Faculty Bibliography

BACKGROUND:The ISCHEMIA-CKD (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease) trial found no advantage to an invasive strategy compared to conservative management in reducing all-cause death or myocardial infarction (D/MI). However, the prognostic influence of angiographic coronary artery disease (CAD) burden and ischemia severity remains unknown in this population. We compared the relative impact of CAD extent and severity of myocardial ischemia on D/MI in patients with advanced chronic kidney disease (CKD). METHODS:Participants randomized to invasive management with available data on coronary angiography and stress testing were included. Extent of CAD was defined by the number of major epicardial vessels with ≥50% diameter stenosis by quantitative coronary angiography. Ischemia severity was assessed by site investigators as moderate or severe using trial definitions. The primary endpoint was D/MI. RESULTS:Of the 388 participants, 307 (79.1%) had complete coronary angiography and stress testing data. D/MI occurred in 104/307 participants (33.9%). Extent of CAD was associated with an increased risk of D/MI (P < .001), while ischemia severity was not (P = .249). These relationships persisted following multivariable adjustment. Using 0-vessel disease (VD) as reference, the adjusted hazard ratio (HR) for 1VD was 1.86, 95% confidence interval (CI) 0.94 to 3.68, P = .073; 2VD: HR 2.13, 95% CI 1.10 to 4.12, P = .025; 3VD: HR 4.00, 95% CI 2.06 to 7.76, P < .001. Using moderate ischemia as the reference, the HR for severe ischemia was 0.84, 95% CI 0.54 to 1.30, P = .427. CONCLUSION/CONCLUSIONS:Among ISCHEMIA-CKD participants randomized to the invasive strategy, extent of CAD predicted D/MI whereas severity of ischemia did not.

RATIONALE AND OBJECTIVES/OBJECTIVE:Asymptomatic COVID-19 carriers and insufficient testing make containment of the virus difficult. The purpose of this study was to determine if unexpected lung base findings on abdominopelvic CTs concerning for COVID-19 infection could serve as a surrogate for the diagnosis of COVID-19 in the community. MATERIALS AND METHODS/METHODS:A database search of abdominopelvic CT reports from March 1,2020 to May 2,2020 was performed for keywords suggesting COVID-19 infection by lung base findings. COVID-19 status, respiratory symptoms, laboratory parameters and patient outcomes (hospitalization, ICU admission and/or intubation, and death) were recorded. The trend in cases of unexpected concerning lung base findings on abdominopelvic CT at our institution was compared to the total number of confirmed new cases in NYC over the same time period. RESULTS:The trend in abnormal lung base findings on abdominopelvic CT at our institution correlated with the citywide number of confirmed new cases, including rise and subsequent fall in total cases. The trend was not mediated by COVID-19 testing status or number of tests performed. Patients with respiratory symptoms had significantly higher ferritin (median = 995ng/ml vs 500ng/ml, p = 0.027) and death rate (8/24, 33% vs 4/54, 9%, p = 0.018) compared to those without. CONCLUSION/CONCLUSIONS:The rise and fall of unexpected lung base findings suggestive of COVID-19 infection on abdominopelvic CT in patients without COVID-19 symptoms correlated with the number of confirmed new cases throughout NYC from the same time period. A model using abdominopelvic CT lung base findings can serve as a surrogate for future COVID-19 outbreaks.

INTRODUCTION Optimal medical therapy (OMT) is the cornerstone of treatment for stable coronary disease with the ISCHEMIA trial showing similar outcomes using OMT with or without an initial invasive approach. OBJECTIVES To describe OMT goal attainment in Polish ISCHEMIA participants compared with other countries. PATIENTS AND METHODS Among 5179 trial participants, 333 were randomized in Poland. The median follow‑up was 3.2 years. OMT targets were: not smoking, high‑intensity statin therapy, low‑density lipoprotein cholesterol (LDL‑C) of less than 70 mg/dl, systolic blood pressure of less than 140 mm Hg, aspirin therapy, and ACEI / ARB, and β‑blocker therapy if indicated. RESULTS Compared with 36 other countries, at randomization, patients in Poland were older (67 [62-75] y vs 65 [58-71] y); P <0.001), more often female (30% vs 22%; P = 0.002), with a longer history of angina (3 [1-9] y vs 1 [0-3] y; P <0.001), and there were more cases of prior myocardial infarction (32% vs 18%; P <0.01) and revascularization (PCI, 40% vs 19%; CABG, 11% vs 3%; P <0.001 for both). The number of OMT goals attained increased from baseline to follow‑up visits (5 [4-5] vs 6 [5-6]; P <0.001) in Poland and other countries alike (P = 0.89 vs P = 0.14). In Poland, significant improvements were achieved regarding high‑intensity statin therapy (27% vs 50%), LDL‑C <70 mg/dl (29% vs 65%), and systolic blood pressure of less than 140 mm Hg (63% vs 81%) (P <0.001 for all), whereas not‑smoking (89% vs 89%), aspirin (90% vs 88%), ACEI / ARB (93% vs 95%), and β‑blocker therapy (94% vs 90%) remained high. CONCLUSIONS With regular surveillance and contemporary medical therapy, high OMT goal attainment was achievable among the participants of the ISCHEMIA trial in Poland relative to other countries. There is still room for improvement in LDL‑C and blood pressure management.

OBJECTIVE:To compare the image quality of an accelerated single-shot T2-weighted fat-suppressed (FS) MRI of the liver with deep learning-based image reconstruction (DL HASTE-FS) with conventional T2-weighted FS sequence (conventional T2 FS) at 1.5 T. METHODS:One hundred consecutive patients who underwent clinical MRI of the liver at 1.5 T including the conventional T2-weighted fat-suppressed sequence (T2 FS) and accelerated single-shot T2-weighted MRI of the liver with deep learning-based image reconstruction (DL HASTE-FS) were included. Images were reviewed independently by three blinded observers who used a 5-point confidence scale for multiple measures regarding the artifacts and image quality. Descriptive statistics and McNemar's test were used to compare image quality scores and percentage of lesions detected by each sequence, respectively. Intra-class correlation coefficient (ICC) was used to assess consistency in reader scores. RESULTS:Acquisition time for DL HASTE-FS was 51.23 +/ 10.1 s, significantly (p < 0.001) shorter than conventional T2-FS (178.9 ± 85.3 s). DL HASTE-FS received significantly higher scores than conventional T2-FS for strength and homogeneity of fat suppression; sharpness of liver margin; sharpness of intra-hepatic vessel margin; in-plane and through-plane respiratory motion; other ghosting artefacts; liver-fat contrast; and overall image quality (all, p < 0.0001). DL HASTE-FS also received higher scores for lesion conspicuity and sharpness of lesion margin (all, p < .001), without significant difference for liver lesion contrast (p > 0.05). CONCLUSIONS:Accelerated single-shot T2-weighted MRI of the liver with deep learning-based image reconstruction showed superior image quality compared to the conventional T2-weighted fat-suppressed sequence despite a 4-fold reduction in acquisition time. KEY POINTS/CONCLUSIONS:• Conventional fat-suppressed T2-weighted sequence (conventional T2 FS) can take unacceptably long to acquire and is the most commonly repeated sequence in liver MRI due to motion. • DL HASTE-FS demonstrated superior image quality, improved respiratory motion and other ghosting artefacts, and increased lesion conspicuity with comparable liver-to-lesion contrast compared to conventional T2FS sequence. • DL HASTE- FS has the potential to replace conventional T2 FS sequence in routine clinical MRI of the liver, reducing the scan time, and improving the image quality.

BACKGROUND:Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS:The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS:<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS:Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Conclusions:Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02347215.

BACKGROUND:Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES/OBJECTIVE:In this post-hoc analysis from ISCHEMIA-CKD, we compared outcomes of patients not listed versus those listed according to management strategy. METHODS:In ISCHEMIA-CKD (n=777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction [MI]) and secondary (death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS:Compared with those not listed, listed patients were younger (60 versus 65 years), less likely of Asian race (15% versus 29%), more likely on dialysis (83% versus 44%), had fewer anginal symptoms, and more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for the primary outcome were 0.91 (0.54-1.54) and 1.03 (0.78-1.37) for those listed and not listed, respectively (pinteraction=0.68). Adjusted HR for secondary outcomes were 0.89 (0.55-1.46) in listed and 1.17 (0.89-1.53) in those not listed (pinteraction=0.35). CONCLUSIONS:In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant.

Purpose : Ophthalmology clinics with minimal statistical analytics capabilities may struggle to implement a quality monitoring system to evaluate patient outcomes. We performed a quality improvement study by designing a quality monitoring system for a low-resource ophthalmology clinic that would use small samples to estimate outcomes for larger patient populations. Methods : We evaluated the proportion of primary open-angle glaucoma (POAG) patients who were treated successfully according to American Academy of Ophthalmology Preferred Practice Patterns (PPPs). We analyzed 100 patients seen in the clinic over 3 months in 2019 as the input for our Bayesian analysis. We also created a standardized note template for use by clinicians in the electronic medical record (EMR) for POAG patient visits to facilitate monitoring of treatment successes without requiring clinical expertise. We evaluated adherence to clinician template use in POAG patient notes on the weekly day of glaucoma patient visits over 9 weeks in 2020. Results : Using Bayesian analysis based on our initial data, we created tables that allow for quality monitoring of future 3 month intervals using parameters from smaller samples. Using a small sample of 30 patients, we were able to determine that there was a 100% probability that the clinic as a whole was not achieving the pre-defined target percentage of 80% of POAG patients successfully treated, as defined by the PPPs. Regarding adherence to use of the note template for POAG patients, the median proportion of patients for which the template was used on a single clinic day was 27%, with a maximum of 53% and a minimum of 11%. Conclusions : Based on the input parameters of the number of patients in the sample, the number of treatment successes in that sample, and the target proportion of successfully treated patients, a small sample Bayesian analysis can be used for quality monitoring of patient outcomes for larger patient populations in low-resource clinical settings. Future work includes creation of an open-access database of tables derived from Bayesian analysis for use as a reference by other low-resource clinics in quality monitoring efforts

Background: The efficacy of an aggressive multiple risk factor intervention approach - optimal medical therapy (OMT) - to reduce major adverse cardiovascular events in patients with CKD has not been tested.
Objective(s): to examine OMT goal attainment in patients with CKD on dialysis (CKD-D) and non-dialysis CKD (CKD-ND) in the ISCHEMIA-CKD trial.
Method(s): OMT was recommended to all participants in ISCHEMIA-CKD. Longitudinal trajectories of individual OMT components (smoking cessation, systolic blood pressure (SBP) <140 mmHg, low density lipoprotein (LDL) cholesterol <70 mg/dL, high-intensity statin use, and aspirin use) were modeled over study follow-up. Covariateadjusted percentage point difference in each OMT goal achieved at 24 months between CKD-D and CKD-ND groups (% difference [95% credible interval (CrI)]) was estimated.
Result(s): There were 415 CKD-D and 362 CKD-ND patients at baseline. CKD-D were younger (61 v 67 yrs, p<0.001) and less often diabetic (53% v 62%, p=0.023). CKD-D patients were 7.9 % (0.7%, 14.8%) more likely than CKD-ND to attain the SBP goal at 24 months (Figure). CKD-D patients were 22.7% (-33.3%, -11.4%) less likely to receive high-intensity statins. There was a steady and similar increase in proportional achievement of OMT during follow up.
Conclusion(s): OMT improved over time in advanced CKD-ND and CKD-D. CKD-D achieved the SBP goal more than CKD-ND, yet CKD-D were less likely to be treated with high-intensity statin. Future studies should explore systemic and patient-related barriers to attainment of OMT in this high-risk cohort.(Figure Presented)