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Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [−18.0 to 32.4] to 57.6 [16.3–98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4–3.5] to 0 [0–1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03471611.

ABSTRACT Background: There are limited data on the temporal trends, incidence, and outcomes of ST-segment-elevation myocardial infarction-cardiogenic shock (STEMI-CS). Methods: Adult (>18 years) STEMI-CS admissions were identified using the National Inpatient Sample (2000–2017) and classified by tertiles of admission year (2000–2005, 2006–2011, 2012–2017). Outcomes of interest included temporal trends, acute organ failure, cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. Results: In ∼4.3 million STEMI admissions, CS was noted in 368,820 (8.5%). STEMI-CS incidence increased from 5.8% in 2000 to 13.0% in 2017 (patient and hospital characteristics adjusted odds ratio [aOR] 2.45 [95% confidence interval {CI} 2.40–2.49]; P < 0.001). Multiorgan failure increased from 55.5% (2000–2005) to 74.3% (2012–2017). Between 2000 and 2017, coronary angiography and percutaneous coronary intervention use increased from 58.8% to 80.1% and 38.6% to 70.6%, whereas coronary artery bypass grafting decreased from 14.9% to 10.4% (all P < 0.001). Over the study period, the use of intra-aortic balloon pump (40.6%–37.6%) decreased, and both percutaneous left ventricular assist devices (0%–12.9%) and extra-corporeal membrane oxygenation (0%–2.8%) increased (all P < 0.001). In hospital mortality decreased from 49.6% in 2000 to 32.7% in 2017 (aOR 0.29 [95% CI 0.28–0.31]; P < 0.001). During the 18-year period, hospital lengths of stay decreased, hospitalization costs increased and use of durable left ventricular assist device /cardiac transplantation remained stable (P > 0.05). Conclusions: In the United States, incidence of CS in STEMI has increased 2.5-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and PCI increased during the study period.

Background: Patients are surviving longer after myocardial infarction (MI), but little is known about the occurrence and predictors of subsequent hospitalizations. Methods: We identified all Olmsted Count residents with incident MI from 1987-2008 and evaluated Olmsted County hospitalizations through 2009. ICD-9 codes were used to determine the primary reason for hospitalization. To account for repeated events, Andersen-Gill models were used to examine the predictors of hospitalization post-MI. Patients were censored at death or last follow-up. Results: A total of 2617 patients (mean 67 years, 41% female, 32% with ST-elevation MI) were diagnosed with incident MI from 1987-2007 and survived MI hospitalization. Over a mean follow-up of 7.1 years, 10116 hospitalizations occurred equating to a median of 3 (range 0 to 43) per person. Only 37.5% (n=3793) of hospitalizations were due to cardiovascular causes, and of these, most were due to ischemic heart disease (n= 1865, 49.2%) and heart failure (n= 733, 19.3%). The proportion of non-cardiovascular hospitalizations increased over time and was higher in women than men, but did not differ by ST-segment status. Several factors were associated with the risk of hospitalization after adjusting for year of diagnosis and sex (Figure). Biomarker levels were not predictors of hospitalization risk. Conclusions: Two-thirds of hospitalizations among incident MI survivors in the community are for non-cardiovascular reasons, and this proportion has increased. Comorbidities are important predictors of recurrent hospitalizations. Therapies focused solely on MI management may be insufficient to prevent the majority of future admissions.

Background: Hospital readmissions are considered to be a quality of care indicator, yet little is known about their occurrence and predictors after myocardial infarction (MI) in the community. Methods: We identified all Olmsted County residents with incident MI from 1987-2007 and evaluated 30-day rehospitalizations. The reason for readmission was categorized based on ICD-9 code. Safety endpoints of revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or fibrinolysis included stroke, acute kidney injury (rise in creatinine post-procedure of >0.5 mg/dL), access site complication (PCI), and gastrointestinal or other bleeding. Cox proportional hazard regression models were used to examine the predictors of readmission. Results: A total of 2617 patients (mean age 67 years, 41% female) had incident MI (32% with ST-elevation) from 1987-2007 and survived their initial hospitalization. A total of 583 readmissions occurred within 30 days among 512 (19.6%) patients. Approximately half (n=286, 49.1%) of readmissions were due to cardiovascular causes, and of these, most were due to ischemic heart disease (n=175, 61.2%) or heart failure (n=56, 19.6%). The proportion of non-cardiovascular rehospitalizations increased over time, from 42.2% from 1993-97 to 59.4% from 2003-07 (p for trend=0.01). A minority of those readmitted for cardiovascular reasons required repeat angiogram (n=110, 38.5%) or revascularization (n=88, 50 PCI, 38 CABG). After adjustment for confounders, key factors were associated with increased rehospitalization risk ( Figure ). Following PCI (n=1230), a stroke or bleeding event (adjusted HR 1.69, 95% CI 1.09-2.61, p=0.02) and acute kidney injury (HR 2.50, 95% CI 1.61-3.87, p<0.01) were associated with markedly increased readmission risk. Conclusions: Half of readmissions within 30 days of MI are for non-cardiovascular reasons, and this proportion has increased. Comorbidity and complications of revascularization are key predictors of readmission.

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.

Background The role of race and ethnicity in the outcomes of cardiac arrest (CA) complicating acute myocardial infarction (AMI) is incompletely understood. Methods and Results This was a retrospective cohort study of adult admissions with AMI‐CA from the National Inpatient Sample (2012–2017). Self‐reported race/ethnicity was classified as White, Black, and others (Hispanic, Asian or Pacific Islander, Native American, Other). Outcomes of interest included in‐hospital mortality, coronary angiography, percutaneous coronary intervention, palliative care consultation, do‐not‐resuscitate status use, hospitalization costs, hospital length of stay, and discharge disposition. Of the 3.5 million admissions with AMI, CA was noted in 182 750 (5.2%), with White, Black, and other races/ethnicities constituting 74.8%, 10.7%, and 14.5%, respectively. Black patients admitted with AMI‐CA were more likely to be female, with more comorbidities, higher rates of non–ST‐segment–elevation myocardial infarction, and higher neurological and renal failure. Admissions of patients of Black and other races/ethnicities underwent coronary angiography (61.9% versus 70.2% versus 73.1%) and percutaneous coronary intervention (44.6% versus 53.0% versus 58.1%) less frequently compared to patients of white race ( p <0.001). Admissions of patients with AMI‐CA had significantly higher unadjusted mortality (47.4% and 47.4%) as compared with White patients admitted (40.9%). In adjusted analyses, Black race was associated with lower in‐hospital mortality (odds ratio [OR], 0.95; 95% CI, 0.91–0.99; P =0.007) whereas other races had higher in‐hospital mortality (OR, 1.11; 95% CI, 1.08–1.15; P <0.001) compared with White race. Admissions of Black patients with AMI‐CA had longer length of hospital stay, higher rates of palliative care consultation, less frequent do‐not‐resuscitate status use, and fewer discharges to home (all P <0.001). Conclusions Racial and ethnic minorities received less frequent guideline‐directed procedures and had higher in‐hospital mortality and worse outcomes in AMI‐CA.

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000–2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age‐, sex‐, and race‐stratified trends in CABG use; in‐hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98–0.98]; P <0.001), in ST‐segment–elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95–0.95]; P <0.001) and non–ST‐segment–elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99–0.99]; P <0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non–ST‐segment–elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In‐hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88–0.89 [ P <0.001]) in the overall cohort, with similar temporal trends in patients with ST‐segment–elevation myocardial infarction and non–ST‐segment–elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST‐segment–elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in‐hospital mortality consistently decreased in this population.

Introduction: The Mayo Clinic Cardiac Intensive Care Unit Admission Risk Score (M-CARS) has been shown to predict hospital mortality in the CICU population better than conventional critical care scoring models. We tested the hypothesis that M-CARS could similarly be used to predict one-year mortality. Methods: We retrospectively reviewed adult CICU patients admitted from 2007 to 2018. M-CARS was calculated using admission data. Groups were compared using Wilcoxon test for continuous variables and chi-squared test for categorical variables. Results: This study included 12428 unique patients with a mean age of 67 ± 15 years (37% females), of whom 11279 (90.8%) survived hospitalization and 2839 patients (22.8%) died within 1 year of admission. The 1-year survival decreased incrementally as a function of increasing M-CARS ( Figure 1A , p<0.0001), and all components of M-CARS were significant predictors of 1-year mortality (p<0.001). 1690 hospital survivors (15.0%) died within 1 year. The 1-year survival decreased incrementally as a function of increasing M-CARS for scores <3 (all p<0.001); however, there was no further adverse 1-year survival for patients with M-CARS ≥3 ( Figure 1B, p=0.99). M-CARS components associated with 1-year mortality among hospital survivors included blood urea nitrogen, red blood cell distribution width, Braden score, and respiratory failure (all p<0.001), while cardiac arrest, cardiogenic shock, and anion gap were not. Conclusions: M-CARS accurately predicts 1-year mortality among CICU admissions, with a plateau effects at high M-CARS scores ≥3. Significant predictors of 1-year mortality among CICU survivors include frailty markers rather than admission severity.

Abstract Aims There are limited contemporary data on the use of initial fibrinolysis in ST-segment elevation myocardial infarction cardiogenic shock (STEMI-CS). This study sought to compare the outcomes of STEMI-CS receiving initial fibrinolysis vs. primary percutaneous coronary intervention (PPCI). Methods Using the National (Nationwide) Inpatient Sample from 2009 to 2017, a comparative effectiveness study of adult (&gt;18 years) STEMI-CS admissions receiving pre-hospital/in-hospital fibrinolysis were compared with those receiving PPCI. Admissions with alternate indications for fibrinolysis and STEMI-CS managed medically or with surgical revascularization (without fibrinolysis) were excluded. Outcomes of interest included in-hospital mortality, development of non-cardiac organ failure, complications, hospital length of stay, hospitalization costs, use of palliative care, and do-not-resuscitate status. Results During 2009–2017, 5297 and 110 452 admissions received initial fibrinolysis and PPCI, respectively. Compared with those receiving PPCI, the fibrinolysis group was more often non-White, with lower co-morbidity, and admitted on weekends and to small rural hospitals (all P &lt; 0.001). In the fibrinolysis group, 95.3%, 77.4%, and 15.7% received angiography, PCI, and coronary artery bypass grafting, respectively. The fibrinolysis group had higher rates of haemorrhagic complications (13.5% vs. 9.9%; P &lt; 0.001). The fibrinolysis group had comparable all-cause in-hospital mortality [logistic regression analysis: 28.8% vs. 28.5%; propensity-matched analysis: 30.8% vs. 30.3%; adjusted odds ratio 0.97 (95% confidence interval 0.90–1.05); P = 0.50]. The fibrinolysis group had comparable rates of acute organ failure, hospital length of stay, rates of palliative care referrals, do-not-resuscitate status use, and lesser hospitalization costs. Conclusions The use of initial fibrinolysis had comparable in-hospital mortality than those receiving PPCI in STEMI-CS in the contemporary era in this large national observational study.

Background: Previous studies have defined preshock as isolated hypotension or isolated hypoperfusion, whereas shock has been variably defined as hypoperfusion with or without hypotension. We aimed to evaluate the mortality risk associated with hypotension and hypoperfusion at the time of admission in a cardiac intensive care unit population. Methods: We analyzed Mayo Clinic cardiac intensive care unit patients admitted between 2007 and 2015. Hypotension was defined as systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg, and hypoperfusion as admission lactate >2 mmol/L, oliguria, or rising creatinine. Associations between hypotension and hypoperfusion with hospital mortality were estimated using multivariable logistic regression. Results: Among 10 004 patients with a median age of 69 years, 43.1% had acute coronary syndrome, and 46.1% had heart failure. Isolated hypotension was present in 16.7%, isolated hypoperfusion in 15.3%, and 8.7% had both hypotension and hypoperfusion. Stepwise increases in hospital mortality were observed with hypotension and hypoperfusion compared with neither hypotension nor hypoperfusion (3.3%; all P <0.001): isolated hypotension, 9.3% (adjusted odds ratio, 1.7 [95% CI, 1.4–2.2]); isolated hypoperfusion, 17.2% (adjusted odds ratio, 2.3 [95% CI, 1.9–3.0]); both hypotension and hypoperfusion, 33.8% (adjusted odds ratio, 2.8 [95% CI, 2.1–3.6]). Adjusted hospital mortality in patients with isolated hypoperfusion was higher than in patients with isolated hypotension ( P =0.02) and not significant different from patients with both hypotension and hypoperfusion ( P =0.18). Conclusions: Hypotension and hypoperfusion are both associated with increased mortality in cardiac intensive care unit patients. Hospital mortality is higher with isolated hypoperfusion or concomitant hypotension and hypoperfusion (classic shock). We contend that preshock should refer to isolated hypotension without hypoperfusion, while patients with hypoperfusion can be considered to have shock, irrespective of blood pressure.