Faculty Bibliography

PURPOSE/OBJECTIVE:To enhance understanding of challenges related to work-life integration in academic medicine and to inform the ongoing implementation of an existing program and the development of other interventions to promote success of physician-scientists. METHOD/METHODS:This study is part of a prospective analysis of the effects of the Fund to Retain Clinical Scientists (FRCS), a national program launched by the Doris Duke Charitable Foundation at ten U.S. institutions, which provides financial support to physician-scientists facing caregiving challenges. In early 2018, 28 of 33 program awardees participated in semi-structured interviews. Questions were about challenges faced by physician-scientists as caregivers and their early perceptions of the FRCS. Multiple analysts reviewed de-identified transcripts, iteratively revised the coding scheme, and interpreted the data using qualitative thematic analysis. RESULTS:Participants' rich descriptions illuminated five interconnected themes: (1) Time is a critical and limited resource, (2) timing is key, (3) limited time resources and timing conflicts may have a particularly adverse effect on women's careers, (4) flexible funds enable reclamation and repurposing of time resources, and (5) FRCS leaders should be cognizant of time and timing conflicts when developing program-related offerings CONCLUSIONS:: Programs such as the FRCS are instrumental in supporting individuals to delegate time-consuming tasks and control how they spend their valuable time. Qualitative analysis suggests that access to and command of valuable time resources is crucial to career advancement, research productivity, and work-life flexibility, especially during critical time points along the physician-scientist trajectory.

BACKGROUND:Risk factor control is the cornerstone of managing stable ischemic heart disease but is often not achieved. Predictors of risk factor control in a randomized clinical trial have not been described. METHODS AND RESULTS/RESULTS:The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) randomized individuals with at least moderate inducible ischemia and obstructive coronary artery disease to an initial invasive or conservative strategy in addition to optimal medical therapy. The primary aim of this analysis was to determine predictors of meeting trial goals for LDL-C (low-density lipoprotein cholesterol, goal <70 mg/dL) or systolic blood pressure (SBP, goal <140 mm Hg) at 1 year post-randomization. We included all randomized participants in the ISCHEMIA trial with baseline and 1-year LDL-C and SBP values by January 28, 2019. Among the 3984 ISCHEMIA participants (78% of 5179 randomized) with available data, 35% were at goal for LDL-C, and 65% were at goal for SBP at baseline. At 1 year, the percent at goal increased to 52% for LDL-C and 75% for SBP. Adjusted odds of 1-year LDL-C goal attainment were greater with older age (odds ratio [OR], 1.11 [95% CI, 1.03-1.20] per 10 years), lower baseline LDL-C (OR, 1.19 [95% CI, 1.17-1.22] per 10 mg/dL), high-intensity statin use (OR, 1.30 [95% CI, 1.12-1.51]), nonwhite race (OR, 1.32 [95% CI, 1.07-1.63]), and North American enrollment compared with other regions (OR, 1.32 [95% CI, 1.06-1.66]). Women were less likely than men to achieve 1-year LDL-C goal (OR, 0.68 [95% CI, 0.58-0.80]). Adjusted odds of 1-year SBP goal attainment were greater with lower baseline SBP (OR, 1.27 [95% CI, 1.22-1.33] per 10 mm Hg) and with North American enrollment (OR, 1.35 [95% CI, 1.04-1.76]). CONCLUSIONS:In ISCHEMIA, older age, male sex, high-intensity statin use, lower baseline LDL-C, and North American location predicted 1-year LDL-C goal attainment, whereas lower baseline SBP and North American location predicted 1-year SBP goal attainment. Future studies should examine the effects of sex disparities, international practice patterns, and provider behavior on risk factor control.

Background: Obesity, assessed as body mass index (BMI), is an established risk factor for development of coronary heart disease (CHD). However, in patients with heart failure and atrial fibrillation there is an "obesity paradox" with better prognosis among obese patients. The association between BMI and cardiovascular outcomes in patients with stable CHD is unclear.
Method(s): The prospective STABILITY trial included 15,828 patients with stable CHD with a follow-up of 3-5 years (median 3.7) on optimal secondary preventive treatment. BMI and waist circumference were measured at baseline (n=15,785). All cardiovascular outcomes were centrally adjudicated. Associations between obesity indices and outcomes were evaluated by multivariable Cox regression analyses with adjustments for age, sex, study treatment, and clinical risk factors.
Result(s): Mean age was 64 years and 19% were females. In total, 3250 (20.9%) patients had BMI <25, 6628 (42.8%), BMI >25 and <30 and 5614 (36.3%), BMI >30. Underweight (BMI <18.5) was seen in 79 patients. Most risk markers (diabetes, hypertension, and levels of inflammatory biomarkers and triglycerides) showed a graded association with higher BMI. The frequency of smoking and levels of HDL, GDF-15 and NT-proBNP were higher at lower BMI. Lower BMI was associated with an increased risk of MACE, total and CV death, and heart failure (Figure). Higher BMI was associated with increased risk of the same outcomes and also with MI. BMI was not associated with the risk of stroke. There was no interaction with age, sex, diabetes or type of MI (type 1 vs type 2-5). Associations between waist circumference and outcomes were weaker and not significant in the fully adjusted model.
Conclusion(s): In patients with stable CHD on optimal secondary prevention BMI had a U-shaped association with the risk of MACE, death, and heart failure and a linear association with the risk of MI. The lowest risk for MACE was seen for BMI between 25 and 30, considered as overweight. The findings do not support current recommendations to achieve an ideal BMI of 20-25 for weight adjustments in patients with CHD. (Figure Presented)

Background Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results Patients ≥65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEMI: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.

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.

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.

Cardiogenic shock occurs in up to 5% to 10% of acute myocardial infarctions(MI) and is associated with high short- and long-term mortality risk. Since its introduction into clinical practice >50 years ago, intra-aortic balloon counterpulsion has been used empirically to provide hemodynamic support in patients undergoing coronary revascularization in the setting of MI and cardiogenic shock. In the landmark SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, conducted between 1993 and 1998, intra-aortic balloon pumps (IABP) were placed in 86% of participants, irrespective of the assigned management strategy.¹ Although expert opinion supported clinical benefit of IABP use in cardiogenic shock, the first large randomized, multi-center trial of IABP, published in 2012, upended this conventional wisdom. The IABP-SHOCK II(Intra-aortic Balloon Pump in Cardiogenic Shock II) trial randomly assigned 600 participants planned for early revascularization of acute MI complicated by cardiogenic shock to either IABP placement or no IABP placement.² The primary end point was 30-day all-cause mortality. At 30 days, all-cause mortality was 40%, with no difference between patients randomized to receive an IABP versus those who were not. There were no differences between treatment groups in secondary outcomes, including bleeding, ischemic complications, stroke, time to hemodynamic stabilization, intensive care unit length of stay, and the dose and duration of catecholamine therapy. A previous intermediate-term report of IABP-SHOCK II trial outcomes demonstrated no difference between treatment groups for allcause mortality at 12 months.³ In this issue of Circulation, Thiele et al⁴ report the 6-year results of the IABPSHOCK II randomized trial. At 6 years of follow-up, all-cause mortality was high and did not differ between the IABP and control groups (66.3% versus 67.0%) in intention-to-treat, per-protocol, and as-treated analyses. No signal for benefit associated with IABP use was observed in any prespecified or post hoc subgroups. There were no differences in the frequency of recurrent MI, repeat revascularization, stroke, or cardiovascular rehospitalization between the 2 groups. Quality of life, measured by the EuroQol 5D questionnaire and New York Heart Association classification, was favorable in survivors of cardiogenic shock. Four of 5 survivors had New York Heart Association Class I or II symptoms, with no difference between patients randomly assigned to IABP and no IABP therapy.

BACKGROUND AND AIMS/OBJECTIVE:Platelets are a major culprit in the pathogenesis of cardiovascular disease (CVD). Circulating monocyte-platelet aggregates (MPA) represent the crossroads between atherothrombosis and inflammation. However, there is little understanding of the platelets and monocytes that comprise MPA and the prevalence of MPA in different CVD phenotypes. We aimed to establish (1) the reproducibility of MPA over time in circulating blood samples from healthy controls, (2) the effect of aspirin, (3) the relationship between MPA and platelet activity and monocyte subtype, and (4) the association between MPA and CVD phenotype (coronary artery disease, peripheral artery disease [PAD], abdominal aortic aneurysm, and carotid artery stenosis). METHODS AND RESULTS/RESULTS:platelets in healthy subjects and in patients with CVD. We found that MPA did not significantly differ over time in healthy controls, nor altered by aspirin use. Compared with healthy controls, MPA were significantly higher in CVD (9.4% [8.2, 11.1] vs. 21.8% [11.5, 44.1], p < 0.001) which remained significant after multivariable adjustment (β = 9.1 [SER = 3.9], p = 0.02). We found PAD to be associated with a higher MPA in circulation (β = 19.3 [SER = 6.0], p = 0.001), and among PAD subjects, MPA was higher in subjects with critical limb ischemia (34.9% [21.9, 51.15] vs. 21.6% [15.1, 40.6], p = 0.0015), and significance remained following multivariable adjustment (β = 14.77 (SE = 4.35), p = 0.001). CONCLUSIONS:Circulating MPA are a robust marker of platelet activity and monocyte inflammation, unaffected by low-dose aspirin, and are significantly elevated in subjects with CVD, particularly those with PAD.