In the retrospective observational study, we found that the TTS patients have a hospital mortality rate of 13.04%. This rate of in-hospital mortality in our study was higher than the rate 2-5% in previous studies3–6, this was due to our study only included the TTS patients admitted to ICU, these patients tend to have more serious and complicated illness condition than the TTS patients in previous studies reported. Our study demonstrated that age, myocardial infarction history, PT, WBC, hematocrit, anion gap, SOFA score were important predictive factors for in-hospital mortality of severe TTS patients. Despite gender (male) and serum potassium concentration in our study without statistical difference (as shown in Table 3), several previous studies have identified that gender (male) have a higher in-hospital mortality compared with female17–18, thus, we also included gender as a predictor in the nomogram. In addition, multiple studies have reported that serum potassium concentration was associated with poor prognosis of acute heart failure patients19–20. Considering that almost all the TTS patients have moderate to severe cardiac insufficiency, thus, we included serum potassium in the final nomogram. The nomogram based on above predictors showed a good predictive ability.
Table 3
Lasso and multivariable regression analysis of risk factors
variable
|
Lasso regression analysis
|
Multivariable regression analysis
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
Age (years old)
|
1.003 (1.001-1.005)
|
0.024
|
1.003 (1.001-1.005)
|
0.016
|
Gender (man)
|
1.078 (0.994-1.170)
|
0.072
|
1.051 (0.970-1.139)
|
0.104
|
myocardial infarction
|
0.924 (0.870-0.988)
|
0.041
|
0.920 (0.864-0.991)
|
0.043
|
Hematocrit
|
0.991 (0.985-0.999)
|
0.009
|
0.988 (0.993-0.999)
|
0.011
|
WBC
|
1.008 (1.003-1.014)
|
0.005
|
1.004 (1.000-1.009)
|
0.032
|
anion gap
|
1.014 (1.004-1.024)
|
0.008
|
1.011 (1.002-1.019)
|
0.026
|
Potassium
|
1.039 (0.975-1.108)
|
0.238
|
1.025 (0.971-1.083)
|
0.876
|
PT
|
1.003 (0.997-1.009)
|
0.121
|
1.005 (1.001-1.009)
|
0.045
|
SOFA
|
1.011 (1.001-1.021)
|
0.038
|
1.010 (1.001-1.017)
|
0.047
|
WBC: white blood cell; PT: prothrombin time; SOFA: sequential organ failure assessment |
Gender is closely related to the onset and prognosis of TTS patients. Male with TTS were reported to have a higher in-hospital mortality compared with female17,18,21 and were viewed as an independent risk factor for in-hospital death in TTS patients in previous study22. In addition, male were related to adverse composite events consist of cardiovascular death, severe pump failure, and fatal ventricular arrhythmias (odds ratio 4.32, 95% CI 1.41–13.6) reported by a multicenter registry study of TTS23. The reason for male gender is more likely to be in-hospital death probably is that men are more possible to exit comorbidities such as COPD, coronary artery disease, a higher peak troponin-I level and to burden the severity of myocardial injury than women. Moreover, men were more likely to have a physical stressor compared with women, TTS patients induced by physicology were more likely to have malignancy, lower hemoglobin, higher serum creatinine and died in the hospital than unphysicology24.
For women, their organism release estrogen which could mitigates myocardial damage. The protective action for myocardial injury performed by estrogen was demonstrated by several studies in animal experimental models25. In our study, 23.1% of our TTS patients were male and the in-hospital death rate was 37.65% (32/85) in males. On the contrary, the in-hospital death rate was 5.65% (16/283) in females. It seems that males have higher in-hospital mortality compared with female (37.65% vs 5.65%, P<0.001). This result was same as the study performed by Yoshihiro Sobue et al22. However, to our surprise, gender was not found to be a risk factor for in-hospital death in either univariate or multivariate regression analyses. Recently, Budnik M et al study found that inhospital outcomes (arrhythmias, mechanical complications, cardiogenic shock, mortality rate) were similar in both male and female groups after adjusted other confounding factors26. These results suggested that gender contribute for the in-hospital death of TTS should be further research.
The sequential organ failure assessment (SOFA) score was applied to describe the time course of multiple organ dysfunction. Recent studies showed that SOFA score was associated with survival in severe cases27. Previous study revealed that increase SOFA during the first few days of ICU admission is a good indicator of prognosis. Both the mean and highest SOFA scores are particularly useful predictors of outcome28. In our study, the SOFA score of in-hospital death patients was statistically higher than survival patients (7.27 vs 5.78, P=0.016). Multivariate logistic regression analysis demonstrates that sofa score was an independent predictive factor for in-hospital mortality in TTS patients. Therefore, SOFA score could be a good predictor for prognosis of TTS patients in intensive care units.
We included myocardial infarction history as predictor in the nomogram and found for the first time patients with myocardial infarction history have lower in-hospital death rate than others without myocardial infarction history. This point hasn’t been reported in previous study. Less is known on the in-hospital outcome role of myocardial infarction history in TTS. In our study, survival patients with myocardial infarction was statistically higher than in-hospital death patients (31.88% vs 18.75%, P=0.093). The protective role of myocardial infarction history on in-hospital outcome for TTS patients deserved us to investigate in the following research.
Currently, there were limited effective clinical predictive model to predict the in-hospital mortality in TTS patients. To the best of our knowledge, it’s the first nomogram for predicting the in-hospital mortality of TTS patients. Santoro F et al. developed the GEIST prognosis score (male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF)) for risk stratification for in-hospital complications in patients with TTS29. Compared with Santoro F et al. study, our study focused on the vital signs and blood laboratory tests information which were more easier to obtain. We performed lasso regression and logistic regression to analysis the relevant clinical indicators in the hospital outcomes of TTS patients, pick out the most important predictors. The results of performance evaluation and validation revealed that our nomogram has a good discrimination. Echocardiographic parameters can provide additional information to identify higher risk of hemodynamic deterioration patients compared to other routine clinical information30. Citro R et al. revealed that LVEF, E/e' ratio, reversible moderate to severe mitral regurgitation were independent correlates of major adverse events30. These parameters have important clinical value, and future studies can add cardiac hyperparameters on the basis of our study to increase the prediction efficiency of the prediction model.
Study limitation
Several limitations must be acknowledged. First, we aimed to establish a rapid and simple nomogram for predicting in-hospital mortality in TTS patients. The situation of TTS patients was very complex and there were many factors related to the prognosis of their hospitalization. We only included the clinical data of the patients within 24 hours after admission, and did not consider the intervention measures at the onset or after hospitalization, which has certain limitations; Second, our study did not further analyze the causes of TTS, such as physical triggers or psychological triggers. Future studies can conduct a subgroup analysis of specific causes of cardiac arrest for provide more evidence for this term.