Takotsubo syndrome (TTS) largely affects postmenopausal women but has been shown to carry increased mortality risk in men. We sought to evaluate nationwide in-hospital outcomes between men and women admitted with TTS to better characterize these disparities. Using the National Inpatient Sample database from 2011 to 2018, we identified a total of 48,300 hospitalizations with the primary diagnosis of TTS. The primary end point was in-hospital all-cause mortality. Secondary end points included in-hospital complications, length of stay, and discharge disposition. Men with TTS accounted for 8.9% of hospitalizations, were younger in age (62.0 ± 15.1 vs 66.8 ± 12.1 years, p <0.001), and were more frequently Black (9.7% vs 5.8%, p <0.001). Nationwide TTS mortality rates were 1.1% overall and may be improving, but remained higher in men than in women (2.2% vs 1.0%, p <0.001). Male gender was associated with increased all-cause mortality (adjusted odds ratios 2.41, 95% confidence interval 1.88 to 3.10, p <0.001), greater length of stay, and discharge complexity. Men carried increased co-morbidity burden associated with increased cardiogenic shock or mortality, including atrial fibrillation, thrombocytopenia, chronic kidney disease, and chronic obstructive pulmonary disease. Men more frequently developed acute kidney injury, ventricular arrhythmias, cardiac arrest, and respiratory failure. Male gender remains associated with nearly 2.5-fold increase in in-hospital mortality risk. In conclusion, early identification of patients with high-risk co-morbidities and close monitoring for arrhythmias, renal injury, or cardiogenic shock may reduce morbidity and mortality.
Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction in the absence of obstructive coronary disease and is often triggered by physical or emotional stress. Affected patients are most commonly postmenopausal women presenting with symptoms of acute coronary syndrome, such as chest pain, dyspnea, or syncope. TTS accounts for 12% of all patients presenting with troponin-positive acute coronary syndrome, and the associated left ventricular dysfunction typically recovers within 4 to 8 weeks of presentation. , However, nearly 10% of courses are complicated by cardiogenic shock (CS), and in-hospital mortality rates range from 1.1% to 8.4%. A number of studies have evaluated gender disparities among patients with TTS and reported that men may have greater risk of CS, cardiac arrest, and mortality. Re-evaluation of nationwide outcomes is warranted to determine whether affected men continue to have increased morbidity and mortality, and what underlying factors may be contributing. In this study, we evaluated the most recently available nationwide hospitalizations of patients with primary diagnosis of TTS between 2011 and 2018 using the National Inpatient Sample (NIS).
Methods
The NIS offers the largest publicly available all-payer database of hospitalizations, representing a 20% random stratified sample of hospital discharges in the United States. International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification diagnostic and procedural codes were used to identify the study population ( Supplementary Table 1 ). Institutional review board approval was not needed, as all patient information was deidentified. Methods for best practices with the use of claims datasets were followed. The NIS database was sampled between January 2011 and December 2018 to identify hospitalizations with primary diagnosis of TTS ( Supplementary Table 1 ). Hospitalizations in which patients did not undergo cardiac catheterization or in which patients required percutaneous coronary intervention or coronary artery bypass graft surgery were excluded, as previously described ( Figure 1 ). ,
Baseline patient characteristics were evaluated, including age, gender, race, ethnicity, and medical co-morbidities. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included total cost and duration of hospitalization, disposition at discharge, and in-hospital complications. Procedures, clinical characteristics, and inpatient outcomes were obtained and reported using International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification codes ( Supplementary Table 1 ). As recommended by the Agency for Healthcare Research and Quality, weighted data were used for all statistical analyses. Categorical variables were compared using the Pearson chi-square test, whereas continuous variables were compared using independent samples t test if normally distributed, and Mann-Whitney U test for non-normally distributed continuous variables. The association between TTS and mortality was analyzed using multivariable logistic regression, adjusted to control for age, race, and co-morbidities that were significantly different between genders (2-tailed p <0.001) on univariate analyses along with clinically relevant variables. Associations were expressed using odds ratios and 95% confidence interval and were considered significant if 2-tailed p <0.001. All statistical analyses were performed using SPSS (IBM SPSS Statistics, Version 26.0. IBM Corp., Armonk, New York).
Results
Between 2011 and 2018, a total of 48,300 patients were admitted with the primary diagnosis of TTS. Nationwide hospitalizations for TTS increased by an average of 3.9% annually, with greater increase among men than among women (6.3% vs 3.7%; Figure 2 ). Overall, TTS continues to predominantly affect women, who accounted for 91.1% of hospitalizations. Men with TTS were younger on average than women, had greater prevalence of Black/African-American race and a number of increased co-morbidities including atrial fibrillation, thrombocytopenia, coronary artery disease, chronic kidney disease (CKD), and chronic obstructive pulmonary disease (COPD), tobacco use, alcohol use, and history of coronary revascularization ( Table 1 ). Conversely, women with TTS had increased prevalence of major depressive disorder, hypothyroidism, and obesity.
| Variable | Men (n = 4,299) | Women (n = 44,001) | p value |
|---|---|---|---|
| Age (years) | 62.0 ± 15.1 | 66.8 ± 12.1 | <0.001 |
| White Black Hispanic Asian/Pacific Islander Native American Other | 3,472 (80.7%) 418 (9.7%) 188 (4.4%) 81 (1.9%) 15 (0.3%) 126 (2.9%) | 36,706 (83.4%) 2,538 (5.8%) 2,755 (6.3%) 637 (1.4%) 225 (0.5%) 1,139 (2.6%) | <0.001 <0.001 <0.001 0.40 0.19 0.21 |
| Diabetes mellitus | 836 (19.6%) | 8,354 (19.1%) | 0.46 |
| Hypertension | 2,829 (71.2%) | 28,895 (69.8%) | 0.06 |
| Hypercholesterolemia | 2,036 (48.3%) | 22,010 (50.8%) | 0.002 |
| Atrial fibrillation | 639 (14.9%) | 5,423 (12.3%) | <0.001 |
| Tobacco use | 2,150 (50.0%) | 16,627 (37.8%) | <0.001 |
| Alcohol use | 510 (11.9%) | 1,306 (3.0%) | <0.001 |
| Major depressive disorder | 473 (11.1%) | 7,689 (17.6%) | <0.001 |
| Posttraumatic stress disorder | 35 (0.8%) | 288 (0.7%) | 0.22 |
| Hypothyroidism | 203 (4.7%) | 8,154 (18.5%) | <0.001 |
| Chronic obstructive pulmonary disease | 992 (23.5%) | 8,161 (18.7%) | <0.001 |
| Anemia | 119 (3.2%) | 1,144 (3.0%) | 0.58 |
| Thrombocytopenia | 243 (5.7%) | 990 (2.3%) | <0.001 |
| Congestive heart failure | 1,393 (32.4%) | 13,999 (31.8%) | 0.45 |
| Coronary artery disease | 2,096 (48.8%) | 18,109 (41.3%) | <0.001 |
| Obesity | 337 (7.8%) | 4,800 (10.9%) | <0.001 |
| Peripheral artery disease | 209 (5.0%) | 1,997 (4.6%) | 0.35 |
| Chronic kidney disease | 365 (8.5%) | 3,025 (6.9%) | <0.001 |
| History of coronary artery bypass graft surgery | 105 (2.4%) | 457 (1.0%) | <0.001 |
| History of percutaneous coronary intervention | 314 (7.3%) | 1,986 (4.5%) | <0.001 |
| History of stroke | 264 (6.1%) | 2,959 (6.7%) | 0.13 |
Between 2011 and 2018, TTS in-hospital all-cause mortality averaged 1.1%, with female mortality rates ranging from 0.5% to 1.6% ( Figure 3 ). Male in-hospitality mortality rates varied widely, peaking at 5.5% in 2013 but stabilizing to 1.6% to 1.9% between 2015 and 2018 ( Figure 3 ).
