Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

BACKGROUND: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. METHODS AND RESULTS: Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). CONCLUSIONS: Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

BACKGROUND: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms. OBJECTIVES: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA). METHODS: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes. RESULTS: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors. CONCLUSIONS: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA.

Acute coronary occlusion and percutaneous coronary intervention after out-of-hospital cardiac arrest.

OBJECTIVES: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population. METHODS: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge. RESULTS: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome. CONCLUSIONS: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Incidence and outcomes of high bleeding risk patients with type 1 and type 2 myocardial infarction in a community-based cohort: Application of the Academic Research Consortium High Bleeding Risk Criteria.

BACKGROUND AND AIMS: The incidence and outcomes of high bleeding risk (HBR) patients in a community cohort according to the Academic Research Consortium (ARC) criteria is not known. We hypothesized that HBR is common and associated with worse outcomes for all-comers with myocardial infarction. METHODS: We prospectively collected all patients with cardiac troponin T > 99th percentile upper limit of normal (≥0.01 ng/mL) in Olmsted County between 2003 and 2012. Events were retrospectively classified as type 1 myocardial infarction (T1MI), type 2 myocardial infarction (T2MI), or myocardial injury. Patients were further classified as HBR based on the "ARC-HBR definition." Outcomes included all-cause mortality, cardiovascular mortality, recurrent MI, stroke, and major bleeding. RESULTS: 2419 patients were included in the final study; 1365 were classified as T1MI and 1054 as T2MI. Patients were followed for a median of 5.5 years. ARC-HBR was more common in T2MI than T1MI (73% vs 46%, p < 0.001). Among patients with T1MI, HBR was associated with higher all-cause mortality (HR 3.7, 95% CI 3.2-4.5, p < 0.001), cardiovascular mortality (4.7, 3.6-6.3, p < 0.001), recurrent MI (2.1, 1.6-2.7, p < 0.001), stroke (4.9, 2.9-8.4, p < 0.001), and major bleeding (6.5, 3.7-11.4, p < 0.001). For T2MI, HBR was similarly associated with higher all-cause mortality (HR 2.1, 95% CI 1.8-2.5, p < 0.001), cardiovascular mortality (2.7, 1.8-4.0, p < 0.001), recurrent MI (1.7, 1.1-2.6, p = 0.02) and major bleeding (HR 15.6, 3.8-63.8, p < 0.001). CONCLUSION: HBR is common among unselected patients with T1MI and T2MI and is associated with increased overall and cardiovascular mortality, recurrent cardiovascular events, and major bleeding on long-term follow up.

Nonatheromatous Coronary Kink Causing Angiographic Obstruction: A Rare Structural Anomaly.

Ischemic symptoms may be explained by a multitude of coronary pathologies, including coronary artery tortuosity, atherosclerosis, fibromuscular dysplasia, vasculitis, coronary vasospasm, or microvascular disease. We present an unusual case of coronary kinking in a patient presenting with exertional jaw pain in the absence of atherosclerotic risk factors. Multimodality imaging, coronary imaging, and coronary physiology helped establish the diagnosis and guide management.

Coronary Reactivity Assessment Is Associated With Lower Health Care-Associated Costs in Patients Presenting With Angina and Nonobstructive Coronary Artery Disease.

BACKGROUND: The financial burden linked to the diagnosis and treatment of patients with chest pain on the health care system is considerable. Angina and nonobstructive coronary artery disease (ANOCA) is common, associated with adverse cardiovascular events, and may lead to repeat testing or hospitalizations. Diagnostic certainty can be achieved in patients with ANOCA using coronary reactivity testing (CRT); however, its financial effect on the patient has not been studied. Our goal was to assess the effect of CRT on health care-related cost in patients with ANOCA. METHODS: Patients with ANOCA who underwent diagnostic coronary angiography (CAG) and CRT (CRT group) were matched to controls who had similar presentation but only underwent a CAG without CRT (CAG group). Standardized inflation-adjusted costs were collected and compared between the 2 groups on an annual basis for 2 years post the index date (CRT or CAG). RESULTS: Two hundred seven CRT and 207 CAG patients were included in the study with an average age of 52.3±11.5 years and 76% females. The total cost was significantly higher in the CAG group as compared with the CRT group ($37 804 [$26 933-$48 674] versus $13 679 [$9447-$17 910]; P<0.001). When costs are itemized and divided based on the Berenson-Eggers Type of Service categorization, the largest cost difference occurred in imaging (any type, including CAG; P<0.001), procedures (eg, percutaneous coronary intervention/coronary artery bypass grafting/thrombectomy) (P=0.001), and test (eg, blood tests, EKG; P<0.001). CONCLUSIONS: In this retrospective observational study, assessment of CRT in patients with ANOCA was associated with significantly reduced annual total costs and health care utilization. Therefore, the study may support the integration of CRT into clinical practice.

Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

Educational Experience of Interventional Cardiology Fellows in the United States and Canada.

BACKGROUND: The COVID-19 pandemic and iodinated contrast shortage may have affected interventional cardiology (IC) fellowship training. OBJECTIVES: The aim of this study was to investigate the educational experience of first-year IC fellows in the United States and Canada. METHODS: A 59-question online survey was conducted among 2021-2022 first-year IC fellows in the United States and Canada. RESULTS: Of the 360 IC fellows invited to participate, 111 (31%) responded; 95% were from the United States, and 79% were men. Participants were mostly from university programs (70%), spent 61 to 70 hours/week in the hospital, and had an annual percutaneous coronary intervention case number of <200 (5%), 200 to 249 (8%), 250 to 349 (33%), 350 to 499 (39%), 500 to 699 (12%), or ≥700 (3%). For femoral access, a micropuncture needle was used regularly by 89% and ultrasound-guided puncture by 81%, and 43% used vascular closure devices in most cases (>80%). Intravascular ultrasound was performed and interpreted very comfortably by 62% and optical coherence tomography (OCT) by 32%, and 20% did not have access to OCT. Approximately one-third felt very comfortable performing various atherectomy techniques. Covered stents, fat embolization, and coil embolization were used very comfortably by 14%, 4%, and 3%, respectively. Embolic protection devices were used very comfortably by 11% to 24% of IC fellows. Almost one-quarter of fellows (24%) were warned about their high radiation exposure. Eighty-four percent considered IC fellowship somewhat or very stressful, and 16% reported inadequate psychological support. CONCLUSIONS: This survey highlights opportunities for improvement with regard to the use of intravascular imaging, atherectomy techniques, complication prevention and management strategies, radiation awareness and mitigation, and psychological support.

Structural Cardiac Abnormalities in Patients with Atrial Fibrillation/Flutter and Myocardial Injury.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTnT) is often increased in patients with atrial fibrillation/flutter, portending a poor prognosis. The etiologies for these increases have not been systematically investigated. Our aim was to define prevalence/significance of structural cardiac abnormalities in patients with atrial fibrillation/flutter and high-sensitivity cardiac troponin T (hs-cTnT) increases. METHODS: This is a retrospective observational cohort study of patients with atrial fibrillation/flutter diagnosis with hs-cTnT measurements, echocardiograms, and coronary angiograms. Myocardial injury was defined as hs-cTnT >10 ng/L for women and >15 ng/L for men. Cases with myocardial injury were adjudicated according to the Fourth Universal Definition of Myocardial Infarction. RESULTS: Patients with definite causes for increased hs-cTnT (n = 875) were tabulated but not evaluated further; common diagnoses were type 1 myocardial infarction, critical illness, and known heart failure. Of the remaining 401, increased hs-cTnT was present in 336 (84%) patients. Of those, 78% had nonischemic myocardial injury, the remaining (n = 75, 22%) had type 2 myocardial infarction. Patients with elevated hs-cTnT had greater left ventricular mass index, left ventricular filling pressures, and right ventricular systolic pressure. They more frequently had significant coronary artery disease (47% vs 31%, P = .016), especially in type 2 myocardial infarction. With logistic regression, age, sex (F), diabetes, left ventricular mass index, e' medial velocity, and right ventricular systolic pressure were independent determinants of myocardial injury. One-year mortality was higher in patients with myocardial injury. CONCLUSIONS: Structural heart abnormalities are common in patients with atrial fibrillation/flutter and increased hs-cTnT. Causes of myocardial injury should be elucidated in each patient to craft appropriate therapies.

Temporal Trends in Use of Complementary Therapies Among Patients With Cardiovascular Disorders.

This study aimed to evaluate the use and frequency of complementary and integrative medicine (CIM) therapies in an outpatient cohort with cardiovascular disease (CVD) and compare trends over time. This cross-sectional point-of-care prospective study assessed patients attending a cardiology outpatient clinic. As in our 2009 cohort, data were collected with a 17-question survey on demographic characteristics, CVD history, current use and future interest in CIM. In total, 964 patients completed the survey. CIM use continues to be high (2009 vs 2018, 83.4% vs 81.8%) (p = 0.34), with dietary supplements the most common therapy (75% in both studies). We observed increased use of mind-body therapies (28.5% vs 23.9%, p = 0.02), especially meditation, yoga, and tai chi. Of the patients receiving CIM therapies, 41.9% reported using CIM for heart-related symptoms. Relaxation, stress management, and meditation were the top three mind-body therapies for CVD-related symptoms in both cohorts. Reporting of CIM use to clinicians is low (15%) and interest on future use is high (47%). In conclusion, CIM is highly used in cardiology patients-4 of 10 patients use CIM for CVD-related symptoms. Most take dietary supplements, with an increased use of mind-body therapies. Our data highlight the importance of documenting CIM use in practice and the need for research to document efficacy.

Cardiogenic shock complicating non-ST-segment elevation myocardial infarction: An 18-year study.

OBJECTIVE: To evaluate the epidemiology and outcomes of non-ST-segment-elevation myocardial infarction-cardiogenic shock (NSTEMI-CS) in the United States. METHODS: Adult (>18 years) NSTEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011 and 2012-2017). Outcomes of interest included temporal trends of prevalence and in-hospital mortality, use of cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. RESULTS: In over 7.3 million NSTEMI admissions, CS was noted in 189,155 (2.6%). NSTEMI-CS increased from 1.5% in 2000 to 3.6% in 2017 (adjusted odds ratio 2.03 [95% confidence interval 1.97-2.09]; P < .001). Rates of non-cardiac organ failure and cardiac arrest increased during the study period. Between 2000 and 2017, coronary angiography (43.9%-63.9%), early coronary angiography (13.6%-25.6%), percutaneous coronary intervention (14.8%-31.6%), and coronary artery bypass grafting use (19.0%-25.8%) increased (P < .001). Over the study period, the use of intra-aortic balloon pump remained stable (28.6%-28.8%), and both percutaneous left ventricular assist devices (0%-9.1%) and extra-corporeal membrane oxygenation (0.1%-1.6%) increased (all P < .001). In hospital mortality decreased from 50.2% in 2000 to 32.3% in 2017 (adjusted odds ratio 0.27 [95% confidence interval 0.25-0.29]; P < .001). During the 18-year period, hospital lengths of stay decreased, and hospitalization costs increased. CONCLUSIONS: In the United States, prevalence of CS in NSTEMI has increased 2-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and percutaneous coronary intervention increased during the study period.

IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

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 1×105 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.

Evolution of the Crush Technique for Bifurcation Stenting.

Bifurcation lesions are frequently encountered, associated with greater procedural complexity and consequently are at higher risk for restenosis and stent thrombosis. Early trials in bifurcation percutaneous coronary intervention favored a provisional stenting approach, but contemporary randomized trials have highlighted potentially superior outcomes using a double-kiss crush technique in unprotected distal left main stem bifurcation lesions. Although the evidence is greatest for double-kiss crush, many operators favor a mini-crush or nano-crush single-kiss approach. In this review, the authors describe the iterations of the crush technique and the evidence for each and review general principles for bifurcation percutaneous coronary intervention.

Case report: acute myocarditis following the second dose of mRNA-1273 SARS-CoV-2 vaccine.

BACKGROUND: The SARS-CoV-2 pandemic has led to the development of the first mRNA vaccines used in humans. The vaccines are well tolerated, safe, and highly efficacious; however, post-marketing surveillance is revealing potential rare adverse effects. We report a case of symptomatic acute myocarditis following administration of the second dose of mRNA-1273 SARS-CoV-2 vaccine. CASE SUMMARY: A 44-year-old man presented with chest pain and ST-segment elevation 4 days after receiving the second dose of mRNA-1273 SARS-CoV-2 Vaccine. Emergent coronary angiogram showed minimal coronary artery disease. Cardiac magnetic resonance imaging confirmed acute myocarditis. Diagnosis of vaccine-associated myocarditis was made given the temporal relationship and supportive treatment initiated. Follow-up at 1 month confirmed complete symptomatic recovery and echocardiogram demonstrated normalization of cardiac function. DISCUSSION: Acute myocarditis should be considered in patients who present with chest pain or dyspnoea within days of receiving mRNA-1273 SARS-CoV-2 vaccination, especially after the second dose. This may be managed successfully with supportive therapies with complete recovery of cardiac function and symptoms. Further research is warranted to determine the mechanisms by which mRNA vaccines may cause myocarditis and for potential long-term cardiovascular injury.

Use of Post-Acute Care Services and Readmissions After Acute Myocardial Infarction Complicated by Cardiac Arrest and Cardiogenic Shock.

OBJECTIVE: To evaluate post-acute care utilization and readmissions after cardiac arrest (CA) and cardiogenic shock (CS) complicating acute myocardial infarction (AMI). METHODS: With use of an administrative claims database, AMI patients from January 1, 2010, to May 31, 2018, were stratified into CA+CS, CA only, CS only, and AMI alone. Outcomes included 90-day post-acute care (inpatient rehabilitation or skilled nursing facility) utilization and 1-year emergency department visits and readmissions. RESULTS: Of 163,071 AMI patients, CA+CS, CA only, and CS only were noted in 3965 (2.4%), 8221 (5.0%), and 6559 (4.0%), respectively. In-hospital mortality was noted in 10,686 (6.6%) patients: CA+CS, 1935 (48.8%); CA only, 2948 (35.9%); CS only, 1578 (24.1%); and AMI alone, 4225 (2.9%) (P<.001). Among survivors, post-acute care services were used in 67,799 (44.5%), with higher use in the CS+CA cohort (1310 [64.6%]; hazard ratio [HR], 1.19; 95% CI, 1.06 to 1.33; P=.003) and CA cohort (2738 [51.9%]; HR, 1.27; 95% CI, 1.20 to 1.35; P<.001) but not in the CS cohort (3048 [61.2%]; HR, 1.03; 95% CI, 0.97 to 1.11; P=.35) compared with the AMI cohort (60,703 [43.3%]). Compared with the AMI cohort (48,990 [35.0%]), patients with CS only (2,085 [41.9%]; HR, 1.16; 95% CI, 1.10 to 1.22; P<.001) but not those with CA+CS (724 [35.7%]; HR, 1.07; 95% CI, 0.98 to 1.17; P=.14) had higher rates of readmissions (P=.03). Readmissions were lower in those with CA (1,590 [30.2%]; HR, 0.94; 95% CI, 0.89 to 0.99). Repeated AMI, coronary artery disease, and heart failure were the most common readmission reasons. There were no differences for emergency department visits. CONCLUSION: CA is associated with increased post-acute care use, whereas CS is associated with increased readmission risk in AMI survivors.

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

AIMS: This study aims to evaluate the impact of the combination of cardiogenic shock (CS) and cardiac arrest (CA) complicating non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: Adult (>18 years) NSTEMI admissions using the National Inpatient Sample database (2000 to 2017) were stratified by the presence of CA and/or CS. Outcomes of interest included in-hospital mortality, early coronary angiography, hospitalization costs, and length of stay. Of the 7 302 447 hospitalizations due to NSTEMI, 147 795 (2.0%) had CS only, 155 522 (2.1%) had CA only, and 41 360 (0.6%) had both CS and CA. Compared with 2000, the adjusted odds ratios (ORs) and 95% confidence interval (CIs) for CS, CA, and both CS and CA in 2017 were 3.75 (3.58-3.92), 1.46 (1.42-1.50), and 4.52 (4.16-4.87), respectively (all P < 0.001). The CS + CA (61.2%) cohort had higher multiorgan failure than CS (42.3%) and CA only (32.0%) cohorts, P < 0.001. The CA only cohort had lower rates of overall (52% vs. 59-60%) and early (17% vs. 18-27%) angiography compared with the other groups (all P < 0.001). CS + CA admissions had higher in-hospital mortality compared with those with CS alone (aOR 4.12 [95% CI 4.00-4.24]), CA alone (aOR 1.69 [95% CI 1.65-1.74]), or without CS/CA (aOR 22.66 [95% CI 22.06-23.27]). The presence of CS, either alone or with CA, was associated with higher hospitalization costs and longer hospital length of stay. CONCLUSIONS: The combination of CS and CA is associated with higher rates of acute non-cardiac organ failure and in-hospital mortality in NSTEMI admissions as compared with those with either CS or CA alone.

Fibrinolysis vs. primary percutaneous coronary intervention for ST-segment elevation myocardial infarction cardiogenic shock.

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 (>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 < 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 < 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.

Sex-specific differences in coronary blood flow and flow velocity reserve in symptomatic patients with non-obstructive disease.

AIMS: Reduced coronary flow velocity reserve (CFVR) is associated with adverse cardiovascular outcomes. Whether CFVR and coronary blood flow (CBF) are similar in men and women with chest pain and non-obstructive CAD remains unknown. We hypothesised sex differences in CFVR and CBF. METHODS AND RESULTS: A total of 1,683 patients with signs/symptoms of ischaemia and angiographically unobstructed coronary arteries (<40% angiographic stenosis) underwent coronary vasomotion evaluation. CFVR was measured as hyperaemic/resting average velocity in the LAD. Mid-LAD diameter was measured with quantitative angiography and CBF calculated at rest (rCBF) and hyperaemia (hCBF). Resting microvascular resistance (rMR) was calculated as mean arterial pressure/rCBF. Of the total number of patients, 1,096 (65%) were women, median age 51 [42, 59] years. Compared to men, women had lower median CFVR (2.7 [2.4, 3.2] vs 3.1 [2.7, 3.6], p<0.001), higher rCBF (49.7 [34.0, 71.1] vs 45.9 [31.8, 68.7] ml/min, p=0.04), lower hCBF (139.5 [93.0, 195.2] vs 147.1 [95.7, 218.6] ml/min, p=0.02), but similar rMR (p=0.82). Female sex was an independent predictor of lower CFVR, higher rCBF, and lower hCBF. CONCLUSIONS: Compared to men, women with signs/symptoms of ischaemia and non-obstructive CAD have lower CFVR, higher rCBF, and lower hCBF. Female sex is a predictor of these sex-specific differences. The clinical diagnostic and prognostic implications of sex differences in coronary physiology need further evaluation.

Ten-year trends, predictors and outcomes of mechanical circulatory support in percutaneous coronary intervention for acute myocardial infarction with cardiogenic shock.

AIMS: There are limited data on the trends and outcomes of mechanical circulatory support (MCS)-assisted early percutaneous coronary intervention (PCI) in acute myocardial infarction with cardiogenic shock (AMI-CS). In this study, we sought to assess the use, temporal trends, and outcomes of percutaneous MCS-assisted early PCI in AMI-CS. METHODS AND RESULTS: Using the National Inpatient Sample database from 2005-2014, a retrospective cohort of AMI-CS admissions receiving early PCI (hospital day zero) was identified. MCS use was defined as intra-aortic balloon pump (IABP), percutaneous left ventricular assist device (pLVAD) and extracorporeal membrane oxygenation (ECMO) support. Outcomes of interest included in-hospital mortality, resource utilisation, trends and predictors of MCS-assisted PCI. Of the 110,452 admissions, MCS assistance was used in 55%. IABP, pLVAD and ECMO were used in 94.8%, 4.2% and 1%, respectively. During 2009-2014, there was a decrease in MCS-assisted PCI due to a decrease in IABP, despite an increase in pLVAD and ECMO. Younger age, male sex, lower comorbidity, and cardiac arrest independently predicted MCS use. MCS-assisted PCI was predictive of higher in-hospital mortality (31% vs 26%, adjusted odds ratio 1.23 [1.19-1.27]; p<0.001) and greater resource utilisation. IABP-assisted PCI had lower in-hospital mortality and lesser resource utilisation compared to pLVAD/ECMO. CONCLUSIONS: MCS-assisted PCI identified a sicker AMI-CS cohort. There was a decrease in IABP and an increase in pLVAD/ECMO.