Mortality in ST-Segment Elevation Myocardial Infarction With Nonobstructive Coronary Arteries and Mimickers.

Importance: The clinical characteristics and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) with nonobstructive coronaries (MINOCA) are largely unknown. Objective: To assess differences in 5-year mortality in patients presenting with STEMI due to MINOCA and MINOCA mimickers as compared with obstructive disease. Design, Setting, and Participants: A retrospective analysis of a prospective registry-based cohort study of consecutive STEMI activations at 3 regional Midwest STEMI programs. STEMI without a culprit artery and elevated troponin levels were categorized as MINOCA (absence of coronary artery stenosis >50% and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) or MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or nonischemic cardiomyopathy). Data were analyzed from March 2003 to December 2020. Main Outcomes and Measures: Adjusted Cox regression analysis was used to assess 5-year mortality risk in STEMI presenting with MINOCA and MINOCA mimickers in comparison with obstructive disease. Results: Among 8560 consecutive patients with STEMI, mean (SD) age was 62 (14) years, 30% were female (2609 participants), and 94% were non-Hispanic White (4358 participants). The cohort included 8151 patients with STEMI due to obstructive disease (95.2%), 120 patients with MINOCA (1.4%), and 289 patients with MINOCA mimickers (3.8%). Patients were followed up for a median (IQR) of 7.1 (3.6-10.7) years. Patients with MINOCA and MINOCA mimickers were less likely to be discharged with cardiac medications compared with obstructive disease. At 5-year follow-up, mortality in STEMI presenting with obstructive disease (1228 participants [16%]) was similar to MINOCA (20 participants [18%]; χ21 = 1.1; log-rank P = .29) and MINOCA mimickers (52 participants [18%]; χ21 = 2.3; log-rank P = .13). In adjusted Cox regression analysis compared with obstructive disease, the 5-year mortality hazard risk was 1.93 times higher in MINOCA (95% CI, 1.06-3.53) and similar in MINOCA mimickers (HR, 1.08; 95% CI, 0.79-1.49). Conclusions and Relevance: In this large multicenter cohort study of consecutive clinical patients with STEMI, presenting with MINOCA was associated with a higher risk of mortality than obstructive disease; the risk of mortality was similar in patients with MINOCA mimickers and obstructive disease. Further investigation is necessary to understand the pathophysiologic mechanisms involved in this high-risk STEMI population.

Association of triglyceride levels with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction.

Although there is an established association between elevated triglyceride (eTG, ≥175 mg/dl) levels and adverse cardiovascular events, some studies have suggested that eTG levels may be linked to neutral or even improved clinical outcomes, particularly among patients with acute myocardial infarction. However, these studies had certain limitations, including small sample sizes, heterogeneous study populations, and inadequate statistical adjustments. To address these limitations, we conducted an analysis of 5347 patients with ST-segment elevation myocardial infarction (STEMI) between March 2003 and December 2020, using a prospective registry-based cohort from two large, regional STEMI centers. We used a triglyceride level of 175 mg/dl as the cutoff point for eTG levels. Of the study participants, 24.5% (n = 1312) had eTG levels. These patients were more likely to be younger, male, and have a higher number of cardiovascular risk factors compared to those with low TG levels. Despite these unfavorable cardiovascular risk profiles, patients with eTG levels had lower unadjusted risks of 1-year major adverse cardiac events (MACE) -a composite of myocardial infarction, stroke, and death- than those with low TG levels (8.8% vs. 11%, p = 0.034). However, after adjusting for certain clinical factors and lipid profile, eTG levels were not associated with a lower 1-year MACE (aHR: 1.10 (0.71-1.70), p = 0.7). In conclusion, a quarter of STEMI patients had eTG levels and these patients had comparable long-term cardiovascular outcomes compared to those with low TG levels after controlling for clinical factors and lipid profile.

Characteristics and Long-term Mortality in Patients with ST-Segment Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries (STE-MINOCA): A High Risk Cohort.

Background: The prognosis of ST-segment elevation myocardial infarction with non-obstructive coronaries (STE-MINOCA) is largely unknown. Methods: The objective of this study is to evaluate the prevalence, characteristics, and 5-year mortality of patients with STE-MINOCA compared to STEMI with coronary artery obstruction (STEMI-Obstruction) using a multicenter cohort of consecutive STEMI patients at 3 regional Midwest STEMI programs from 2003 to 2020. STE-MINOCA was defined based on (1) coronary stenosis < 60% by visual estimation, (2) ischemia with elevated troponin, and (3) no alternative diagnosis. STE-MINOCA was further classified based on American Heart Association (AHA) definition as AHA STE-MINOCA and AHA STE-MINOCA Mimicker. Results: 8,566 STEMI patients, including 420 (4.9%) STE-MINOCA (26.9% AHA STE-MINOCA and 73.1% AHA STE-MINOCA Mimicker) were followed for a median of 7.1 years. Compared to STEMI-Obstruction, STE-MINOCA were younger, more often female, had fewer cardiovascular risk factors, and were less likely to be discharged on cardiac medications. At five years, mortality was higher in STE-MINOCA compared with STEMI-Obstruction (18% vs. 15%, p=0.033). In propensity score-matched analysis, STE-MINOCA had a 1.4-fold (95% CI: 1.04-1.89, p=0.028) higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Furthermore, 5-year mortality risk was significantly higher in AHA STE-MINOCA Mimicker (19% vs. 15%, p=0.043) but similar in AHA STE-MINOCA (17% vs. 15%, p=0.42) compared with STEMI-Obstruction. Conclusions: In this large multicenter STEMI cohort, nearly 5% of patients presented with STE-MINOCA. At five years, mortality approached 20% among patients with STE-MINOCA. Despite the lower risk profile, STE-MINOCA patients were at 40% higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Additionally, 5-year all-cause mortality risk was higher in AHA STE-MINOCA Mimicker but similar in AHA STE-MINOCA compared to STEMI-Obstruction.

STEMI: Considerations for Left Main Culprit Lesions.

PURPOSE OF REVIEW: There is a paucity of data regarding the prevalence, clinical characteristics, and outcomes of patients presenting with ST elevation myocardial infarction (STEMI) due to left main (LM) culprit vessel. RECENT FINDINGS: LM culprit STEMI (LMCSTEMI) is an uncommon, but frequently catastrophic event. Prior meta-analyses and registries have described a varying prevalence of LMCSTEMI, associated cardiogenic shock, and in-hospital mortality among those surviving to hospital presentation. These observed clinical discrepancies may be partially attributable to diverse clinical and angiographical subsets among this STEMI population. STEMI due to LM culprit artery disease represents a clinically high-risk subset of patients with substantial in-hospital mortality. In this paper, we summarize the available clinical data pertaining to STEMI with LM culprit, discuss unique ECG characteristics, and discuss contemporary revascularization therapy. We also report the preliminary findings from a contemporary, STEMI database describing clinical characteristics and angiographically defined subsets of LM culprit STEMI.

Diabetic Patients Who Present With ST-Elevation Myocardial Infarction.

BACKGROUND: The long-term outcomes of diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) in contemporary practice have received limited study. METHODS: We evaluated the clinical characteristics and outcomes of STEMI patients with and without diabetes in a large regional STEMI program designed to facilitate timely primary percutaneous coronary intervention (PCI) (Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN). The primary and secondary outcome measures were in-hospital mortality, 1-year major adverse cardiovascular events (MACE) (stroke, myocardial infarction, unplanned PCI or coronary artery bypass graft [CABG] surgery, and all-cause mortality), and 5-year mortality. RESULTS: Of the 6292 patients included, 1158 (18.4%) had Diabetes Mellitus (DM) (95.3% Type II, 4.7% Type I). Patients with DM were older (mean age 66 vs. 62.8 years, p < 0.01), had more co-morbidities and were more likely to receive medical therapy without reperfusion (13% vs. 10%, p = 0.003). Patients with DM had higher in-hospital (8% vs. 5%, p = 0.001), 1-year (8% vs. 4%, p < 0.001) and 5-year mortality (16% vs. 9%, p < 0.001) compared to non-diabetics. On Cox proportional hazards analysis, DM was independently associated with worse mortality (hazard ratio: 1.70, 95% confidence interval (CI): 1.32-2.19, p < 0.001) and MACE [HR: 1.63 (95% (CI)): 1.28-2.08, p < 0.001]. CONCLUSIONS: Despite advancements in medical therapy and revascularization strategies for STEMI, DM remains independently associated with higher short- and long-term morbidity and mortality in contemporary practice.

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial.

BACKGROUND: Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility. METHODS: In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF <45% and 15% or greater LV scar size were randomised in 2:1 ratio to receive intracoronary infusion of allogenic CDCs or placebo, respectively. Change in segmental myocardial circumferential strain (Ecc) by MRI from baseline to 6 months was compared between CDCs and placebo groups. RESULTS: In total, 124 patients completed the 6-month follow-up (mean (SD) age 54.3 (10.8) and 108 (87.1%) men). Segmental Ecc improvement was significantly greater in patients receiving CDC (-0.5% (4.0)) compared with placebo (0.2% (3.7), p=0.05). The greatest benefit for improvement in segmental Ecc was observed in segments containing scar tissue (change in segmental Ecc of -0.7% (3.5) in patients receiving CDC vs 0.04% (3.7) in the placebo group, p=0.04). CONCLUSIONS: In patients with post-MI LV dysfunction, CDC administration resulted in improved segmental myocardial function. Our findings highlight the importance of segmental myocardial function indices as an endpoint in future clinical trials of patients with post-MI. TRIAL REGISTRATION NUMBER: NCT01458405.

Comparison of Outcomes of Patients with vs without Previous Coronary Artery Bypass Graft Surgery Presenting with ST-Segment Elevation Acute Myocardial Infarction.

The outcomes of patients with previous coronary bypass graft surgery (CABG) presenting with ST-segment elevation acute myocardial infarction (STEMI) have received limited study. We compared the clinical and procedural characteristics and outcomes of STEMI patients with and without previous CABG in a contemporary multicenter STEMI registry between 2003 and 2020. The primary outcomes of the study were mortality and major cardiac adverse events (MACE: death, MI or stroke). Survival curves were derived using the Kaplan-Meier method and compared with the log-rank test. Of the 13,893 patients included in the analyses, 7.2% had previous CABG. Mean age was 62.4 ± 13.6 years, most patients (71%) were men and 22% had diabetes. Previous CABG patients were older (69.0 ± 11.7 vs 61.9 ± 13.6 years, p <0.001) and more likely to have diabetes (40% vs 21%, p <0.001) compared with patients without previous CABG. Previous CABG patients had higher mortality and MACE at 5 years (p <0.001). Outcomes were similar with saphenous vein graft vs native coronary culprits. Previous CABG remained associated with mortality from discharge to 18 months (p = 0.044) and from 18 months to 5 years (p <0.001) after adjusting for baseline characteristics. Long term outcomes after STEMI were worse among patients with previous CABG compared with patients without previous CABG, even after adjustment for baseline characteristics.

Initial Findings From the North American COVID-19 Myocardial Infarction Registry.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). OBJECTIVES: The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. METHODS: A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. RESULTS: As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p < 0.001 relative to PUIs). COVID+ patients were more likely to present with cardiogenic shock (18%) but were less likely to receive invasive angiography (78%) (all p < 0.001 relative to control patients). Among COVID+ patients who received angiography, 71% received PPCI and 20% received medical therapy (both p < 0.001 relative to control patients). The primary outcome occurred in 36% of COVID+ patients, 13% of PUIs, and 5% of control patients (p < 0.001 relative to control patients). CONCLUSIONS: COVID+ patients with STEMI represent a high-risk group of patients with unique demographic and clinical characteristics. PPCI is feasible and remains the predominant reperfusion strategy, supporting current recommendations.

The Midwest ST-Elevation Myocardial Infarction Consortium: Design and Rationale.

BACKGROUND: Over the past 20 years, the development of regional ST-elevation myocardial infarction (STEMI) care systems has led to remarkable progress in achieving timely coronary reperfusion with attendant improvement in clinical outcomes, including survival. Despite this progress, contemporary STEMI care does not consistently meet the national guideline-recommended goals, which offers an opportunity for further improvement in STEMI outcomes. The lack of single, comprehensive, national STEMI registry complicates our ability to improve STEMI outcomes in particular for high-risk STEMI subsets such as cardiac arrest (CA) and/or cardiogenic shock (CS). OBJECTIVES: To address this need, the Midwest STEMI Consortium (MSC) was created as a collaboration of 4 large, regional STEMI care systems to provide a comprehensive, multicenter, and prospective STEMI registry without any exclusionary criteria. METHODS: The MSC is a collaboration of 4 large, regional STEMI care systems: Iowa Heart Center in Des Moines, IA; Minneapolis Heart Institute Foundation in Minneapolis, MN; Prairie Heart Institute in Springfield, IL; and The Christ Hospital in Cincinnati, OH. Each has similar standardized STEMI protocol and together include 6 percutaneous coronary intervention (PCI)-capable hospitals and over 100 non-PCI-capable hospitals. Each center had a prospective database that was transferred to a data coordinating center to create the multicenter database. The comprehensive database includes traditional risk factors, cardiovascular history, medications, time to treatment data, detailed angiographic characteristics, and short- and long-term clinical outcomes up to 5-year for myocardial infarction, stroke, and cardiovascular and all-cause mortality. Ten-year mortality rates were assessed by using national death index. RESULTS: Currently, the comprehensive database (03/2003-01/2020) includes 14,911 consecutive STEMI patients with mean age of 62.3 ± 13.6 years, female gender (29%), and left anterior descending artery as the culprit vessel (34%). High risk features included: Age >75 years (19%), left ventricular ejection fraction <35% (15%), CA (10%), and CS (8%). CONCLUSION: This collaboration of 4 large, regional STEMI care systems with broad entry criteria including high-risk STEMI subsets such as CA and/or CS provides a unique platform to conduct clinical research studies to optimize STEMI care.

The kinetics of integrilin limited by obesity: a multicenter randomized pharmacokinetic and pharmacodynamic clinical trial.

BACKGROUND: KILO tested 2 novel weight-based eptifibatide dosing strategies compared with standard dosing in obese patients undergoing elective percutaneous coronary intervention (PCI). Eptifibatide dosing is weight adjusted for patients up to 121 kg. Patients above this weight receive the same maximal dose, although it is unknown if this provides adequate eptifibatide concentration or platelet inhibition. METHODS: Sixty-seven patients weighing ≥125 kg undergoing elective PCI were randomized to 1 of 3 eptifibatide dosing regimens: standard dosing using a weight of 121 kg, actual body weight (ABW)-based dosing with no upper limit, or ideal body weight (IBW)-based dosing. Boluses of 180 µg/kg were given 10 minutes apart, followed by a 2.0 µg/kg per minute infusion. Plasma eptifibatide concentrations were drawn at 12 to 18 hours after initiating the infusion. Platelet aggregation was assessed at baseline and 10 minutes after the second bolus. RESULTS: Sixty-seven patients were randomized to standard (n = 22), ABW (n = 23), or IBW (n = 22) dosing. The median (25th, 75th) steady-state plasma eptifibatide concentrations were 1,740 ng/mL (1,350, 2,350), 1,780 ng/mL (1,510, 2,350), and 1,055 ng/mL (738, 1,405), respectively (P < .001). Ten-minute median (25th, 75th) platelet aggregation units were 7 (0, 21), 2 (0, 8), and 14 (8, 20), respectively (P = .001). CONCLUSIONS: Actual body weight eptifibatide dosing leads to higher plasma concentrations and greater platelet inhibition than standard or IBW dosing in obese patients undergoing PCI. Current recommendations for eptifibatide dosing may be inadequate in patients >121 kg. Further study is warranted to define the optimal dosing of eptifibatide and other medications in obese patients.

Circadian rhythms in patients with ST-elevation myocardial infarction.

BACKGROUND: Circadian rhythms with regard to time of symptom onset for patients with acute myocardial infarction have been observed, although their relationship to outcomes has been debated. We evaluated these rhythms in patients with ST-elevation myocardial infarction as a function of the 24-hour circadian cycle. METHODS AND RESULTS: The relationship between onset of symptoms during the 24-hour circadian cycle and prehospital delays from symptom onset to hospital arrival, timeliness of reperfusion, and in-hospital death was assessed in 2143 patients with ST-elevation myocardial infarction presenting from 2004-2008 at 1 of 3 tertiary-care healthcare ST-elevation myocardial infarction systems. There was a significant association between time of onset and the circadian cycle, with the greatest percentage (39%) of patients experiencing onset between 8 AM and 3 PM (P<0.001). Time of onset was associated with prehospital delay and timeliness of reperfusion. Patients with onset from 12 AM to 5:59 AM had median prehospital delays of 121 minutes versus 70 minutes from 12 PM to 5:59 PM (P<0.001). Patients with onset time from 12 AM to 5:59 AM had median door-to-balloon times of 75 minutes versus 60 minutes from 6 AM to 11:59 AM (P<0.001). Using multivariable modeling to control for baseline patient characteristics, prehospital delay, and timeliness of reperfusion, there was no significant association between time of symptom onset with in-hospital death. CONCLUSIONS: Patients with ST-elevation myocardial infarction exhibit significant circadian patterns in symptom onset, prehospital delay, and timeliness of reperfusion. Patients who develop symptoms from 12 AM to 5:59 AM present with longer prehospital delays and have longer door-to-balloon times. After multivariable adjustment, there was no significant association between circadian patterns of time of onset and in-hospital death.

Rural interhospital transfer of ST-elevation myocardial infarction patients for percutaneous coronary revascularization: the Stat Heart Program.

BACKGROUND: In Europe, interhospital transfer of ST-elevation myocardial infarction (STEMI) patients for primary percutaneous coronary intervention (PCI) from non-PCI-capable (STEMI-referral) to PCI-capable (STEMI-accepting) facilities has been shown to be a superior reperfusion strategy compared with on-site fibrinolysis. The feasibility of such programs in the United States remains poorly defined. METHODS AND RESULTS: We describe an observational cohort of 230 consecutive presumed STEMI patients who underwent interhospital transfer between January 2005 and March 2007 among 6 STEMI-referral and 2 STEMI-accepting hospitals in rural central Illinois. A standard treatment protocol using rapid interhospital transfer for primary PCI or rescue PCI after full-dose intravenous fibrinolysis (in event of unanticipated transfer delays) was initiated by the STEMI-referral emergency department physician. Three time intervals were evaluated: STEMI-referral care (door 1 to departure), transport time (door 1 departure to STEMI-accepting hospital arrival [door 2]), and STEMI-accepting hospital care (door 2 to balloon). Primary PCI was performed in 165 STEMI-confirmed patients (87.7%), whereas fibrinolysis was required in 16 patients (8.5%), with 56% undergoing rescue PCI. The median door 1-to-departure time was 46 minutes (25th and 75th percentiles, 32 and 62 minutes); approximately two thirds of this delay was attributable to the wait for transport arrival and departure. The transport and door 2-to-balloon times were 29 minutes (25th and 75th percentiles, 25 and 35 minutes) and 35 minutes (25th and 75th percentiles, 32 and 46 minutes), respectively. The door 1-to-balloon time was 117 minutes (25th and 75th percentiles, 98 and 137 minutes), with 12.2% and 58% of patients achieving a time of < or = 90 and < or = 120 minutes, respectively. No adverse clinical events occurred during interhospital transport. CONCLUSIONS: In rural US communities, emergency department physician-initiated interhospital transfer of STEMI patients for primary or rescue PCI is feasible and was safely executed with achievement of timely reperfusion when performed within coordinated healthcare networks.

Assessing the effect of publication of clinical guidelines on the management of unstable angina and non-ST elevation myocardial infarction in the TIMI III (1990-1993) and the GUARANTEE (1995-1996) Registries.

BACKGROUND: The clinical guidelines for unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care Policy Research (AHCPR) were intended to help improve treatment. No large study, however, has evaluated the effect of the guidelines on clinical practice METHODS: We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990-1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS: More patients in GUARANTEE received guideline-recommended medication than did those in TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3% versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta-blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001). These changes were similar in all subgroups, but the greatest improvement in medication use was seen in patients admitted to a tertiary care hospital and in those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers. Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs. 44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION: After publication of clinical guidelines for UA/NSTEMI, more patients received appropriate pharmacologic treatment, but a significant number of patients remained under-treated. Efforts to improve compliance with guideline recommendations via education and critical pathways are warranted, especially in nontertiary care settings.