Mortality in male patients with Takotsubo cardiomyopathy appears to be double that of Women. The goal of this study was to determine whether a higher mortality rate is associated with a higher complication rate in male adults. Using ICD-10 codes for Takotsubo cardiomyopathy, we evaluated differences in the occurrence of complications between Men and women. A total of 199,890 patients were diagnosed with Takotsubo cardiomyopathy, comprising 34,770 male and 195,120 female patients. All major complications are significantly higher in men than in women, despite multivariate adjustment for age and cardiovascular risk factors. Cardiogenic Shock: 9.88% versus 5.98% p <0.001, OR 1.57, 95% confidence interval (CI) 1.43 to 1.73, Atrial Fibrillation: 23.96% versus 20.12%, p <0.001, OR 1.55, 95% CI 1.45 to 1.66, Cardiac Arrest: 5.71% versus 2.94%, p <0.001, OR 1.71, 95% CI 1.51 to 1.94, Congestive Heart Failure: 39.52% versus 35.18% p <0.001, OR 1.23, 95% CI 1.16 to 1.30, Stroke: 7.45% versus 4.94%, p <0.001, OR 1.51, 95% CI 1.36 to 1.68. In conclusion, all major cardiovascular complications are higher in men compared to women with a diagnosis of Takotsubo cardiomyopathy, as a plausible explanation for the higher mortality in men.
Takotsubo Syndrome, also known as Takotsubo Cardiomyopathy (TC), is a stress-induced cardiomyopathy triggered by emotional or physical stress and characterized by transient regional left ventricular dysfunction. Nomenclature has varied, with earlier labels such as “transient cardiac ballooning” or “apical ballooning syndrome,” though “stress cardiomyopathy” may better capture variants beyond the classic apical form. First described by Dote et al. TC was initially considered benign, but accumulating evidence has shown that it is associated with notable short-term morbidity and mortality, with complication rates similar to acute coronary syndromes (ACS). , Echocardiographically, TC displays circumferential wall-motion abnormalities that extend beyond a single coronary territory, and coronary angiography is typically normal, helping distinguish it from ACS. ,, Additionally, TC is often accompanied by modest troponin elevations that are disproportionately low relative to the degree of wall-motion abnormality, further aiding its distinction from ACS.
Epidemiological studies show that TC predominantly affects postmenopausal women. ,, Emotional stressors are more common triggers in women, whereas men more often develop TC after physical stressors such as surgery, infection, or acute illness. , Anatomic variants also exist; the reverse (basal) form occurs more often in younger patients and is usually stress-triggered. Proposed mechanisms include catecholamine-mediated myocardial stunning, microvascular dysfunction, and transient LV outflow tract obstruction, , further supported by catecholamine-excess patterns seen in reverse TC. Estrogen-related cardioprotection, through improved endothelial function and reduced sympathetic activation, may contribute to the more favorable outcomes seen in women.
Although diagnosed less commonly in men, multiple studies report significantly worse clinical outcomes among male TC patients, including higher rates of in-hospital mortality, cardiogenic shock, and need for circulatory or ventilatory support. ,, For instance, Abusnina et al. found a more than 2-fold increase in in-hospital death and cardiogenic shock in men compared to women, and Maskoun et al. showed that men were more likely to experience severe hemodynamic instability requiring invasive support. A recent analysis also confirmed that male sex independently predicts mortality in TC, though underlying causes remain unclear.
To evaluate whether higher rates of complications explain the increased mortality in men with TC, we analyzed sex-based differences in in-hospital cardiovascular complications using the Nationwide Inpatient Sample (NIS) from 2016 to 2020.
Methods
Data source
This study is deemed institutional review board exempt as the NIS is a publicly available deidentified database. The NIS database includes weighted discharge information for about 35 million patients each year, 20% of all inpatient admissions to nonfederal hospitals in the United States.
Study population
In this retrospective observational cohort study, all patients aged >18 years from the 2016 to 2020 NIS database were included. Our target population was patients hospitalized with TC, which was identified using the International Classification of Diseases, Tenth Revision (ICD-10) code I51.81. The key complications of interest including myocardial rupture (I23.2, I23.3, I23.4, I23.5), cardiogenic shock (R57.0), atrial fibrillation (I48), cardiac arrest (I46), congestive heart failure (CHF; I52, I53, I54), and stroke (I60, I61, I62, I63) were also recorded. Prior cardiovascular risk factors, including diabetes, hypertension, hyperlipidemia, and chronic kidney disease, were evaluated. Patient demographics include age, sex, race or ethnicity, and hospital demographics, including median household income, expected primary payer, hospital bed size, location and teaching status of hospital, hospital region, control of hospital, along with average hospital length of stay, and average total charges were evaluated.
Study outcomes
The patient outcome examined was in-hospital complications, including cardiogenic shock, atrial fibrillation, cardiac arrest, congestive heart failure, and stroke, with diagnoses of TC. In multivariate analysis, adjustments were made for demographic factors (age, race, primary payer, median household income by zip code), hospital characteristics (bed size, teaching status, and region), and patient comorbidities (hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease, and dyslipidemia).
Statistical analysis
Patient demographic, clinical, and hospital characteristics are reported as percentages in Table 1 . Odds ratios (ORs) and 95% confidence intervals (CI) 95% CIs are calculated for continuous variables and proportions and 95% CIs for categorical variables. We studied outcome data over the 5-year period (2016 to 2020). Categorical outcomes were assessed using chi-squared analysis. Multivariate logistic regression models were constructed to evaluate the association between sex and the occurrence of in-hospital cardiovascular complications, including cardiogenic shock, atrial fibrillation, cardiac arrest, congestive heart failure, and stroke. All analyses accounted for the NIS sampling design using appropriate survey weights to generate nationally representative estimates. Statistical significance was defined as a 2-sided p Value <0.05. Statistical analyses were performed using Stata version 16.0 (StataCorp, College Station, TX).
Table 1
Baseline characteristics of patients hospitalized with Takotsubo cardiomyopathy, 2016 to 2020
| Total (N = 199,890) | Male (N = 34,770) (17.4) | Female (N = 165,120) (82.6%) | p‑Value | |
|---|---|---|---|---|
| Age | <0.001 | |||
| Mean ± SD | 67.09 ± 14.15 | 63.13 ± 16.26 | 67.93 ± 13.52 | |
| Median (IQR) | 68 (59 to 77) | 65 (54 to 75) | 69 (60 to 78) | |
| LOS | <0.001 | |||
| Mean ± SD | 7 ± 10 | 9 ± 12 | 6 ± 9 | |
| Median (IQR) | 4 (2 to 8) | 5 (3 to 11) | 4 (2 to 7) | |
| Age group | <0.001 | |||
| 18 to 30 | 1.93% | 5.05% | 1.27% | |
| 31 to 45 | 5.48% | 9.10% | 4.71% | |
| 46 to 60 | 21.55% | 23.84% | 21.07% | |
| 61+ | 71.04% | 62.01% | 72.94% | |
| Race | <0.001 | |||
| White | 80.39% | 74.69% | 81.57% | |
| Black | 8.19% | 11.30% | 7.55% | |
| Hispanic | 6.38% | 7.64% | 6.12% | |
| Asian/Pac Islander | 2.12% | 2.96% | 1.95% | |
| Native American | 0.64% | 0.63% | 0.64% | |
| Minor loss of function | 5.62% | 2.76% | 6.22% | |
| Moderate loss of function | 30.85% | 20.83% | 32.96% | |
| Major loss of function | 30.54% | 27.56% | 31.17% | |
| Extreme loss of function | 32.99% | 48.86% | 29.65% | |
| Year of Discharge | <0.001 | |||
| 2016 | 19.51% | 17.90% | 19.84% | |
| 2017 | 19.20% | 17.76% | 19.50% | |
| 2018 | 19.70% | 19.20% | 19.81% | |
| 2019 | 20.94% | 21.51% | 20.82% | |
| 2020 | 20.66% | 23.63% | 20.03% |
Results
In this analysis of the Nationwide Inpatient Sample (NIS) from 2016 to 2020, we identified a weighted total of 199,890 adult patients hospitalized with a primary diagnosis of TC using the ICD-10 codes. The cohort included 34,770 male patients and 165,120 female patients. All analyses were conducted following the application of population discharge weights to provide nationally representative estimates.
Baseline characteristics
The baseline characteristics of the study population are presented in Table 1 . The mean age of the overall cohort was 67.09 ± 14.15 years, with male patients being significantly younger than female patients (63.13 ± 16.26 years vs 67.93 ± 13.52 years; p < 0.001). Men also had a longer median length of hospital stay compared to women (5 [IQR 3 to 11] days vs 4 [IQR 2 to 7] days; p < 0.001).
In terms of age distribution, male patients were more likely to be younger, with 5.05% aged 18 to 30 years compared to 1.27% of female patients. Female patients were more likely to be aged 61 years or older (72.94% vs 62.01%; p <0.001). There were significant differences in racial distribution, with Black and Hispanic patients comprising a larger proportion of the male group.
Male patients were more likely to have Medicaid (14.68% vs 9.96%) and self-pay hospitalizations (4.28% vs 2.34%), while female patients were more likely to be covered by Medicare (65.29% vs 53.98%; p <0.001). Most hospitalizations occurred in large, urban teaching hospitals across all groups.
In-hospital complications
Compared to female patients, men had a higher prevalence of smoking (28.75% vs 27.13%; p = 0.008) and diabetes (25.61% vs 23.81%; p = 0.002). Conversely, women had a significantly higher prevalence of hypertension (67.82% vs 61.52%; p <0.001) and hyperlipidemia (47.13% vs 38.86%; p <0.001). Chronic kidney disease (CKD) was more common in male patients (18.39% vs 14.84%; p <0.001). These findings are summarized in Table 2 .
Table 2
In‑hospital complications and baseline comorbidities by sex
| Total (N = 199,890) | Male (N = 34,770) (17.4%) | Female (N = 165,120) (82.6%) | p Value | Adjusted odds ratio (95% CI) | |
|---|---|---|---|---|---|
| Complications | |||||
| Myocardial rupture | 0.020% | 0.000% | 0.020% | NA | 1 |
| Cardiogenic shock | 6.66% | 9.88% | 5.98% | <0.001 | 1.57 (1.43 to 1.73) |
| Atrial fibrillation | 20.79% | 23.96% | 20.12% | <0.001 | 1.55 (1.45 to 1.66) |
| Cardiac arrest | 3.42% | 5.71% | 2.94% | <0.001 | 1.71 (1.51 to 1.94) |
| Congestive heart failure | 35.93% | 39.52% | 35.18% | <0.001 | 1.23 (1.16 to 1.30) |
| Stroke | 5.38% | 7.45% | 4.94% | <0.001 | 1.51 (1.36 to 1.68) |
| Comorbidities | |||||
| Diabetes | 24.13% | 25.61% | 23.81% | 0.002 | 1.10 (1.04 to 1.17) |
| Hypertension | 66.72% | 61.52% | 67.82% | <0.001 | 0.76 (0.72 to 0.80) |
| Hyperlipidemia | 45.29% | 38.86% | 47.13% | <0.001 | 0.71 (0.66 to 0.75) |
| Chronic kidney disease | 15.46% | 18.39% | 14.84% | <0.001 | 1.29 (1.21 to 1.38) |
| Smoking | 27.41% | 28.75% | 27.13% | 0.008 | 1.08 (1.02 to 1.15) |
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