Faculty Bibliography

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.

BACKGROUND:Acute left ventricular (LV) apical ballooning with normal coronary angiography occurs rarely in obstructive hypertrophic cardiomyopathy (OHCM); it may be associated with severe hemodynamic instability. METHODS, RESULTS/UNASSIGNED:We searched for acute LV ballooning with apical hypokinesia/akinesia in databases of two HCM treatment programs. Diagnosis of OHCM was made by conventional criteria of LV hypertrophy in the absence of a clinical cause for hypertrophy and mitral-septal contact. Among 1519 patients, we observed acute LV ballooning in 13 (0.9%), associated with dynamic left ventricular outflow tract (LVOT) obstruction and high gradients, 92 ± 37 mm Hg, 10 female (77%), age 64 ± 7 years, LVEF 31.6 ± 10%. Septal hypertrophy was mild compared to that of the rest of our HCM cohort, 15 vs 20 mm (P < 0.00001). An elongated anterior mitral leaflet or anteriorly displaced papillary muscles occurred in 77%. Course was complicated by cardiogenic shock and heart failure in 5, and refractory heart failure in 1. High-dose beta-blockade was the mainstay of therapy. Three patients required urgent surgical relief of LVOT obstruction, 2 for refractory cardiogenic shock, and one for refractory heart failure. In the three patients, surgery immediately normalized refractory severe LV dysfunction, and immediately reversed cardiogenic shock and heart failure. All have normal LV systolic function at 45-month follow-up, and all have survived. CONCLUSIONS:Acute LV apical ballooning, associated with high dynamic LVOT gradients, may punctuate the course of obstructive HCM. The syndrome is important to recognize on echocardiography because it may be associated with profound reversible LV decompensation.

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/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.

BACKGROUND:Myocardial infarction (MI) presentations are more common during winter months and morning hours. However, it is unknown whether MI with obstructive coronary artery disease (MI-CAD) and non-obstructive CAD (MINOCA) display similar patterns. METHODS:We evaluated seasonal and circadian patterns of MI presentation by coronary artery disease (CAD) status and sex in patients with MI from 2007 to 2014 in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment Intervention Outcomes Network (ACTION) Registry-Get With the Guidelines. Adult patients who underwent coronary angiography for MI were included. Patients with missing age, sex, or angiographic data, cocaine use, thrombolytic therapy prior to catheterization, or prior revascularization were excluded. Baseline demographics and characteristics of symptom onset, including season and time of day of presentation, were compared by CAD status and sex. RESULTS:Among 322,523 patients, 112,547 were female (35%); 18,918 had MINOCA (5.9%). There was no seasonal pattern of MI overall. However, both men and women with MINOCA presented more often in the summer and fall while MI-CAD presentations were equally distributed across seasons. The most common time of presentation was 8 am-2 pm regardless of CAD status or sex. A secondary peak in women with MINOCA during late afternoon hours was also identified. CONCLUSIONS:Seasonal variation of MI differed between MINOCA and MI-CAD, with a small increase in MINOCA incidence in the summer and fall. MINOCA and MI-CAD most commonly occurred in the morning, with a secondary peak in late afternoon in women with MINOCA. These differences in presentation may relate to underlying MI pathophysiology.