Faculty Bibliography

Background Detection of flow-limiting left main (LM) coronary artery disease (CAD) has both prognostic and therapeutic implications. Stress testing is the most common method to detect obstructive CAD, however stress markers of LM CAD remain unclear. We set out to identify markers of LM CAD using clinical and stress testing parameters. Methods The population consisted of patients enrolled in the ISCHEMIA trial who underwent non-imaging exercise tolerance testing, stress nuclear imaging or stress echocardiography (SE) and who underwent coronary computed tomography angiography (CCTA). Patients were enrolled based on local determination of moderate or severe ischemia. Those with prior coronary artery bypass grafting were excluded. Multivariate modeling was used to identify predictors of >=50% LM diameter stenosis ("LM disease"), first without and then with stress testing parameters included in the model. Results Of the 5145 patients included (mean age: 63 years, male: 74%), 414 (8%) had LM disease. Predictors of LM disease are shown in the Table. The models were weakly predictive of LM disease (C index 0.643 for clinical model, 0.671 for clinical + stress model). Conclusion In patients with moderate or severe ischemia on stress testing, clinical and stress testing parameters were weakly predictive of LM disease on CCTA. SE-detected TID and ST depression during ETT provided incremental information independent of clinical and other stress modality specific parameters for the prediction of LM disease. [Figure presented]
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BACKGROUND:or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS:We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS:Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS:Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).

Importance/UNASSIGNED:While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization. Objective/UNASSIGNED:To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants. Design, Setting, and Participants/UNASSIGNED:This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018. Interventions/UNASSIGNED:CCTA and angina assessment. Main Outcomes and Measures/UNASSIGNED:Sex differences in stress test, CCTA findings, and symptom severity. Results/UNASSIGNED:Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76). Conclusions and Relevance/UNASSIGNED:Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01471522.

Most of the guideline-recommended treatment strategies for patients with acute coronary syndromes have been tested in large randomised clinical trials. Still, a major challenge is represented by patients with acute myocardial infarction admitted with impending or established cardiogenic shock. Despite early revascularization the mortality of cardiogenic shock remains high and roughly half of patients do not survive until hospital discharge or 30-day follow-up. However, there is only limited evidence-based scientific knowledge in the cardiogenic shock setting. Therefore, recommendations and actual treatments are often based on retrospective or prospective registry data and extrapolations from randomised clinical trials in acute myocardial infarction patients without cardiogenic shock. This position statement will summarise the current consensus of the diagnosis and treatment of patients with acute myocardial infarction complicated by cardiogenic shock based on current evidence and will provide advice for clinical practice.

Background Sex differences in ischemia, coronary anatomy and symptoms have not been investigated among patients who have moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary CT angiography (CCTA) was required to have obstructive CAD to undergo randomization. We describe sex differences in stress testing and CCTA findings as well as symptoms in the ISCHEMIA trial. Methods ISCHEMIA enrolled patients based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most participants. Stress tests and CCTAs were reviewed at core laboratories. Those with no obstructive coronary artery disease (CAD) or with left main CAD >=50% were excluded. Angina was assessed using the Seattle Angina Questionnaire (SAQ). Results Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA), 34% versus 11%, p<0.001, resulting in more women excluded after enrollment. Randomized women (n=1168) had more angina at baseline than randomized men (n=4011), despite less extensive CAD on CCTA and less severe ischemia in women vs. men with stress imaging (Figure). Conclusion Women randomized in the ISCHEMIA trial had more frequent angina despite less extensive CAD and less ischemia than men. Our findings likely reflect inherent sex differences in the complex relationships between angina, atherosclerosis and ischemia that may have implications for testing and treatment of patients with suspected ischemic heart disease. [Formula presented]
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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: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.