Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Bivalirudin use in patients undergoing percutaneous coronary intervention for acute myocardial infarction. Insights from the prospective, multi-centre EUROVISION registry.

BACKGROUND: The effectiveness of bivalirudin in patients undergoing percutaneous coronary intervention for acute myocardial infarction has been tested in clinical trials, but its use in a real-world scenario has never been reported. METHODS: From the total number of patients enrolled in the EUROVISION registry, 678 subjects affected by ST-elevation myocardial infarction were selected and included in the analysis. Posology and usage patterns of bivalirudin, as evaluated by dose and time of drug bolus and infusion administered, were evaluated. The 30-day outcome has been assessed by efficacy and safety endpoints. RESULTS: All patients received an initial intravenous bolus of bivalirudin (0.70±0.25 mg/kg) followed by an infusion (1.58±0.47 mg/kg/h; duration: 60 [30, 107] min) in 99.3% of cases. An additional bolus (0.49±0.06 mg/kg) was administered in 9.3% of patients. Bivalirudin infusion was prolonged after procedure in 62.2%. Death occurred in 2.1% of patients, non-fatal myocardial reinfarction in 0.3%, unplanned revascularization in 0.6% and non-fatal stroke in 0.4%. Acute stent thrombosis was not observed. Major bleeding occurred in 1.5% of patients. CONCLUSIONS: Bivalirudin usage in the setting of primary PCI provided excellent results in terms of 30-day outcome even in a real-world population.

Adjunctive therapies in the cath lab. Successful medical therapy of left main thrombosis: value of serial coronary angiography.

Acute coronary syndromes (ACS), including unstable angina, non-Q wave myocardial infarctions (MI) and Q-wave MIs, are usually the result of plaque rupture and subsequent thrombus formation. Commonly, patients with ACS have significant underlying coronary artery disease (CAD) demonstrable by coronary angiography and are candidates for prompt revascularization. In many cases, however, ACS are due to coronary thrombosis in the absence of obstructive CAD and therefore aggressive medical therapy may be sufficient. Coronary angiography is an invaluable resource for individualized treatment decisions. We describe a patient with thrombosis of the left main coronary artery successfully treated with aggressive and prolonged antiplatelet and anticoagulant therapy under the guidance of serial coronary angiography.

Elevated interleukin-6 levels in patients with asymptomatic left ventricular systolic dysfunction.

BACKGROUND: Elevated interleukin-6 (IL-6) levels are present in patients with New York Heart Association (NYHA) class III and IV congestive heart failure (CHF) and are associated with a poor prognosis. We sought to determine whether elevated IL-6 levels are also present in patients with left ventricular (LV) dysfunction but without clinical symptoms. METHODS: Blood samples were obtained from the femoral artery of 58 patients who underwent cardiac catheterization for recognized clinical indications. In a subgroup of 44 patients, samples were also obtained from the femoral vein, the left main coronary artery, and the coronary sinus. Patients with prior coronary artery bypass surgery, recent acute coronary syndrome, or steroid therapy were excluded. All samples were obtained before heparin or contrast administration. IL-6 was measured by enzyme-linked immunosorbent assay and values are expressed in picograms per milliliter. RESULTS: Three groups of patients were identified: controls, no CHF, LV ejection fraction >/=0.55 (n = 32); asymptomatic LV systolic dysfunction, no CHF, LV ejection fraction <0.55 (n = 14); and CHF, pulmonary edema (n = 12). IL-6 levels were higher at all sampling sites in both the asymptomatic LV systolic dysfunction and CHF groups compared with controls with the IL-6 levels inversely related to LV ejection fraction. CONCLUSIONS: Elevated IL-6 levels are present in patients with LV dysfunction even in the absence of the clinical syndrome of CHF. These data suggest that IL-6 may be involved in the progression of subclinical LV dysfunction to clinical CHF. IL-6 may be a marker of patients at risk for progression to clinical CHF or a novel target for therapeutic intervention.

Role of nuclear factor-kappa B (NF-kappa B) in inflammation, periodontitis, and atherogenesis.

Atherosclerosis, the major cause of death and disability in the United States, is a chronic disease with inflammatory components. The first objective of this review is to explain how activation of NF-kappa B contributes to atherosclerosis. The second objective is to describe a potential link between inflammation, activation of NF-kappa B, and periodontitis. The nuclear transcription factor NF-kappa B controls the expression of many genes linked to atherogenesis including those involved with inflammation. We hypothesize that one unifying mechanism in this complex disease is the activation of NF-kappa B. The mechanism(s) that activates NF-kappa B in atherogenesis is unknown and the effect of inhibiting NF-kappa B activation on atherogenesis is untested. Periodontal disease has now been established as a risk factor for atherosclerosis and its thrombotic complications. It is unknown if periodontal disease contributes to the initiation or progression of atherosclerosis. We hypothesize that the chronic and intense inflammatory response accompanying periodontal disease produces an excess burden of circulating mediators of inflammation that initiate or exacerbate the inflammatory components of atherogenesis. Further understanding of the mechanisms involved in the activation of NF-kappa B in atherosclerosis could lead to important therapeutic applications especially as it relates to the impact of periodontitis.

Sites of interleukin-6 release in patients with acute coronary syndromes and in patients with congestive heart failure.

This study examines the source of elevated interleukin-6 (IL-6) levels in patients with acute coronary syndrome (ACS) and congestive heart failure (CHF). IL-6 is elevated in the peripheral blood of patients with ACS and CHF, but it is not known if this proinflammatory cytokine is from a cardiac or extracardiac source. Blood samples were obtained from the femoral artery, femoral vein, left main coronary artery, and coronary sinus in 57 patients during cardiac catheterization. IL-6 levels from 12 patients with ACS and 12 patients with CHF were compared with the IL-6 levels in 33 patients who had neither of these clinical conditions. Median IL-6 levels in the peripheral and coronary circulation were a minimum fivefold higher in patients with ACS or CHF relative to control patients. An elevated transcardiac IL-6 gradient (coronary sinus-left main level) was present in patients with ACS (median 5.2; 25th and 75th percentiles 3.9 and 29.3 pg/ml, respectively) compared with control patients (median 0, -0.7 and 0.5 pg/ml; p < 0.001), but not in patients with CHF (median 0.4, -0.7 and 3.5 pg/ml; p = NS). Elevated IL-6 levels in patients with ACS derive from a cardiac source, presumably from "inflamed" coronary plaques and areas of myocardial necrosis, whereas elevated levels in patients with CHF are most likely the result of extracardiac production.

Preoperative factors predisposing to early postoperative atrial fibrillation after isolated coronary artery bypass grafting.

An analysis of 183 patients in sinus rhythm who underwent coronary artery bypass grafting was conducted to determine the association of multiple preoperative factors, including an elevated left ventricular end-diastolic pressure, with early postoperative atrial fibrillation. An association with advanced age, a history of atrial fibrillation, and preoperative digoxin use was found, but not with an elevated left ventricular end-diastolic pressure, irrespective of left ventricular systolic function.