Resolution Of Pulmonary Embolism Research Articles

Clot Imaging Using Photostable Nanodiamond.

While thrombosis is the leading cause of morbidity and mortality in the United States, an understanding of its triggers, progression, and response to anticoagulant therapy is lacking. Intravital fluorescence microscopy has advanced the study of thrombus formation by providing targeted, multi-color contrast. However, photodegradation of fluorophores limits the application in longitudinal studies (e.g., clot progression and/or dissolution). Fluorescent nanodiamond (FND) is a fluorophore which utilizes intrinsic fluorescence of chromogenic centers within and protected by the diamond crystalline lattice. Recent developments in diamond processing have allowed for the controlled production of nanodiamonds emitting in green or red. Here, the use of FND to label blood clots and/or clot lysis is demonstrated and compared to commonly used organic fluorophores. Model ex vivo clots were formed with incorporated labeled fibrinogen to allow imaging. FND was shown to match the morphology of organic fluorophore labels absent of photobleaching over time. The addition of tissue plasminogen activator (tPa) allowed visualization of the clot lysis stage, which is vital to studies of both DVT and pulmonary embolism resolution.

P224 PRIMITIVE DILATED CARDIOMYOPATHY IN YOUNG MAN NOT ELIGIBLE FOR CARDIAC TRANSPLANTATION: COMBINED USE OF DEFIBRILLATOR, CARDIAC CONTRACTILITY MODULATION (CCM) AND CARILLON

Abstract Acute heart failure refers to rapid or gradual onset of symptoms and/or signs of chronic heart failure due to precipitating factors. Many patients with heart failure progress into a phase of advanced heart failure, characterized by persistent symptoms despite maximal therapy. Prognosis remains poor, with high 1–year mortality. Prognostic stratification is important to identify the ideal time for referral to an appropriate center capable of providing advanced therapies. We present the case of a 36–year–old black homeless man was admitted to Cardiological intensive care unit for acute heart failure complicated by intermediate–high risk bilateral subsegmentary pulmonary embolism, left endoventricular thrombosis, severe biventricular systolic dysfunction and secondary severe mitral insufficiency. After infusional diuretic and anticoagulant therapy, coronary angiography was performed documenting non–obstructive epicardial coronary arteries. Thereafter the therapy with sacubitril/Valsartan was falled, due to marked hypotension. Due to the high risk of sudden cardiac death, a single–chamber ICD was implanted in primary prevention. He was not eligible for long–term mechanical assistance (VAD) implantation and/or heart transplantation from referral centers, because of the patient‘s precarious psychosocial background. Furthermore, in the fullness of his faculties, the patient refused this possibility for religious reasons. Discharged in fair compensation, after resolution of pulmonary embolism and intracavitary thrombosis, he was again hospitalized for an exacerbation of chronic heart failure. Once labile hemodynamic compensation was reached, a cardiac contractility modulation device (CCM) was positioned, with the aim of improving symptoms. After optimization of therapy, with persistence of severe symptoms despite optimal medical and device therapy, options for intervention on the mitral valve were evaluated before further deterioration of the clinical conditions. Since this is a highly symptomatic patient at high risk for surgery, we opted for a coronary sinus mitral annuloplasty repair with Carillon, performed in the absence of complications. At the follow–up there was a mitral regurgitant volume reduction, improvement symptoms, in the absence of further hospitalizations.

Chronic thromboembolic pulmonary hypertension: a review of risk factors, management and current challenges

ABSTRACT Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is an under-diagnosed complication of acute pulmonary embolism (PE), whereby there is incomplete resolution of pulmonary emboli, which then become organized into obstructive fibrotic material with an associated small vessel vasculopathy. CTEPH is diagnosed by abnormal lung perfusion despite 3-months of oral anticoagulation with persistent pulmonary artery thromboembolic/ fibrotic material confirmed on cross sectional imaging and pulmonary hypertension on right heart catheterization. Without treatment the prognosis is bleak, but there are now three treatment modalities that are effective in treating patients with CTEPH: pulmonary endarterectomy (PEA) surgery, balloon pulmonary angioplasty (BPA) and medical therapy. Areas Covered We provide a comprehensive review of the literature with particular emphasis on the epidemiology, pathophysiology, diagnosis, and the established and emerging treatments of CTEPH. Expert opinion It is important to recognize that CTEPH is complication of an acute PE as there are effective and sometimes curative treatments available. In European and North American practice, PEA surgery remains the cornerstone of therapy in patients with CTEPH and accessible disease without significant comorbidity. For those patients with a disease burden that is inaccessible or fails to justify the risk of major surgery, initiating medical therapy and considering BPA is appropriate. Those with persistent pulmonary hypertension after PEA should also receive medical therapy and be considered for BPA or re-do endarterectomy. The available therapies are not necessarily mutually exclusive, and the treatment decision is often subjective and individualized, based on the local available expertise. Further research is needed to understand the optimal treatment strategy for patients and in particular to identify ‘responders’ and assess the synergies between these three treatment strategies.

Dynamic (4D) CT perfusion offers simultaneous functional and anatomical insights into pulmonary embolism resolution

ObjectiveResolution and long-term functional effects of pulmonary emboli are unpredictable. This study was carried out to assess persisting vascular bed perfusion abnormalities and resolution of arterial thrombus in patients with recent pulmonary embolism (PE). Methods and materials26 Patients were prospectively evaluated by dynamic (4D) contrast enhanced CT perfusion dynamic pulmonary CT perfusion. Intermittent volume imaging was performed every 1.5–1.7s during breath-hold and perfusion values were calculated by maximum-slope technique. Thrombus load (modified Miller score; MMS) and ventricular diameter were determined. Perfusion maps were visually scored and correlated with residual endoluminal filling defects. ResultsThe mean initial thrombus load was 13.1±4.6 MMS (3–16), and 1.2±2.1 MMS (0–8) at follow up. From the 24 CTPs with diagnostic quality perfusion studies, normal perfusion was observed in 7 (29%), and mildly-severely abnormal in 17 (71%). In 15 patients with no residual thrombus on follow up CTPA, normal perfusion was observed in 6, and abnormal perfusion in 9. Perfusion was abnormal in all patients with residual thrombus on follow up CTPA. Pulmonary perfusion changes were classified as reduced (n=4), delayed (systemic circulation pattern; n=5), and absent (no-flow; n=5).The right ventricle was dilated in 12/25 (48%) at presentation, and normal in all 26 follow up scans. Weak correlation was found between initial ventricular dilatation and perfusion abnormality at follow up (r=0.15). ConclusionsMost patients had substantial perfusion abnormality at 3–6 months post PE. Abnormal perfusion patterns were frequently observed in patients and in regions with no corresponding evidence of residual thrombus on CTPA. Some defects exhibit delayed, presumed systemic, enhancement (which we have termed ‘stunned’ lung). CT perfusion provides combined anatomical and functional information about PE resolution.

Cardiac findings and long-term thromboembolic outcomes following pulmonary embolism in children: a combined retrospective-prospective inception cohort study

In paediatric pulmonary embolism, cardiac findings and thromboembolic outcomes are poorly defined. We conducted a mixed retrospective-prospective cohort study of paediatric pulmonary embolism at the Children's Hospital Colorado between March, 2006 and January, 2011. A total of 58 consecutive children - age less than or equal to 21 years - with acute pulmonary embolism were enrolled. Data collection included clinical and laboratory characteristics, treatments, serial echocardiographic and electrocardiographic findings, and outcomes of pulmonary embolism non-resolution and recurrence. The median age was 16.5 years ranging from 0 to 21 years. The most prevalent clinical risk factors were oral contraceptive pill use (52% of female patients), presence of a non-infectious inflammatory condition (21%), and trauma (21%). Thrombophilias included heterozygous factor V Leiden in 21%; antiphospholipid antibody syndrome was established in 31% overall. Proximal pulmonary artery involvement was present in 34%. At presentation, nearly half of the patients had hypoxaemia and 37% had tachycardia. The classic electrocardiographic finding of S1Q3T3 was present in 12% acutely; tricuspid regurgitation greater than 3 metres per second, septal flattening, and right ventricular dilation were each present on acute echocardiogram in 25%. Nearly all patients received therapeutic anticoagulation, with initial systemic tissue plasminogen activator administered in 16% for occlusive iliofemoral deep venous thrombosis and/or massive pulmonary embolism. Pulmonary embolism resolution was observed in 82% by 6 months. Recurrent pulmonary embolism occurred in 9%. There were no pulmonary embolism-related deaths. Right ventricular dysfunction was rare in follow-up. These data indicate that acute heart strain is common, but chronic cardiac dysfunction is rare, following aggressive management of acute pulmonary embolism in children.

Rate of Resolution of Pulmonary Emboli at Different Orders of Pulmonary Arteries

Rate of Resolution of Pulmonary Emboli at Different Orders of Pulmonary Arteries

Tenecteplase in the treatment of acute pulmonary thrombo-embolism

This is a retrospective study documenting the use of tenecteplase in 41 cases of suspected or confirmed pulmonary embolism receiving in-hospital tenecteplase as per weight-adjusted dosing in addition to standard heparin and oral anticoagulant therapy. The presenting symptoms of dyspnoea, chest pain, hemoptysis and syncope were found in 40 (97.56%), 19 (46.34%), 6 (14.63%) and 9 (21.95%) patients, respectively. There was one case of mortality who was a 26 yrs old female of postpartum pulmonary thrombo-embolism with severe hypotension, cyanosis, bilateral crepitations in lungs and pulmonary hypertension. In the 40 survived patients, there was alleviation of dyspnoea and hemoptysis in all patients. Significant reduction in tachycardia (P < 0.0001) and increase in the oxygen saturation (SaO₂) (P < 0.0001) were seen at discharge as compared to at the time of presentation. Eighteen patients had hypotension which recovered in all patients till the time of discharge (P < 0.0001). There was a significant reduction in right ventricular systolic pressure in all 18 patients who underwent 2-D echocardiography both before and after the tenecteplase therapy. Resolution of pulmonary embolism on CT pulmonary angiography was documented in only two patients. No bleeding events or any other adverse events were reported during this study. The present study suggests favourable efficacy of tenecteplase in patients with suspected or confirmed acute pulmonary embolism. Although no major adverse events were noted, a large prospective study on the use of tenecteplase in pulmonary embolism is suggested.

Resolution of Pulmonary Embolism on CT Pulmonary Angiography

The objective of our study was to retrospectively determine the rate of resolution of pulmonary emboli (PEs) in individual vessels and the rate of complete resolution of PEs on CT angiography. Follow-up CT pulmonary angiograms, obtained during the period from January 2006 through May 2009, of 69 patients with acute PE from two hospitals were assessed. Initial and follow-up CT angiograms were reread together by one radiologist at both of the hospitals. Images were obtained using a 10-, 16-, 40-, or 64-MDCT angiography unit with a 0.5-mm collimation, 1.25- to 2.0-mm reconstruction, 0.3- to 0.5-second rotation time, and 7.5-mm/rotation table speed. All CT angiograms were obtained using a PE protocol. Follow-up CT angiograms were obtained in 35 men and 34 women who ranged in age from 17 to 92 years (mean age, 58 +/- 17 [SD] years). Complete CT angiographic resolution of PE was seen in six of 15 patients (40%) 2-7 days after diagnostic imaging. After day 28, complete resolution occurred in 17 of 21 patients (81%). The main pulmonary arteries showed complete PE resolution during days 2-7 in seven of nine patients (78%) and after day 28 in 34 of 36 (94%). The lobar pulmonary arteries showed complete resolution of PE during days 2-7 in 23 of 33 patients (70%) and after 28 days in 44 of 48 (92%). The segmental pulmonary arteries showed complete resolution during days 2-7 in eight of 21 patients (38%) and after day 28 in 38 of 38 (100%). Most patients (81%) showed complete resolution of PE on CT angiography after 28 days. PEs resolved faster in the main and lobar pulmonary arteries than in the segmental branches.

Resolution of Pulmonary Embolism on Computed Tomographic Angiography

How quickly does pulmonary embolism (PE) resolve on computed tomographic angiography (CTA)? Investigators addressed this question in a retrospective study at two Michigan hospitals that involved 814 patients who exhibited acute PE on CTA and did not receive thrombolytic …

Multiorgan paradoxical embolism consequent to acute pulmonary thromboembolism with patent foramen ovale: a case report

Paradoxical embolism is defined as a systemic arterial embolism requiring the passage of a venous thrombus into the arterial circulatory system through a right-to-left shunt. It is a relatively rare phenomenon, representing about 2% of all cases of arterial embolism. We report a case of a 79-years-old woman admitted to hospital because of dyspnea and lower left limb pain. CT scan revealed multiple thrombi to kidney, lower limb and superior mesenteric artery during acute pulmonary embolism. Echocardiogram documented a patent foramen ovale with a right-to-left shunt. The patient was treated with thrombolytic therapy and heparin with progressive improvement of symptoms and resolution of pulmonary embolism and peripheral thrombosis. Patent foramen ovale closure was not performed because a life-long anticoagulation therapy was necessary, a tunnel-type patent foramen ovale may increases difficulty in realizing device implantation and there are no clear evidence-based guidelines to date addressing treatment in presence of a patent foramen ovale.

Pulmonary embolism—experience at a single children's hospital

Introduction Pulmonary embolism in children is a rare, potentially life threatening condition. The clinical characteristics of pediatric pulmonary embolism have not been well studied and the exact incidence in children is not known. We report a case series of fourteen patients with pulmonary embolism and describe their clinical characteristics. Materials and methods Inpatient and outpatient clinic charts of patients with proven pulmonary embolism (PE) followed at the Hemostasis and Thrombosis Center at Children's Hospital of Michigan were reviewed for relevant clinical and laboratory information. Results All patients with PE were symptomatic but accurate diagnosis of PE was often delayed in the outpatient setting. Screening testing with D-dimer was normal in 40% of patients. Acquired risk factors and lower extremity clots were more common in patients analyzed. Treatment regimens differed but most patients had resolution of pulmonary emboli on follow-up. Conclusions A high index of suspicion is needed for the diagnosis of pediatric PE. D-Dimer may be normal in some children with PE. Pediatric multicenter trials are needed to evaluate clinical characteristics, risk factors, long-term outcome and effects of PE on pulmonary and cardiac function.

Submassive and Massive Pulmonary Embolism: A Target for Thrombolytic Therapy?

Thrombolytic agents have been consistently demonstrated to dissolve pulmonary thrombi much more rapidly and effectively than heparin alone. Rapid resolution of pulmonary embolism (PE) is accompanied by a significant decrease in pulmonary artery pressure and an improvement in right ventricular function. However, it is no longer than 7 days until the findings of patients treated with heparin improve to a similar extent. Previous studies were not designed to determine whether this short-lasting difference in favor of thrombolysis can indeed affect the prognosis of patients with PE and thus justify the 1% (or even higher) risk of cerebral or fatal bleeding. Recently, two large registries demonstrated the importance of right ventricular dysfunction assessed by echocardiography as an independent predictor of mortality. Thrombolytic treatment was shown in one of these registries to be associated with a 50% reduction of death risk in clinically stable patients with right ventricular enlargement. It was thus possible to identify a group of patients with massive PE who are most likely to benefit from early thrombolysis. These findings now have to be confirmed by a prospective randomized trial which will compare thrombolysis with heparin alone in this high-risk patient population, focusing on clinical end points such as overall and event-free survival in the acute phase of PE.

Resolution of Pulmonary Embolism: Effect of Therapy and Putative Age of Emboli

The purpose of this study was to evaluate functional and scintigraphic improvement in patients with pulmonary embolism (PE) according to the kind of treatment and the putative age of the emboli. The study includes 20 patients with both scintigraphic and angiographic diagnosis of PE enrolled in Pisa as a part of two previous multicenter trials: PAIMS 2 and BAPE. All patients were admitted to the Pulmonary Unit of the University of Pisa and treated with recombinant tissue-type plasminogen activator (rt-PA) plus heparin (H) (n = 10) or with H alone (n = 10). Results confirmed previous data, namely that perfusion damage decreases significantly from embolization to 7 days later in both patients treated with rt-PA + H and H alone (p < 0.001), although patients treated with rt-PA + H have a significantly higher perfusion restoration (p < 0.001) and a standard PaO2 increase (p < 0.01). Interestingly, our data also showed that the putative age of the emboli does not influence the efficacy of rt-PA + H treatment, while it does influence that of H treatment alone; in other words, rt-PA + H therapy may act efficaciously not only in fresh, but also in old pulmonary emboli.

Influence of cardiopulmonary disease on resolution of pulmonary embolism. A mathematical model to predict remaining defects at six months.

Recovery of lung perfusion after pulmonary embolism (PE) is conditioned by several factors. The aim of this study was to analyze the differences of reperfusion after PE between patients with and without preexisting cardiopulmonary disease, and to develop a mathematical model to predict, at diagnosis, the size of defects in lung perfusion scan at 6 months after treatment. We included 83 patients with diagnosis of PE in a non-concurrent cohort study (cohort I: 26 with preexisting cardiopulmonary disease, and cohort II: 57 without previous cardiopulmonary disease). Lung perfusion scan was performed at diagnosis, 7-10 days after treatment and at 6 months. The defect size was quantified following a numerical score. The recovery of perfusion after 7-10 days was 33% in cohort I and 45% in cohort II, and 50% and 72%, respectively, at the last control at 6 months. A multiple-regression analysis was performed using the final size of defects at 6 months (y) as the dependent variable, and the defect size at diagnosis (x) and the presence of preexisting cardiopulmonary disease (z) as independent variables. The regression equation was y = 1.29 + 0.15x + 2.98z. We conclude that: (1) in patients with cardiopulmonary diseases, the remaining defects at 6 months were larger; (2) at diagnosis, using a mathematical model, it is possible to predict the size of the defects in lung perfusion scan at 6 months in patients with or without previous cardiopulmonary disease.

Deep venous thrombosis and pulmonary embolism after lung transplantation

The incidence of deep venous thrombosis or pulmonary embolism after lung or heart-lung transplantation has not been well defined. Pulmonary embolism may be of particular concern in the postoperative period owing to an inadequately developed or absent collateral bronchial circulation and potential risk of pulmonary infarction. Fourteen (12.1%) of 116 patients undergoing either lung ( n = 87) or heart-lung ( n = 29) transplantation developed thromboembolic complications 10 days to 36 months after operation. Deep vein thrombosis developed in nine patients, including three with upper body thrombosis related to indwelling central venous catheters. Seven patients (6%) had pulmonary embolism, and three of them died. Resolution of pulmonary embolism was successfully accomplished by selective pulmonary artery infusion of urokinase in three patients without complications. Our experience indicates that deep vein thrombosis and pulmonary embolism are significant problems after lung transplantation. Mortality is high in those patients in whom pulmonary embolism develops. Therefore, a comprehensive prevention protocol is warranted. (J T HORAC C ARDIOVASC S URG 1995;110:540-4)

Rapid Resolution of Pulmonary Embolism by Tissue Plasminogen Activator

A case of multiple bilateral pulmonary emboli demonstrating complete resolution 48 hours after the intravenous administration of tissue plasminogen activator is presented.

Fibrinolytic Effects of Urokinase and Heparin in Acute Pulmonary Embolism: A Randomized Clinical Trial

Dissolution of pulmonary emboli with heparin and urokinase is ascribed, respectively, to anticoagulation and fibrinolysis. Since truly independent assessment of these effects in man is lacking, we administered each drug alone. Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three randomized groups of 10 patients each: groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase, respectively, and group B who received heparin. After 6 h of treatment, fibrinogen fell in all the groups, while, after 12 h, remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly. Up to 60 h, statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion. These observations suggest that heparin may induce a lytic state. As to signs of pulmonary emboli resolution, no differences between groups were found in lung perfusion and gas exchange recovery at any time (from 1 day to 1 year) and in pulmonary artery pressure reduction at 1 week. The greater angiographic and scintigraphic recovery observed with urokinase, versus heparin alone, after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out. The indications of heparin and urokinase should be evaluated in the light of these results.

Indices of Fibrinogen Proteolysis and Platelet Activation During the Resolution of Pulmonary Embolism

Indices of fibrinogen cleavage by thrombin (fibrinopeptide A, FPA); by plasmin (BB1-42 and serum FDP); of the platelet release reaction (beta thromboglobulin and platelet factor 4); and antithrombin III (AT III) levels were measured serially in 46 patients with pulmonary emboli in whom either substantial (SR) or impaired (IR) resolution was documented. The mean FPA level in the 25 patients with IR was significantly higher than the level in the 21 patients with SR (p less than 0.01). The increased thrombin activity in the IR group was not due to AT III deficiency or increased platelet reactivity but the elevated FPA levels in the presence of therapeutic levels of anticoagulation indicated that the dose of heparin was inadequate. The higher BB1-42 and FDP levels in this group reflected the increased plasmin activity that follows increased thrombin activity. In a multivariate discriminant analysis, only the FPA data could be used to predict the degree of resolution. Increased thrombin action impairs resolution presumably by producing greater amounts of accreted fibrin on the impacted embolus.

CHAPTER X: Clinical and Electrocardiographic Observations

Clinical findings were not sensitive indicators of the presence or resolution of pulmonary emboli. However, patients with massive pulmonary embolism who received urokinase tended to have more rapid resolution of dyspnea, ↑S 2 P, and gallop sounds (at 24 hours) and more complete resolution at 14 days than comparable heparin patients. The preinfusion electrocardiogram was abnormal in the great majority of patients. Rhythm disturbances were infrequent, but QRS and ST-T changes were present in the majority. The most frequent single finding was T-wave inversion. Much less frequent were those changes of classic acute cor pulmonale. The limitations of electrocardiographic changes, therefore, are related to the inverse relation of their frequency and specificity. Moreover, the electrocardiogram did not sensitively reflect the resolution of pulmonary emboli.

The effect of heparin on the early resolution of pulmonary emboli in the dog.

An experimental model has been developed to study the effect of heparin on pulmonary emboli in the dog. This has demonstrated that emboli impacted in the “lobar” arteries of the dog's lung lose an appreciable amount of their weight in 24 hours, and that this weight loss remains the same despite adequate anti‐coagulation with heparin. Massive emboli lodging in the main pulmonary artery have their weight loss at 24 hours approximately doubled by heparin. The implications of these results in the behaviour of pulmonary emboli in the human are discussed.