An Unusual Case of Paroxysmal Third-Degree Atrioventricular Block: Thinking Outside the Box.

During the assessment of a third-degree atrioventricular (AV) block in a patient with syncope, different etiologies should be considered and evaluated. Extrinsic vagal paroxysmal AV block, extrinsic idiopathic AV block and intrinsic paroxysmal AV block are among the types of third-degree AV block in the differential diagnoses. Extrinsic vagal paroxysmal third-degree atrioventricular block (EV-AVB) is linked to parasympathetic influence on cardiac conduction and can be observed in bladder distention and urinary retention. Topical and ophthalmic beta-blockers have shown systemic effects such as bradycardia with and without syncope. We present the case of an 80-year-old male with symptomatic EV-AVB likely precipitated by bladder outlet obstruction and chronic use of an ophthalmic beta-blocker, often overlooked causes of third-degree AV block.

Association between off-label use of drug-eluting stents and subsequent stent thrombosis: a case-control analysis.

OBJECTIVES: We sought to examine the association between off-label drug-eluting stent (DES) use and stent thrombosis (ST) in unselected patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: DES are frequently used in clinical and angiographic scenarios not initially tested and approved by the FDA (off-label use) resulting in lingering concerns about the higher risk of ST in these situations. METHODS: Out of 5,383 patients undergoing PCI at a single center between 2004 and 2006, 380 had death or myocardial infarction within 1 year. After adjudication using Academic Research Consortium definitions, patients with possible, probable or definite ST were termed cases. Cases were matched with controls, free of ST at 1 year, using geographic and temporal similarities. Off-label usage was defined using manufacturer's instructions and other standard criteria. RESULTS: Overall, the proportion of off-label usage was higher among cases than controls (58% vs. 43%; p = 0.002) and both cases with definite/probable ST (77% vs. 59%; p = 0.08) and possible ST (54% vs. 37%; p = 0.002) had a higher off-label use than respective controls. Off-label use among cases with ST remained higher within the following subgroups: off-label by manufacturer's criteria (36% vs. 27%; p = 0.05), left main stent implantation (2% vs. 0%; p = 0.01), ostial (12% vs. 6%; p = 0.04) and bifurcated lesions (26% vs. 9%; p < 0.001). In multivariate analysis, being a case independently predicted off-label use (OR 1.68, 95% CI: 1.10-2.57; p = 0.02). CONCLUSIONS: In this case-control analysis, off-label use of DES was independently associated with ST within 1 year, although the increased risk was moderate.

Endothelial cell activation in patients with decompensated heart failure.

BACKGROUND: Vascular endothelial functions, other than nitric oxide (NO)-mediated control of vasomotor tone, are poorly characterized in patients with chronic heart failure (CHF). Veins and arteries are exposed to the same circulating proinflammatory mediators in patients with CHF. The present study tested whether endothelial cell activation occurs in veins of patients with decompensated CHF and whether activation, if present, subsides with return to a clinically compensated state. METHODS AND RESULTS: Fifteen patients with decompensated CHF requiring transient inotropic support and 6 age-matched, healthy controls were studied. Endothelial cells and blood were collected from a forearm vein, and brachial artery flow-mediated dilation (FMD) was measured before and 24 hours after discontinuation of short-term inotropic therapy, when patients had returned to a steady compensated state. Nitrotyrosine immunoreactivity (an intracellular marker of oxidative stress), cyclooxygenase-2 (COX-2), and inducible NO synthase (iNOS) expression were significantly higher in venous endothelial cells of patients in clinical decompensation when compared with healthy subjects. Return to a compensated state resulted in a significant reduction in nitrotyrosine immunoreactivity, COX-2, and iNOS expression. Concomitantly, a significant increase in FMD and a decline in plasma total 8-isoprostane and bicycloprostaglandin E2 levels were observed. Venous endothelial NOS expression was unaffected by clinical decompensation. CONCLUSIONS: Clinical decompensation in CHF is associated with activation of the venous endothelium. Return to a compensated state after short-term inotropic therapy results in a significant reduction in endothelial nitrotyrosine formation, COX-2, and iNOS expression.

Biopsy coupled to quantitative immunofluorescence: a new method to study the human vascular endothelium.

Limited availability of endothelial tissue is a major constraint when investigating the cellular mechanisms of endothelial dysfunction in patients with metabolic and cardiovascular diseases. We propose a novel approach that combines collection of 200-1,000 endothelial cells from a superficial forearm vein or the radial artery, with reliable measurements of protein expression by quantitative immunofluorescence analysis. This method was validated against immunoblot analysis in cultured endothelial cells. Levels of vascular endothelial cell activation, oxidative stress, and nitric oxide synthase expression were measured and compared in five patients with severe chronic heart failure and in four healthy age-matched subjects. In summary, vascular endothelial biopsy coupled with measurement of protein expression by quantitative immunofluorescence analysis provides a novel approach to the study of the vascular endothelium in humans.