The role of echocardiography in the diagnosis and management of patients with pulmonary hypertension.

Pulmonary hypertension (PH) is defined as an increased mean pulmonary artery pressure (P(pa)) >25 mmHg at rest as assessed by right heart catheterisation (RHC). However, this technique is invasive and noninvasive alternatives are desirable for early diagnosis of PH. Although estimation of systolic pulmonary arterial pressure is easily obtained using Doppler echocardiography, cases of under- and over-estimations are not rare and direct measurement of P(pa) is not possible using this method. Therefore, echocardiography should be considered as a tool for assessment of the likelihood rather than the definite presence or absence of PH. Transthoracic echocardiography may be useful for noninvasive screening of patients at risk of PH. On the basis of an echocardiographic assessment, patients showing signs suggestive of PH can be referred for a confirmatory RHC. A number of variables measured during echocardiography reflect the morphological and functional consequences of PH and have prognostic value. The presence of pericardial effusion, reduced tricuspid annular plane excursion and right atrial enlargement are associated with a poorer prognosis. Echocardiography is also an important procedure for monitoring the response of patients to therapy, and is recommended 3-4 months after initiation of, or a change in, therapy. Echocardiographic assessment as part of a goal-oriented approach to therapy is essential for the effective management of PH patients.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion.

Diagnostic utility of CYFRA 21-1 and CEA assays in pericardial fluid for the recognition of neoplastic pericarditis.

A positive cytology result in pericardial fluid is the gold standard for recognition of malignant pericardial effusion. Unfortunately, in 30-50% of patients with malignant pericardial effusion cytological examination of the pericardial fluid is negative. Tumor marker assessment in pericardial fluid may help to recognize malignant pericardial effusion. The aim of our study was to estimate the value of CYFRA 21-1 and CEA measurement in pericardial fluid for the recognition of malignant pericardial effusion. To our knowledge this is the first study on CYFRA 21-1 assessment in pericardial effusion. The examined group consisted of 50 patients with malignant pericardial effusion and 34 patients with non-malignant pericardial effusion. Median CEA concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 80 ng/mL (0-317) and 0.5 ng/mL (0-18.4), respectively (p<0.001). Median CYFRA 21-1 concentrations in malignant pericardial effusion and non-malignant pericardial effusion were 260 ng/mL (5.3-10080) and 22.4 ng/mL (1.87-317.6), respectively (p<0.001). The optimal cutoff value for CYFRA 21-1 in pericardial effusion was 100 ng/mL. CYFRA 21-1 >100 ng/mL or CEA >5 ng/mL were found in 14/15 patients with malignant pericardial effusion and negative pericardial fluid cytology. We therefore strongly recommend the use of CYFRA 21-1 and/or CEA in addition to pericardial fluid cytology for the recognition of malignant pericardial effusion. (Int J Biol Markers 2005; 20: 43-49).

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.

Changes in bone density during long-term administration of low-molecular-weight heparins or acenocoumarol for secondary prophylaxis of venous thromboembolism.

BACKGROUND: Indications for long-term anticoagulation are expanding. Osteoporosis is a complication which can develop after prolonged treatment with unfractionated heparin and is probably multifactorial. Data on osteoporosis associated with low-molecular-weight heparins (LMWH) are contradictory. Vitamin K participates in bone metabolism and since oral anticoagulants antagonize vitamin K, their use may also increase the risk of osteoporosis. AIM: To assess and compare the effects of long-term secondary venous thromboembolic prophylaxis with LMWH or acenocoumarol on bone structure. METHODS: We assessed bone mineral density (BMD) by densitometry in 86 patients receiving LMWH or acenocoumarol for 3-24 months. The initial BMD was compared to the final result expressed as the percentage difference. The Z-score was also assessed and defined for individual patients as the number of standard deviations of BMD from its ideal value calculated for age and sex groups. RESULTS: Excessive decrease in BMD was evidenced, which seemed to relate to the duration as well as type of treatment. At 1 and 2 years of follow-up, the mean decrease in BMD of the femur was 1.8% and 2.6% in patients on acenocoumarol and 3.1 and 4.8% in patients on enoxaparin, respectively. CONCLUSIONS: Long-term exposure to treatment and prophylaxis of venous thromboembolism cause a modest but progressive decrease in BMD, more evident in patients on LMWH than on acenocoumarol. It might be advisable to perform densitometry before starting long-term anticoagulation and to repeat it every 12 months, especially in patients with concomitant risk factors for osteoporosis in order to identify patients in need of its prophylaxis.

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.

Diagnostic value of transoesophageal echocardiography in suspected haemodynamically significant pulmonary embolism.

OBJECTIVE: To assess the value of transoesophageal echocardiography (TOE) for diagnosing suspected haemodynamically significant pulmonary embolism and signs of right ventricular overload at standard echocardiography. METHODS: 113 consecutive patients (58 male; 55 female), mean (SD) age 53.6 (13.3) years, in whom there was clinical suspicion of pulmonary embolism and right ventricular overload on transthoracic echocardiography, underwent TOE in addition to routine diagnostic procedures to identify pulmonary artery thrombi. RESULTS: TOE revealed thrombi in 32 of 51 patients who had suspected acute pulmonary embolism and in 31 of 62 with suspected chronic pulmonary embolism. In one patient a pulmonary angiosarcoma rather than chronic pulmonary embolism was found at surgery. The diagnosis of pulmonary embolism was confirmed in 77 patients by scintigraphy, spiral computed tomography, angiography, or necropsy (reference methods). While TOE failed to provide a diagnosis of pulmonary embolism in 15 of these 77 patients, no false positive findings were reported (sensitivity 80.5%, specificity 97.2%). In 11 and 26 cases, respectively, the thrombi were confined to the left or right pulmonary artery. Bilateral thrombi were found in 25 patients. Mobile thrombi were observed only in acute pulmonary embolism (in 19 of 32 patients). No complications of TOE were noted. CONCLUSIONS: TOE permits visualisation of pulmonary arterial thrombi, confirming the diagnosis in the majority of patients with pulmonary embolism and right ventricular overload. This may be useful for prompt decision making in patients with haemodynamic compromise considered for thrombolysis or embolectomy.

Efficacy of sequential antiarrhythmic treatment in sinus rhythm maintenance after successful electrocardioversion in patients with chronic non-valvular atrial fibrillation.

BACKGROUND: Sequential use of antiarrhythmic drugs may improve prognosis in chronic atrial fibrillation (AF). We conducted a prospective study of the efficacy of sequential antiarrhythmic drug therapy in sinus rhythm (SR) maintenance after a successful electrocardioversion (CV) in pts with chronic AF. MATERIAL AND METHODS: 58 pts (64.3 +/- 4.3 years old) with chronic AF underwent CV. After SR restoration (Group I) pts received one of the following antiarrhythmic drugs (Drug I): propafenone, sotalol or disopyramide. In case of arrhythmia recurrence, second CV was performed and pts received another drug from those mentioned above (Drug II). If treatment proved to be unsuccessful pts received amiodarone (Drug III) and third CV was attempted. After first unsuccessful CV (Group II) pts received a loading dose of amiodarone and another CV was attempted. In case of SR restoration amiodarone was administered continuously. RESULTS: After 12 months 81% pts were on SR; 85% pts received amiodarone continuously. After 1 year 6 (10%) pts presented with SR treated with Drug I (median 71 days); Drug II proved to be ineffective in all patients (median 27 days). 28 pts continued to receive amiodarone (no median). CONCLUSIONS: Sequential antiarrhythmic drug therapy improves arrhythmia prognosis in AF within a 12-month observation period. Amiodarone seems to be the most effective antiarrhythmic drug also in pts who required second CV proceeded by amiodarone treatment to restore SR.

The role of echocardiography in suspected and established PE.

Acute obstruction of more than 30% of the pulmonary arterial bed often results in abnormal right ventricular (RV) transthoracic Doppler echocardiography (TTE), usually defined as RV dysfunction, dilatation, or hypokinesis. The presence of such changes strongly increases the clinical probability of pulmonary embolism (PE) (specificity, 81 to 94%; PPV, 71 to 86%) and indicates a worse prognosis, especially if a patent foramen ovale is found at contrast TTE. Normal RV echocardiography indicates a good prognosis. Integrating TTE with venous ultrasound and transesophageal imaging increases the possibility of immediate definitive justification for specific therapy. This strategy permits direct visualization of thrombi either in proximal veins, pulmonary arteries, or right heart chambers. Mobile thrombi require immediate thrombolysis or urgent embolectomy. Whether any echo-based criteria might identify normotensive patients with PE who should receive thrombolytic therapy remains a subject for an overdue large prospective trial.

[Pulmonary embolism: the past and . . . the future]. / Embolia polmonare: il passato e ... il futuro.

The history of pulmonary embolism cannot be reconstructed reliably beyond the last two centuries, starting with the Napoleon's times by the works of Laennec. We owe the first pathological and clinical descriptions to European scientists, especially French, German and Italian. Interestingly, some ideas regarding pathophysiology and even hemodynamics can be found in papers published as early as the end of the 19th century. Of note, the strong relationship between venous thrombosis and pulmonary embolism, suspected already in the middle of the 19th century, resulted later in a new clinical entity named venous thromboembolic disease. Only just before the second world war "modern" diagnostic tests entered into the clinical arena. Beginning with electrocardiography and X-ray techniques including pulmonary angiography, the progress in the field of imaging continued with lung scan, echocardiography, computed tomography, and finally still largely unexplored ultra-fast magnetic resonance imaging techniques: despite this technological development the correct diagnosis of pulmonary embolism in daily practice remains an important challenge. This is due to the lack of a single test which would combine high diagnostic power, round-the-clock availability and reasonably low cost. Though thrombotic origin of pulmonary embolism was well documented for almost two centuries, anticoagulation as a treatment for venous thromboembolism dates back much less than a century and thrombolysis was initiated only 30 years ago. What is even worse, those 30 years were not enough for us to identify clear-cut criteria in the selection between thrombolysis and anticoagulation in individual patients. Not to speak about the problem regarding optimal duration of secondary prophylaxis after a thromboembolic episode. Still how long shall we be debating about the same problems at the bed of our patients with venous thromboembolism? Or maybe the near future will bring completely new answers to our old questions? What type of case report related to pulmonary embolism will have the chance to be accepted for publication in the Italian Heart Journal in the year ... 2050? Future will show? But only if we help it....