Epidemiology and Outcomes of Takotsubo Syndrome in Hospitalizations With Systemic Sclerosis

Background Systemic Sclerosis (SSc) is associated with chronic inflammation which leads to macrophage activation and thus vascular insult and fibrosis. Macrophage activation is shown to precede Takotsubo syndrome (TTS) which may be a common pathophysiologic link to SSc.  Methods We queried the National Inpatient Sample (2008-2014) for adult SSc-related hospitalizations and TTS using relevant International Classification of Diseases Clinical Modification, 9th Revision codes. We assessed the prevalence and trends in TTS during this time. We further assessed demographics, comorbidities, and outcomes were in SSc with and without TTS. The primary outcomes of the analysis were all-cause mortality and in-hospital complications including cardiac arrest and acute myocardial infarction (AMI), arrhythmias, and venous thromboembolism, and stroke.  Results A total of 213,728 SSc-related hospitalizations were found, of which 357 experienced TTS (0.2%) with rising trends in TTS from 2008-2014 (0.06% to 0.3%, relative increase of 24%, ptrend<0.001). The TTS cohort was older (median age 68 vs 62 years), with 92.8% females and 80.1% white adults with TTS (p<0.001). Co-morbidities were higher in the TTS cohort including hypertension (62.2% vs. 51.5%, p<0.001), dyslipidemia (41.5% vs. 22.8, p<0.001), smoking (28.9% vs. 20.1%, p<0.001), peripheral vascular disease (17.8% vs. 9.1%, p<0.001), uncomplicated diabetes (18.1% vs. 11.9%, p<0.001). The all-cause in-hospital mortality (11% vs. 4.6%; adjusted odds ratio=1.82, 95% confidence interval: 1.21-2.72, p<0.005), cardiovascular complications like AMI (29% vs. 2.9%,p<0.001), arrhythmias (38.9% vs. 21.5%, p<0.001), and median length of stay [6 vs. 4 days] were significantly higher in the TTS cohort as compared to the non-TTS cohort. Conclusion This analysis revealed a nearly 10 times higher prevalence of TTS in SSc-related hospitalizations compared to the general inpatient population. Concomitant TTS occurrence in SSc-related hospitalizations led to nearly two times higher odds of all-cause mortality. Cardiovascular co-morbidities in SSc may increase the risk of TTS and worsened outcomes.