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Background: Exertional dyspnea is a frequently encountered complaint in clinical practice. However, the prevalence of pulmonary embolism (PE) among patients with dyspnea on exertion has not been reported. Objective: The objective of this study was to assess the prevalence of objectively confirmed PE among consecutive patients visiting an emergency department because of recent onset of exertional dyspnea. Methods: Patients aged ≤75 years with recent (

Aims In patients with prolonged atrioventricular (AV) conduction and pacemaker (PM) indication due to sinus node disease (SND) or intermittent AV-block who do not need continuous ventricular pacing (VP), it may be difficult to determine which strategy to adopt. Currently, the standard of care is to minimize unnecessary VP by specific VP avoidance (VPA) algorithms. The superiority of this strategy over standard DDD or DDD rate-responsive (DDD/DDDR) in improving clinical outcomes is controversial, probably owing to the prolongation of the atrialventricular conduction (PR interval) caused by the algorithms. Conduction system pacing (CSP) may offer the most physiological-VP approach, providing appropriate AV conduction and preventing pacing-induced dyssynchrony. Methods and results PhysioVP-AF is a prospective, controlled, randomized, single-blind trial designed to determine whether atrial-synchronized conduction system pacing (DDD-CSP) is superior to standard DDD-VPA pacing in terms of 3-year reduction of persistent-AF occurrence. Cardiovascular hospitalization, quality-of-life, and safety will be evaluated. Patients with indication for permanent DDD pacing for SND or intermittent AV-block and prolonged AV conduction (PR interval > 180 ms) will be randomized (1:1 ratio) to DDD-VPA (VPA-algorithms ON, septal/apex position) or to DDD-CSP (His bundle or left bundle branch area pacing, AV-delay setting to control PR interval, VPA-algorithms OFF). Approximately 400 patients will be randomized in 24 months in 13 Italian centres. Conclusion The PhysioVP-AF study will provide an essential contribution to patient management with prolonged AV conduction and PM indication for sinus nodal disease or paroxysmal 2nd-degree AV-block by determining whether CSP combined with a controlled PR interval is superior to standard management that minimizes unnecessary VP in terms of reducing clinical outcomes.

Micro-Abstract In this limited retrospective analysis, we report on 52 “high risk” AL amyloidosis patients treated with first line bortezomib based chemotherapy. Achieving a hematological complete response (CR+VGPR) at day 30 confirmed its prognostic value. Nevertheless, patients who reached a suboptimal response (PR) at day 30 have a reasonable chances of survival, and do not necessarily need a change in therapeutic strategy even in the face of permissive clinical conditions. On the other hand, an early identification of NR patients should prompt a shift in therapy trying to improve the well-known dismal prognosis of these patients. We have also shown that even “high-risk” AL amyloidosis patients can be managed safely and effectively in a hematology ward. Purpose To assess the feasibility and the results of Bortezomib-based treatment of “high-risk” AL-amyloidosis patients in a hematology ward. Methods We report on 52 high-risk amyloidosis patients treated with first-line bortezomib-based chemotherapy. Results At day 30 from the beginning of the therapy, 23 patients (44%) achieved a hematological response (complete response plus very good partial response); 14 patients (27%) achieved a partial response; 15 patients (29%) were non-responders. After a median follow-up of 28.5 months, the survival rates were 18/23 (78%) for responders; 9/14 (64%) for partial responders and 3/15 (20%) for non-responders with a median overall survival of 43, 24 and 11 months, respectively (log-rank test: p Conclusions These results show that high-risk AL-amyloidosis patients can be managed safely and effectively in a hematology ward. A partial hematologic response may herald a later better response, organ response, and can allow a subsequent second-line therapy and a good survival.

Introduction In patients with sinus node disease (SND), the dual-chamber pacemaker (PM) is programmed in DDDR mode with an algorithm to avoid unnecessary right ventricular (RV) pacing. This pacing mode may prolong PR interval with consequently atrioventricular (AV) asynchrony which is associated with a higher risk of atrial fibrillation (AF). We evaluate whether preserving AV synchrony by setting a fixed AV delay during physiological RV pacing, that is, His bundle pacing (HBP), could reduce the risk of AF occurrence in comparison with a standard pacing mode with an algorithm to avoid unnecessary RV pacing (DDD-VPA). Methods and results We collected retrospective data from 313 consecutive patients who had undergone PM for SND. The first occurrence of persistent AF (>7 consecutive days) as a function of the pacing mode was evaluated. HBP and DDD-VPA were implemented in 82 and 231 patients, respectively. Persistent AF occurred in 128 (40.9%) patients over a median follow-up of 70 months (67-105). The DDD-VPA pacing mode was significantly correlated with the occurrence of persistent AF only when the basal PR was long (>180 ms). The risk of persistent AF was significantly lower in patients on HBP than in those on DDD-VPA, adjusted HR = .57 (95% CI, .36- .89, p=.014). Other independent predictors of persistent AF occurrence were: A history of AF (HR = 3.91; 95% CI, 2.48-6.19, p = .001), age, and long PR interval (HR = 2.98; 95% CI, 2.00-4.43, p=.001). Conclusion In SND patients and long basal PR interval, the HBP may reduce the risk of persistent AF in comparison with the DDD-VPA.

Background: Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are lacking. Aim: To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD). Methods: All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included. Results: Among 3264 patients [65% males, 67% cirrhotics, eGFR 88 (9–264) ml/min], CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33–45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively). Conclusions: During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.

Real-life studies complement data from registrative trials. Because of the delayed registration of direct oral anticoagulants in Italy, scarce real-life data on such treatments is available for the Italian population. The aim of the MAC project is to collect real-life clinical information in unselected patients given oral anticoagulants for venous thromboembolism, during a 5-year follow-up period. This is a prospective-cohort, multi-center, observational study performed in four Italian centers. The estimated samples size is 4,000 patients. The efficacy outcomes are: incidence of symptomatic recurrent venous thromboembolism and of post-thrombotic syndrome. The safety outcomes are: incidence of major bleeding, clinically relevant non-major bleeding, minor bleeding, serious adverse events, and mortality. The MAC project has the potential to improve our understanding of the epidemiology and of the therapeutic strategies adopted in Italian patients with venous thromboembolism.Clinical Trial Registration: WWW.ClinicalTrials.Gov, identifier: NCT0432939.

Background & Aims: In the direct-acting antiviral era, treatment of genotype-3 HCV (HCV-GT3) is still challenging. Real-life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir (DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap. Methods: Sustained virological response 12weeks after treatment completion (SVR12) was assessed for all HCV-GT3 patients consecutively treated within the Lombardia web-based Navigatore HCV-Network; differences in SVR12 across regimens were evaluated by logistic regression. Results: Of the 2082 subjects with HCV-GT3, 1544 were evaluable for comparisons between regimens: SOF+DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV-positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV-RNA. SVR12 was similar across groups: 94.8% in SOF+DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P=.065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P=.007) and lower median pretreatment Log10HCV-RNA (5.87 vs 6.20, P=.001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF+DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV-RNA were independently associated with SVR12. Conclusions: In a large real-life setting of HCV-GT3-infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF+DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier-to-treat patients allows ribavirin-free and shorter schedules without mining SVR12 in this <> genotype.

Despite thromboprophylaxis, patients with coronavirus‐19 disease (COVID‐19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of the study was to evaluate the incidence of venous thromboembolism in COVID‐19 patients admitted to both intensive care unit and medical ward. Consecutive patients admitted for COVID‐19 to medical ward and intensive care unit at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of internal jugular, upper and lower limbs veins every 7(±1) days after the admission; and if negative, once‐weekly until discharge or death. In case of suspected pulmonary embolism, a multi‐detector computed tomographic angiography was performed. The primary outcome was the proportion of any deep‐vein thrombosis and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020 a total of 85 patients were investigated, 44 (52%) in medical ward and 41 (48%) in intensive care unit. Despite thromboprophylaxis, venous thromboembolism occurred in 12 medical ward (27.3%) and 31 intensive care unit patients (75.6%) with an Odds Ratio of 9.3 (95%CI, 3.5 to 24.5;p

Background: Despite thromboprophylaxis, patients with COVID-19 exhibit intense coagulation activation and higher risk of venous thromboembolism (VTE), even though the real VTE incidence is still unknown. We evaluated the incidence of objectively documented VTE in COVID-19 patients admitted to both intensive care unit (ICU) and medical ward (MW). Methods: Consecutive patients admitted for COVID-19 to MW and ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of internal jugular, upper and lower limbs veins every 7(±1) days after the admission; and if negative, once-weekly until discharge or death. In case of suspected pulmonary embolism, a multi-detector computed tomographic angiography was performed. The primary outcome was the proportion of any deep-vein thrombosis and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. Findings: From March 4 to April 30, 2020 a total of 85 patients were investigated, 44 (52%) in MW and 41 (48%) in ICU. Despite thromboprophylaxis, VTE occurred in 12 MW (27·3%) and 31 ICU patients (75·6%) with an OR of 9·3 (95%CI, 3·5 to 24·5, p

PurposeIn order to increase the responder rate to CRT, stimulation of the left ventricular (LV) from multiple sites has been suggested as a promising alternative to standard biventricular pacing (BIV). The aim of the study was to compare, in a group of candidates for CRT, the effects of different pacing configurationsBIV, triple ventricular (TRIV) by means of two LV leads, multipoint (MPP), and multipoint plus a second LV lead (MPP + TRIV) pacingon both hemodynamics and QRS duration.MethodsFifteen patients (13 male) with permanent AF (mean age 767years; left ventricular ejection fraction 337%; 7 with ischemic cardiomyopathy; mean QRS duration 178 +/- 25ms) were selected as candidates for CRT. Two LV leads were positioned in two different branches of the coronary sinus. Acute hemodynamic response was evaluated by means of a RADI pressure wire as the variation in LVdp/dtmax.Resultsp id="Par3"Per patient, 2.7 +/- 0.7 veins and 5.2 +/- 1.9 pacing sites were evaluated. From baseline values of 998 +/- 186mmHg/s, BIV, TRIV, MPP, and MPP-TRIV pacing increased LVdp/dtmax to 1200 +/- 281mmHg/s, 1226 +/- 284mmHg/s, 1274 +/- 303mmHg, and 1289 +/- 298mmHg, respectively (p

Aims We tested the hypothesis that atrioventricular (AV) junction ablation in conjunction biventricular pacing [cardiac resynchronization (CRT)] pacing is superior to pharmacological rate-control therapy in reducing heart failure (HF) and hospitalization in patients with permanent atrial fibrillation (AF) and narrow QRS. Methods and results We randomly assigned 102 patients (mean age 72 ± 10 years) with severely symptomatic permanent AF (>6 months), narrow QRS (≤110 ms), and at least one hospitalization for HF in the previous year to AV junction ablation and CRT (plus defibrillator according to guidelines) or to pharmacological rate-control therapy (plus defibrillator according to guidelines). After a median follow-up of 16 months, the primary composite outcome of death due to HF, or hospitalization due to HF, or worsening HF had occurred in 10 patients (20%) in the Ablation+CRT arm and in 20 patients (38%) in the Drug arm [hazard ratio (HR) 0.38; 95% confidence interval (CI) 0.18-0.81; P = 0.013]. Significantly fewer patients in the Ablation+CRT arm died from any cause or underwent hospitalization for HF [6 (12%) vs. 17 (33%); HR 0.28; 95% CI 0.11-0.72; P = 0.008], or were hospitalized for HF [5 (10%) vs. 13 (25%); HR 0.30; 95% CI 0.11-0.78; P = 0.024]. In comparison with the Drug arm, Ablation+CRT patients showed a 36% decrease in the specific symptoms and physical limitations of AF at 1 year follow-up (P = 0.004). Conclusion Ablation+CRT was superior to pharmacological therapy in reducing HF and hospitalization and improving quality of life in elderly patients with permanent AF and narrow QRS. Clinicaltrials.gov identifier NCT02137187 (May 2018, date last accessed).

The association between venous and arterial thrombotic disorders is still unclear. We assessed the association between residual vein thrombosis (RVT) and subclinical atherosclerosis in a cohort of patients with unprovoked (or associated with weak risk factors) proximal deep-vein thrombosis (DVT).In a multicenter cross-sectional study, consecutive patients over 40years free from atherosclerotic disorders received the ultrasound assessment of the leg vein system and that of carotid arteries approximately three months after an episode of proximal DVT. In each center the evaluation was done by two independent assessors. The presence of RVT was defined as the incompressibility of at least 4mm in either the popliteal or the common femoral vein, and that of subclinical atherosclerosis as the presence of increased (0.9mm) intima-media tickness (IMT) and/or carotid plaques.Out of 252 patients (mean age, 67; males, 53%; unprovoked, 77%), the presence of RVT was found in 139 (55.2%). An increased IMT was shown in 76 (54.7%) patients with and in 35 (31.0%) without RVT (p0.001). At least one carotid plaque was found in 80 (57.6%) patients with and in 36 (31.9%) without RVT (p0.001). After adjusting for the baseline characteristics, the odds ratio of subclinical atherosclerosis (increased IMT and/or carotid plaques) was 2.8 (95% CI, 1.6 to 4.7).The ultrasound detection of RVT after an episode of proximal DVT that is either unprovoked or triggered by weak risk factors is associated with a higher prevalence of subclinical atherosclerosis. These findings may have implications for patient prognosis.

Background The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. Methods In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4 mm of incompressibility of the proximal veins. Results RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48–0.81) after three months, and 0.17 (95% CI; 0.11–0.26) after six months. Conclusions In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

Background & Aims Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. Methods All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. Results A total of 179 patients were included: median age 57 (18–88) years, 74% males, median HCV-RNA 1,081,817 (482–25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). Conclusions SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. Lay summary This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.

Estimating left ventricular electrical delay (Q-LV) from a 12-lead ECG may be important in evaluating cardiac resynchronization therapy (CRT).The purpose of this study was to assess the impact of Q-LV interval on ECG configuration.One hundred ninety-two consecutive patients undergoing CRT implantation were divided electrocardiographically into 3 groups: left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (IVCD). The IVCD group was further subdivided into 81 patients with left (L)-IVCD and 15 patients with right (R)-IVCD (resembling RBBB, but without S wave in leads I and aVL). The Q-LV interval in the different groups and the relationship between ECG parameters and the maximum Q-LV interval were analyzed.Patients with LBBB presented a long Q-LV interval (147.7 ± 14.6 ms, all exceeding cutoff value of 110 ms), whereas RBBB patients presented a very short Q-LV interval (75.2 ± 16.3 ms, all110 ms). Patients with an IVCD displayed a wide range of Q-LV intervals. In L-IVCD, mid-QRS notching/slurring showed the strongest correlation with a longer Q-LV interval, followed, in decreasing order, by QRS duration150 ms and intrinsicoid deflection60 ms. Isolated mid-QRS notching/slurring predicted Q-LV interval110 ms in 68% of patients. The R-IVCD group presented an unexpectedly longer Q-LV interval (127.0 ± 12.5 ms; 13/15 patients had Q-LV110 ms).Patients with LBBB have a very prolonged Q-LV interval. Mid-QRS notching in lateral leads strongly predicts a longer Q-LV interval in L-IVCD patients. Patients with R-IVCD constitute a subgroup of patients with a long Q-LV interval.

Background: Chronic venous disease (CVD) is a common clinical condition, especially relevant for its impact on public health and its related economic burden. Veno-Active Drugs (VAD) are an heterogeneous group of drugs, widely used in the treatment of CVD. In the last years some food supplements, similar to VAD but with different compounds concentrations raised some confusion in this field. The complex Lypoic acid, Ginkgoselect phytosome and Leucoselect phytosome is a food supplement based on molecules exhibiting different but synergic activities never prospectively tested in patients with CVD. Methods: Consecutive ambulatory patients with objectively documented CVD and a CEAP “C” up to 5 were eligible for the study. Patients were to take 1 fast-slow tablet of the complex twice-daily for 2 months, followed by 1 fast-slow tablet once-daily for other 4 months, for a total of 6 months. Presence and magnitude of CVD-related signs and symptoms (with “C” of the CEAP classification), evaluation of patients’ quality of life (with VEINES-QoL/Sym questionnaire) and assessment of safety and tolerability of the complex at baseline and after 2 and 6 months (with revised Venous Clinical Severity Score, rVCSS) were recorded. Results: 97 patients enrolled and evaluated. The proportion (65%) of the patients with a rVCSS score>5 at baseline decreased to 35% at 6 months (P

Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of hepatocellular carcinoma (HCC) during/after therapy with DAAs. The aim of this study was to evaluate the incidence of newly diagnosed HCC and associated risk factors in patients with advanced hepatitis C treated with DAAs.The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in the Veneto region of Italy. The inclusion criteria were: fibrosis stage ≥F3. The exclusion criteria were: Child-Turcotte-Pugh (CTP)-C, liver transplantation before DAAs, history or presence of HCC, follow-up4 weeks after starting DAAs. A total of 3,917 out of 4,234 consecutive patients were included, with a mean follow-up of 536.2 ± 197.6 days.Overall, HCC was diagnosed in 55 patients. During the first year, HCC incidence was 0.46% (95% CI 0.12-1.17) in F3, 1.49% (1.03-2.08) in CTP-A and 3.61% (1.86-6.31) in CTP-B cirrhotics; in the second year, HCC incidences were 0%, 0.2%, and 0.69%, respectively. By multivariate analysis, HCC was significantly associated with an aspartate aminotransferase to platelet ratio ≥2.5 (hazard ratio [HR] 2.03; 95% CI 1.14-3.61; p = 0.016) and hepatitis B virus infection (HR 3.99; 1.24-12.91; p = 0.021). Failure to achieve a sustained virological response was strongly associated with development of HCC (HR 9.09; 5.2-16.1; p = 0.0001). A total of 29% of patients with HCC had an aggressive tumor, often seen in the early phase of treatment.These data, obtained in a large, prospective, population-based study, indicate that in patients with advanced hepatitis C receiving DAAs, the risk of "de novo" hepatocarcinoma during the first year is not higher, and might be lower, than that of untreated patients. The risk further declines thereafter. Early hepatocarcinoma appearance may reflect pre-existing, microscopic, undetectable tumors.Hepatocellular carcinoma is one of the complications of hepatitis C related cirrhosis. Treating patients with advanced hepatitis C with the new interferon-free direct-acting antiviral agents has been associated with improvement in liver function and survival, while more conflicting data have been reported regarding the risk of hepatocellular carcinoma. We report the results of a prospective population study on the incidence of newly diagnosed hepatocellular carcinoma in patients with advanced hepatitis C treated with direct-acting antiviral agents, clearly indicating that the residual hepatocellular carcinoma risk is reduced and declines progressively with time after a sustained virological response. Development of a liver tumor during/after therapy was associated with known risk factors and with virological failure.

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 d P /d t max 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 d P /d t max coincided with the maximum Q-LV interval. Q-LV interval correlated with the increase in LV d P /d t max in all patients at each site (AR1 ρ=0.98; P 95 ms corresponded to a >10% in LV d P /d t max . An inverse correlation between paced QRS duration and improvement in LV d P /d t max 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 d P /d t max . 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 d P /d t max of ≥10%.

Aims Right ventricular apex (RVA) pacing has adverse effects on left atrial (LA) function and may contribute to atrial arrhythmias. The effects of Hisian area (HA) pacing on LA function are still lacking. The objective of this study is to assess the left ventricular (LV) electromechanical activation/relaxation, systolic (S), diastolic (D) phases, and their effects on LA function during pacing from HA and RVA. Methods and results Thirty-seven patients with normal cardiac function underwent permanent HA pacing. In all patients, a RVA backup lead was added. The patients first underwent 3 months of HA pacing, followed by 3 months of RVA pacing. After each 3-month period, we compared by echocardiography: S–D LV electromechanical delay (S–D EMD), S–D intra-LV dyssynchrony, LV S–D phases, and their function evaluated by myocardial performance index (MPI) and mitral annular tissue Doppler early diastolic velocity ( E ′), pulmonary arterial systolic pressure (PASP), and LA function (LA phasic volumes and their emptying fraction). Right ventricular apex compared with HA pacing increased S–D EMD ( P < 0.001) and intra-LV dyssynchrony ( P < 0.001). As a consequence, a significant longer LV isovolumetric contraction time ( P < 0.001) and LV isovolumetric relaxation time ( P = 0.05) were measured during RVA compared with HA pacing, whereas LV ejection time was shorter ( P = 0.033). Moreover, HA pacing resulted in significantly better MPI ( P = 0.039), higher value of E ′ ( P = 0.049), and lower PASP ( P < 0.001). Finally, RVA compared with HA pacing was associated to higher LA volumes pre-atrial contraction ( P = 0.001) and minimal volume ( P = 0.003) with reduction in passive emptying fraction ( P < 0.001) and total emptying fraction ( P = 0.005). Conclusion Hisian area compared with RVA pacing resulted in a more physiological LV electromechanical activation/relaxation and consequently better LA function.

Background 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. Objective 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. Methods 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). Results 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. Conclusion 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.

Background: The right ventricular septum (RVS) and Hisian area (HA) are considered more “physiological” pacing sites than right ventricular apex (RVA). Studies comparing RVS to RVA sites have produced controversial results. There are no data about variability of electromechanical activation obtained by an approach using fluoroscopy and electrophysiological markers. This study compared the variability of left ventricular (LV) electromechanical activation in patients undergoing short-term RVA and RVS with that measured during HA pacing based on fluoroscopy and electrophysiological markers. Methods: Tissue Doppler echocardiography was performed in 142 patients before and after RVA (54), RVS (44), and HA (44) pacing. Electromechanical activation was assessed by: (1) electromechanical latency (EML)-interval between QRS onset and mechanical activation of basal LV; (2) intra-LV dyssynchrony (intra-LV)-interval between earliest to the latest LV basal motion. The intra- and interpatients variability among pacing groups were assessed. Results: Pacing from RVA showed longer EML and higher degree of intra-LV than RVS and HA pacing. RVA and RVS showed a higher variability than HA pacing with regard to intrapatient changes of EML (RVA vs RVS, P = 0.4; RVS vs HA, P = 0.01, RVA vs HA, P = 0.0002) and intra-LV (RVA vs RVS, P = 0.2; RVS vs HA, P = 0.04; RVA vs HA, P = 0.005). Similar results were found in interpatients variability from paced-values. Conclusions: RVA and RVS pacing produce a variable effect on LV electromechanical activation that is significantly more pronounced than HA pacing. A pacing site such as HA selected by fluoroscopic and electrophysiological markers maintains baseline and homogeneous LV activation pattern. (PACE 2010; 566–574)

Giuseppe Camporese1, Enrico Bernardi2, Franco Noventa31Unit of Angiology and 3Department of Clinical and Experimental Medicine, Clinical Epidemiology Group, University Hospital of Padua, Italy; 2Department of Emergency and Accident Medicine, Hospital of Conegliano Veneto, ItalyAbstract: Parnaparin is a low-molecular-weight heparin that has widely shown its efficacy and safety in prevention of venous thromboembolism, in the treatment of chronic venous disorders, and in the treatment of venous and arterial (stable and unstable angina, acute ST-segment elevation myocardial infarction) thrombosis. Parnaparin at the respective dosages of 3200, 4250, 6400, or 12800 IUaXa for a period ranging from 3 to 5 days to 6 months, is usually administered subcutaneously by means of once-daily regimen and is better tolerated than unfractionated heparin at the injection site. In the variety of commercially available low-molecular-weight heparins, parnaparin represents a useful therapeutic option, even though little evidence is available comparing the superiority or the equivalent efficacy and safety of parnaparin to that of the unfractionated heparin or placebo. This review summarizes the available literature on the use of parnaparin in different settings of cardiovascular diseases, including papers published during the past year and ongoing studies.Keywords: low-molecular-weight heparin, heparin, parnaparin, acute coronary syndromes, venous thromboembolism

The aim of the study was to determine variables that could be used to predict survival in patients with ruptured abdominal aortic aneurysm (RAAA) and to assess the accuracy of the Glasgow Aneurysm Score (GAS) and the Acute Physiology Chronic Health Evaluation II (APACHE-II). From January 1998 to July 2006, 103 patients underwent operations for RAAA. For each patient, 44 variables were retrospectively recorded in a database. Data were analyzed with univariate and multivariate methods. In the univariate analysis significant predictors of death were hypotension (p=0.001), preexisting peripheral vascular disease (p0.001), renal insufficiency (p=0.037), chronic obstructive pulmonary disease (p=0.028), level of HCO(3)(-) (p0.001), intraperitoneal rupture (p=0.001), blood transfused (p0.001), cardiac complications (p0.001), and APACHE-II score (p=0.001). Multivariate analysis confirmed statistical significance for coexisting peripheral vascular disease (p0.001), diastolic blood pressure at admission60 mm Hg (p=0.039), APACHE-II score18.5 (p=0.025), HCO(3)(-)21 mg/dL (p0.001), and intraperitoneal rupture of the aneurysm (p=0.011) as predictors of death. Results of the study suggested that different factors can be helpful in identifying those patients whose operative risk is prohibitive. APACHE-II, contrary to GAS, is an accurate system to predict postoperative death after repair for RAAA.

El objetivo de este estudio fue determinar las variables de utilidad para predecir la supervivencia en los pacientes con rotura de aneurisma aortico abdominal (RAAA) y evaluar la precision de los sistemas de puntuacion Glasgow Aneurysm Score (GAS) y Acute Physiology Chronic Health Evaluation II (APACHE-II). Entre enero de 1998 y julio de 2006, 103 pacientes fueron sometidos a intervenciones con RAAA. En cada paciente se registraron 44 variables de forma retrospectiva en una base de datos. Los datos fueron analizados mediante metodos uni y multivariante. En el analisis multivariante, los factores significativos predictores de fallecimiento fueron: hipotension (p = 0,001), vasculopatia periferica preexistente (p 18,5 (p = 0,025), HCO-3

Les buts de l'etude etaient de determiner les variables qui pourraient etre employees pour prevoir la survie des patients presentant un anevrysme de l'aorte abdominale rompu (AAAR) et d'evaluer l'exactitude des scores Glasgow pour anevrysme (GAS) et APACHE-II. De janvier 1998 a juillet 2006, 103 patients ont ete operes pour AAAR. Pour chaque patient, 44 variables ont ete retrospectivement enregistrees dans une base de donnees. Les donnees ont ete analysees avec des methodes univariees et multivariees. Dans l'analyse univariee les facteurs predictifs significatifs de mortalite etaient l'hypotension (p = 0,001), l'existence d'une atteinte vasculaire peripherique (p 18.5 (p = 0,025), du taux de HCO3

The staging of liver fibrosis is pivotal for defining the prognosis and indications for therapy in hepatitis C. Although liver biopsy remains the gold standard, several noninvasive methods are under evaluation for clinical use. The aim of this study was to validate the recently described sequential algorithm for fibrosis evaluation (SAFE) biopsy, which detects significant fibrosis (≥F2 by METAVIR) and cirrhosis (F4) by combining the AST-to-platelet ratio index and Fibrotest-Fibrosure, thereby limiting liver biopsy to cases not adequately classifiable by noninvasive markers. Hepatitis C virus (HCV) patients (2035) were enrolled in nine locations in Europe and the United States. The diagnostic accuracy of SAFE biopsy versus histology, which is the gold standard, was investigated. The reduction in the need for liver biopsies achieved with SAFE biopsy was also assessed. SAFE biopsy identified significant fibrosis with 90.1% accuracy (area under the receiver operating characteristic curve = 0.89; 95% confidence interval, 0.87-0.90) and reduced by 46.5% the number of liver biopsies needed. SAFE biopsy had 92.5% accuracy (area under the receiver operating characteristic curve = 0.92; 95% confidence interval, 0.89-0.94) for the detection of cirrhosis, obviating 81.5% of liver biopsies. A third algorithm identified significant fibrosis and cirrhosis simultaneously with high accuracy and a 36% reduction in the need for liver biopsy. The patient's age and body mass index influenced the performance of SAFE biopsy, which was improved with adjusted Fibrotest-Fibrosure cutoffs. Two hundred two cases (9.9%) had discordant results for significant fibrosis with SAFE biopsy versus histology, whereas 153 cases (7.5%) were discordant for cirrhosis detection; 71 of the former cases and 56 of the latter cases had a Fibroscan measurement within 2 months of histological evaluation. Fibroscan confirmed SAFE biopsy findings in 83.1% and 75%, respectively. Conclusion: SAFE biopsy is a rational and validated method for staging liver fibrosis in hepatitis C with a marked reduction in the need for liver biopsy. It is an attractive tool for large-scale screening of HCV carriers. (HEPATOLOGY 2009.)