Faculty Bibliography

BACKGROUND:Myocardial infarction (MI) is a multifactorial disease with complex pathogenesis, mainly the result of the interplay of genetic and environmental risk factors. The regulation of thrombosis, inflammation and cholesterol and lipid metabolism are the main factors that have been proposed thus far to be involved in the pathogenesis of MI. Traditional risk-estimation tools depend largely on conventional risk factors but there is a need for identification of novel biochemical and genetic markers. The aim of the study is to identify differentially expressed genes that are consistently associated with the incidence myocardial infarction (MI), which could be potentially incorporated into the traditional cardiovascular diseases risk factors models. METHODS:The biomedical literature and gene expression databases, PubMed and GEO, respectively, were searched following the PRISMA guidelines. The key inclusion criteria were gene expression data derived from case-control studies on MI patients from blood samples. Gene expression datasets regarding the effect of medicinal drugs on MI were excluded. The t-test was applied to gene expression data from case-control studies in MI patients. RESULTS:A total of 162 articles and 174 gene expression datasets were retrieved. Of those a total of 4 gene expression datasets met the inclusion criteria, which contained data on 31,180 loci in 93 MI patients and 89 healthy individuals. Collectively, 626 differentially expressed genes were detected in MI patients as compared to non-affected individuals at an FDR q-value = 0.01. Of those, 88 genes/gene products were interconnected in an interaction network. Totally, 15 genes were identified as hubs of the network. CONCLUSIONS:Functional enrichment analyses revealed that the DEGs and that they are mainly involved in inflammatory/wound healing, RNA processing/transport mechanisms and a yet not fully characterized pathway implicated in RNA transport and nuclear pore proteins. The overlap between the DEGs identified in this study and the genes identified through genetic-association studies is minimal. These data could be useful in future studies on the molecular mechanisms of MI as well as diagnostic and prognostic markers.

BACKGROUND: Adequacy of major depressive disorder (MDD) treatment among cardiovascular disease (CVD) patients has been linked with improved CVD outcomes. OBJECTIVE: The current study examined the association between MDD care adequacy and healthcare resource use (HCRU) and costs among patients with prior myocardial infarction (MI) or stroke. METHODS: This was a retrospective cohort study conducted using the Truven Health MarketScan Claims Database (2010-2015) among adults diagnosed with MDD following an initial MI or stroke. The date of the first MI/stroke diagnosis was defined as the index CVD date and the first date of a subsequent MDD diagnosis was the index MDD date. Adequacy of MDD care was assessed during the 90-day period post index MDD date using 2 measures: dosage adequacy (average fluoxetine equivalent dose of 20 mg/day for nonelderly and 10 mg/day for elderly patients) and duration adequacy (measured as the proportion of days covered of 80% or higher for all MDD drugs). Patients who did not meet either of these criteria were categorized as receiving inadequate MDD care. Multivariate logistic regression adjusted for baseline characteristics was used to calculate the propensity of receiving adequate MDD care. Propensity-score adjusted annual HCRU outcomes were estimated using generalized linear models (GLM) with Poisson distribution. Adjusted costs were estimated using two-part logit-GLMs. RESULTS: Of 1,568 CVD patients who were treated for MDD, 937 (59.8%) were categorized as receiving inadequate MDD care. Patients receiving inadequate MDD care had 14% higher (IRR: 1.14 [95% CI: 1.01-1.30]; P = 0.036) and 21% longer (IRR: 1.21 [95% CI: 1.15-1.27]; P < 0.001) all-cause hospitalizations,4% more all-cause outpatient visits (IRR: 1.04 [95% CI: 1.02-1.06]; P < 0.001), 24% longer CVDrelated hospitalizations (IRR: 1.24 [95% CI: 1.17-1.31]; P < 0.001), 17% more CVD-related outpatient visits (IRR: 1.17 [95% CI: 1.13-1.21]; P < 0.001), and 13% more CVD-related ER visits (IRR: 1.13 [95% CI: 1.03-1.24]; P = 0.006) compared to patients receiving adequate MDD care. Adjusted per patient CVD-related hospitalization costs ($21,485 vs. $17,756; P < 0.001), all-cause outpatient costs ($2,820 vs. $2,055; P < 0.001), and CVD-related ($520 vs. $434; P < 0.001) outpatient costs were significantly higher for CVD patients receiving inadequate MDD care versus those receiving adequate care. CONCLUSIONS: Among patients with newly diagnosed MI or stroke, inadequate MDD care was associated with a significantly higher economic burden. Hospitalization was the key driver of this increased burden

Background Standardization of evidence-based medical therapies has improved outcomes for patients with non- ST -segment-elevation myocardial infarction ( NSTEMI ). Although racial differences in NSTEMI management have previously been reported, it is uncertain whether these differences have been ameliorated over time. Methods and Results The ARIC (Atherosclerosis Risk in Communities) Community Surveillance study conducts hospital surveillance of acute myocardial infarction in 4 US communities. NSTEMI was classified by physician review, using a validated algorithm. From 2000 to 2014, 17 755 weighted hospitalizations for NSTEMI (patient race: 36% black, 64% white) were sampled by ARIC . Black patients were younger (aged 60 versus 66 years), more often female (45% versus 38%), and less likely to have medical insurance (88% versus 93%) but had more comorbidities. Black patients were less often administered aspirin (85% versus 92%), other antiplatelet therapy (45% versus 60%), β-blockers (85% versus 88%), and lipid-lowering medications (68% versus 76%). After adjustments, black patients had a 24% lower probability of receiving nonaspirin antiplatelets (relative risk: 0.76; 95% confidence interval, 0.71-0.81), a 29% lower probability of angiography (relative risk: 0.71; 95% confidence interval, 0.67-0.76), and a 45% lower probability of revascularization (relative risk: 0.55; 95% confidence interval, 0.50-0.60). No suggestion of a changing trend over time was observed for any NSTEMI therapy ( P values for interaction, all >0.20). Conclusions This longitudinal community surveillance of hospitalized NSTEMI patients suggests black patients have more comorbidities and less likelihood of receiving guideline-based NSTEMI therapies, and these findings persisted across the 15-year period. Focused efforts to reduce comorbidity burden and to more consistently implement guideline-directed treatments in this high-risk population are warranted.

AIMS/OBJECTIVE:The influence of community acute kidney injury on patients with myocardial infarction has not been explored. The Veterans Affair electronic health system was analyzed to test the hypothesis that patients who have myocardial infarction complicated by community acute kidney injury have higher short- and long-term mortality and cardiovascular outcomes than those who do not suffer acute kidney injury. MATERIALS AND METHODS/METHODS:Odd ratios were calculated for in-hospital mortality. Cox proportional hazard model was used to assess hazard ratios for long-term mortality comparing patients with and without community acute kidney injury. Secondary outcomes included recurrent cardiovascular events including hospitalization for congestive heart failure, stroke, or repeat myocardial infarction. RESULTS:10,689 patients were available for evaluation, 679 had community acute kidney injury and 10,010 with no acute kidney injury. Community acute kidney injury resulted in higher odds for inpatient mortality (odds ratio 5.87, p < 0.001), and adjusted hazard ratio for mortality at 5 years as compared to no acute kidney injury (hazard ratio 1.67, p < 0.001). No differences in cardiovascular outcomes were identified in Cox proportional hazard analysis. CONCLUSION/CONCLUSIONS:In patients with myocardial infarction, community acute kidney injury is associated with delays in or not receiving appropriate myocardial infarction related process of care measures. In addition it is an independent predictor of short- and long-term mortality.
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AIMS/OBJECTIVE:To evaluate the safety and efficacy of BioMime™ sirolimus-eluting coronary stent (SES) compared to the XIENCE family everolimus-eluting coronary stent (EES) in the treatment of patients with de novo native coronary artery lesions. METHODS AND RESULTS/RESULTS:The meriT-V is a prospective, multicenter, randomized, open-label, active-controlled, and non-inferiority trial. A total of 256 patients with up to two de novo native coronary artery lesions were enrolled and randomly assigned (2:1) to BioMime SES or XIENCE EES. BioMime SES was non-inferior to XIENCE EES for the primary endpoint of in-stent late lumen loss (0.15±0.27 mm vs. 0.15±0.29 mm; difference: -0.006 mm; 95% confidence interval: -0.085 to 0.072; p=0.87; p for non-inferiority <0.0001) at 9-month follow-up. The major adverse cardiac event rate was numerically lower in BioMime SES group (2.98% vs. 7.14%; p=0.13), driven by a statistically significant lower risk of any myocardial infarction (0.60% vs. 4.76%; p=0.03), when compared with the XIENCE EES group. There was no difference in target vessel myocardial infarction (p=0.62) between the groups. There was no definite or probable stent thrombosis in either group. CONCLUSIONS:In the treatment of de novo native coronary artery lesions, the biodegradable polymer ultra-thin SES (BioMime) was non-inferior to durable polymer EES (XIENCE) at 9-month follow-up. Further studies powered for clinical endpoints are needed.

BACKGROUND:Patients with chronic kidney disease (CKD) and stable ischemic heart disease are at markedly increased risk of cardiovascular events. Prior trials comparing a strategy of optimal medical therapy (OMT) with or without revascularization have largely excluded patients with advanced CKD. Whether a routine invasive approach when compared with a conservative strategy is beneficial in such patients is unknown. METHODS:or on dialysis) and moderate or severe ischemia on stress testing. Participants were randomized in a 1:1 fashion to the invasive or a conservative strategy. The primary end point is a composite of death or nonfatal myocardial infarction. Major secondary endpoints are a composite of death, nonfatal myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest; angina control; and disease-specific quality of life. Safety outcomes such as initiation of maintenance dialysis and a composite of initiation of maintenance dialysis or death will be reported. The trial is projected to have 80% power to detect a 22% to 24% reduction in the primary composite end point with the invasive strategy when compared with the conservative strategy. CONCLUSIONS:ISCHEMIA-CKD will determine whether an initial invasive management strategy improves clinical outcomes when added to OMT in patients with advanced CKD and stable ischemic heart disease.

There are no dedicated data to guide drug eluting stent (DES) versus bare metal stent (BMS) selection in patients with end stage renal disease undergoing dialysis (ESRD-D). It is unclear whether long-term benefits of a specific stent-type outweigh risks in this population at high risk for both bleeding and ischemic events. We performed a meta-analysis of non-randomized studies extracted from PubMed, Scopus, and EMBASE; assessing the safety and effectiveness of DES versus BMS in ESRD-D patients. Odds ratios (OR) and 95% confidence intervals (CI) were computed with the Mantel-Haenszel method. Random-effects model was used for all analyses. A total of 17 non-randomized studies (N=63,157; 41,621 DES and 21,536 BMS) met the inclusion criteria and were included for the final quantitative analysis; median follow-up of 1 year (range: 9 months - 6 years). The use of DES in ESRD-D patients was associated with lower all-cause mortality (OR 0.75, 95%CI 0.64-0.89, P<0.001) compared with BMS. The use of DES was also associated with lower rates of cardiovascular mortality (OR 0.75, 95%CI 0.60-0.99, P=0.047) and target lesion/vessel revascularization (TLR/TVR) (OR 0.78, 95%CI 0.64-0.94, P=0.01). However, there were no differences in non-cardiovascular mortality, myocardial infarction, stent thrombosis, stroke or major bleeding in DES versus BMS. In this largest meta-analysis of long-term outcomes following percutaneous coronary intervention in ESRD-D patients, DES was associated with lower rates of all-cause mortality, TLR/TVR, and cardiovascular death.