Cardiology

Velasco, C. E. and C. Howard (2017). “Trouble on both sides; pulmonary embolism with pneumothorax.” Am J Med: 2017 Jan [Epub ahead of print].

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Potential causes of syncope range from fairly trifling to life threatening. For a 49-year-old, previously healthy, African American man, the trigger proved dangerous. While unloading cargo from a truck, he fainted and fell about 3 feet to the ground. When emergency medical services arrived, his manager reported that the patient lost consciousness but was unable to quantify the period of time. The patient, upon awakening, complained of shortness of breath with severe right-sided chest and back pain. He attributed his accident to fatigue, stating that he had worked as a security guard the previous night, was tired, and simply fell asleep while emptying the vehicle. He denied seizure-like activity, prodrome, drug use, a family history of syncope, and loss of bowel or bladder function.

Cutlip, D. E., K. N. Garratt, V. Novack, M. Barakat, P. Meraj, L. Maillard, A. Erglis, R. Jauhar, J. J. Popma, R. Stoler and S. Silber (2017). “9-month clinical and angiographic outcomes of the cobra polyzene-f nanocoated coronary stent system.” JACC Cardiovasc Interv 10(2): 160-167.

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OBJECTIVES:The aim of this study was to assess the safety and effectiveness of the COBRA Polyzene-F NanoCoated Coronary Stent System (CeloNova Biosciences, San Antonio, Texas) for the treatment of de novo coronary artery lesions.BACKGROUND: Polyzene-F-coated coronary stents have shown reduced thrombogenicity and inflammation in preclinical studies. METHODS: Patients with de novo coronary artery lesions meeting eligibility criteria were enrolled in a nonrandomized, prospective clinical trial. The primary endpoint was target vessel failure (TVF) (defined as a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularization) at 9 months. A pre-specified subset was planned for routine repeat angiographic follow-up at 9 months. The powered secondary endpoint was mean late lumen loss (LL). The comparator was a performance goal derived from meta-analysis of historical bare-metal stent trials of 19.62% for TVF and 1.1 mm for LL. Other secondary endpoints were clinically driven target lesion revascularization and definite or probable stent thrombosis. CONCLUSIONS: The COBRA Polyzene-F stent met performance goals for TVF and LL at 9 months. There was an excellent safety profile, with infrequent late myocardial infarction and no stent thrombosis.

Packer, M. and J. J. McMurray (2016). “Importance of endogenous compensatory vasoactive peptides in broadening the effects of inhibitors of the renin-angiotensin system for the treatment of heart failure.” Lancet: 2016 Dec [Epub ahead of print].

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The magnitude of the clinical benefits produced by inhibitors of the renin-angiotensin system in heart failure has been modest, possibly because of the ability of renin-angiotensin activity to escape from suppression during long-term treatment. Efforts to intensify pharmacological blockade by use of dual inhibitors that interfere with the renin-angiotensin system at multiple sites have not yielded consistent incremental clinical benefits, but have been associated with serious adverse reactions. By contrast, potentiation of endogenous compensatory vasoactive peptides can act to enhance the survival effects of inhibitors of the renin-angiotensin system, as evidenced by trials that have compared angiotensin-converting enzyme inhibitors with drugs that inhibit both the renin-angiotensin system and neprilysin. Several endogenous vasoactive peptides act as adaptive mechanisms, and their augmentation could help to broaden the benefits of renin-angiotensin system inhibitors for patients with heart failure.

McCullough, P. A., A. Vasudevan, L. R. Lopez, C. Swift, M. Peterson, J. Bennett-Firmin, R. Schiffmann and T. Bottiglieri (2016). “Oxidative stress reflected by increased F2-isoprostanes is associated with increasing urinary 11-dehydro thromboxane B2 levels in patients with coronary artery disease.” Thromb Res 148: 85-88.

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Our study demonstrated that: 1) CAD patients with higher levels of 8-isoPGF2α had higher levels of 11dhTxB2, which could be related to poor inhibition of COX-1 pathway in spite of adequate ASA treatment, 2) 8-isoPGF2α is an independent determinant of 11dhTxB2 and 3) 8-isoPGF2α levels were significantly higher in females and patients with diabetes and COPD. Patients with diabetes and central obesity have been observed to have an incomplete ASA response manifested as incomplete inhibition of thromboxane production, in a pro-inflammatory background with enhanced oxidative stress. Oxidative stress enhances the production of platelet isoprostanes and is believed to mitigate the aspirin mediated TxA2 inhibition among diabetic patients on low-dose aspirin [9]. Among F2-isoprostanes metabolites, 8-isoPGF2α is a marker of in vivo oxidative stress, which has been shown to stimulate the activation of platelets by direct binding to the thromboxane platelet receptor. Elevated 8-isoPGF2α levels in our ASA-treated CAD patients indicate the presence of an active oxidative stress environment that is not affected by ASA treatment. Because ASA inhibits over 95% of platelet COX-1 activity in practically all subjects, the residual platelet activation in poor ASA responders can be explained by alternative sources of TxA2 produced by non-platelet inflammatory COX-2 pathways. Our findings are congruent with the notion that oxidative stress mechanisms play an important role in platelet activation in addition to their role on the initiation, progression, and consequences of atherogenesis. Excessive production of ROS may damage lipoproteins creating an inflammatory and atherogenic background and also enhance the arachidonic acid production of F2-isoprostanes that are capable of activating platelets and making them resistant to the therapeutic effect of ASA. These observations support the concept that oxidative stress maintains platelet hyperactivity linking proatherogenic mechanisms to platelet dysfunction in patients with stable CAD. Considering that thromboxanes are not the only factor contributing to platelet activation and atherothrombosis, it is not surprising that a single anti-platelet agent such as ASA does not prevent all adverse events. Cyclo-oxygenase-1 derived TxA2 activates the same and nearby platelets in an autocrine signaling fashion. Due to the very short half-life of TxA2 (20–30 s) and low concentrations (1–60 pg/mL), a constant production of TxA2 is necessary to maintain a homeostatic (physiologic) control of platelet activity. However, the half-life of 8-isoPGF2α is much longer (10 min), with concentrations that are thirty-fold higher. If 8-isoPGF2α can bind and stimulate thromboxane platelet receptors with similar affinity, its longer half-life and concentration makes it a relevant agonist for platelet activation in patients with an underlying oxidative process. Because ASA blocks most of COX-1 activity reducing the production of TxA2, it is possible that the thromboxane platelet receptor can still be activated by TxA2 produced via the 8-isoPGF2α pathway. In this situation, blocking 8-isoPGF2α TPR stimulation could be a potential therapeutic target instead of increasing the dose of ASA. Sex related differences in platelet function and ASA pharmacokinetics exist with female gender associated with elevated 11dhTxB2. We found that females had significantly higher 8-isoPGF2α levels, suggesting an enhanced oxidative stress and lesser attenuation of TxA2. Elevated 11dhTxB2 was found to increase the risk of adverse events in patients with stable CAD and myocardial infarction. (Excerpt from text, p. 86-87.)

Parasca, C. A., S. J. Head, M. Milojevic, M. J. Mack, P. W. Serruys, M. C. Morice, F. W. Mohr, T. E. Feldman, A. Colombo, K. D. Dawkins, D. R. Holmes, Jr. and P. A. Kappetein (2016). “Incidence, characteristics, predictors, and outcomes of repeat revascularization after percutaneous coronary intervention and coronary artery bypass grafting: The syntax trial at 5 years.” JACC Cardiovasc Interv 9(24): 2493-2507.

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OBJECTIVES: The study sought to determine the incidence, predictors, characteristics, and outcomes of repeat revascularization during 5-year follow-up of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) trial. BACKGROUND: Limited in-depth long-term data on repeat revascularization are available from randomized trials comparing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: Incidence and timing of repeat revascularization and its relation to the long-term composite safety endpoint of death, stroke, and myocardial infarction were analyzed in the SYNTAX trial (n = 1,800) using Kaplan-Meier analysis. RESULTS: At 5 years, repeat revascularization occurred more often after initial PCI than after initial CABG (25.9% vs. 13.7%, respectively; p < 0.001), and more often consisted of multiple repeat revascularizations (9.0% vs. 2.8%, respectively; p = 0.022). Significantly more repeat PCI procedures were performed on de novo lesions in patients after initial PCI than initial CABG (33.3% vs. 13.4%, respectively; p < 0.001). At 5-year follow-up, patients who underwent repeat revascularization versus patients not undergoing repeat revascularization had significantly higher rates of the composite safety endpoint of death, stroke, and myocardial infarction after initial PCI (33.8% vs. 16.6%, respectively; p < 0.001), and a trend was found after initial CABG (22.4% vs. 15.8%, respectively; p = 0.07). After multivariate adjustment, repeat revascularization was an independent predictor of the composite safety endpoint after both initial PCI (hazard ratio [HR]: 2.2; 95% confidence interval [CI]: 1.6 to 3.0; p < 0.001) and initial CABG (HR: 1.8; 95% CI: 1.2 to 2.9; p = 0.011). CONCLUSIONS: Repeat revascularization rates are significantly higher after initial PCI than after initial CABG for complex coronary disease. Repeat revascularization is an independent predictor of death, stroke, and myocardial infarction for myocardial revascularization.