Gosk−Bierska, Izabela

Aim. Thromboembolic presentation (stroke, mesenteric or limb ischemia) in non-valvular atrial fibrillation may occur randomly or may identify unique subpopulations of patients with this dysrhythmia. The aim of this study was to determine whether future major adverse cardiovascular event rates (myocardial infarction, stroke, peripheral arterial embolism, death) differ between patients with peripheral embolism (AFPE) compared to those suffering stroke (AFS). Methods. An inception cohort (1995–2005) with AFPE (n=216) were compared to randomly selected AFS patients (n=241). Results. Patients with AFPE were older than AFS patients (79±10 vs 73±13 years; p<0.001) with a greater percentage of women (71% vs 45%; p<0.001). The most common presentation of AFPE patients was limb ischemia (90%). Except for prior stroke, all CHADS-2 variables were more prevalent in AFPE (Table ). During 3.3±3.6 years of follow up, survival was lower in AFPE compared to either AFS (p<0.001) or age/gender matched controls (p<0.001; Figure ). AFPE patients had lower survival free from recurrent embolization compared to AFS (82% vs 100%; p=0.005). Recurrence free survival for MI and stroke were similar. Conclusions. Patients with peripheral embolization represent a unique subset of non-valvular atrial fibrillation with an increased risk of recurrence and high mortality rates compared to those suffering stroke. Comparison of clinical and echocardiographic characteristics

Background and Aim: Cardioembolic stroke from non-valvular atrial fibrillation (NVAF) begins with the development of left atrial appendage thrombus (LAAT). Although nearly 15% of patients with NVAF have LAAT by transesophageal echocardiography, the annual stroke rate is 5% on average. The overall aim of this project is to identify variables associated with embolic propensity of LAAT. Materials and Methods: LAAT specimens were obtained during cardiac surgery (MAZE procedure; n=26). Embolized thrombi (n=51) were obtained during surgical embolectomy from lower (n=36) and upper extremities (n=11) and mesenteric arteries (n=4). Platelet-rich regions within sectioned thrombi were sampled by punch biopsy from which total RNA was extracted and analyzed for expression of 5 platelet specific genes: A1 domain of factor XIII, (F13A1); integrin α 2b β 3 (ITGA2B); glycoprotein IX (GP9), platelet factor 4 (PF4), glycoprotein Ib (GP1BB). Gene expression was quantified using TaqMan MGB-probe based quantitative real-time polymerase chain reaction normalized to β 2 macroglobulin using cDNAs reverse transcribed from total RNA. Results: Factor XIII gene expression (Figure ) was significantly lower in embolic (mean fold change 0.08) compared to left atrial thrombi in situ (mean fold change 0.28; p=0.03). Expression of other genes did not show significant change by embolic status. Conclusions: Variable Factor XIII gene expression in thrombi generated during NVAF may in part explain the propensity to embolization. Whereas Factor XIII stabilizes thrombi by crosslinking fibrin without influencing atrial attachment, this data suggests that embolization occurs through fragmentation.

Abstract Renal vein thrombosis (RVT), although uncommon, is associated with considerable morbidity and mortality. Neither the etiology nor the natural history of RVT has been adequately described in a large case series. Objective: To determine whether incident RVT is associated with an increased likelihood of recurrent local and systemic venous thromboembolic disease. Methods: Cases were identified by reviewing the Diagnostic Index for all patients with RVT at our institution between 1981 and 2000. Results: The study group consisted of 240 patients (34% women) with a mean age 55± 19 years. The diagnosis of RVT was made by CT (35%), Duplex Ultrasound (35%), MRI±gadolinium (10%) and either at surgery or autopsy in the remainder. The underlying etiology was deemed to be malignancy in 65% of cases. Of these, renal cell carcinoma (74%) and Wilms tumor (3%) made up the majority. Nephrotic syndrome primarily membranous glomerulonephritis was the second most common underlying etiology (23%). Of those tested, a definable thrombophilia was found in only 13 cases including lupus anticoagulant/antiphospholipid antibody (n=4); deficiencies of protein C or S, (n=2 each); heparin induced thrombocytopenia (n=2); antithrombin deficiency, dysfibrinogenemia and hyperhomocysteinemia (n=1 each). Eighty-one patients (34%) were treated with warfarin. Over a mean follow up of 3 years, the rate of recurrence of venous thrombosis at any site was 5%. The mortality rate over this time period was 49%. Conclusion: RVT represents a distinct clinical entity relative to venous thromboembolism of the lower extremity. The observed low rate of recurrence may be explained by the high mortality rate owing to a high percentage of renal malignancy. RVT should prompt an evaluation for an underlying renal malignancy.

AbstractIntroductionReticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes.Methods and resultsExpression of six platelet‐predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3–4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse‐transcribed assayed against selected genes utilizing real‐time qPCR, and expressed as mean cycle threshold (ΔCt) using beta‐2‐microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9 vs. 5.7 ± 1.6, P < 0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0 vs. 6.7+5.4, P < 0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged.ConclusionsNVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.

AbstractAimsPlatelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non‐valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3‐4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR).Methods and ResultsRNA from isolated platelets were reverse transcribed, assayed against 15 genes using real‐time qPCR, and expressed as mean cycle threshold (ΔCt) using beta‐2‐microglobulin as endogenous control. Expression of all evaluated genes, except cathepsin A gene, was significantly lower (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. Insulin‐like growth factor binding protein acid labile subunit gene (IGFALS) had expression more than 16 fold‐lower (17.0±2.8 vs 12.5±3.8, P<.001), follow by genes encoding for prostacyclin receptor, and for von Willebrand factor which had fourfold lower expression compared to NSR controls. Gender, type of atrial fibrillation, heart failure, hypertension, prior stroke, diabetes mellitus, and atherosclerosis were associated with different gene expression. Following PVI, expression of four genes significantly increased, particularly IGFALS gene (increased 256‐fold) and ADAMT gene increased 16‐fold); expression of three genes significantly decreased, and expression of eight genes has not changed.ConclusionsPlatelets are capable to respond to the circulatory environment of NVAF by altering transcript and changing prothrombotic status. This shows platelet potential for molecular “reprogramming” possibly induced by flow disturbances of NVAF.