even though most patients with SSc initially present without cardiac symptoms, occult primary cardiac involvement may be present and responsible for a significant death rate, reaching 70% at 5 years. As such, careful and timely identification of cardiac involvement is crucial and should include most advanced diagnostic techniques [22–25].
Systolic dysfunction can be diagnosed early in the course of the disease with more sensitive echocardiographic parameters, such as LV GLS. Van Wijngaarden et al. showed in 234 SSc cases, followed-up for a median period of 2.3 years (IQR 1.3–3.9), that LV GLS reduction occurs in a relative short timeframe from diagnosis, even though LVEF did not change over time [26]. In their study, a significant reduction of GLS (i.e., ≥ 15%) was found in 19% of cases, and these patients were more likely to have proximal muscle weakness, lung fibrosis, renal impairment and elevated NTproBNP at follow-up, alongside a higher risk of all-cause mortality [26].
However, in SSc patients, LV diastolic dysfunction is 4–5 times more frequent as compared to systolic dysfunction. Its assessment is based on a multi-parametric algorithm, in which LAVi plays a central role [3, 27]. But, LAVi has limited diagnostic value in the early stages of diastolic dysfunction, while changes in left atrial function have been shown to precede LA dilatation and remodeling and to better correlate with LV filling pressures [4, 5, 28, 29]. Therefore, in the latest EACVI consensus document on imaging in heart failure with preserved ejection fraction, ƐR is recommended as an additional parameter for the evaluation of LV filling pressures [6].
LA strain and its association with outcome have been evaluated in different studies including different cardiovascular disorders, such as ischemic and valvular heart disease, diabetes, hypertension, and atrial fibrillation [19, 30–33]. Furthermore, ƐR showed association with atrial fibrosis quantified by late gadolinium enhancement in CMR studies [34, 35].
In SSc, Agoston et al. compared 42 cases with 42 age and gender-matched controls [7]. The 2 groups did not differ in respect to LV systolic function or LAVi, but patients with SSc had lower values of ƐR and higher E/e' [7]. As such, authors concluded that changes in LA strain are able to mirror myocardial fibrosis before abnormalities in LAVi occur, and suggested to use alterations in LA function as an early indicator of cardiac disease in SSc [7].
Another study comparing 72 SSc cases with 30 healthy controls found two thirds of the SSc patients with LV diastolic dysfunction and with reduced ƐR across all SSc subgroups, further emphasizing that the alteration of LA mechanics might represent an early indicator of cardiac disease in SSc [8]. However, no outcomes were reported by these initial studies.
Recently, a multicentric retrospective study which used feature-tracking CMR-derived strain evaluation of the LV and LA analyzed 100 SSc patients for two endpoints: NYHA class II - IV heart failure symptoms at the time of CMR and all-cause mortality at follow-up [36]. Based on spline curve analysis, a cut-off of 27% for ƐR was proposed, which was very close to the one identified in the current study [36]. After dichotomizing patients in NYHA I class (39%) and NYHA II-IV class (61%) they observed that ƐR was associated with the presence of heart failure symptoms at baseline and with all-cause mortality at follow-up [36]. In addition, ƐR demonstrated incremental prognostic value over the variables known to alter the prognosis of SSc patients [36]. Although this study demonstrated for the first time that lower values of LA strain are associated with higher rates of mortality at follow-up, it was performed using CMR, an advanced imaging method which is not readily available and cannot be repeated easily at follow-up. To the best of our knowledge, our study is the first to assess the correlation between ƐR measured by echocardiography and all-cause mortality in a large SSc population. By demonstrating its independent association with mortality, it therefore suggests that this parameter might be used to (timely) identify cardiac involvement and as such, patients at high risk that might merit closer follow-up or specific treatments.