Long-term effects of acute pulmonary embolism on echocardiographic Doppler indices and functional capacity.

BACKGROUND AND HYPOTHESIS: Hemodynamic and functional consequences of acute pulmonary embolism (APE) are believed to be reversible with antithrombotic treatment. To verify this hypothesis, we reassessed our patients at least 1 year after an episode of APE. METHODS: We compared echo Doppler indices and 6-min walking test parameters (6-MWT) of 36 patients (13 men, 23 women, age 66 +/- 11 years), studied on average 3.1 +/- 2.2 years after an acute episode of pharmacologically treated massive or submassive APE, with data of 30 age-matched subjects (12 men, 18 women, age 67 +/- 12 years). RESULTS: At least 1 year after APE, right ventricular (RV) diameter remained increased in patients compared with controls (27 +/- 2 vs. 23 +/- 2 mm, p<0.001). Also, acceleration time of pulmonary ejection (AcT) was markedly shorter (97 +/- 19 vs. 123 +/- 19 ms, p<0.001) and the diameter of the pulmonary trunk was significantly larger in patients than in controls (21 +/- 2.6 vs. 18 +/- 2.2, p<0.001). Although the mean value of the tricuspid valve peak systolic gradient (TVPG) in the APE group at follow-up was similar to that in controls, TVPG>30 mmHg was recorded in three patients with APE (8.3%). There was no difference in the distance of 6-MWT between both groups; however, the mean desaturation after 6-MWT was higher in the APE group than in controls (3.04 +/- 2.08 vs. 1.45 +/- 0.69%, p=0.0005). CONCLUSIONS: Pharmacologic treatment of acute pulmonary embolism does not prevent mild persistent changes in morphology and function of the cardiovascular system. Despite normalization of pulmonary artery systolic pressure and similar exercise capacity, survivors of APE present signs suggesting RV dysfunction and/or its disturbed coupling to the pulmonary arterial bed, as well as ventilation to perfusion mismatch at exertion persisting long after the acute embolic episode.

The conversion of thyroxine to triiodothyronine in the lung: comparison of activity of type I iodothyronine 5' deiodinase in lung cancer with peripheral lung tissues.

UNLABELLED: Triiodothyronine (T3) is the main active hormone, which is derived 20% from the thyroid gland and 80% from peripheral tissues. Thyroxin--5' deiodinases play a leading role in maintaining appropriate T3 concentrations in the different cells and organs: including the lung. The deiodinases present in pneumocytes were found to be localised in endoplasmatic reticulum. Aims of this study were: 1. To estimate activities of Type I and Type II iodothyronine 5' deiodinases (DI, DII) in two histological types of lung cancer. 2. To investigate possible differences in DI and DII activities between tumour tissue and peripheral lung tissue. 3. To study whether DI and DII activities are related to the extent of the disease process and grade of differentiation of lung cancer. MATERIAL: We studied 44 patients undergoing thoracotomy due to lung cancer. Histologically: 23 pts--squamous cell cancer, 21 pts adenocarcinoma. In all patients both tumour and peripheral lung tissue were studied. DI activity was measured in pmol 1251- released from 125 IrT3/min/mg of proteins, DII activity--in fmol 125I- released from 125IT4/hour/mg of protein. RESULTS: In most specimens DI and DII activities were observed. DI activity in specimens from lung peripheral tissue was: 3.3-58.3 pmol/min/mg of protein (mean 22.20) and in lung cancer tissue was: 2.0-44.7 pmol/min/mg of proteins (mean 13.3). DII activity in lung peripheral tissue ranged from 19 to 242 fmol/h/mg protein (mean 94.4) and in lung cancer ranged from 21 to 253 fmol/h/mg protein (mean 107.9). CONCLUSIONS: 1. Conversion of T4 to T3 occurs also in the lung. 2. The activity of DI is statistically significantly lower, in lung cancer than in peripheral lung tissue (13.3 +/- 9.5 vs 22.20 +/- 13.4 pmol/min/mg protein) respectively, p < 0.001. 3. DII activity in lung is present and similar in peripheral lung and lung cancer tissue. 4. There is a non-significant trend for correlation of DI activity and grade of differentiation (G1-G3) of tumour tissue and stage of lung cancer. Abbreviations' list: T3--triiodothyronine, T4--thyroxine, FT4--free thyroxine, rT3--revers triiodothyronine TSII--Thyroid Stimulating Hormone Type I lodothyronine 5'deiodinase = type I 5'deiodinase = 5'DI = DI Type II Iodothyronine 5'deiodinase = typeII 5'deiodinase = 5'DII = DII E.S.S.--Euthyroid Sick Syndrome, hDII = human type II iodothyronine deiodinase HDII-b, hDII-c = two novel splice variants SCC--Squamous Cell Cancer, A--adenocarcinoma, BMI--Body Mass Index BSA--Bovine Standard Albumin, DTT-1,4 Dithio-L-treitol, PTU--Propylothiouracil TCA--Tricholoroacetic Acid, TNM--Tumour Nodule Metastases (class.) G1-G3-grade of differentiation, COPD--Chronic Obstructive Pulmonary Disease.

N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism.

Plasma brain natriuretic peptide (BNP), released from myocytes of ventricles upon stretch, has been reported to differentiate pulmonary from cardiac dyspnoea. Limited data have shown elevated plasma BNP levels in acute pulmonary embolism (APE), frequently accompanied by dyspnoea and right ventricular (RV) dysfunction. The aim of this study was to assess plasma N-terminal proBNP (NT-proBNP) in APE, and to establish whether it reflects the severity of RV overload and if it can be used to predict adverse clinical outcome. On admission, NT-proBNP and echocardiography for RV overload were performed in 79 APE patients (29 males), aged 63 +/- 16 yrs. Plasma NT-proBNP was elevated in 66 patients (83.5%) and was higher in patients with (median 4,650 pg x mL(-1) (range 61-60,958)) than without RV strain (363 pg x mL(-1) (16-16,329)). RV-to-left ventricular ratio and inferior vena cava dimension correlated with NT-proBNP. All 15 in-hospital deaths and 24 serious adverse events occurred in the group with elevated NT-proBNP, while all 13 (16.5%) patients with normal values had an uncomplicated clinical course. Plasma NT-proBNP predicted in-hospital mortality. Plasma N-terminal pro-brain natriuretic peptide is elevated in the majority of cases of pulmonary embolism resulting in right ventricular overload. Plasma levels reflect the degree of right ventricular overload and may help to predict short-term outcome. Acute pulmonary embolism should be considered in the differential diagnosis of patients with dyspnoea and abnormal levels of brain natriuretic peptide.

Fatal primary pulmonary hypertension in a 30-yr-old female with APECED syndrome.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by mutations in the autoimmune regulator (AIRE) gene, which has a central function in maintaining immunological tolerance. A number of conditions with proven or likely autoimmune pathogenesis occur in APECED: hypoparathyroidism, adrenocortical insufficency, candidiasis, hypogonadism, type 1 diabetes, hypothyroidism, hypophysitis, hepatitis, malabsorption, nail dystrophy, enamel hypoplasia and keratopathy. It is not clear which factors are responsible for variation in clinical picture of APECED, but human leukocyte antigen (HLA) genotype may be important. The authors report the first description of a case of primary pulmonary hypertension (PPH) in patient with APECED, caused by R257X mutation in AIRE. The HLA genotype of the patient (DRB1*01/DRB1*11, DQB1*0301/DQB1*0501) has been previously reported as a predisposing factor to PPH. The findings from this study, provided that other similar cases are reported, suggest that immune deregulation plays a role in the pathogenesis of primary pulmonary hypertension.

Management of purulent pericarditis.

A 50 year old man was admitted to ICU due to purulent pericarditis, purulent inflammation of the soft tissue of the neck, purulent mediastinitis and pneumonia. Subxyphoid periocardiotomy followed by the insertion of a drain into the pericardial space was performed. Four other drains were also inserted to drain purulent fluid from the neck (two drains) and mediastinum (two drains). During the surgical procedure, 700 ml of purulent pericardial fluid from the pericardial sac and 200 ml of purulent fluid from the mediastinum were drained. Antibiotic therapy was started upon admission to the hospital. Streptococcus species, Acinetobacter baumani and Enterococcus casseliflavus were cultured. Antibiotic therapy was adjusted to the results of the antibiogram. Despite revised antibiotic therapy, daily drainage from the pericardium--during several days after surgery--was around 200 ml. Due to the huge purulent pericardial drainage streptokinase, delivered directly into pericardial space, was given. The clinical effect of intrapericardial streptokinase administration was excellent. After 17 days drainage of purulent pericardial fluid was not observed. No clinical signs and symptoms of constrictive pericarditis developed. Repeated echocardiography examinations showed no signs of constrictive pericarditis and no pericardial fluid. The patient was discharged in good general condition.

[Usefulness of measuring levels of d-dimer for diagnosis of hospital venous thromboembolism]. / Przydatnosc oznaczania stezenia d-dimeru w diagnostyce szpitalnej zylnej choroby zakrzepowo-zatorowej (z.ch.z.z.).

D-dimer measurement with highly sensitive tests seems useful to rule out pulmonary embolism (PE) and deep vein thrombosis (DVT). However, nonspecific increase in d-dimer is common among inpatients. The aim of our study was to check: 1) whether the frequency of normal DD level in inpatients justifies its assessment as a part of diagnostic strategy for VTE, 2) whether tests that we are using are sensitive enough to exclude PE and DVT. In 27 (47%) out of 58 hospitalised patients evaluated by ultrafast ELISA (VIDAS bioMerieux), but in none of 20/58 patients with confirmed VTE, DD-level was found normal. In 35 of those patients DD was measured also with microlatex tests--Tinaquant and BC d-dimer. In 14/35 patients imaging test confirmed VTE. Sensitivity, specificity and negative predictive value (NPV) respectively were following: VIDAS: 100%, 80%, 100%, Tinaquant: 100%, 48%, 100%, BC d-dimer: 29%, 90%, 70%. Our results suggest that: 1) the relatively high frequency of normal DD-level among inpatients justifies its use in diagnostic strategies involving hospitalised patients, 2) negative VIDAS test confirms its as reliability for excluding VTE while 3) high sensitivity found for Tinaquant test encourages further prospective studies, 4) sensitivity of BC d-dimer is too low to be useful for excluding VTE.

[Echocardiography improves the chance of conclusive results in spiral computed tomography of suspected pulmonary embolism]. / Echokardiografia okresla szanse diagnostycznego wyniku spiralnej tomografii komputerowej w podejrzeniu zatorowosci plucnej.

While highly specific for detecting thromboembolism in proximal pulmonary arteries, spiral computed tomography (spiral CT) cannot reliably exclude pulmonary embolism. Therefore "negative" spiral CT in patients with high clinical probability of acute pulmonary embolism should be considered as non-conclusive. The goal of our study was to check whether echo/Doppler could stratify patients with suspected pulmonary embolism according to the chance of obtaining a conclusive spiral CT result. Echo/Doppler recordings of 51 patients (27 F, mean aged 50 +/- 19) admitted to ICU with high probability of acute pulmonary embolism were compared with the results of spiral CT of pulmonary artery. Pulmonary embolism was revealed by spiral CT in 36 pts. who at echocardiography were found to have shorter acceleration time (AcT 86 +/- 27 vs 117 +/- 7 ms, p < 0.00001) and right ventricle enlargement (PK 30 +/- 5 vs 25 +/- 2 mm p < 0.0001). The velocity of tricuspid regurgitation (TVPG) could not be measured in 19 patients. Among patients with long AcT (> or = 120 ms) or without right ventricle enlargement 8 of 14 and 14 of 28 patients, respectively had no intrapulmonary clots at spiral CT. Echo/Doppler helps in preselection of patients in whom confirmation of PE with spiral CT is highly probable. In patients without indirect echocardiographic sings of pulmonary embolism, despite high clinical probability the chance of a conclusive spiral CT is 40-50%. This should be kept in mind when selecting the most effective diagnostic strategy in individual cases.

[Differences in hemodynamics of thromboembolic and primary pulmonary hypertension]. / Róznice w hemodynamice pierwotnego i zatorowego nadcisnienia plucnego.

It is not clear whether right ventricle to pulmonary artery coupling is modified by the site of vascular obstruction in patients with chronic severe pulmonary hypertension. We compared invasively (Swan Ganz) and non-invasively (echo/ /Doppler) assessed hemodynamics between two groups of patients with severe chronic thromboembolic pulmonary hypertension (CTEPH)--(n = 6; 52 +/- 24 yrs) and pulmonary arterial hypertension (PAH) (n = 5; 42 +/- 9 yrs) who had similar invasively measured right ventricular systolic pressure (CTEPH: 78 +/- 14 mm Hg; PAH: 83 +/- 17 mm Hg; p = NS), mean pulmonary arterial pressure (CTEPH: 51 +/- 10; PAH 56 +/- 11 mm Hg, p = NS) and pulmonary vascular resistance (CTEPH: 15.6 +/- 4.4 l/min; PAH: 19.2 +/- 6.1; p = ns). Patients with CTEPH have significantly shorter acceleration time corrected to ejection time (RVET): (AcT/RVET % = 24 +/- 5% vs 32 +/- 6% in PAH; p = 0.04) as well as AcT corrected by RR distance was highly significantly shorter (8 +/- 2% vs 12 +/- 2%; p = 0.006). AcT in the CTEPH group was shorter than in the PAH (60 +/- 5 vs 75 +/- 15; p = 0.047). The mid-systolic deceleration was significantly more frequent in the CTEPH group than in the PAH group (88% vs 30%; p = 0.005). If the mid-systolic deceleration was present in patients with PAH, the time to mid-systolic deceleration (t-N) had tendency to be longer in CTEPH group (118 +/- 22 ms vs 150 +/- 28 ms in PAH; p = 0.09). Significant differences appeared after correction t-N to RVET (t-N/RVET % = 46 +/- 9% vs 61 +/- 4%; p = 0.027) and to RR interval (t-N/RVET % = 16 +/- 2% vs 24 +/- 1%; p = 0.002). Doppler derived RV index proposed by Tei was slightly higher in CTEPH (0.81 +/- 0.18 vs 0.65 +/- 0.32 in PAH) but not significantly. Taken together our observations indicate that dynamical coupling between RV and pulmonary arteries is more disturbed in CTEPH than in PPH despite similar levels of chronically increased PAP.

[Transesophageal echocardiography--a method for prompt diagnosis of acute hemodynamically significant pulmonary embolism]. / Echokardiografia przezprzelykowa--metoda szybkiego rozpoznania istotnej hemodynamicznie ostrej zatorowosci plucnej.

UNLABELLED: Patients with acute pulmonary embolism (PE) may require prompt confirmation of PE before aggressive therapy such as embolectomy or thrombolysis. However, emergency availability of routine diagnostic tests often remains a problem. Therefore, we assessed prospectively the diagnostic value of transesophageal echocardiography (TEE), recently reported to be useful in the diagnosis of PE. TEE was performed in 76 consecutive patients (42 F, 34 M) aged 66.7 +/- 15.8 yrs with suspected acute PE with echocardiographic signs of right ventricular pressure overload, but without known coexisting cardiorespiratory diseases. Pulmonary artery thrombi (TH) were visualized at TEE in 69.7% (53) pts. PE was confirmed by high probability lung scintigraphy and/or spiral CT in all these cases. Additionally, PE was diagnosed in 11 others without TEE-reported TH. In the 12 remaining patients PE was eventually excluded (specificity 100%, sensitivity 82.8%). Therefore, TEE in the diagnosis of hemodynamically significant PE reached 100%. No clinically important adverse events were observed during TEE. CONCLUSION: Transesophageal echocardiography is reliable and safe method of prompt confirmation of hemodynamically significant acute pulmonary embolism with relatively high sensitivity in adequately preselected patients. However, due to topographic limitations negative result of TEE does not exclude PE.

[Pulmonary thrombendarterectomy in treatment of patients with chronic thromboembolic pulmonary hypertension]. / Trombendarterektomia tetnic plucnych w leczeniu chorych z nadcisnieniem plucnym w przebiegu przewleklej zatorowosci plucnej.

20 consecutive patients with thromboembolic pulmonary hypertension underwent pulmonary thromboendarterectomy. Mean pulmonary artery pressure decreased from mean 49.9 +/- 9.8 to 25.1 +/- 8.8 mm Hg (p < 0.0001), pulmonary vascular resistance decreased from mean 5.58 +/- 2.58 to 1.62 +/- 0.79 mm Hg/l*min-1 (p < 0.0001) and cardiac output increased from 3.71 +/- 1.18 to 6.92 +/- 1.64 l/min. Sixteen patients had marked clinical improvement. Two patients died in early and 2 patients in late postoperative period due to unrelieved pulmonary hypertension and postoperative complications.

[Thrombectomy in a patient with a mobile clot in the inferior vena cava--case report]. / Trombektomia u pacjenta z balotujaca skrzeplina w zyle glównej dolnej--opis przypadku.

Switching from heparin to acenocoumarol was complicated by severe retroperitoneal bleeding in a 50-years old patient with massive pulmonary embolism and deep venous thrombosis. The haematomas were evacuated by surgical procedure. Planned insertion of a vena cava filter was abandoned because of a mobile clot in inferior vena cava (IVC) reaching above renal veins as evidenced by spiral computed tomography (SCT). Patient was transferred to the Surgical Department of Medical Academy in Warsaw where thrombectomy was performed. In spite of mechanical and pharmacological methods of venous thrombosis prophylactic, thrombectomy was complicated by massive proximal deep venous thrombosis of right leg and distal part of IVC. Patient was successfully treated with UFH i.v. followed by low molecular weight heparins. No bleeding complications were observed. Screening for thrombophilia and cancer were negative. This case report is an example of difficulties in clinical management in a patient who has both life-threatening thromboembolic disease and bleeding.

[Recombinant hirudine in suspected heparin induced thrombocytopenia--case report of pulmonary embolism]. / Rekombinowana hirudyna w podejrzeniu trombocytopenii zwiazanej z heparyna--opis przypadku zatorowosci plucnej.

A case of 68 years old women suffering from chronic anemia, myelodysplastic syndrome and treated with progestogen due to endometrial hypertrophy is presented. Initially she was admitted to a regional hospital because of progressive weakness and exertional dyspnea. Three months earlier she reported an episode of acute dyspnea and chest pain. On the basis of clinical symptoms and perfusion lung scintigraphy pulmonary embolism (PE) was diagnosed. Patient received i.v. heparin which was changed to s.c. nadroparine subcutaneously. Platelet count dropped to 55,000'/ml on fifth day of treatment from initial level of about 200,000'/ml. Heparin induced thrombocytopenia was diagnosed, heparin was stopped and ticlopidine was recommended. After 3 weeks symptoms suggesting recurrent PE were observed. The patient was transferred to National Tuberculosis and Lung Diseases Research Institute. Recombinant hirudine (Refludan) was administrated (bolus 0.4 mg/kg and initial dose of infusion 0.1 mg/kg/h) overlapping with acenocoumarol from second day. Dose of r-hirudine was adjusted to achieve APTT prolongation 1.5 to 2.5 times of mid-normal range. During treatment with r-hirudine no bleeding and new thromboembolic complications occurred. Platelets count remained within normal range. After 14 days clinical improvement was observed, though symptoms of right ventricular overload and hypoxemia were still present after 6 months of treatment with oral anticoagulants suggesting chronic thromboembolic pulmonary hypertension.

Effects of the correction of renal artery stenosis on blood pressure, renal function and left ventricular morphology.

The aim of this study was to evaluate the effect of renal artery stenosis (RAS) correction in hypertensive patients on 24 h SBP, 24 h DBP, creatinine clearance (GFR), urinary albumin excretion (UAE) and LV morphology and mass (LVMI). A total of 61 hypertensive patients with RAS undergoing PTRA and/or surgical treatment entered the prospective study. The final analysis was done in 44 patients (age range 45.8 +/- 16.2 years) with RAS (atherosclerosis (ASC) 31 patients, fibromuscular dysplasia (FMD) 12 patients, arteritis 1 patient) who underwent PTRA (34 patients) or surgical treatment (10 patients) and presented no Doppler signs of restenosis (or a new stenosis) during 1-year observation. The pre-interventional assessment repeated after 6 and 12 months included ABPM, GFR, UAE and echocardiography. The results were analysed in the combined group (CG) and in according aetiology. 24 h SBP and 24 h DBP decreased in all groups 6 months post-intervention and did not change further. Cure of HT was observed in 35% and 29% of ASC patients at 6 and 12 months respectively; and in 58% of FMD patients. Failure rate at 12 months was 48% in ASC against 25% in FMD. The mean GFR in CG was higher 12 months after intervention. The increase in GFR was noted in 45% of patients, the decrease in 25% of patients at 12 months. Normal values of UAE were found in 71% of patients, pre- and post-intervention alike. Mean LVMI and number of patients with LVH in CG decreased already during the initial 6 months post-intervention and did not change further. In conclusion, correction of RAS leads to cure of or improved control of hypertension in the majority of the patients with FMD, but in the ASC group in about half of cases no BP cure or improvement was seen. The renal function was improved or stable in two-thirds of patients after revascularization. Successful renal revascularization was followed by regression of LVH, which was evident within 6 months post-intervention.

Proximal pulmonary emboli modify right ventricular ejection pattern.

Analysis of the systolic flow velocity curve (SFVC) in the right ventricular outflow tract is considered as an alternative to the tricuspid valve pressure gradient (TVPG) method for echo-Doppler assessment of pulmonary arterial pressure (P(pa)). The present study checked whether or not SFVC is affected by the cause of pulmonary hypertension. Doppler recordings of 86 patients (39 female, aged 55.5+/-15.2 yrs) with acute (AP-PE) or chronic (CP-PE) proximal pulmonary embolism, chronic obstructive pulmonary disase (COPD) or primary pulmonary hypertension (PPH) were retrospectively analysed by two observers unaware of the purpose of the study. Despite having the lowest TVPG (48+/-13 mmHg), patients with AP-PE had the shortest acceleration time (t(acc); 56+/-15 ms) and time to midsystolic deceleration (t(msd); 105+/-16 ms). t(acc) <60 ms in patients with TVPG <60 mmHg had 98% specificity and 48% sensitivity for AP-PE. In PPH, SFVC was less abnormal (t(acc) 64+/-14 ms, t(msd) 125+/-25 ms, both p<0.03) despite having a TVPG twice as high (92+/-12 mmHg, p< 0.001). In contrast to t(acc), TVPG showed strong correlation with direct P(pa) measurements whenever performed (r=-0.43, p=0.02, versus r=0.80, p<0.001; n=30). There was no correlation between t(acc) and TVPG in a pooled study group and SFVC seemed strongly affected by the presence of both AP-PE and CP-PE. While potentially useful for evaluation of the true right ventricular afterload during pulsatile flow conditions, the systolic flow velocity curve does not provide a reliable estimate of pulmonary arterial pressure.