Faculty Bibliography

BACKGROUND: An independent association between gout and coronary artery disease is well established. The relationship between gout and valvular heart disease, however, is unclear. The aim of this study was to assess the association between gout and aortic stenosis. METHODS: We performed a retrospective case-control study. Aortic stenosis cases were identified through a review of outpatient transthoracic echocardiography (TTE) reports. Age-matched controls were randomly selected from patients who had undergone TTE and did not have aortic stenosis. Charts were reviewed to identify diagnoses of gout and the earliest dates of gout and aortic stenosis diagnosis. RESULTS: Among 1085 patients who underwent TTE, 112 aortic stenosis cases were identified. Cases and non-aortic stenosis controls (n=224) were similar in age and cardiovascular comorbidities. A history of gout was present in 21.4% (n=24) of aortic stenosis subjects compared with 12.5% (n=28) of controls (unadjusted OR 1.90, 95% CI 1.05-3.48, p=0.038). Multivariate analysis retained significance only for gout (adjusted OR 2.08, 95% CI 1.00-4.32, p=0.049). Among subjects with aortic stenosis and gout, gout diagnosis preceded aortic stenosis diagnosis by 5.8 +/- 1.6 years. The age at onset of aortic stenosis was similar among patients with and without gout (78.7 +/- 1.8 vs. 75.8 +/- 1.0 years old, p=0.16). CONCLUSIONS: Aortic stenosis patients had a markedly higher prevalence of precedent gout than age-matched controls. Whether gout is a marker of, or a risk factor for the development of aortic stenosis remains uncertain. Studies investigating the potential role of gout in the pathophysiology of aortic stenosis are warranted and could have therapeutic implications.

PURPOSE OF REVIEW: This study aims to determine if percutaneous coronary intervention (PCI) does improve survival in stable ischemic heart disease (SIHD). RECENT FINDINGS: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial will evaluate patients with moderate to severe ischemia and will be the largest randomized trial of an initial management strategy of coronary revascularization (percutaneous or surgical) versus optimal medical therapy alone for SIHD. Although the ISCHEMIA trial may show a benefit with upfront coronary revascularization in this high-risk population, cardiac events after PCI are largely caused by plaque rupture in segments outside of the original stented segment. Furthermore, given the robust data from prior randomized trials, which showed no survival benefit with PCI, and the likelihood that the highest risk patients in ISCHEMIA will be treated with surgery, it is unlikely that the ISCHEMIA trial will show a survival benefit particular to PCI. RECENT FINDINGS: Although PCI relieves symptoms, the evidence base indicates that it does not prolong survival in SIHD.

OBJECTIVE: To determine how two different types of iodinated contrast media (CM), low-osmolar ionic dimer ioxaglate (Hexabrix) and iso-osmolar non-ionic dimer iodixanol (Visipaque), affect multiple indices of hemostasis. BACKGROUND: In vitro models demonstrate differential effects of ionic and non-ionic CM on markers of hemostasis. METHODS: This blinded endpoint trial randomized 100 patients to ioxaglate or iodixanol. The primary endpoint was change in endogenous thrombin potential (ETP) following diagnostic angiography. Secondary endpoints included change in markers of fibrinolysis [tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1)] and platelet aggregation following diagnostic angiography and percutaneous coronary intervention (PCI) with bivalirudin. Data are presented as median [interquartile range]. RESULTS: ETP significantly decreased after diagnostic angiography in both ioxaglate (baseline 1810 nM*minute [1540-2089] to post-angiography 649 nM*minute [314-1347], p < 0.001) and iodixanol groups (baseline 1682 nM*minute [1534-2147] to post-angiography 681 nM*minute [229-1237], p < 0.001), but the decrease was not different between CM (p = 0.70). There was a significant increase in ETP during PCI (n = 45), despite the use of bivalirudin, suggesting a prothrombotic effect of PCI (post-angiography 764 nM*minute [286-1283] to post-PCI 1081 nM*minute [668-1552], p = 0.02). There were no significant differential effects on tPA, PAI-1, and markers of platelet activity. CONCLUSION: There were no significant differential effects between ioxaglate and iodixanol. Both CM led to significant reductions in thrombin generation and no significant effects on fibrinolytic activity or platelet activity, thereby contributing to a favorable antithrombotic milieu. (c) 2015 Wiley Periodicals, Inc.

BACKGROUND: Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. METHODS: Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. RESULTS: Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. CONCLUSIONS: Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients.

Patients with diabetes mellitus (DM) have more severe CAD and higher mortality in acute coronary syndrome (ACS) than patients without DM. The optimal mode of revascularization-coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)-remains controversial in this setting. For patients with DM and ST-segment elevation myocardial infarction, prompt revascularization of the culprit artery via PCI is generally preferable. In non-ST-elevation ACS, the decision on mode of revascularization is more challenging. Trials comparing CABG with percutaneous transluminal coronary angioplasty, bare metal stents, and first-generation drug-eluting stents in DM patients with multivessel have demonstrated decreased mortality in those receiving CABG. On the other hand, trials and retrospective analyses comparing CABG to PCI with second-generation drug-eluting stents have not shown a statistically significant mortality benefit favoring CABG. This potentially narrowed that gap between CABG and PCI requires further investigation.

Background: Unlike for coronary artery disease, the association between neutrophil-lymphocyte ratio (NLR) and peripheral artery disease (PAD) has not been well established. The aim of this study was to determine the association between neutrophil-lymphocyte ratio and the severity of lower extremity peripheral artery disease. Methods: A retrospective chart review analysis identified 928 patients referred for peripheral angiography at a tertiary care center between December 2012 and June 2015. NLR was assessed from routine pre-procedural hemograms with automated differentials and available in 733 (79%) patients. Outcomes of interest included extent of disease on peripheral angiography and target vessel revascularization. Median follow-up was 10.4 months. Odds ratio (OR) [95% confidence intervals] was assessed using a logistic regression model. Results: There was a significant association between elevated NLR and the presence of severe multi-level PAD versus isolated suprapopliteal or isolated infrapopliteal disease (OR 1.42 [1.18-1.70], p=<0.001). This association between NLR and severe multi-level PAD remained significant even after adjustment for age (OR 1.31 [1.09-1.58], p=0.004); age, sex, race, and body mass index (OR 1.27 [1.05-1.5], p=0.015); and age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, and creatinine (OR 1.25 [1.03-1.53], p=0.024). In patients who underwent endovascular intervention (n=523), there was no significant difference in the rate of target vessel revascularization on follow-up across tertiles of NLR (1st tertile 14.8%, 2nd tertile 14.1%, 3rd tertile 20.1%; p= 0.32). Conclusion: In a contemporary cohort of patients undergoing peripheral angiography with possible endovascular intervention, elevated NLR was independently associated with severe multi-level PAD

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

OPINION STATEMENT: Hyperglycemia in the setting of coronary revascularization is associated with increased adverse cardiovascular events in patients with or without diabetes mellitus. Data suggest that acute peri-procedural hyperglycemia causes an increase in inflammation, platelet activity, and endothelial dysfunction and is associated with plaque instability and infarct size. While peri-procedural blood glucose level is an independent predictor of adverse outcomes in patients undergoing coronary revascularization, treatment strategies remain uncertain. Randomized clinical trials of glucose-insulin-potassium infusions have consistently shown no benefit, while those comparing insulin therapy versus standard of care have demonstrated mixed results, likely due to the failure to reach euglycemia with these strategies. Although no glucose-lowering agent has been shown to be superior in peri-procedural glycemic control, the continuation of clinically prescribed long-acting glucose-lowering medications in patients with diabetes mellitus prior to coronary angiography and possible percutaneous coronary intervention may be the simplest and most effective approach to maintain euglycemia and decrease the associated increase in inflammation and platelet activity. However, alternative strategies such as therapies targeted at the underlying mechanism of harm (e.g., more potent anti-platelet therapy, anti-inflammatory therapy) should also be considered and warrant further investigation.