Evidence Of Thromboembolism Research Articles

Deep Vein Thrombosis with Diffuse Alveolar Hemorrhage: An Uncommon Presentation of Acute Leukemia

Deep Vein Thrombosis with Diffuse Alveolar Hemorrhage is an uncommon Presentation of acute Leukemia. Early diagnosis of acute respiratory failure etiology in patients with Acute Leukemia and Pulmonary Infiltrates is essential. We report a case in a 51- years old male who presented with shortness of breath & cough with blood admixed sputum with a history of right leg pain acutely. CTPA showed signs suggestive of DAH with no evidence of thromboembolism which let us evaluate him further leading to a diagnosis of DAH.

Clinical outcomes of moderate to severe COVID-19 patients receiving invasive vs. non-invasive ventilation

Objective: To evaluate the in-hospital outcome of moderate to severe COVID-19 patients admitted in High Dependency Unit (HDU) in relation to invasive vs. non-invasive mode of ventilation. Methods: In this study, the patients required either non-invasive [oxygen ≤10 L/min or >10 L/min through mask or nasal prongs, rebreather masks and bilevel positive airway pressure (BiPAP)] or invasive ventilation. For analysis of 30-day in hospital mortality in relation to use of different modes of oxygen, Kaplan Meier and log rank analyses were used. In the end, independent predictors of survival were determined by Cox regression analysis. Results: Invasive ventilation was required by 15.1% patients while 84.9% patients needed non-invasive ventilation. Patients with evidence of thromboembolism, high inflammatory markers and hypoxemia mainly required invasive ventilation. The 30-day in hospital mortality was 72.7% for the invasive group and 12.9% for the non-invasive group (1.8% oxygen <10 L/min, 0.9% oxygen >10 L/min, 3.6% rebreather mask and 4.5% BiPAP). The median time from hospital admission to outcome was 7 days for the invasive group and 18 days for the non-invasive group (P<0.05). Age, presence of co-morbidities, number of days requiring oxygen, rebreather, BiPAP and invasive ventilation were independent predictors of outcome. Conclusions: Invasive mechanical ventilation is associated with adverse outcomes possibly due to ventilator associated lung injury. Thus, protective non-invasive ventilation remains the necessary and safe treatment for severely hypoxic COVID-19 patients.

Abstract 13129: Chest Pain and Inflammation: A Story Where Hickam’s Dictum Prevailed

A 39-year-old male presented with a chief complaint of chest pain that worsened with deep breathing for one day. He was found to be tachycardic, with distant heart sounds and a skin nodule over his right upper extremity. ECG revealed diffuse ST elevations and PR segment depressions with TTE showing a small pericardial effusion. Troponin I was 8.98 ng/mL and NT-proBNP was 981 pg/mL. One day after admission, he developed respiratory distress, and repeat TTE showed a large pericardial effusion with collapse of the RV free wall during diastole with variation of mitral and tricuspid valve inflows consistent with tamponade. Pulsus paradoxus was 24 mmHg and he was taken for pericardiocentesis. Skin nodule biopsy revealed nodular and interstitial granulomatous dermatitis. Anti-nuclear antibody and double stranded DNA antibody were positive with pericardial fluid cytology showing acute inflammation with lupus erythematosus cells. Based upon this constellation of findings, he was diagnosed with systemic lupus erythematosus (SLE) myopericarditis, and started on colchicine and immunosuppression, with resolution of symptoms. One week into hospitalization, the chest pain recurred but was sharp and substernal, with a rising troponin from 1.23 ng/mL to 8.23 ng/mL. TTE showed depressed LVEF of 45% and RCA territory hypokinesis without effusion. CTA PE showed no evidence of thromboembolism and CT coronary demonstrated mural thickening of the mid LAD and aneurysmal dilation of the left main to the LAD and left circumflex bifurcation concerning for vasculitis. The mid RCA was occluded, and patient was taken to the cardiac catherization laboratory revealing thrombotic occlusion of the proximal-to-mid RCA. Despite serial balloon dilation, thrombotic occlusion persisted, Aspiration thrombectomy evacuated organized thrombus prior to deployment of two overlapping drug-eluting stents in the proximal-to-mid RCA, restoring flow. TTE prior to discharge showed normal LVEF and no effusion. This case illustrates various cardiac manifestations of SLE and the unusual dynamic nature of this patient’s multiple presentations of chest pain. Avoiding “diagnostic anchoring” is important to diagnosing and treating conditions such as SLE, that can affect the heart in multiple ways.

Evaluation of Antiplatelet and Anticoagulation Therapy in High-Risk COVID-19 Patients

BackgroundHypercoagulability is a well-known mechanism of injury in patients with COVID-19 (Rico-Mesa et al Cardiology 2020). There are several clinical reports suggesting higher incidence of venous as well as arterial thromboembolism in the infected individuals. Patients with evidence of thromboembolism are at higher risk of poor outcomes as well (Bilaloglu et al JAMA 2020). The underlying mechanism is thought to be due to increased platelet aggregation and activation (Manne et al Blood 2020) along with inflammatory activation of the coagulation cascade that can lead to a hypercoagulable state (McGonagle et al Lancet Rheumatology 2020). There is a suggestion that anticoagulation is associated with reduction in mortality in COVID-19 infections (Paranjpe et al Cardiology 2020). However, the role of antiplatelet therapy has not been very well described or studied. In this study we investigated the outcomes for patients who were on antiplatelet therapy or full dose anticoagulation at baseline who developed COVID-19 infections.MethodsThis is a retrospective electronic chart review of patients admitted to New York-Presbyterian Brooklyn Methodist Hospital (NYP BMH), a Weill Cornell Medicine-affiliated hospital in Brooklyn, NY. Patients who were diagnosed and hospitalized for COVID-19 between March to April 2020 were included. Clinical data was extracted manually from electronic medical record (EMR). Patients were divided into 3 cohorts, considered “high risk” due to chronic comorbidities which required therapeutic anticoagulation and/or antiplatelet therapy. The first cohort included patients on single or dual antiplatelet therapy (Aspirin, Clopidogrel, Ticagrelor, Prasugrel, Aspirin-Dipyridamole or dual antiplatelet therapy) prior to admission and continued on admission (AP only). The second cohort included patients on anticoagulation (therapeutic Coumadin, Apixaban, Rivaroxaban, Enoxaparin) without antiplatelet therapy prior to admission, and continued on equivalent anticoagulation inpatient (AC only). The third included patients who were on both antiplatelet therapy and therapeutic anticoagulation (AP + AC). Additionally, we collected data on baseline characteristics, demographics, and outcomes. The primary outcome of the study was inpatient mortality. Secondary outcomes were median length of stay, ICU admission, Intubation requirement, bleeding, transfusions of blood products, development of venous thromboembolism and myocardial infarction. Chi-squared analyses were performed to determine statistical significance.ResultsWe analysed 684 hospitalized patients who were diagnosed with COVID-19. Ages ranged from 18 to 101 years old, 52% were male, and 48% were black, with a median age of 70. There were 146 patients in the AP group, 34 patients in the AC group, 24 patients in the AP + AC group, and 480 patients were on neither. Our data was significant for mortality of 82% in the AC group, 36% in the AP group, and 38% in the AP + AC group (p value <0.00001). 37% of AP patients required ICU admission, 44% of AC patients, and 46% for AP + AC patients. 31% of AP patients required intubation, 32% of AC patients, and 21% of AP + AC patients. 24% of AC patients required at least 1 unit packed red blood cell transfusion, and 25% of AP + AC patients (Table 1).ConclusionWe determined our patients to be those at high risk of thrombosis at baseline due to their requirement of antiplatelets or anticoagulation prior to hospitalization for COVID-19 infection. Our study suggests that mortality is higher for these patients who already required anticoagulation prior to COVID infection. Significantly, we demonstrated that patients on both therapeutic anticoagulation and antiplatelet therapy had less mortality than patients on anticoagulation alone, suggesting that antiplatelets in addition to anticoagulation might be protective against mortality in COVID-19 infection. Additionally, patients on antiplatelets and anticoagulation had less development of respiratory failure requiring intubation than either alone. This study provides proof of concept for prospective clinical trials for assessing the role of combination of antiplatelet therapy and therapeutic anticoagulation in high risk patients.DisclosuresNo relevant conflicts of interest to declare.

Clustered cases of acral perniosis: Clinical features, histopathology, and relationship to COVID-19.

Background/ObjectivesA recent marked increase in pediatric and adult patients presenting with purpuric acral lesions concerning for ischemia, thrombosis and necrosis has been observed in COVID‐19 prevalent regions worldwide. The clinical and histopathological features and relationship to COVID‐19 have not been well described. The objective of this case series is to describe the clinical features and determine the histopathologic findings and clinical implications of the clusters of acral perniosis cases identified in pediatric patients.MethodsWe describe six otherwise healthy adolescents—three siblings per family from two unrelated families—presented within a 48‐hour period in April, 2020, with acral perniosis‐like lesions in the context of over 30 similar patients who were evaluated within the same week.ResultsAffected patients had mild symptoms of viral upper respiratory infection (URI) or contact with symptomatic persons 1‐2 weeks preceding the rash. They all presented with red to violaceous macules and dusky, purpuric plaques scattered on the mid and distal aspects of the toes. Skin biopsies performed on each of the six patients demonstrated near identical histopathologic findings to those of idiopathic perniosis, with a lymphocytic inflammatory infiltrate without evidence of thromboembolism or immune complex vasculitis. While SARS‐CoV‐2 polymerase chain reaction was negative, testing was performed 1‐2 weeks after URI symptoms or sick contact exposure.ConclusionWe offer a clinical approach to evaluation of patients with this presentation and discuss the possibility that these skin findings represent a convalescent‐phase cutaneous reaction to SARS‐CoV‐2 infection.

P1242 Giant right atrium aneurysm presenting as right heart failure

Abstract Introduction Idiopathic aneurysmal dilatations of the right atrium are rare anomalies. It can be diagnosed at any time between foetal and adult life. This exceptional condition can be confused with other conditions that involve enlargement of right atrium. We report a clinical case of a symptomatic adult who was diagnosed with giant right atrium aneurysm. Case report An 83-year-old female presented with complaints of fatigue, paroxysmal nocturnal dyspnoea, exertional dyspnoea, orthopnoea and cough since last week. There were no history of syncope, convulsions or evidence of thromboembolism. There were a medical history of diverticulosis and atrial fibrillation (warfarin therapy). The principal findings on physical examination included holosystolic murmur at the left middle sternal border, pulmonary rales, jugular venous distension, enlarged liver and peripheral oedema. An electrocardiogram showed an atrial fibrillation with a controlled heart rate response, right axis deviation, right bundle-branch block. A chest radiography posteroanterior view showed a markedly enlarged cardiac silhouette, increased pulmonary vascular congestion, and bilateral pleural effusions. Computed tomography (CT) scan showed aneurysmal dilated right atrium communicating with right ventricle. Right ventricle (RV) and RV outflow tract were dilated with normal pulmonary arteries. Two-dimensional transthoracic echocardiography revealed aneurysmal dilated right atrium measuring 398mL/m2. The tricuspid valve was no displaced. There was severe tricuspid regurgitation and no stenosis. The right atrium was kinetic without any intracavitary thrombus. The intertrial and interventricular septa were intact. The right ventricle and outflow tract were mildly dilated with preserved systolic function. The left atrium and left ventricle were normal. The patient was admitted to the cardiology department with the diagnosis of right heart failure. Conclusion Aneurysm of right atrium is an uncommon condition. It is diagnosed as a disproportionately enlarged right atrium compared to the other cardiac chambers in the absence of other cardiac or hemodynamic abnormalities and must be distinguished from other anomalies causing structural pathology of the right atrium. Approximately, one-half of the patients have no symptoms. Others presented with arrhythmia, palpitations, chest pain, shortness of breath, and fatigue. The major rhythm abnormality is atrial fibrillation or atrial flutter. Our patient presented with symptoms of right heart failure and atrial fibrillation. The right enlargement is usually associated with tricuspid annular dilatation responsible for functional regurgitation, which can be severe in some cases. The diagnosis of right atrium malformation can be established by echocardiography, CT or magnetic resonance imaging. Literature reports various ways to manage these patients. Treatment ranges from conservative to surgical resection specially in the presence of arrhythmias. Abstract P1242 Figure. Aneurysm of right atrium

Analysis of apoptotic, platelet-derived, endothelial-derived, and tissue factor-positive microparticles of children with acute lymphoblastic leukemia during induction therapy.

Thromboembolism is one of the most common complications during induction therapy of pediatric acute lymphoblastic leukemia (ALL). Procoagulant microparticles in the circulation may cause thromboembolic events. The aim of our study was to determine the levels of apoptotic, platelet-derived, endothelial-derived, and tissue factor-positive microparticles of children with ALL at diagnosis and during induction therapy. Sixteen precursor B-cell ALL cases and 30 healthy children between 1 and 18 years of age were included. Microparticle levels were analyzed from peripheral blood samples at initial diagnosis, on days 12 and 13 (before and after the first L-asparaginase administration), and on day 33 of ALL-BFM 2000 treatment protocol. Microparticle levels were analyzed by using flow cytometry. At initial diagnosis, platelet, endothelial-derived, and tissue factor-positive microparticle levels were significantly high in children with ALL. They increased significantly after prednisone and L-asparaginase administration. Apoptotic microparticle levels were not elevated at diagnosis, but remained high during all induction therapy period. None of the patients had evidence of thromboembolism during induction therapy. Our study demonstrated that children with ALL have increased levels of apoptotic, platelet-derived, endothelial-derived, and tissue factor-positive microprticles during induction therapy. Further studies are needed in larger groups of patients in order to evaluate the risk of elevated microprticles for development of thromboembolism during induction therapy period in children with ALL.

Fc-Silent Anti-CD154 Domain Antibody Effectively Prevents Nonhuman Primate Renal Allograft Rejection.

The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004). The anti-CD154 dAb effectively blocked CD40-CD154 interactions but lacked crystallizable fragment (Fc) binding activity and resultant platelet activation. In a nonhuman primate kidney transplant model, anti-CD154 dAb was safe and efficacious, significantly prolonging allograft survival without evidence of thromboembolism (Median survival time 103 days). The combination of anti-CD154 dAb and conventional immunosuppression synergized to effectively control allograft rejection (Median survival time 397 days). Furthermore, anti-CD154 dAb treatment increased the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. This study demonstrates that the use of a novel anti-CD154 dAb that lacks Fc binding activity is safe without evidence of thromboembolism and is equally as potent as previous anti-CD154 agents at prolonging renal allograft survival in a nonhuman primate preclinical model.

Safe use of anti-CD154 monoclonal antibody in pig islet xenotransplantation in monkeys.

Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months. Monkeys were monitored for complications, and blood monitoring was carried out frequently. After euthanasia, multiple biopsies of all organs were examined for histological features of thromboembolism. Anti-CD154mAb prevented rejection of genetically engineered pig islets in all monkeys. No significant complications were attributable specifically to anti-CD154mAb. There was no evidence of thromboembolism in multiple histological sections from all major organs, including the brain. Our data suggest that in diabetic monkeys with pig islet grafts, anti-CD154mAb would appear to be an effective and safe therapy, and is not associated with thromboembolic complications.

Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid.

Bleeding during endoscopic sinus surgery and open surgeries can easily obstruct the surgeons' field of view and increase morbidity and risk of intraoperative complications. Intraoperative bleeding could potentially be addressed by a hemostatic agent that safely disperses itself through the escaping blood. We tested the safety and efficacy of a self-propelling formulation of thrombin and tranexamic acid (SPTT) in stopping bleeding in a paranasal sinus injury and in an open surgical carotid injury sheep model. Interventional animal study. SPTT was tested in the sinonasal space following endoscopic injury to the inferior turbinate of six sheep, and to the common carotid artery following open surgical injury in eight sheep. In the nasal cavity, bleeding time and local inflammation were measured and compared to plain gauze. Following carotid arteriotomy, successful hemostasis and markers of thrombosis and coagulopathy were compared to Floseal. SPTT significantly decreased bleeding times in the sinonasal space compared to plain gauze (mean difference = 3.8 minutes, P = .002). All of the carotid bleeds (100%) were successfully controlled with SPTT after 10 minutes of application under pressure, compared to 25% with Floseal. No adverse events were noted, and there was no evidence of thromboembolism. SPTT significantly reduced bleeding time in a sheep model of surgical sinus bleeding and successfully stopped bleeding following catastrophic carotid artery injury, with no adverse events observed. NA Laryngoscope, 127:787-793, 2017.

Perioperative blood loss in total hip and knee arthroplasty: Outcomes associated with intravenous tranexamic acid use in an academic medical center.

Objectives:Clinical trials have reported decreased blood loss with the use of tranexamic acid during joint reconstruction. The purpose of this study was to assess the individual practice implications of tranexamic acid use in joint replacement surgery.Methods:Health records of adults undergoing total knee arthroplasty and total hip arthroplasty over a 12-month period were retrospectively reviewed. The treatment group comprised patients who received intravenous tranexamic acid perioperatively. The control group comprised patients who did not receive tranexamic acid.Results:Patients in the treatment group (n = 64) and the control group (n = 99) were well matched for demographics, orthopedic diagnosis, and comorbidities. In-hospital postsurgical mean decreases in hemoglobin concentrations were −4.05 g/dL and −4.94 g/dL in the treatment and control groups, respectively (p < 0.001). Postsurgical mean decreases in hematocrit levels were −11.2% and −14.2% in the treatment and control groups, respectively (p < 0.001). Three patients in the treatment group (5%) and 21 patients in the control group (21%) received red blood cell transfusions (p = 0.006). As compared to control, the relative risk of transfusion in the treatment group was 0.23 (95% confidence interval = 0.07–0.76) and the number needed to treat to avoid one transfusion was 7.0 (95% confidence interval = 3.8–14.4). No evidence of thromboembolism or other serious complications were observed in either group.Conclusions:In patients undergoing joint replacement surgery, perioperative administration of tranexamic acid was associated with diminished blood loss and lesser resource utilization.

Incidence of Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Embolism: A Retrospective Analysis in a University Teaching Hospital

*Corresponding author: Won-Il Choi, MD Department of Internal Medicine, Keimyung University School of Medicine, 194 Dongsan-dong, Jung-gu, Daegu 700-712, Korea Tel: +82-53-250-7572 Fax: +82-53-250-7434 E-mail: wichoi@dsmc.or.kr Purpose: Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with considerable morbidity and mortality. Its incidence after pulmonary embolism and associated risk factors in the Korean population are not well documented. Methods: A retrospective cohort study was conducted to assess the incidence of symptomatic CTEPH in patients with an acute episode of pulmonary embolism without prior history of venous thromboembolism. Patients experiencing unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography, ventilation–perfusion lung scanning and computed tomography (CT) pulmonary angiography. CTEPH was considered to be present if estimated systolic pulmonary-artery pressure exceeded 40 mm Hg with evidence of thromboembolism on either ventilation-perfusion scanning or CT pulmonary angiography. Results: The cumulative incidence of symptomatic CTEPH was 1.9 percent at six months, 3.2 percent at one year, and 3.9 percent at three years. One case of recurrence after three years was noted among the patients with more than three years of follow-up data. Conclusion: CTEPH is a not uncommon disease and suggests the need for careful evaluation of pulmonary embolism during follow-up.

Bilateral ischemic lumbosacral plexopathy from chronic aortoiliac occlusion presenting with progressive paraplegia

Spinal cord ischemia is rare but causes significant morbidity and mortality. Spinal cord ischemia has been reported after open and endovascular interventions of the thoracic and abdominal aorta, and, rarely, acute occlusion of aorta from in situ thrombosis or acute embolic occlusion. Acute interruption of the critical blood supply to the spinal cord or root contributes to this devastating neurologic deficit. However, gradually worsening lumbosacral plexopathy and consequent paraplegia related to chronic aortic occlusion is extremely rare. We present a case of a 58-year-old man with progressive lower limb paralysis from atherosclerotic aortoiliac occlusion without history of aortic surgery or evidence of thromboembolism.

An uncommon cause of pleural effusions in a dialysis patient

A 42-year-old woman presented in October, 2011, describing dyspnoea, a non-productive cough, left-sided pleuritic chest discomfort, and 10 kg weight loss over 2 months. She had been receiving maintenance haemodialysis via a right brachiocephalic arteriovenous fi stula (fi gure) for 2 years having reached end-stage renal failure (ESRF) due to glomerulonephritis. She had smoked heavily for many years. Clinical examination showed cachexia with a body-mass index of 17 kg/m2, fl uctuating pyrexia, and persistent tachycardia of 120 bpm. Blood pressure was 124/78 mm Hg. Heart sounds were normal and no murmurs were audible. There was a large left pleural eff usion. Blood tests showed a low haemoglobin of 84 g/L, a white cell count of 8∙0×109/L, and a high C-reactive protein (CRP) concentration of 249 mg/L. Serum albumin was low at 18 g/L. Chest radi ography confi rmed a large left pleural eff usion. ECG showed sinus tachycardia, and echocardiography showed an undilated left ventricle with moderate systolic impairment, mild left atrial dilatation, and moderate mitral regurgitation (MR). The right heart was normal. Of note, a year earlier the left atrium and ventricle had been normal with mild MR on echocardiography. CT showed no evidence of thromboembolism or malignancy. The pleural eff usion was drained and found to be an exudate. Despite serially negative microbiology, the patient was treated with broad-spectrum antibiotics, for presumed infection, with little improvement. 3 weeks into her hospital stay, the left pleural eff usion re-accumulated with a new right eff usion. At 6 weeks there was a marked deterioration with the patient developing worsening tachycardia and MR alongside a gallop rhythm. Blood pressure was maintained. Echocardiography (see webvideo 1 and 2) now showed a dilated left ventricle with severe systolic dysfunction, moderate MR, and new pulmonary hypertension (pul monary arterial pressure about 48 mm Hg). We noted that the patient’s fi stula seemed large for her body size, with a

Left ventricular thrombus in patients with acute myocardial infarction:Case report and Caribbean focused update.

Despite the well documented benefit of echocardiography in acute coronary syndromes, its wide-scale use in the Caribbean is limited by access, health literacy and affordability. Because of the limited use of echocardiography in the region, routine complications of acute myocardial infarction (AMI) are not fully appreciated and may go unrecognized, further contributing to increased cardiovascular morbidity and mortality. It is therefore necessary to bring focus to this common clinical condition and highlight the clinical utility of echocardiography in facilitating timely and accurate diagnosis. We report here a case of large left ventricular (LV) thrombus in a patient with AMI. Coronary angiography showed completely occluded left anterior descending artery (LAD) with angiographically normal remaining vessels. Immediate anticoagulation was commenced with heparin and overlapped with warfarin. No Primary Angioplasty (PA) was done based on the evidence from occluded artery trial. LV thrombus was completely resolved on echocardiography at three months. No evidence of thrombo-embolism was found during the resolution of LV thrombus.

Canine Streptococcal Toxic Shock Syndrome associated with Necrotizing Fasciitis: An Overview

Canine Toxic Shock Syndrome (CSTSS) is a serious often fatal disease syndrome seen in dogs caused as a result of an infection caused by gram positive cocci of the family Streptococci. The main bacterium involved in the etiology of Canine Streptococcal Toxic Shock Syndrome is Streptoccoccus canis, which was discovered by Deveriese in 1986 and implicated as a cause of this disease syndrome in 1996 by Miller and Prescott. The clinical findings in this syndrome are very much similar to those seen in the infamous 'Toxic Shock 'caused by staphylococcal toxins in humans, especially females. Like in humans, the reason for emergence/reemergence of Canine Streptococcal Toxic Shock Syndrome (CSTSS) is unclear and very little is known about its transmission and prevention. The disease is characterized by multi systemic organ failure and a shock like condition in seemingly healthy dog often following an injury. In absence of proper and prompt diagnosis and subsequent treatment by injectable antibiotics and aggressive shock therapy, dog often succumbs to the disease within a few hours. The dog may have some rigidity and muscle spasms or convulsions and a deep unproductive cough followed by haemorrhage from nasal and mouth along with melena. On necropsy, these dogs show severe edema of the gastrointestinal tract, congestion of multiple organs, severe pulmonary congestion and evidence of thrombo embolism. Necrotizing fasciitis is a localized form of streptococcal infection seen as extensive soft tissue sloughing and necrosis along the fascial planes. No vaccination is available so avoidance of the probable causal factors mainly participation in community events, estrus, change of environment and shipping is the only way to keep pet dogs away from this disease.

Chronic in vivo testing of the Penn State infant ventricular assist device.

The Penn State Infant Ventricular Assist Device (VAD) is a 12-14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute Pediatric Circulatory Support program. In this report, we describe the seven most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 ± 4.1 kg. The goal of 4-6 weeks survival was achieved in five of seven studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into two protocol groups: the first based on a target activated partial thromboplastin time of 1.5-2 times normal, and a second group using a target thromboelastography R-time of two times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals and are encouraging given the extremely low levels of anticoagulation in the second group.

Development of a Long-Term Superficial Device for Partial Circulatory Support

The Symphony is a new circulatory support device that can be implanted with a superficial operation and provides synchronous, partial circulatory support. Potential advantages are:1) less invasive operation,2) promotes heart recovery,3) improved hemodynamics to allow up-titration of meds, and 4)avoids sternotomy. We present pre-clinical implant data in support of the first-in-man clinical trial. The Symphony system has 3 components:1) 30 ml pumping chamber that is sewn via a short graft to the subclavian artery, 2) a wearable (<2.3 kg) pneumatic driver and, 3) subcutaneous (subQ) EKG leads. The device is placed through an infraclavicular incision as for pacemaker placement. Hemocompatibility is achieved with tangential inflow that creates continuous washing and no objects (valves, impellers) in blood path. The device removes blood from arterial circulation during systole to provide afterload reduction and returns blood during diastole to augment coronary and systemic flow. In a bovine model, the device was sewn to the carotid artery with superficial placement in the neck to assess the subQ leads (n=4,7 days, n=2, 14 days) and final device design (n=5, 14 days, n=6, 30 days-2 complete,4 ongoing). All animals were maintained on support with no episodes of device malfunction. At explant, all pumps and grafts had excellent hemocompatibility with absence of deposits on all blood contacting surfaces. There was no significant hemolysis. Necropsies had no evidence of thromboembolism. SubQ EKG leads were easily placed through the original incision. R wave detection with subQ leads was equal to epicardial leads at rest (beats analyzed 133,627, PPV(positive predicted value) =95.6%,sensitivity=95.1%) and with exercise (beats analyzed 37,154, PPV=92.7%, sensitivity=90.0%). We have demonstrated excellent hemocompatibilty and device function. This is the first long-term circulatory support device that can be placed with a minor operation. This operartive approach combined with synchronized suppport may increase the incidence of myocardial recovery and improve tolerance of HF meds. Device and implant costs will be less than current devices. Final preparations for a FIM clinical trial are underway. The Symphony is a new circulatory support device that can be implanted with a superficial operation and provides synchronous, partial circulatory support. Potential advantages are:1) less invasive operation,2) promotes heart recovery,3) improved hemodynamics to allow up-titration of meds, and 4)avoids sternotomy. We present pre-clinical implant data in support of the first-in-man clinical trial. The Symphony system has 3 components:1) 30 ml pumping chamber that is sewn via a short graft to the subclavian artery, 2) a wearable (<2.3 kg) pneumatic driver and, 3) subcutaneous (subQ) EKG leads. The device is placed through an infraclavicular incision as for pacemaker placement. Hemocompatibility is achieved with tangential inflow that creates continuous washing and no objects (valves, impellers) in blood path. The device removes blood from arterial circulation during systole to provide afterload reduction and returns blood during diastole to augment coronary and systemic flow. In a bovine model, the device was sewn to the carotid artery with superficial placement in the neck to assess the subQ leads (n=4,7 days, n=2, 14 days) and final device design (n=5, 14 days, n=6, 30 days-2 complete,4 ongoing). All animals were maintained on support with no episodes of device malfunction. At explant, all pumps and grafts had excellent hemocompatibility with absence of deposits on all blood contacting surfaces. There was no significant hemolysis. Necropsies had no evidence of thromboembolism. SubQ EKG leads were easily placed through the original incision. R wave detection with subQ leads was equal to epicardial leads at rest (beats analyzed 133,627, PPV(positive predicted value) =95.6%,sensitivity=95.1%) and with exercise (beats analyzed 37,154, PPV=92.7%, sensitivity=90.0%). We have demonstrated excellent hemocompatibilty and device function. This is the first long-term circulatory support device that can be placed with a minor operation. This operartive approach combined with synchronized suppport may increase the incidence of myocardial recovery and improve tolerance of HF meds. Device and implant costs will be less than current devices. Final preparations for a FIM clinical trial are underway.

Transapical miniaturized ventricular assist device: Design and initial testing

Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure. HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated. The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5-6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0-30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs. We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis.

Development of Pulmonary Hypertension in Adults after Ventriculoatrial Shunt Implantation

Background: The insertion of ventriculoatrial (VA) shunts for the treatment of hydrocephalus is thought to be associated with the development of pulmonary hypertension in adults. Objectives: It was the aim of this study to describe the frequency and the clinical spectrum of pulmonary hypertension in adults with VA shunts. Methods: Patients with pulmonary hypertension were retrospectively evaluated from January 1999 to December 2006. Results: Among the 575 patients with pulmonary hypertension, 6 (mean age 42.5 ± 8.3 years) were identified as having received a VA shunt. Mean pulmonary artery pressure for these patients was 53.3 ± 14.9 mm Hg. The interval between shunt placement and the diagnosis of pulmonary hypertension was 9–27 years (median 16.5). While ventilation perfusion scans showed multiple bilateral perfusion defects in all patients, chest CT or pulmonary angiography demonstrated pulmonary thromboembolism in only 2 of the 6 patients. These 2 patients subsequently underwent pulmonary endarterectomy. Another patient required heart-lung transplantation because of severe pulmonary hypertension; lung histology showed prominent eccentric medial hypertrophy and intimal proliferation without evidence of thromboembolism. Contrary to earlier reports, outcomes were generally good, with a 100% survival rate for the first 8 years following diagnosis. Conclusions: Severe pulmonary hypertension can develop in adult patients with VA shunts. Therefore, clinicians should consider pulmonary hypertension as a potential cause for respiratory symptoms in patients who have received VA shunts.