The Scleroderma Tango: Unraveling the Delicate Dance of Diastolic Dysfunction and Interstitial Lung Disease

In this issue of The Journal of Rheumatology, Fairley and colleagues investigated the effects of concomitant left ventricular diastolic dysfunction (LVDD) in a small cohort of patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) derived from the larger Australian Scleroderma Cohort Study.¹ Consistent with prior reports, the authors found that patients with SSc-ILD with LVDD experienced dyspnea and reduced survival. In addition, these patients were older, had longer SSc disease duration exceeding 6 years, received treatment with immunosuppressive drugs, and had additional cardiovascular (CV) comorbidities. SSc-specific features, such as skeletal muscle involvement, chronic inflammation, and gastrointestinal issues, were shown to further elevate the risk of LVDD. The significant correlation of LVDD with muscle atrophy suggests a potential association between LVDD and myopathy or physical frailty in SSc-ILD. Regardless of the underlying mechanism, the presence of LVDD was consistently linked to diminished survival and increased breathlessness in patients with SSc-ILD.

Numerous studies have emphasized the significance of SSc-associated LVDD, a disease characterized by pathogenic replacement myocardial fibrosis and resultant diminished chamber compliance and contractility.^2-4 In addition to established CV comorbidities, such as increasing age, essential hypertension, obesity, diabetes, and coronary artery disease, patients with SSc are also affected by disease-specific risk factors, such as longer SSc disease duration, lower diffusing lung capacity for carbon monoxide (DLCO), anti–Scl-70 positivity, and history of SSc-associated renal crisis and severe gastrointestinal disease.⁵ Disease-specific factors with and without the influence of traditional CV risk factors contribute to increased prevalence of LVDD and further result in increased incidence of heart failure, both of which are associated with a 4-fold increase in mortality.^5-7

The 26% prevalence of LVDD in the current study¹ aligns with previous reports,^5,6 and is an early cardiac manifestation of SSc-associated heart disease. Cardiac involvement remains a challenging aspect of SSc management, rendering clinicians grappling with its elusive nature and limited early diagnostic capabilities. Although the authors correctly acknowledge the difficulty of generalizing the increased morbidity and mortality observed in this small cohort study, they underscore the critical role of echocardiography as a screening and early detection tool for the myriad cardiopulmonary manifestations that can arise in SSc. However, the dependence on echocardiography for the screening and early detection of LVDD in SSc relies heavily on accurate and consistent reporting, which is hampered by the complexities and nuances involved in accurate diastolic assessment.⁸ The majority of studies in this area have also depended on extracting discrete variables from clinical echocardiography reports, conducting cross-sectional associations, and performing survival analyses. The small cohort size in the present study underscores these limitations,¹ particularly considering the known prevalence of both ILD and LVDD in SSc, drawing into question the use of previously acquired echo reports and extraction of retrospective discrete variables.

Further, it is challenging to ascertain the extent to which LVDD directly affects diminished survival in adults with SSc-ILD. Specifically, it is unclear whether LVDD serves as a direct contributor to increased morbidity and mortality, or is simply a marker of longer disease duration, older age, cardiac comorbid conditions, or a more severe SSc phenotype. Addressing this question is made more challenging by the complexities inherent in the underlying heterogeneity of SSc pathogenesis. A potential future approach to this inquiry would involve a prospective study of occult diastolic dysfunction in patients with ILD, incorporating provocative measures such as leg raise and supine bicycle echocardiogram in patients with SSc^9-11 presenting with indeterminate diastology and/or unexplained dyspnea due to the limitations in diastolic assessment at rest alone. It is now well established that provocative maneuvers, including exercise or straight leg raise, are required to rule out occult diastolic dysfunction that may not be present at rest. Indeed, for patients with unexplained dyspnea and normal resting diastolic measures on echocardiography, diastolic exercise testing is now recommended as part of societal guidelines.^8,12 In the specific case of SSc, changes in contractile and relaxation measures with exercise are predictive of incident pulmonary hypertension, which portends substantial mortality in this at-risk population.¹¹ Indeed, detectable abnormalities in resting diastolic parameters on echocardiography signify established LVDD. Although the authors offer compelling evidence regarding the risk associated with LVDD in SSc-ILD,¹ prioritizing earlier provocative testing, particularly within SSc subgroups with heightened LVDD risk, remains essential. This refined approach to diastolic assessment facilitates identification and intervention at an early stage, before the onset of significant disease, thereby offering the opportunity for therapeutic interventions to mitigate or delay disease progression.

In summary, Fairley et al present more supporting evidence that underscores prior reports of patients with SSc-ILD with concurrent LVDD experiencing heightened morbidity and mortality.¹ These findings highlight the ongoing significance of occult diastolic dysfunction in SSc symptomatology and emphasize the crucial role of echocardiographic screening and early detection to manage these patients effectively.

• Copyright © 2024 by the Journal of Rheumatology