Increased Mortality and Cardiovascular Events in Male Patients with Systemic Sclerosis: Left Ventricular Global Longitudinal Strain as Possible Screening Tool

Jeska de Vries-Bouwstra¹, Tea Gegenava², Federico Fortuni³, Nina Van Leeuwen⁴, Anders Tennoe⁵, Anna Maria Hoffmann-Vold⁶, Ruxandra Jurcut⁷, Adrian Giuca⁷, Laura Groseanu⁸, Felix Tanner⁹, Oliver Distler¹⁰, Jeroen Bax¹¹ and Nina Ajmone Marsan¹¹, ¹Leiden University Medical Center, Leiden, Netherlands, ²Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre; Department of Internal Medicine,Tbilisi State Medical University, Tbilisi, Georgia, ³Department of Cardiology, San Giovanni Battista Hospital, Foligno, Italy, ⁴Department of Rheumatology, Leiden University Medical Centre, Leiden, Netherlands, ⁵Department of Rheumatology, Oslo University Hospital, Oslo, Norway, ⁶Oslo University Hospital, Department of Rheumatology, Oslo, Norway, ⁷Department of Cardiology, Emergency Institute for Cardiovascular Diseases “Prof .Dr. C. C. Iliescu”, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania, ⁸University of Medicine and Pharmacy "Carol Davila", Department of Internal Medicine -Rheumatology; Santa Maria Clinical Hospital, Internal Medicine and Rheumatology, Bucharest, Romania, ⁹Department of Cardiology, University Heart Centre, University Hospital Zurich, Zurich, Switzerland, ¹⁰Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, ¹¹Department of Cardiology, Heart Lung Centre, Leiden University Medical Centre, Leiden, Netherlands

Meeting: ACR Convergence 2023

Keywords: Cardiovascular, gender, Mortality, Scleroderma, Systemic, Ultrasound

Session Information

Date: Monday, November 13, 2023

Title: Abstracts: Systemic Sclerosis & Related Disorders II: Clinical Research

Session Type: Abstract Session

Session Time: 4:00PM-5:30PM

Background/Purpose: Systemic sclerosis (SSc) is less frequent in males, but the risk of severe outcomes is higher in males than in females(1). Seven to 30% of SSc patients have cardiovascular involvement, which is associated with poor prognosis. Cardiovascular events are reported to be more frequent in male SSc patients(2). However, the cause of this sex-specific cardiovascular risk in SSc is unknown, and commonly available screening tools including echocardiography and ECG are not sensitive to detect early cardiac dysfunction in SSc(3). Objective of this longitudinal prospective study was to assess sex differences in echocardiographic characteristics. We specifically analysed whether a difference in left ventricular global longitudinal strain (LV GLS) can explain sex difference in cardiovascular outcomes in SSc, and can be applied as prognostic screening tool for cardiovascular events in SSc.

Methods: A total of 746 SSc patients from four SSc expert centers, including 628 (84%,54±13 years) women and 118 (16%,55±15 years) men, were evaluated with standard and advanced echocardiographic examinations. The independent association of the echocardiographic parameters with the combined endpoint of cardiovascular events-hospitalization/death was evaluated.

Results: Men and women with SSc showed significant differences in disease characteristics and cardiac function. After adjusting for the most important clinical characteristics (age, disease duration since Raynaud, skin involvement, interstitial lung disease (ILD), DLCO-SB % predicted, smoking), LV ejection fraction (LVEF) and diastolic function were not significantly different anymore. However, men still presented with more impaired LV GLS as compared to women (-19% (IQR-20%-[-17%]) vs.-21%(IQR:-22%-[-19%]),p< 0.001). After median follow-up of 48 months (IQR:26–80), the combined endpoint occurred in 182 patients (24%). Kaplan-Meier survival curves showed that men experienced higher cumulative rates of cardiovascular events-hospitalization/death as compared to women (Chi-square 8.648; Log rank 0.003. Figure 1). When using propensity score matching to match men and women according to clinical characteristics (age, disease duration since Raynaud, subtype of SSc, ILD, DLCO-SB% predicted and NT-proBNP, n=140 patients), men still experienced higher cumulative rates of cardiovascular events/death as compared to women (Chi-square 7.211; Log rank 0.007. Figure 2A). Sex-difference in outcome disappeared when matching the groups according to the LV GLS on top of the abovementioned clinical characteristics (n=112 patients, Chi-square 0.474; Log rank 0.491, Figure 2B).

Conclusion: In SSc patients, male sex is associated with worse cardiovascular outcomes after adjusting for important clinical characteristics. LV GLS was more impaired in men as compared to women and potentially explains the sex difference in cardiovascular outcomes. Using LV GLS for early assessment of myocardial involvement may improve risk stratification and surveillance in SSc patients for both sexes.

1. Ann Rheum Dis; 2010; 69 (10): 1809.
2. Ann Rheum Dis; 2017; 76 (11): 1897.
3. JACC Cardiovacs Im. 2019; 12 (11 Pt 1): 2273.

Table 1. Baseline clinical characteristic in the overall population and for male and female patients

Figure 1. Survival function (for cardiovascular hospitalization/death) in women and men patients with systemic sclerosis (SSc).

Figure 2. Survival function in women and men patients with SSc in Panel A after adjusting for age, disease duration (since Raynaud), type of SSc, lung fibrosis, DLCO-SB and NT-proBNP, in Panel B after adjusting for age, disease duration (since Raynaud), type of SSc, lung fibrosis, DLCO-SB, NT-proBNP and LV GLS.

Disclosures: J. de Vries-Bouwstra: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, galapagos, 5, Janssen, 2, 6, Janssen-Cilag, 5, Roche, 5; T. Gegenava: None; F. Fortuni: None; N. Van Leeuwen: None; A. Tennoe: None; A. Hoffmann-Vold: Arxx Therapeutics, 2, Boehringer-Ingelheim, 2, 5, 6, 12, Support for travel, Genentech, 2, Janssen, 2, 5, 6, Medscape, 2, 6, 12, Support for travel, Roche, 2, 6, 12, Support for travel; R. Jurcut: None; A. Giuca: None; L. Groseanu: None; F. Tanner: None; O. Distler: 4P-Pharma, 2, 5, 6, AbbVie, 2, 5, 6, Acceleron, 2, 5, 6, Alcimed, 2, 5, 6, Altavant Sciences, 2, 5, 6, Amgen, 2, 5, 6, AnaMar, 2, 5, 6, Arxx, 2, 5, 6, AstraZeneca, 2, 5, 6, Bayer, 2, 5, 6, Blade Therapeutics, 2, 5, 6, Boehringer Ingelheim, 2, 5, 6, Citus AG, 12, Co-Founder, Corbus Pharmaceuticals, 2, 5, 6, CSL Behring, 2, 5, 6, Galapagos, 2, 5, 6, Galderma, 2, 5, 6, Glenmark, 2, 5, 6, Gossamer, 2, 5, 6, Horizon Therapeutics, 2, 5, 6, Janssen, 2, 5, 6, Kymera, 2, 5, 6, Lupin, 2, 5, 6, Medscape, 2, 5, 6, Miltenyi Biotec, 2, 5, 6, Mitsubishi Tanabe, 2, 5, 6, MSD, 2, 5, 6, Novartis, 2, 5, 6, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143), 10, Prometheus Biosciences, 2, 5, 6, Redx Pharma, 2, 5, 6, Roivant, 2, 5, 6, Topadur, 2, 5, 6; J. Bax: None; N. Ajmone Marsan: None.

To cite this abstract in AMA style:

de Vries-Bouwstra J, Gegenava T, Fortuni F, Van Leeuwen N, Tennoe A, Hoffmann-Vold A, Jurcut R, Giuca A, Groseanu L, Tanner F, Distler O, Bax J, Ajmone Marsan N. Increased Mortality and Cardiovascular Events in Male Patients with Systemic Sclerosis: Left Ventricular Global Longitudinal Strain as Possible Screening Tool [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/increased-mortality-and-cardiovascular-events-in-male-patients-with-systemic-sclerosis-left-ventricular-global-longitudinal-strain-as-possible-screening-tool/. Accessed .

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