Use of High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia: A Cohort Study.

Background: Many patients with coronary artery disease (CAD) are routinely referred for surveillance stress testing despite recommendations against it. Objective: To determine whether low levels of resting high-sensitivity cardiac troponin I (hs-cTnI) can identify persons without inducible myocardial ischemia. Design: Observational study. Setting: A university-affiliated hospital network. Patients: Persons with stable CAD: 589 in the derivation group and 118 in the validation cohort. Measurements: Presence of inducible myocardial ischemia was determined by myocardial perfusion imaging with technetium-99m single-photon emission computed tomography during either treadmill or pharmacologic stress testing. Resting plasma hs-cTnI was measured within 1 week of the stress test, and the negative predictive value (NPV) for inducible ischemia was calculated. The derivation cohort was followed for 3 years for incident cardiovascular death and myocardial infarction. Results: In the derivation cohort, 10 of 101 patients with an hs-cTnI level below 2.5 pg/mL had inducible myocardial ischemia (NPV, 90% [95% CI, 83% to 95%]) and 3 of 101 had inducible ischemia involving at least 10% of the myocardium (NPV, 97% [CI, 92% to 99%]). In the validation cohort, 4 of 32 patients with an hs-cTnI level below 2.5 pg/mL had inducible ischemia (NPV, 88% [CI, 71% to 96%]) and 2 of 32 had ischemia of 10% or greater (NPV, 94% [CI, 79% to 99%]). After a median follow-up of 3 years in the derivation cohort, no adverse events occurred in patients with an hs-cTnI level below 2.5 pg/mL, compared with 33 (7%) cardiovascular deaths or incident myocardial infarctions among those with an hs-cTnI level of 2.5 pg/mL or greater. Limitation: The data may not be applicable to a population without known CAD or to persons with unstable angina, and the modest sample sizes warrant further validation in a larger cohort. Conclusion: Very low hs-cTnI levels may be useful in excluding inducible myocardial ischemia in patients with stable CAD. Primary Funding Source: National Institutes of Health.

Sleep Duration and Mortality in Patients With Coronary Artery Disease.

Extremes in sleep duration are associated with higher cardiovascular risk in the general population, but their impact in patients with documented coronary artery disease (CAD) remains unknown and potentially of clinical significance. We hypothesized that both short and long sleep duration are associated with higher mortality in CAD. We inquired about sleep durations in 2,846 patients enrolled in the Emory Cardiovascular Biobank (mean age 64 years, 38% female, 23% Black, and 82% with obstructive CAD, defined by positive coronary angiography), who were then followed for all-cause and cardiovascular mortality. Multivariate Cox proportional hazard models were calculated to examine the association of sleep duration and mortality. Sleep durations of <6.5 hours (short), ≥6.5 to <7.5 hours (normal), and ≥7.5 hours (long) were reported by 39%, 26% and 35% of the cohort, respectively. On follow-up (median 2.8 years), mortality rates were 15%, 11%, and 17%, respectively. After adjusting for demographics and risk factors, both short and long sleep duration were associated with higher all-cause mortality (hazard ratio 1.44, 95% confidence interval [1.10 to 1.89], and 1.41 [1.08 to 1.85], respectively). A similar pattern was demonstrated for cardiovascular mortality only for short (hazard ratio 1.48 [1.05 to 2.09]), but not long sleep duration. In conclusion, in patients with frank CAD, both short and long sleep duration were independently associated with higher all-cause mortality, and short sleep was independently associated with higher cardiovascular mortality. In conclusion, our study is the first to extend the observations of sleep duration and mortality from population-based studies to patients with documented cardiac disease.

Living in Food Deserts and Adverse Cardiovascular Outcomes in Patients With Cardiovascular Disease.

Background Food deserts ( FDs ), defined as low-income communities with limited access to healthy food, are a growing public health concern. We evaluated the impact of living in FDs on incident cardiovascular events. Methods and Results We recruited 4944 subjects (age 64±12, 64% male) undergoing cardiac catheterization into the Emory Cardiovascular Biobank. Using the US Department of Agriculture definition of FD , we determined whether their residential addresses had (1) poor access to healthy food, (2) low income, or (3) both (= FD ). Subjects were prospectively followed for a median of 3.2 years for myocardial infarction (MI) and death. Fine and Gray's subdistribution hazard models for MI and Cox proportional hazard models for death/ MI were used to examine the association between area characteristics ( FD , poor access, and low income) and the rates of adverse events after adjusting for traditional risk factors. A total of 981 (20%) lived in FDs and had a higher adjusted risk of MI (subdistribution hazard ratio, 1.44 [95% CI, 1.06-1.95]) than those living in non- FDs . In a multivariate analysis including both food access and area income, only living in a low-income area was associated with a higher adjusted risk of MI (subdistribution hazard ratio, 1.40 [1.06-1.85]) and death/ MI (hazard ratio, 1.18 [1.02-1.35]) while living in a poor-access area was not significantly associated with either (subdistribution hazard ratio, 1.05 [0.80-1.38] and hazard ratio, 0.99 [0.87-1.14], respectively). Conclusions Living in an FD is associated with a higher risk of adverse cardiovascular events in those with coronary artery disease. Specifically, low area income of FDs , not poor access to food, was significantly associated with worse outcomes.

Diagnostic Utility of PD-L1 Expression in Lung Adenocarcinoma: Immunohistochemistry and RNA In Situ Hybridization.

BACKGROUND: Programmed death receptor and programmed death ligand (PD-L1) are immunoregulatory proteins. Nonsmall cell lung cancer bypasses the immune system through the induction of protumorigenic immunosuppressive changes. The better understanding of immunology and antitumor immune responses has brought the promising development of novel immunotherapy agents like programmed death receptor checkpoint inhibitors. The aim of this study was to investigate the expression of PD-L1 in lung adenocarcinoma (ADC), comparing 2 different technologies: immunohistochemistry (IHC) by 2 methods versus RNA in situ hybridization (RISH). METHODOLOGY: In total, 20 cases of ADC of the lung and 4 samples of metastatic colon ADC were selected. Evaluation of PD-L1 expression was performed by IHC and RISH. RISH was performed using RNAscope. Both methods were scored in tumor cells and quantified using combined intensity and proportion scores. RESULTS: Eight of 20 (40%) lung ADC and 2 of 4 (50%) colon ADC were positive for PD-L1 with Cell Signaling IHC, and 65% lung ADC were positive by Dako IHC (13/20). All 4 cases of colon ADC were negative. When evaluated by RISH, 12 lung ADC (60%) and 1 colon ADC (25%) were PD-L1 positive. CONCLUSIONS: RNAscope probes provide sensitive and specific detection of PD-L1 in lung ADC. Both IHC methods (Cell Signaling and Dako) show PD-L1 expression, with the Dako method more sensitive (40% vs. 65%). This study illustrates the utility of RISH and Cell Signaling IHC as complementary diagnostic tests, and Food and Drug Administration approved Dako IHC as a companion diagnostic test.

Coronary and Peripheral Vasomotor Responses to Mental Stress.

BACKGROUND: Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. METHODS AND RESULTS: In 38 patients aged 59±8 years undergoing coronary angiography, endothelium-dependent and endothelium-independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate-pressure product by 22% (±23%) and constricted epicardial coronary arteries by -5.9% (-10.5%, -2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [-10.9%, 8.2%], P=not significant). The MS-induced CBF response correlated with endothelium-dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand-adjusted change in CBF during MS (r=-0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. CONCLUSIONS: The coronary microvascular response to MS is determined by endothelium-dependent, but not endothelium-independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.

High-Sensitivity Troponin I Levels and Coronary Artery Disease Severity, Progression, and Long-Term Outcomes.

BACKGROUND: The associations between high-sensitivity troponin I (hsTnI) levels and coronary artery disease (CAD) severity and progression remain unclear. We investigated whether there is an association between hsTnI and angiographic severity and progression of CAD and whether the predictive value of hsTnI level for incident cardiovascular outcomes is independent of CAD severity. METHODS AND RESULTS: In 3087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms >3 months before enrollment. Patients were followed up for incident all-cause mortality and incident cardiovascular events. Of the total population, 11% had normal angiograms, 23% had nonobstructive CAD, 20% had 1-vessel CAD, 20% had 2-vessel CAD, and 26% had 3-vessel CAD. After adjusting for age, sex, race, body mass index, smoking, hypertension, diabetes mellitus history, and renal function, hsTnI levels were independently associated with the severity of CAD measured by the Gensini score (log 2 ß=0.31; 95% confidence interval, 0.18-0.44; P<0.001) and with CAD progression (log 2 ß=0.36; 95% confidence interval, 0.14-0.58; P=0.001). hsTnI level was also a significant predictor of incident death, cardiovascular death, myocardial infarction, revascularization, and cardiac hospitalizations, independent of the aforementioned covariates and CAD severity. CONCLUSIONS: Higher hsTnI levels are associated with the underlying burden of coronary atherosclerosis, more rapid progression of CAD, and higher risk of all-cause mortality and incident cardiovascular events. Whether more aggressive treatment aimed at reducing hsTnI levels can modulate disease progression requires further investigation.