From the Department of Medical and Surgical Sciences (PP, EB, PS, RP, DT, AP), Department of Clinical and Experimental Medicine, Group of Clinical Epidemiology (FN), and Department of Cardiothoracic ...and Vascular Sciences (VP), University of Padua, Padua; Department of Internal Medicine, Angiology Unit, Arcispedale Santa Maria Nuova, (AG, MI), Reggio Emilia, Italy
Correspondence: Paolo Prandoni, Department of Medical and Surgical Sciences, 2 nd Chair of Internal Medicine, University of Padua, Via Ospedale Civile 105, 35128, Padua, Italy. E-mail: paoloprandoni{at}tin.it
Background and Objectives: While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence.
Design and Methods: We followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion.
Results: After a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5–12.5) after 1 year, 19.6% (17.5–21.7) after 3 years, 29.1% (26.3–31.9) after 5 years, and 39.9% (35.4–44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82–2.90) in patients whose first VTE was unprovoked, 2.02 (1.52–2.69) in those with thrombophilia, 1.44 (1.03–2.03) in those presenting with primary DVT, 1.39 (1.08–1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06–1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change.
Interpretation and Conclusions: Besides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age.
Key words: venous thrombosis, venous thromboembolism, deep vein thrombosis, pulmonary embolism, anticoagulation, thrombophilia, heparin, warfarin.
Approximately one-third of the patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) fail to respond. Positioning the left ventricular (LV) pacing lead in the area of ...the latest electrical delay may improve the response to CRT. Multipoint pacing (MPP) of the LV has been shown to improve the acute hemodynamic response.
The purpose of this study was to test the hypothesis that patients treated with MPP in whom LV pacing location is optimized have better long-term clinical outcomes than do patients treated with conventional CRT.
We evaluated the echocardiographic and clinical response of 110 patients with HF treated for nearly 1 year with either conventional CRT (standard STD group, n = 54, 49%), CRT with hemodynamic and electrical optimization of the LV pacing site (optimized OPT group, n = 36, 33%), or OPT combined with MPP (OPT + MPP group, n = 20, 18%). Responders were classified in terms of reduction in end-systolic volume index ≥15%, reduction in New York Heart Association (NYHA) class ≥1, and Packer score variation (NYHA response with no HF-related hospitalization events or death).
In STD, OPT, and OPT + MPP groups, 56%, 72%, and 90% of patients, respectively, were end-systolic volume index responders (P = .004) and 67%, 78%, and 95% were NYHA class responders (P = .012); 59%, 67%, and 90% of patients exhibited a 1-year Packer score of 0 (P = .018). These trends remained significant after adjustment for confounding factors by multivariate logistic analysis.
Combining MPP with optimal positioning of the LV lead on the basis of electrical delay and hemodynamics enhances reverse remodeling and improves clinical outcomes beyond the effect due to conventional CRT.
Objective The goal of this study was to evaluate the role of intraoperative aneurysm sac embolization during endovascular aneurysm repair (EVAR) using a standard dose of coils and fibrin glue in the ...prevention of type II endoleak (EII). Methods Two groups were compared: 83 patients underwent standard EVAR during the period 2008-2009 (group A) and 79 patients underwent EVAR during the period 2010-2011 (group B). Computed tomography scans were evaluated with Osirix Pro 4.0 software to obtain aneurysm sac volume. EII rates at the first computed tomography scan follow-up, as well as midterm freedom from EII and freedom from related reintervention, were compared. Preoperative number of patent aortic side branches (inferior mesenteric artery, lumbar arteries, accessory renal arteries), sac thrombus, and sac volume were evaluated for their association with EII in the two groups using multiple logistic regressions. Results Patient characteristics, Society for Vascular Surgery comorbidity scores (0.85 ± 0.44 vs 0.82 ± 0.46; P = .96), and operative time (185 ± 52 vs 179 ± 49; P = .92) were similar for groups A and B. The first computed tomography scan (≤3 months) revealed a significantly larger number of EIIs in group A than in group B (23% vs 10%; P = .02). Spontaneous EII resolution occurred in 65% of patients in group A and in 79% in group B ( P = 1.0), whereas sac volume increased in 25% and 10% ( P = .63) of cases, respectively. At 18 months (range, 6 months to 4.4 years), overall mean differences in sac volume shrinkage (27 ± 12 cm3 vs 25 ± 12 cm3 ; P = .19) and freedom from EII (92% vs 96%; P = .33) were similar, whereas freedom from reintervention was significantly lower in group A (93% vs 99%; P = .03) than in group B. Multivariate analysis showed preoperative aneurysm sac volume >125 cm3 to be the only independent significant predictor of EII (odds ratio, 4.0; 95% confidence interval, 1.5-10.5; P = .005). Conclusions Although further confirmatory studies are needed, sac embolization during EVAR may be a valid approach to preventing EII and its complications during short- and midterm follow-up. More aggressive intraoperative embolization should be considered for patients with a preoperative aneurysm sac volume >125 cm3.
BACKGROUND—One of the reasons for patient nonresponse to cardiac resynchronization therapy is a suboptimal left ventricular (LV) pacing site. LV electric delay (Q-LV interval) has been indicated as a ...prognostic parameter of cardiac resynchronization therapy response. This study evaluates the LV delay for the optimization of the LV pacing site.
METHODS AND RESULTS—Thirty-two consecutive patients (23 men; mean age, 71±11 years; LV ejection fraction, 30±6%; 18 with ischemic cardiomyopathy; QRS, 181±25 ms; all mean±SD) underwent cardiac resynchronization therapy device implantation. All available tributary veins of the coronary sinus were tested, and the Q-LV interval was measured at each pacing site. The hemodynamic effects of pacing at different sites were evaluated by invasive measurement of LV dP/dtmax at baseline and during pacing. Overall, 2.9±0.8 different veins and 6.4±2.3 pacing sites were tested. In 31 of 32 (96.8%) patients, the highest LV dP/dtmax coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV dP/dtmax in all patients at each site (AR1 ρ=0.98; P<0.001). A Q-LV value >95 ms corresponded to a >10% in LV dP/dtmax. An inverse correlation between paced QRS duration and improvement in LV dP/dtmax was seen in 24 patients (75%).
CONCLUSIONS—Pacing the LV at the latest activated site is highly predictive of the maximum increase in contractility, expressed as LV dP/dtmax. A positive correlation between Q-LV interval and hemodynamic improvement was found in all patients at every pacing site, a value of 95 ms corresponding to an increase in LV dP/dtmax of ≥10%.
Response to cardiac resynchronization therapy (CRT) remains challenging. Pacing from multiple sites of the left ventricle (LV) has shown promising results.
The purpose of this study was to ...systematically compare the acute hemodynamic effects of multipoint pacing (MPP) by means of a quadripolar lead with conventional biventricular (BiV) pacing.
Twenty-nine patients (23 men; mean age 72 ± 12 years; LV ejection fraction 29% ± 7%; 15 with ischemic cardiomyopathy, 17 with left bundle branch block; mean QRS 183 ± 23 ms) underwent CRT implantation. Per patient, 3.2 ± 1.2 different veins and 6.3 ± 2.4 pacing sites were tested. LV electrical delay (Q-LV) was measured at each location, along with the increase in LV dP/dtmax (maximum rate of rise of LV pressure) obtained by BiV and MPP. The effect of MPP, by means of simultaneous pacing from distal and proximal dipoles, was investigated at all available sites.
Overall, 3.2 ± 1.2 different MPP measurements were collected per patient. When all sites were considered, LV dP/dtmax increased from 951 ± 193 mm Hg/s at baseline to 1144 ± 255 and 1178 ± 259 mm Hg/s on BiV and MPP, respectively. When the best site was considered, LV dP/dtmax increased from a baseline value of 942 ± 202 mm Hg/s to 1200 ± 267 mm Hg/s (BiV) and 1231 ± 267 mm Hg/s (MPP). The mean QRS duration at any site during MPP and conventional CRT was 171 ± 18 and 175 ± 16 ms (P = .003), respectively.
Compared with BiV pacing at any LV site, MPP yielded a small but consistent increase in hemodynamic response. A correlation between the increase in hemodynamics and Q-LV on MPP was observed for all measurements, including those taken at the best and worst sites. The MPP-induced improvement in contractility was associated with significantly greater narrowing of the QRS complex than conventional BiV pacing.
In chronic hepatitis C, biopsy is the gold standard for assessment of liver fibrosis. Non-invasive markers have been proposed but their use is limited by diagnostic accuracy. Our aim was to increase ...the diagnostic performance of non-invasive markers of liver fibrosis by combining them in sequential algorithms.
One hundred and ninety patients with chronic hepatitis C were evaluated for AST to platelets ratio (APRI), Forns' index and Fibrotest at the time of liver biopsy and stepwise combination algorithms were developed and validated prospectively in 100 additional patients.
Three algorithms were developed: (1) significant fibrosis (
F≥2 by METAVIR) was identified with high diagnostic performance (>94% accuracy) using APRI as screening test, followed by Fibrotest in APRI non-classified cases and restricting liver biopsy to patients classified F0–F1 by non-invasive tests. (2) A slightly modified algorithm had similar performance when applied to hepatitis C carriers with normal ALT. (3) Identification of cirrhosis (95% accuracy) was achieved using a dedicated algorithm with different cut-off, reducing by 60–70% the liver biopsies needed.
Stepwise combination of non-invasive markers of liver fibrosis improves the diagnostic performance in chronic hepatitis C. Need for liver biopsy is reduced by 50–70% but cannot be completely avoided.
Summary
Among the so called‘antiphospholipid antibodies’, the presence of Lupus Anticoagulant (LA) is associated with thrombosis-related events and defines the antiphospholipid syndrome. The role of ...anti-cardiolipin (aCL) antibodies and anti-human β2-glycoprotein I (aβ2GPI) antibodies is less striking. Since the problem of standardization for these tests is far from resolved, we evaluated whether the combination of results (antiphospholipid laboratory profiles) could help to better classify these patients. Over a 6-year period, 618 consecutive subjects (55% of whom had previous documented thrombosis-related events) were referred to our clinic for Antiphospholipid antibody detection. LA was detected according to internationally accepted recommendations. ACL and aβ2GPI antibodies were detected by Enzyme-Linked-Immunosorbent Assay (ELISA). Patients’ records were reviewed for the presence of previous thromboembolic events or obstetric complications according to Sapporo’s clinical criteria for the diagnosis of antiphospholipid syndrome (APS) and each patient underwent a physical examination. When individual tests were considered in a multivariate analysis which took into account age, gender, the presence of SLE or other autoimmune diseases and established risk factors for venous and arterial thromboembolism, LA (Odds Ratio 4.4, Confidence Interval 1.5–13.3) and aβ2GPI antibodies (Odds Ratio 2.9, Confidence Interval 1.1–7.5) but not aCL antibodies (Odds Ratio 1.2, Confidence Interval 0.5–2.7) were found to be independent risk factors for thrombosis-related events. When antiphospholipid antibody profiles instead of individual test positivity were analyzed in the above mentioned model, triple positivity resulted a strong independent risk factor (Odds Ratio 33.3, Confidence Interval 7.0–157.6), retaining its significance when the association with venous or arterial thromboembolism was considered. Double positivity with negative LA was close to significance for thrombosis-related events (Odds Ratio 2.2, Confidence Interval1.0–5.2, p=0.056) and highly significant risk factor for obstetric complications (Odds Ratio 10.8, Confidence Interval 2.9–40.8). Other combinations did not reach statistical significance. The mean level of IgG aβ2GPI antibodies was statistically higher in triple positive profile and might account for positive LA. As compared to a single test, the analysis of a complete antiphospholipid antibody profile can better determine patients at risk.
Chronic hepatitis B is usually a benign disease in Caucasian children; however, the long-term prognosis remains unsettled. This report describes the results of a 29-year longitudinal study including ...99 white children with chronic hepatitis B, mainly acquired horizontally: 91 were hepatitis B e antigen (HBeAg) positive (4 had cirrhosis), and 8 were HBeAg negative at presentation. Of the 91 HBeAg-positive children, 89 underwent HBeAg seroconversion after a mean period of 5.2 +/- 4.0 years and were included in the study. Of the 85 children without cirrhosis, one had HBeAg-negative hepatitis and the other 84 became inactive carriers. During a mean follow-up of 14.5 +/- 6.1 years after HBeAg seroclearance, 4 carriers experienced reactivation, and 3 of them had HBeAg-negative hepatitis at the last follow-up. Of the 8 initially HBeAg-negative children, 2 had HBeAg-negative hepatitis, and 6 were inactive carriers. Of the 4 children with cirrhosis, 2 had hepatocellular carcinoma (HCC) and remained alive and 2 lost the histological features of cirrhosis in adulthood. Two patients with HBeAg-negative hepatitis and 1 with cirrhosis had experienced drug abuse. At the end of follow-up, 15 of the 89 initially HBeAg-positive patients and 2 of 8 initially HBeAg-negative children had cleared hepatitis B surface antigen. In conclusion, the overall prognosis for chronic hepatitis B in horizontally infected Caucasian children is favorable; however, some patients progress to HCC and HBeAg-negative hepatitis. Long-term monitoring is important, as is counseling on cofactors of liver damage, such as alcohol and drug abuse.
Background
Whether the carriership of inherited antithrombin (AT), protein C (PC), and protein S (PS) deficiency increases the risk of arterial thromboembolic events (ATE) is controversial. This ...information has the potential to inform the management of family members of probands with inherited deficiency of natural anticoagulants.
Patients/methods
We conducted a large prospective family cohort study in 640 subjects (of whom 341 carriers and 299 non-carriers) belonging to 86 families with inherited deficiency of AT, PC, or PS.
Results
A total of 4240 and 3810 patient-years were available for carriers and non-carriers, respectively. Risk factors for atherosclerosis were similarly distributed in the two groups. Of the 26 ATE that were recorded, 19 occurred in carriers (5.6%), as compared to 7 in non-carriers (2.3%)
p
= 0.07. After adjusting for confounders, the hazard ratio (HR) for ATE was 4.9 (95% CI 1.5–16.3) in carriers as compared to non-carriers.
Conclusions
Among family members of probands with an inherited deficiency of natural anticoagulants, carriers exhibit a risk of ATE that is almost five times higher than in non-carriers.
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