Epidemiology of cardiogenic shock and cardiac arrest complicating non-ST-segment elevation myocardial infarction: 18-year US study

Introduction

Non-ST-segment elevation myocardial infarction (NSTEMI) has become the leading cause of hospitalization in patients with ischaemic heart disease and continues to be associated with high morbidity and mortality.^{1, 2} Increased use of revascularization and potent anti-thrombotic, anti-ischaemic and secondary prevention medications has resulted in low in-hospital mortality and shorter hospital stay in NSTEMI populations.³ About 5–7% of NSTEMI patients have concomitant cardiogenic shock (CS) and/or cardiac arrest (CA), which is associated with significantly higher in-hospital mortality and morbidity.^{4, 5} There are limited data on the overlap of CS and CA in NSTEMI patients,^5-7 as prior studies have treated both entities in isolation.^{7, 8} We previously demonstrated that CA was associated with worse clinical outcomes in a national database of nearly 4.5 million admissions with acute MI and CS admissions.⁵ A recent statement on CS classification from the Society of Cardiovascular Angiography and Intervention emphasized the additional risk portended by CA at every CS stage.^{9, 10} In light of these data, it is crucial to define the epidemiology, clinical management, and outcomes of CS and CA complicating NSTEMI in the contemporary era.^{7, 8}

In this study, we sought to assess the in-hospital mortality, resource utilization and temporal trends of CA and CS complicating NSTEMI admissions using a nationally representative database. We hypothesized that the combination of CA and CS was associated with higher in-hospital mortality than either entity alone.

Methods

Results

In the period from 1 January 2000 to 31 December 2017, there were 7 302 447 admissions with a primary NSTEMI diagnosis, of which CS, CA and both were noted in 147 795 (2.0%), 155 522 (2.1%) and 41 360 (0.6%), respectively. The four cohorts had comparable age and race distributions (Table 1). Compared with the cohort without CS/CA, the CS + CA, CS only and CA only had higher rates of prior heart failure and were admitted more frequently to urban and large-sized hospitals (Table 1 and Supporting Information, Table S2). The cohort with CA, either alone or in combination with CS, was more often male and non-white, compared with the other cohorts (Table 1). During this 18-year period, there was a temporal decrease in NSTEMI admissions without CS/CA and a stable trend in the unadjusted rates of CA only (Figure 1). After adjustment for patient and hospital characteristics, there was a modest increase in the risk of CA (adjusted OR 1.46 [95% CI 1.42–1.50]), and a substantially larger increase in CS (adjusted OR 3.75 [95% CI 3.58–3.92]) and CS + CA (adjusted OR 4.52 [95% CI 4.16–4.87]) in 2017 compared with 2000 (all P < 0.001) (Figure 1).

CS + CA was associated with higher rates of acute non-cardiac organ failure than either CS or CA alone (Table 1). The CS only cohort had higher rates of organ failure across all domains except neurologic compared with CA alone (Table 1). Over time, there was a steady increase in single-organ and multi-organ failure over the study period, with consistently higher rates in admissions with a combination of CS and CA (Figure 2). Coronary angiography and PCI were performed less commonly in the CA only cohort (51.6% and 25.3%, respectively) compared with the other cohorts (59–60% and 27–33%, respectively) (Table 1). The presence of CS, either alone or in combination with CA, was associated with higher rates of invasive haemodynamic monitoring, CABG, MCS, mechanical ventilation, and acute haemodialysis use (all P < 0.001) (Table 1). Over time, there was a steady increase in coronary angiography and PCI use, whereas CABG use remained relatively stable across all four cohorts (Figure 3). MCS use initially increased with a peak in 2009 and subsequently decreased in the CS + CA and CS only cohorts (Figure 3). Timing of coronary angiography was available in 3 637 205 (49.8%) admissions. The presence of CS either alone or in combination with CA was associated with higher use of early coronary angiography; however, the overall rates were <30% (Table 2).

Compared with NSTEMI admissions without CS or CA (in-hospital mortality 2.7%), the all-cause in-hospital mortality was higher in the other cohorts, that is, CS + CA (59.5%; OR 56.40 [95% CI 55.27–57.55]), CS only (28.5%; OR 15.34 [95% CI 15.16–15.53]), and CA only (46.4%; OR 33.24 [95% CI 32.87–33.61]) (all P < 0.001). The unadjusted in-hospital mortality in the cohort with CS + CA was higher than those with CS only (OR 3.68 [95% CI 3.59–3.76]) and CA only (OR 1.70 [95% CI 1.66–1.74] (all P < 0.001). In-hospital mortality steadily declined across all categories during the study period (Figure 1 and 1). After adjustment for potential confounders, risk of in-hospital mortality was higher in all three cohorts compared with NSTEMI without CS/CA, that is, CS + CA (adjusted OR 22.66 [95% CI 22.06–23.27]), CS only (adjusted OR 5.61 [95% CI 5.52–5.71]), and CA only (adjusted OR 24.48 [95% CI 24.13–24.85]) (all P < 0.001) (Table 3). Similar results were observed in pre-specified sub-groups stratified by age, sex, race, time period, use of PCI and use of MCS (Supporting Information, Table S3). The CS + CA cohort had higher adjusted in-hospital mortality compared with those with CS alone (adjusted OR 4.12 [95% CI 4.00–4.24]) or CA alone (adjusted OR 1.69 [95% CI 1.65–1.74]) (all P < 0.001). The CS + CA and CS only cohorts had higher use of palliative care referral and DNR status than the other groups (Table 2). The presence of CS, either alone or in combination with CA, was associated with longer hospital length of stay, higher hospitalization costs, and fewer discharges to home (all P < 0.001) (Table 2).

Discussion

Among NSTEMI admissions in the United States during this 18-year study period, either CS or CA was noted in 4.7% of all admissions and 0.6% of admissions had a combination of the two conditions. There was a steady increase in CS over time with relatively stable rates in CA. The presence of CS or CA complicating NSTEMI was associated with worse outcomes, and the combination of the two diagnoses was associated with higher rates of acute organ failure and in-hospital mortality compared with either alone. The presence of CS, either alone or in combination with CA, was associated with longer length of stay and greater hospitalization costs.

Our study is consistent with population-based studies from Olmsted County, Minnesota, and Worchester, Massachusetts, that have demonstrated an increase in the prevalence of NSTEMI over time.^{29, 30} The use of cardiac troponin-T criteria and, more recently, high-sensitivity cardiac troponin-T criteria, in addition to an increase in the co-morbidity profile of patients, has resulted in a higher frequency of NSTEMI diagnosis in recent times.²⁹ Using the HCUP-NIS database from 2006 to 2012, Kolte et al. demonstrated 2.5% of all NSTEMI admissions to be complicated by CS.⁸ CA was found to complicate 0.6–1.5% of all NSTEMI presentations in other national databases, such as NCDR-ACTION (National Cardiovascular Data Registry Acute Coronary Treatment And Intervention Outcomes Network) and NCDR-CathPCI registries.^{6, 7} The overlap of CS and CA in NSTEMI populations has not been as well studied as the STEMI populations.^{5, 7, 10, 31} We noted 11% of NSTEMI admissions with either CS or CA to have a combination of the two diagnoses. In 9682 MI patients with CA from the NCDR-ACTION registry, Kontos et al. showed concomitant CS in 38–45% of the population.⁶ Similarly, in 171 patients from the National Cardiogenic Shock Initiative study, 35–50% of patients had either in-hospital or out-of-hospital CA.³² These rates are significantly higher than our study because they included both STEMI and NSTEMI populations. CS and CA are more common in STEMI, which constitute nearly 70% of all MI patients with either CS or CA.^{6, 7, 32} In an older study from the NCDR-CathPCI registry, Gupta et al. showed CS to complicate 38% of all NSTEMI admissions with CA.⁷ These differences could be due to the inclusion of a longer time period in our study, the use of selective reporting (voluntary databases, PCI only databases), the use of administrative codes for the identification of CS and CA, and the nationally representative nature of this study. Furthermore, the prevalence of CA and CS is likely modulated by the use of an early invasive strategy, which remains sub-optimally utilized in this high-risk NSTEMI population.^{4, 8} Only one of four NSTEMI admissions with CS received early coronary angiography, although this rate was higher than for those without CS. Early coronary angiography, although recommended in high-risk NSTEMI patients, has been infrequently performed nationally.^{4, 33}

In addition to highlighting the epidemiology of these conditions, our study highlights the clinical course and outcomes of the overlap of CS and CA in NSTEMI admissions. Our group previously demonstrated that concomitant CA was more common in admissions with multi-organ failure in CS complicating acute MI.⁵ CS follows a ‘haemo-metabolic cascade’ wherein the initial haemodynamic insult results in a worsening shock state characterized by systemic inflammation, metabolic injury, and end-organ damage.^{5, 34} This is further potentiated by the low-flow state during concomitant CA, contributing to worsening shock and organ injury. After CA, the presence of myocardial dysfunction worsens haemodynamic status and drives development of CS.³⁵ Given the uncertainty regarding the optimal timing of coronary angiography in CA patients without ST-segment elevation on electrocardiogram, the NSTEMI population suffers from the additional vulnerability of delayed coronary revascularization.³⁶ Furthermore, the lower rates of coronary angiography and PCI in this study are consistent with prior real-world literature that reflects reluctance to perform angiography in higher risk cohorts despite robust guideline recommendations supporting early coronary angiography in CS patients.³³ The harmful effects of CA, in association with delayed coronary angiography and delayed recognition of CS, may contribute to the poor outcomes in this population.

The combination of CS and CA has been associated with worse in-hospital outcomes in acute MI.^5-7 In over 400 000 acute MI-CS admissions, our group noted the presence of CA to be associated with three-fold higher in-hospital mortality.⁵ Using a cardiac intensive care unit patient database of 10 000 patients, our group demonstrated that CA is associated with incremental in-hospital mortality in patients with CS across the spectrum of CS severity, including in patients admitted with an acute MI.¹⁰ Using the NCDR-CathPCI registry, Gupta et al. demonstrated that the presence of CS in NSTEMI patients was associated with higher in-hospital mortality (38.5% vs. 6.6%).⁷ This study is of incremental value to these prior studies. In addition to in-hospital mortality, our study highlights the health care utilization—costs, hospital length of stay, and post-acute care utilization—all of which are notably higher in the cohort with CS and CA. Further studies are needed to understand the long-term implications of these disease states and their association with repeat hospitalizations and emergency department visits.

Conclusions

CS, CA, and their combination complicate nearly 5% of all NSTEMI admissions and are associated with significantly higher in-hospital mortality. Although the overall mortality from uncomplicated NSTEMI remains low (<3%), the combination of CS and CA is associated with significantly higher rates of acute non-cardiac organ failure and an in-hospital mortality rate of nearly 60%. Despite increase in use of coronary angiography and PCI in NSTEMI with/without CS and CA, there remains a crucial need to evaluate protocoled care for these patients including the timely incorporation of MCS devices. Further dedicated research related to the interactions of CS and CA in NSTEMI is crucial to improve the short-term outcomes in this acutely ill cohort.

Conflict of interest

None declared.

Funding

Dr. Saraschandra Vallabhajosyula is supported by the Clinical and Translational Science Award (CTSA) Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH.

Author contributions

S.V., J.C.J., A.P., L.R.S., K.K., N.D.S., and S.M.D. did the study design, literature review, and statistical analysis. S.V., J.C.J., A.P., L.R.S., K.K., N.D.S., and S.M.D. carried out the data management, data analysis, and drafting manuscript. S.V., J.C.J., A.P., L.R.S., K.K., N.D.S., and S.M.D. had access to data. J.C.J., A.P., L.R.S., K.K., N.D.S., and S.M.D. are responsible for the manuscript revision, intellectual revisions, and mentorship. All authors did the final approval of the study.