European Journal of Cardiovascular Medicine

Notwithstanding advancements in acute cardiovascular treatment, cardiogenic shock following acute myocardial infarction (AMI-CS) still carries a considerable morbidity and mortality. With fatality rates of almost 50%, 1–6 CS is the primary cause of death for AMI patients who arrive at the hospital alive and mostly occurs in the first 48 hours of admission.7. The cause of this death is thought to be cardiac pump failure, which results in ongoing hypotension, hypoperfusion of the organs, and eventually multi-organ failure.2, 3, 8–10 The management and results of patients with AMI-CS have been shown to exhibit ongoing health care disparities, including sex-based disparities.11, 12 Relative to their male counterparts, women with AMI-CS often had fewer episodes of coronary angiography, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and mechanical circulatory support (MCS).11, 13, 14 Nevertheless, there is evidence to suggest that women may benefit more from more aggressive, prompt, and suitable cardiac treatments.4, 13–17

Patients in their teenage years are often under-represented in these studies because most of them have been done on older adults or all-comers. In modern times, AMI is rising in the younger demographic due to the rising incidence of being obese and other heart disease co-morbidities.14, 19, 20 There is limited data on the outcomes of AMI-CS in the young population. Whether sex disparities are prevalent in this extremely chosen population of individuals is unclear because younger women might have fewer conventional atherosclerosis cardiovascular indicators, a greater likelihood of put off reperfusion, and more frequently received target lesion inability compared to matched by age men. Women are additionally associated with smaller obstructive coronary artery disease, as well as a consequence of their AMI a difference to outcome is unknown.14, 17

Using a nationally-representative population, we sought to determine if there are sex disparities in the clinical management and outcomes of AMI-CS in the young. We hypothesized that young women with AMI-CS would receive less frequent cardiac procedures and would have higher in-hospital mortality as compared to young men

The biggest all-payer network of hospital inpatient stays in India is called IACTS Database. It is a component of the Agency for Healthcare Research and Quality's Healthcare Quality and Utilization Project (HCUP) and includes discharge data from a 20% stratified sample of community hospitals. Patient demographics, the primary payer, hospital features, the primary diagnosis, up to 24 secondary diagnoses, and procedure diagnoses are all included in the information about each discharge. The HCUP-NIS records all the data related to a specific admission rather than specific patient information. Approval from the Institutional Review Board was not required because this database was de-identified and accessible to everybody. A retrospective cohort study of admissions between the ages of 18 to 55 years, with AMI in the primary diagnosis field (International Disease Classification 9.0 Clinical Modification [ICD-9CM] 410.x and ICD-10CM I21.x-22.x) and CS (ICD-9CM 785.51, ICD-10CM R57.0) as a secondary diagnosis were found. We excluded admissions without information about sex or in-hospital mortality. The burden of co-morbid disease was determined using the Deyo's modification of the Charlson Comorbidity Index. Using previously employed techniques from our group, the demographics, hospital features, acute organ failure, coronary angiography, PCI, MCS, and usage of non-cardiac organ support were determined for each admission. Early coronary angiography was defined as that which was done on the first hospital day; concurrent operations were timed on the same hospital day.

The in-hospital mortality rate for both male and female admissions was the main result. We assessed the temporal trends of cardiac procedure utilisation, in-hospital mortality, and prevalence of CS. In both male and female AMI-CS admissions, secondary outcomes included hospital duration of stay, hospitalisation expenditures, usage of do-not-resuscitate (DNR) status, referral to palliative care, and discharge disposition.

Statistical Analysis:

Chi-square/one-way analysis of variance and t-tests were used to compare 2/≥2 categorical and continuous variables, respectively. Multivariable logistic regression was used to analyze trends over time (referent year 2000). Univariable analysis for trends and outcomes was performed and was represented as odds ratio (OR) with 95% confidence interval (CI). Multivariable logistic regression analysis incorporating age, sex, race, primary payer status, socio-economic stratum, hospital characteristics, comorbidities, acute organ failure, AMI-type, cardiac procedures, non-cardiac procedures, DNR status, and palliative care referral was performed for assessing temporal trends of prevalence and in-hospital mortality. For the multivariable modeling, regression analysis with purposeful selection of statistically (liberal threshold of p<0.20 in univariate analysis) and clinically relevant variables was conducted. There was a statistically significant interaction between sex and adjusted temporal trends of prevalence and in-hospital mortality (p=0.02 and p=0.04 for interaction, respectively). Multiple sub-group analyses stratifying the population by race, presence of cardiac arrest, type of AMI, receipt of PCI and MCS, were performed to confirm the results of the primary analysis. Given the large sample size, all p-values that are statistically significant may not be clinically significant.

In the period from January 1, 2000 to December 31, 2017, there were over 11 million AMI admissions, of which 2,540,100 (23.1%) were aged 18–55 years. CS complicated 90,648 of these younger admissions (3.6%) with a comparable prevalence between men (67,004; 3.6%) and women (23,644; 3.5%) (p<0.001). The 18-year temporal trends of CS prevalence in young AMI admissions by sex are presented in fig 1. CS was noted in 2–5% of AMI admissions with a steady increase in trend in both sexes, though men had higher rates of CS compared to young women. Compared to men, women with AMI-CS were more often black, from a lower socio-economic status, with higher comorbidity, and were admitted more frequently to rural and small hospitals (all p<0.001) (Table 1).

Figure1- Trends in the prevalence and in-hospital mortality in younger AMI-CS admissions stratified by gender

Table 1. Baseline characteristics of young adults with AMI-CS stratified by sex (Represented as percentage or mean ± standard deviation).

Table 2. In-hospital characteristics of young adults with AMI-CS stratified by Gender

Table 3. Clinical outcomes of young adults with AMI-CS stratified by Gender

Women were shown to have greater rates of comorbidity, be more likely to be black, and experience sudden cardiac death and non-cardiac organ failure less frequently than men in this analysis of young AMI-CS hospitalisations. Compared to younger males, fewer younger women underwent PCI, MCS, and coronary angiography procedures. Over the course of the 18-year study, female sex was found to be an independent predictor of increased in-hospital mortality, with a consistently higher temporal trend. In high-risk subgroups such as those with ST-segment elevation AMI-CS presentation, concurrent cardiac arrest, and those not receiving PCI or MCS assistance, female sex was associated with greater in-hospital mortality.

The investigations found that although women benefited from revascularisation just as much as men did, and that their in-hospital outcomes were comparable. However, they also revealed that women experience more mechanical complications, comorbidity, and clinically significant events more frequently than men do. They also mentioned that women were less likely than men to receive treatments based on guidelines.19 However, previous research conducted by our lab has demonstrated that older (≥75 years) women with AMI-CS perform worse than men.11

Younger AMI patients differ from these populations in that they have a more diverse range of AMI aetiologies, a lower load of comorbidities, a higher incidence of high-risk lifestyle behaviors, and a lower healthcare utilisation rate.20 It's uncertain if younger women with AMI-CS experience comparable gender differences to younger men. Women had equivalent in-hospital mortality and lower rates of CS compared to men, despite having a larger comorbidity burden, according to a research by Bandyopadhyay et al. on AMI patients ≤45 years.19 According to Epps et al., young women are more likely to experience target vessel and target lesion failure even when their coronary angiography shows less severe disease.18 The VIRGO study examined the impact of gender on the outcomes of young AMI patients and found that female sex associated with reperfusion delay in young patients with ST-segment elevation AMI.16.

Taken in aggregate, these findings suggest that sex-specific disparities exist in young AMI patients. Our study adds to this literature by specifically evaluating AMI-CS admissions. We note higher in-hospital mortality in young women with AMI-CS. In addition to the potential reasons as stated above, this current analysis indicates that, a) women had a worse comorbidity profile, higher rates of prior chronic kidney disease and cancer, and greater use of invasive mechanical ventilation, all of which portent a poor prognosis and may have served as a deterrent for performance of invasive procedures  b) despite an increase in the uptake of coronary angiography, early coronary angiography and PCI over time, women consistently received these therapies less frequently; c) women had a lower socio-economic status, which is associated with lower access to healthcare resources and poorer baseline management of comorbidities prior to hospitalization; d) it is conceivable that consistent with prior literature, women present with delayed and atypical symptoms and are often misdiagnosed resulting in less frequent guideline-directed care;14, 20 and e) a significant portion of young women were admitted to small and rural hospitals, which we have previously shown to be associated with worse outcomes in AMI-CS.1, 5 It is important to note that the etiology of AMI-CS in this young population could not be assessed in this study, and further details are needed to clarify the etiology given the high rates of non-plaque rupture mechanisms in this population.14, 20 Lastly, hospital-level disparities in this population are worthy of further evaluation for future studies

Regarding treatment and results, there are still notable gender differences in young (≤55 years) AMI-CS admissions. In-hospital mortality was higher in younger women, and they also exhibited higher comorbidity, lower disease acuity, and decreased usage of PCI and coronary angiography. In order to better understand the underlying causes of these variations in resource utilisation in this high-risk population and what can be done to improve the outcome, more quantitative and qualitative study in these vulnerable populations is required.

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