Discussion
To the best of our knowledge, this is the first study demonstrating the prevalence, temporal trends and impact of TTS in patients with AIS. In this nationally representative sample of hospitalizations with AIS, we demonstrate an estimated 0.4% of TTS cases from 2007-14 which were associated with higher all-cause mortality, adverse hospital-related complications and longer LOS as compared to AIS patients without TTS. This rate is nearly 20 times higher than the TTS rate reported in the general inpatient population (0.02%). Previous analyses studying TTS in AIS have either been single-center studies or case reports [12-15].
There has been an increasing trend in the prevalence of TTS with AIS from 2007-2014, with the highest number of cases recorded during 2014 (N=1081). The highest proportion of TTS cases among AIS were recorded among elderly >65 years (69.8%) and female (82.2%) patients. A study by Jung et al. of 23 AIS patients reported similar findings of increasing rates of TTS among the elderly with a mean age of 70.7±13.9 years consisting predominantly of females (73.9%) [16]. Female predominance was seen in another study by Templin et al [17]. Consistent with our study findings, a study by Murugiah et al. reported white patients representing almost 90.2% of the total TTS population [18].
The baseline characteristics and comorbidities could define prognosis in AIS patients with TTS. We observed a significantly higher prevalence of congestive heart failure, chronic pulmonary disease, coagulopathy, fluid and electrolytes disorders, hypothyroidism, obesity, previous myocardial infarction, depression and coronary atherosclerosis among AIS patients with TTS. In one study by Brinjikji et al. reported the higher prevalence of chronic cardiovascular morbidities among TTS patients [19]. These data could help better risk stratify patients at risk of TTS with AIS.
In our study, we observed higher odds of developing adverse events during AIS hospitalizations with TTS. These included cardiogenic shock (OR=8.84), cardiac arrest (OR=3.17), and venous thromboembolism (OR=1.68). Moreover, the AIS-TTS cohort was at higher risk of developing respiratory failure (OR=3.13) and requiring mechanical ventilation/intubation (OR=4.09) more frequently. Increased risk of cardiovascular complications in AIS-TTS cohort could be due to higher proportion of elderly patients with underlying chronic medical illness. Similar findings were observed in a study by Brinjikji et al, in which higher odds of complications were seen among elderly patients with underlying chronic cardiovascular risk factors [19].
TTS occurrence in AIS also had a worse impact on healthcare resource utilization. We observed frequent step down of AIS-TTS cohort to more chronic care centers including SNF, ICF etc. In addition, we observed an extended hospital stay of TTS cohort (8.59±10.03 vs 5.22±6.24) compared to non-TTS cohort. This could be attributed to increased risk of complications requiring longer stay and more advanced care. Prolonged hospital stay among AIS-TTS cohort was also associated with more than two times higher mean total hospital charges ($85,854 vs $37,924). This further signifies the importance of identifying AIS patients early to prevent complications and associated economic repercussions.
The all-cause inpatient mortality observed in AIS patients with TTS was double (10.2% vs 5.1%) than non-TTS cohort. In addition to the added burden of TTS-related complications, this could be explained by the higher prevalence of chronic comorbidities, which increases risk of in-hospital adverse events among AIS patients with TTS. In a prospective observational study, higher mortality risk along with adverse events was observed in older age groups [20].