Antonio Palla

Risk stratification and outcomes in hemodynamically stable patients with acute pulmonary embolism: a prospective, multicentre, cohort study with three months of follow-up

Summary.  Background: The role of risk stratification in normotensive patients with acute pulmonary embolism (PE) is still unclear. Objectives: We evaluated, in these patients, the usefulness of six prognostic markers for predicting in‐hospital adverse events related to PE and 3‐month mortality. Patients/Methods: Two hundred and one consecutive patients with confirmed acute PE and normal blood pressure, who were administered conventional anticoagulation, were recruited in a multicentre prospective cohort study with 3 months of follow‐up. At baseline, they received a comprehensive risk‐evaluation including echocardiographic assessment of right ventricular dysfunction, determination of troponin I, brain natriuretic peptide and D‐dimer, arterial blood gas analysis and a clinical score. Primary outcome of the study was PE‐related in‐hospital death or clinical deterioration. Secondary outcomes were in‐hospital and 3‐month all‐cause mortality. Results: The primary outcome occurred in one patient (0.5%), who died from PE during hospitalization. The in‐hospital and 3‐month all‐cause mortality were 2% and 9%, respectively. None of the prognostic markers was predictive of the primary outcome. Clinical score, troponin I and hypoxemia predicted in‐hospital all‐cause mortality (P = 0.02, 0.01 and < 0.01, respectively). Clinical score (HR, 4.7; 95% CI, 1.9–12.0), D‐dimer (4.8; 1.4–16.3), hypoxemia (5.7; 2.1–15.1) and troponin I (7.5; 2.5–22.7) were predictors of 3‐month all‐cause mortality on univariate analysis. On multivariate analysis clinical score and troponin I remained independently predictive. Conclusions: We did not find prognostic markers useful as predictors of in‐hospital PE‐related adverse events. Clinical score, troponin I and hypoxemia predicted in‐hospital all‐cause mortality. Clinical score and troponin I independently predicted 3‐month all‐cause mortality.

Sleep Apnea in Morbidly Obese Patients: Prevalence and Clinical Predictivity

Background: Little is known about the prevalence of obstructive sleep apnea-hypopnea syndrome (OSAHS) in morbidly obese patients and whether such patients show peculiar clinical findings that may make it easier to suspect and diagnose OSAHS. Objectives: To investigate prevalence of OSAHS in patients with morbid obesity and find a simple structured model for predicting the results of polysomnography. Methods: The study enrolled a group of 101 consecutive inpatients (33 males, age range 20–80 years) with a body mass index ≥40, whose symptoms of OSAHS were not known, and a validation group of 45 patients. Results: Habitual snoring, nocturnal apneas or awakening as well as diurnal sleepiness were frequent findings (90.1, 40.6, 50.5 and 61.4%, respectively). Chronic obstructive pulmonary disease, hypertension, diabetes and myocardial ischemia were also frequently associated (22.8, 56.4, 30.7 and 6.9%, respectively). OSAHS was found in 61 (60.4%) patients, in 33.7% it was of severe degree. A multivariate logistic regression model allowed to select the independent predictors of OSAHS: age, male sex, diurnal sleepiness and the value of minimum nocturnal saturation. Sensitivity of 97%, specificity of 77% as well as positive and negative predictive values of 87% and 95%, respectively, were obtained; similar results were found in the validation group. When the best obtainable cutoff on the receiver operating characteristic curve is below 40%, the instrumental diagnosis might be excluded in as many as 33% of cases, since they are not affected by OSAHS or have OSAHS of mild degree. Conclusions: OSAHS is present in almost two thirds of morbidly obese patients. By applying the prediction model we propose, one may calculate the probability of a morbidly obese patient of being affected by OSAHS.

Prolonged Prophylaxis with Unfractioned Heparin Is Effective to Reduce Delayed Deep Vein Thrombosis in Total Hip Replacement

The aim of this study was to assess the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) until 45 days after elective total hip replacement (THR) and the efficacy of prolonged unfractioned heparin (UH) prophylaxis up to postoperative day 30. To this end 79 of 96 patients admitted consecutively to the University Hospital of Pisa for THR were randomly assigned to short- or long-term UH prophylaxis. Sixty-one patients completed the study: 28 of them received short-term prophylaxis (subcutaneous UH 15,000 IU/24 h for 15 days) and 33 prolonged prophylaxis (subcutaneous UH 15,000 IU/24 h for 30 days). Lower limb phlebography was performed in all patients on day 45 after THR. DVT was demonstrated in 10 (16.3%) cases after hospital discharge. Among them, 2 patients also had symptomatic PE. The incidence of DVT was 21.4% in short- and 12.1% in long-term UH-treated patients. The incidence of only proximal DVT was 17.8% in short- and 3.0% in long-term UH-treated patients; although the difference was only close to significance (p = 0.085), the relative risk of developing proximal DVT was about six times greater in the former group of patients. We concluded that the risk for thromboembolism persists at least until 45 days after surgery in patients subjected to THR. Prophylaxis with UH given up to postoperative day 30 appears more effective and safer in reducing the delayed thromboembolic risk compared to prophylaxis with UH given up to discharge only.

Is Incidentally Detected Pulmonary Embolism in Cancer Patients Less Severe? A Case-Control Study

Incidental pulmonary embolism (PE) in cancer patients is usually thought to be of mild degree. We investigated the severity of PE and evaluated the potential of raising the suspicion of PE in such patients. The computed tomography (CT) extent of PE was evaluated in 19 consecutive unsuspected and 19 randomly selected symptomatic patients. A clinical pattern useful for suspecting PE was also searched. On CT, number of embolized vessels, location of emboli, and simple instrumental findings were not different in the two groups. PE is not less severe in unsuspected cancer patients; moreover, PE may be clinically suspected in such patients.

CT evaluation of chronic thromboembolic pulmonary hypertension

Eight patients with chronic thromboembolic pulmonary hypertension (CTPH) that had been demonstrated by perfusion lung scan, pulmonary arteriography, and right heart catheterization had their pulmonary circulation evaluated by CT. Eight subjects without lung pathology were also studied for comparison. High resolution CT from apex to base with 1 cm thick sections after intravenous injection of contrast medium was performed in each individual. Emboli lodged in main pulmonary arteries on arteriography were regularly shown by CT, whereas those in segmental or smaller arteries were not detected. Diameters of the main pulmonary arteries measured on CT correlated with systolic pulmonary artery pressure (p < 0.001). The ratio between diameters of segmental arteries and the corresponding bronchi (A/B ratio) on CT was > 1 in 72 of 144 examined pulmonary segments (18 segments for each patient) in patients with CTPH. The ratio was > 1 in only 10 of 144 examined segments in normal control subjects. Dilatation of bronchial arteries was present in four of eight patients with CTPH. The parenchymal density in patients with CTPH was significantly higher in the axial than in the middle or peripheral lung compartments. In conclusion, CT may help with the diagnosis of CTPH by detecting thrombi of main arteries and by showing characteristic findings; moreover, it is accurate in estimating pulmonary arterial pressure secondary to thromboembolic obstruction.

Procoagulant, Tissue Factor-Bearing Microparticles in Bronchoalveolar Lavage of Interstitial Lung Disease Patients: An Observational Study

Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H2O2 was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons). Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r2 = .27 and .31, respectively; p<.05 for both correlations). Exposure of lung epithelial cells to H2O2 caused an increase in microparticle-bound tissue factor without affecting tissue factor mRNA. Procoagulant microparticles are increased in interstitial lung diseases and correlate with functional impairment. These structures might contribute to the activation of factor X and to the factor Xa-mediated fibrotic response in lung injury.

Early and Late Follow-Up of Pulmonary Embolism

This study includes 61 patients referred with pulmonary embolism (PE) during 1 year. At admission, blood gas analysis, chest radiography and pulmonary lung scan were obtained in each patient; in a subset of patients pulmonary angiography was also performed to make the definitive diagnosis. Patients were treated with heparin and, later, with oral anticoagulants. Blood gas analysis, chest radiograph and perfusion lung scan were repeated 7, 30, 180 and 365 days after the diagnosis to evaluate the usefulness of these techniques in the follow-up of PE. Arterial hypoxemia and perfusion impairment recovered in parallel, both in the acute phase after embolism (7 days) and later up to 1 year. The great majority of recovery occurred within the first month after embolization. Radiographic signs compatible with PE tended to decrease early and disappeared almost completely after 30 days. Arterial blood gas analysis and perfusion scintigraphy detected 8 recurrences of PE that would be missed by chest radiograph. Arterial hypoxemia and the enlargement of descending pulmonary artery were positively correlated with the number of unperfused lung segments and, thus, may help predicting the severity of perfusion impairment in the acute stage. In conclusion, blood gas analysis and chest radiograph may be employed with or without perfusion lung scan to follow patients with PE up to 1 month after embolization; after that, only blood gas analysis and perfusion lung scan may give useful information about recovery from or recurrence of PE.

Advantages of Real Time Three‐Dimensional Echocardiography in the Assessment of Right Ventricular Volumes and Function in Patients with Pulmonary Hypertension Compared with Conventional Two‐Dimensional Echocardiography

In recent years, right ventricular (RV) function has acquired greater relevance as a clinical and prognostic marker in many physiopathological conditions. The study aims to point out the value of real time three‐dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) in the evaluation of patients affected by pulmonary hypertension (PH), compared with conventional two‐dimensional (2D) echocardiography.

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.

A Way to Select on Clinical Grounds Patients with High Risk for Pulmonary Embolism: A Retrospective Analysis in a Nested Case-Control Study

We studied 196 patients with suspicion of pulmonary embolism (PE), subsequently confirmed in 98 by positive pulmonary angiography and excluded in 98 by normal or near-normal perfusion lung scan. Patients had a clinical questionnaire for history, and, soon after. a radiograph, blood gas analysis, and an ECG. Clinical and instrumental signs were matched in patients with confirmed and unconfirmed PE to find those more frequent in embolic patients and, thus, more characteristic of PE. The following were: previous PE, immobilization and thrombophlebitis (p < 0.05); dyspnea and cough (p < 0.05); enlarged descending pulmonary artery (DPA), enlarged right heart, pulmonary infarction, Westermark sign (p < 0.001), and elevated diaphragm (p < 0.05); hypoxemia. No ECG sign was more frequent in PE. Thereafter, all variables were processed separately with a logistic multiple regression analysis and those significantly associated to PE were tested in a final logistic model that was able to predict the actual result of angiography or scintigraphy; accordingly, previous PE, immobilization, thrombophlebitis, enlarged DPA, pulmonary infarction, Westermark sign, hypoxemia were significantly associated with a high risk of PE (from 2.8 to 15 times greater than in patients without these signs). Therefore, we may conclude that clinical assessment and noninvasive tests may help to detect patients at higher risk for PE where heparin coverage should be started while waiting for conclusive diagnostic procedures.