Faculty Bibliography

Background Takotsubo syndrome (TTS) mimics acute myocardial infarction in the absence of culprit coronary artery disease and is more common in women. Spontaneous coronary artery dissection (SCAD) shares a predilection for women, can result in left ventricular wall motion abnormalities similar to TTS, and may manifest subtle angiographic findings. The aim of this study was to determine the frequency of SCAD misdiagnosed as TTS. Methods and Results Coronary angiograms of patients presenting with a provisional diagnosis of TTS were retrospectively reviewed by an independent expert blinded to left ventriculography and the specific purpose of the study to assess for SCAD. TTS was defined using European Society for Cardiology criteria. SCAD was categorized according to the Saw angiographic classification. Among 80 women with a provisional diagnosis of TTS, 2 (2.5%) met angiographic criteria for definite SCAD. Both dissections were located in the distal left anterior descending coronary artery and classified as type 2b. The wall motion abnormality was apical in both cases. An additional 7 patients (9%) had angiography that was indeterminate for SCAD. Clinical characteristics of patients with and without SCAD were similar. Conclusions Among patients with a provisional diagnosis of TTS, definite SCAD in the left anterior descending coronary artery was present in 2.5% of cases, and coronary angiography was indeterminate for SCAD in an additional 9%. Careful review of coronary angiography may avoid missed diagnoses of SCAD in patients with myocardial infarction, nonobstructive coronary arteries, and wall motion abnormalities consistent with TTS. Intracoronary imaging maybe considered to establish a definitive diagnosis of SCAD when angiography is inconclusive.

Introduction: Myocardial Infarction (MI) with Non-Obstructive Coronary Arteries (MINOCA) is now a recognised MI subtype. A 2013 systematic review of MINOCA literature indicated that MINOCA prognosis is favourable compared to those with MI and obstructive coronary artery disease (MICAD), but healthy controls were not included. With the growth of recent literature and evaluation of MINOCA prognosis, we performed an in-depth analysis of MINOCA prognosis, in relation to 1-year all-cause mortality and 1-year re-infarction compared with MICAD patients and a healthy cohort.
Method(s): An unrestricted literature search was conducted on the terms "MI", "non-obstructive", "angiography" and "prognosis" using PubMed and Embase. Publications with non-consecutive recruitment, less than 100 MINOCA patients or selection bias (i.e. restricted age group) were excluded. MINOCA & MICAD were defined as the presence of an MI (as per the universal criteria) in the absence & presence of CAD (i.e. epicardial vessel with a stenosis >=50% on angiography), respectively. The healthy cohort was defined as those with no history of cardiovascular diseases. Unpublished data were accumulated via the MINOCA Global Collaboration. Data from the included studies were pooled and analysed using DerSimonian-Laird random-effects meta-analysis. Heterogeneity was assessed using Cochran's Q and I2 statistics. Odds ratios (ORs), mean differences and 95% confidence intervals (CI) were calculated for proportion and continuous data respectively.
Result(s): The search identified 2889 unique publications, of which 27 included prognosis data. Of the 563660 consecutive MI patients, the overall pooled prevalence of MINOCA wasat 8.7% (95% CI: 7.5%-9.9%). The 1- year mortality and 1-year re-infarction data by diagnosis are presented in the table.
Conclusion(s): This pooled analysis shows that MINOCA accounts for almost one in ten MI presentations. The risks of re-infarction and death among MINOCA patients are much higher than in healthy controls, but lower than for MICAD patients. Efforts are needed to improve understanding of the optimal management and secondary prevention strategies in this unique and heterogeneous population. (Table Presented)

PURPOSE/OBJECTIVE:Patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) may present with or without ST-elevation (STE) on the electrocardiogram (ECG). Previous studies have shown that STE was associated with higher risk of early mortality and long-term major adverse coronary events, and that cardiac magnetic resonance imaging (CMR) can help to determine whether the cause of a MINOCA presentation is ischemic or non-ischemic. We set out to determine the relationship between STE and CMR findings in patients presenting with MINOCA. DESIGN/METHODS:Patients who underwent CMR based on a provisional diagnosis of MINOCA were pooled from three prospective cohort studies: the multicenter Stockholm Myocardial Infarction with Normal Coronaries, a prospective University of Adelaide study, and a prospective NYU School of Medicine diagnostic imaging study. STE was defined as ≥1 mm in ≥2 contiguous leads. RESULTS:Among 292 patients, average age was 57.0 years (±11.9), and 68% were female. Fifty-seven had STE, 231 had no STE and four had left bundle branch block. There was no difference between patients with vs. without STE in the likelihood of the CMR findings of infarction (21% vs. 18%), myocarditis (10% vs. 14%), left ventricular wall motion pattern consistent with takotsubo syndrome on CMR (16% vs. 14%). CONCLUSION/CONCLUSIONS:STE on the presenting ECG was not associated with CMR findings in patients with a provisional diagnosis of MINOCA. Based on these findings, increased risk among MINOCA patients with STE does not appear to be related to variation in these CMR findings.

Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Background/UNASSIGNED:Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction with symptoms and ECG changes mimicking acute myocardial infarction (AMI). The objective of the present study was to evaluate in-hospital death and hospital readmission in patients with TTS and to compare outcomes to patients with AMI. Methods/UNASSIGNED:Patients diagnosed with TTS and AMI were identified using the United States Nationwide Readmission Database from 2010-2014. In-hospital outcomes for the index admission, and rates and causes of 30-day readmissions were compared between TTS patients and AMI patients without TS. Results/UNASSIGNED:61,412 patients with TTS and 3,470,011 patients with AMI without TTS were identified. Patients with TTS were younger, more often women (89% vs. 41%), and less likely to have cardiovascular risk factors than AMI patients. Mortality during the index admission was lower in TTS compared to AMI (2.3% vs. 10.2%, p < 0.0001). Cardiogenic shock occurred at the same frequency (5.7%) with TTS or AMI. Among TTS survivors, 7,132 patients (11.9%) were readmitted within 30 days, and mortality associated with readmission was 3.5%. The most common reason for readmission after TTS was heart failure (10.6% of readmissions). Conclusions/UNASSIGNED:TTS is associated with substantial morbidity and mortality. Although outcomes are more favorable than AMI, ∼2% of patients died in-hospital and ∼12% of survivors were readmitted within 30-days; heart failure was the most frequent indication for re-hospitalization. Careful outpatient follow-up of TTS patients may be warranted to avoid readmissions. Condensed Abstract/UNASSIGNED:We evaluated in-hospital death and hospital readmission in patients with Takotsubo syndrome (TTS) and compared outcomes to those of patients after acute myocardial infarction (AMI) in the United States using the Nationwide Readmission Database from 2010-2014. Mortality during the index admission was lower with TTS than AMI (2.3% vs. 10.2%, p < 0.0001). Readmission within 30 days occurred in 11.9% of TTS survivors associated with 3.5% mortality during readmission. Readmission rates were lower after TTS than AMI (16.7%), p < 0.0001 vs. TTS. The most common reason for readmission was heart failure (10.6% of TTS survivors). TTS is associated with substantial morbidity and mortality.

Importance/UNASSIGNED:It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective/UNASSIGNED:To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants/UNASSIGNED:The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018. Main Outcomes and Measures/UNASSIGNED:Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported. Results/UNASSIGNED:A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging. Conclusions and Relevance/UNASSIGNED:The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01471522.

BACKGROUND:Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is common. There are limited data on the mechanisms and prognosis for reinfarction in MINOCA patients. METHODS:In this observational study of MINOCA patients hospitalized in Sweden and registered in the SWEDEHEART registry between July 2003 and June 2013 and followed until December 2013 we identified 9,092 unique patients with MINOCA out of 199,163 MI admissions in total. The 570 (6.3%) MINOCA patients who were hospitalized due to a recurrent MI constituted the study group. RESULTS:The mean age was 69.1 years and 59.1% were women. The median time to readmission was 17 months. A total of 340 patients underwent a new coronary angiography and 180 (53%) had no obstructive coronary artery disease (CAD) and 160 (47%) had obstructive CAD; 123 had one-vessel, 26 had two-vessel, 9 had three-vessel disease and two had left main together with one-vessel disease. Male gender, diabetes, peripheral vascular disease, higher levels of creatinine and ST-elevation at presentation were more common in patients with MI with obstructive CAD than in patients with a recurrent MINOCA. Mortality during a median follow-up of 38 months was similar whether the reinfarction event was MINOCA or MI with obstructive CAD 13.9% vs. 11.9% (p=0.54). CONCLUSIONS:About half of patients with reinfarction after MINOCA who underwent coronary angiography had progression of coronary stenosis. Angiography should be strongly considered in patients with MI after MINOCA. Mortality associated with recurrent events was substantial, though there was no difference in mortality between those with or without significant CAD.

BACKGROUND:Systemic lupus erythematosus (SLE) is a complex autoimmune disease associated with an elevated risk for premature cardiovascular disease. Platelets express receptors contributing to inflammation and immunity including FcγRIIA, the low affinity receptor of the Fc portion of IgG antibodies. The variation at a single amino acid substitution, H131R, in the extracellular binding domain alters the affinity for IgG, which may account for individual variation in platelet activity and platelet mediated disease. OBJECTIVES/OBJECTIVE:This study was performed to investigate the association between FcγRIIA genotype, preclinical atherosclerosis, platelet reactivity, and vascular health. METHODS:FcγRIIA was genotyped in 80 SLE patients and 30 healthy controls. Carotid ultrasound plaque, soluble E-selectin, and platelet aggregability were evaluated in SLE and matched controls. RESULTS:Carotid plaque was significantly more prevalent in SLE patients carrying a variant allele compared to those who were homozygous ancestral (58% vs. 25%, P=0.04). In contrast, prevalent carotid plaque was not associated with genotype in controls. Consistently, SLE variant FcγRIIA carriers vs. ancestral had a significant increase in the levels of soluble E-selectin, which was not observed in controls. Monocyte and leukocyte-platelet aggregation and platelet aggregation in response to submaximal agonist stimulation were significantly elevated in SLE patients with the variant vs. ancestral genotype. CONCLUSIONS:Carotid ultrasound plaque, soluble E-selectin levels and platelet activity were more frequently prevalent in SLE patients carrying variant FcγRIIA. The interplay between FcγRIIA-mediated platelet activation and endothelial cells might represent a mechanism underlying the pathogenesis of cardiovascular disease in SLE patients.