OUTpatient intravenous LASix Trial in reducing hospitalization for acute decompensated heart failure (OUTLAST).

BACKGROUND: Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. METHODS: In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. RESULTS: Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. CONCLUSION: The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Physiologic Guidance of Infrainguinal Vascular Interventions Using the Pressure Wire.

OBJECTIVES: To assess the relationship between the resting (RG) and hyperemic (HG) translesional peripheral gradients, with the functional and anatomic parameters before and after an infrainguinal endovascular procedure. BACKGROUND: RGs and HGs are objective tools in defining the hemodynamic significance of an arterial stenosis. METHODS: In 25 subjects with infrainguinal arterial stenosis, RG and HG were measured via a pressure wire before and after angioplasty. Before and after the procedure, all subjects had an ankle-brachial index (ABI) and Duplex ultrasound evaluation, recording prelesion and in-lesion peak systolic velocity (PSV-L), and calculating a peak systolic velocity ratio (PSV-R). A Pearson R correlation coefficient was calculated. RESULTS: The mean age was 73 ± 12 years, 70% were men, median Rutherford class 3. At baseline and after angioplasty, mean ABI was 0.78 ± 0.2 and 0.99 ± 0.1, mean PSV-L was 459 ± 110 cm/s and 126 ± 35 cm/s, and mean PSV-R was 6.7 ± 4 and 1.2 ± 0.5, respectively. RG and HG significantly improved (P<.001) from baseline to after angioplasty (28.7 ± 20.5 mm Hg to 5 ± 13 mm Hg and 40.2 ± 21.4 mm Hg to 10 ± 13 mm Hg, respectively). RG before and after the procedure correlated well with ABI (r = -0.58; r = -0.41), PSV-L (r = 0.40; r = 0.52), and PSV-R (r = 0.46; r = 0.42). An improvement of 9 mm Hg in RG predicted a change of 0.1 in ABI. CONCLUSIONS: Improvement in RG during endovascular intervention in superficial femoral artery correlates well with the improvement in ABI, PSV-L, and PSV-R. A postprocedural decrease in RG of 9 mm HG predicts an improvement in ABI of 0.1.

Recurrent coronary artery thrombosis after anomalous right coronary artery re-implantation to the aorta.

Anomalous origin of the right coronary artery (RCA) from the pulmonary artery is a rare entity. The current recommendation is corrective operation even in asymptomatic patients when this cardiac malformation is found. We report a case of a 21-year-old male who initially presented with ST elevations. After surgical repair with re-implantation of the RCA to the aorta, he was found to have an acute thrombus in his left circumflex and several months later developed a thrombus in the proximal left anterior descending artery. We propose that the change from a hyperkinetic high flow state to a slow flow state in the setting of inadequate coronary flow reserve and endothelial function predisposed our patient to thrombus formation in the persistently dilated coronary arteries. It is expected that restoration of normal flow pattern in all coronary arteries will result in normalization of perfusion, decrease in feeding artery size, and return of endothelial function. Because this anomaly is rare, limited information exists on the effects of the procedure on myocardial perfusion. These findings raise the question of whether re-implantation of the anomalous artery is truly the superior approach.

Quality of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation in the community setting.

BACKGROUND: The benefit of oral anticoagulation therapy with warfarin for stroke prevention in atrial fibrillation (AF) is directly dependent on the quality of anticoagulation (QoA), which in the US is provided predominantly in the community setting. With the emergence of new oral anticoagulation agents, the current QoA needs to be assessed. OBJECTIVES: The purpose of our study is to define the QoA with warfarin in patients with nonvalvular AF who are managed exclusively in community practices, and to compare the quality in the community setting with the quality demonstrated in the recent large randomized control trials. In addition, this study will assess the differences in the QoA based on cardiology vs primary care practices. METHODS: This is a retrospective, observational, multi-center study of 392 patients with AF in the community who were initiated on anticoagulation with warfarin for stroke prevention. International Normalized Ratio (INR) values were collected over a one-year period and the QoA was expressed as time in therapeutic range (TTR) calculated by the linear interpolation method. RESULTS: One hundred patients from cardiology practices and 292 patients from primary care were studied. During the one-year period, the overall mean TTR was 56.7%. The TTR in the primary care vs cardiology practices was 55.3% vs. 60.8% (p=0.02). Both practices had similar percent of time below therapeutic range, 29.8% vs. 29.2%. However, the primary care practice patients were above the therapeutic range 15% of the time vs. 10% in cardiology (p<0.001). There were one death secondary to intracranial bleed and one major bleed in the primary care group. There were no strokes during the study period in either group. CONCLUSION: The QoA with warfarin, as assessed by TTR, in the current community setting remains suboptimal, and there has been little to no improvement in current clinical practices. TTR should be considered when assessing the recent comparative studies evaluating novel pharmacologic agents to warfarin for the treatment of AF. SUBJECT AREAS: Arrhythmias, preventive cardiology, anticoagulation, thromboembolism, cardiovascular disease risk factors.

Endoluminal treatment of peripheral chronic total occlusions using the Crosser® recanalization catheter.

PURPOSE: Revascularization of lower extremity chronic total occlusions (CTOs) is technically challenging. The Crosser® recanalization catheter was designed to facilitate distal vessel intraluminal entry that is both rapid and safe. We present our experience with the Crosser device as primary therapy for peripheral CTOs. METHODS: Subjects undergoing evaluation for arterial insufficiency at our institution between 2008-2010 who were noted to have a CTO in the lower extremity by duplex ultrasonography and who subsequently underwent Crosser recanalization were enrolled. Clinical characteristics, ankle-brachial indices, Rutherford-Becker symptom category, and angiographic CTO parameters were collected. Primary technical success was intraluminal delivery of the guidewire into the distal vessel solely by the Crosser device. Secondary technical success was assisted delivery using the Outback LTD® re-entry device. Safety endpoints were the occurrence of dissections, thromboembolism, and perforations related to the Crosser device. Statistical analysis was performed to find independent predictors for failure to achieve Crosser recanalization. RESULTS: Fifty-six subjects with 73 CTOs were enrolled. The mean Crosser use time was 17.6 ± 12.7 minutes. The overall primary and secondary technical success rates for Crosser recanalization were 76.7% and 87.7%, respectively. Technical success was highest for CTOs located in the aorto-iliac (90.0%) and tibial (95.2%) arterial segments. There were no perforations related to the Crosser device. For successful cases, the mean ABI improved significantly from pre- to post-intervention (0.57 ± 0.13 to 0.89 ± 0.15, p < 0.001). The only predictors for failure were lesion length longer than 100 mm (p = 0.04) and calcification within 10 mm of the exit cap (p = 0.02). CONCLUSION: The Crosser device is safe and shows excellent efficacy in facilitating guidewire distal lumen entry, especially for aorto-iliac and tibial occlusions. The technical success rate for the femoral and popliteal occlusions is comparable to those reported with other recanalization techniques.

Orbital atherectomy for symptomatic lower extremity disease.

BACKGROUND: Plaque-debulking technologies have been proposed as alternative treatment options for peripheral arterial disease. Orbital atherectomy (OA), using the DiamondBack360 device, has emerged as one promising modality. METHODS: We evaluated the safety and efficacy of OA in the first 200 lesions treated at our institution. Patient demographics, clinical characteristics, and lesion and procedural variables were collected and analyzed. The primary safety endpoint was the 30-day major adverse events (MAE), including death, myocardial infarction, stroke, unplanned amputation, or target lesion revascularization. Other safety endpoints included access-site complications, occurrence of dissections, perforations, distal embolization, spasm, and hemolysis. The efficacy endpoints were procedural success, need for adjunctive therapy, and improvement in ankle-brachial index. Multivariate analysis was performed to find independent predictors of the safety endpoints. RESULTS: One hundred seventeen (58.5%) lesions were femoral, 31 (15.5%) were popliteal, and 52 (26.0%) were tibial. The procedural success (residual stenosis ≤30%) was comparable between the femoral and tibial lesions (86.3% vs. 92.5%, P = 0.18), but significantly lower for the popliteal lesions when compared with femoral and tibial (64.7% vs. 86.3%, P = 0.058, and 64.7% vs. 92.5%, P = 0.007 respectively). MAE at 30-days occurred in 3 (2.2%) procedures, and major access-site complications also occurred in 3 (2.2%). There were 31 (15.5%) dissections; independent predictors were diabetes mellitus (OR: 7.3, P = 0.008), crown-to-RVD ratio <0.6 (OR: 11.6, P = 0.005), and atherectomy time >360 sec (OR: 11.8, P = 0.001). There were 2 (1.0%) distal embolizations, 6 (3.0%) arterial spasms, and no perforations. Laboratory evidence of hemolysis was noted in 33.8% of cases. CONCLUSION: Orbital atherectomy allows for a significant procedural success, limited need for stenting, and favorable safety profile.

Endogenously expressed nef uncouples cytokine and chemokine production from membrane phenotypic maturation in dendritic cells.

Immature dendritic cells (DCs), unlike mature DCs, require the viral determinant nef to drive immunodeficiency virus (SIV and HIV) replication in coculture with CD4(+) T cells. Since immature DCs may capture and get infected by virus during mucosal transmission, we hypothesized that Nef associated with the virus or produced during early replication might modulate DCs to augment virus dissemination. Adenovirus vectors expressing nef were used to introduce nef into DCs in the absence of other immunodeficiency virus determinants to examine Nef-induced changes that might activate immature DCs to acquire properties of mature DCs and drive virus replication. Nef expression by immature human and macaque DCs triggered IL-6, IL-12, TNF-alpha, CXCL8, CCL3, and CCL4 release, but without up-regulating costimulatory and other molecules characteristic of mature DCs. Coincident with this, nef-expressing immature DCs stimulated stronger autologous CD4(+) T cell responses. Both SIV and HIV nef-expressing DCs complemented defective SIVmac239 delta nef, driving replication in autologous immature DC-T cell cultures. In contrast, if DCs were activated after capturing delta nef, virus growth was not exacerbated. This highlights one way in which nef-defective virus-bearing immature DCs that mature while migrating to draining lymph nodes could induce stronger immune responses in the absence of overwhelming productive infection (unlike nef-containing wild-type virus). Therefore, Nef expressed in immature DCs signals a distinct activation program that promotes virus replication and T cell recruitment but without complete DC maturation, thereby lessening the likelihood that wild-type virus-infected immature DCs would activate virus-specific immunity, but facilitating virus dissemination.