Non invasive estimation of mean right atrial pressure utilizing the 2D-Echo transverse diameter of the left hepatic vein

Aim of our study was to assess if the 2D-Echo transverse diameter of the left hepatic vein (LHV) obtained from the subcostal approach is correlated with invasive mean right atrial pressure (RAP). Thirty-two consecutive patients with acute myocardial infarction were studied by simultaneous 2D-Echo and right heart catheterization. LHV could be adequately imaged in 90% of patients. Mean RAP values at catheterization ranged from 0 to 15mmHg (mean 6±3.5 mmHg). A correlation was found between mean RAP and LHV diameter calculated after inspiration (r=0.81, SEE=1.54 mm, slope=0.71,p< 0.001) as well as after expiration (r=0.82, SEE=1.32mm, slope=0.62,p< 0.001) or during post-expiratory apnoea (r=0.85, SEE=1.3 mm, slope=0.71,p< 0.001). Moreover, percent increments of LHV diameter correlated well with percent changes of mean RAP during rapid infusion of 250–500 cc of saline in 4 patients (r=0.98,p< 0.001). Thus, the 2D-Echo LHV diameter is a feasible measurement that seems to correlate well with invasive mean RAP over a wide range of mean RAP values in patients with myocardial infarction; the changes in LHV diameter correlate well with the percent increase in central venous pressure obtained with saline infusion. Underestimation of invasive RAP occurs when mean RAP value exceeds 12 mmHg and can be explained by limited venous compliance. However these preliminary results suggest that this method may represent a valid alternative to obtain a non invasive estimate of mean RAP with 2D-Echocardiography.     

Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies

Marfan Syndrome (MFS) is an autosomal dominant disorder of the connective tissue due to mutations of Fibrillin-1 gene (FBN1) in more than 90% of cases and Transforming Growth Factor-Beta-Receptor2 gene (TGFB2R) in a minority of cases. Genotyping is relevant for diagnosis and genotype-phenotype correlations. We describe the FBN1 genotypes and related phenotypes of 81 patients who were referred to our attention for MFS or Marfan-like phenotypes. Patients underwent multidisciplinary pertinent evaluation in the adult or paediatric setting, according to their age. The diagnosis relied on Ghent criteria. To optimise DHPLC analysis of the FBN1 gene, all coding regions of the gene were directly sequenced in 19 cases and 10 controls: heterozygous amplicons were used as true positives. DHPLC sensitivity was 100%. Then, DHPLC was used to screen 62 other cases. We identified 74 FBN1 mutations in 81 patients: 64 were novel and 17 known. Of the 81 mutations, 41 were missense (50.6%), 27, either nonsense or frameshift mutations and predicted a premature termination codon (PTC) (33%), 11 affected splice sites (13.6%), and two predicted in-frame deletions (2.5%). Most mutations (67.9%) occurred in cbEGF-like modules. Genotype was clinically relevant for early diagnosis and conclusion of the diagnostic work-up in patients with incomplete or atypical phenotypes.     

Results of dipyridamole plus atropine echo stress test for the diagnosis of coronary artery disease

Sensitivity of dipyridamole stress echocardiography (DIP-E) has been reported to be less than ideal in particular subsets of patients such as those with less severe extent of coronary artery disease (CAD). To verify if sensitivity could be improved, ATRO (1 mg in 2 minutes) was added at the end of a negative high-dose (0.84 mg/kg over 10 minutes) DIP-E in 61 consecutive patients (58 men, aged 53±7 years) evaluated for chest pain (33%) or for detection of residual ischemia after acute myocardial infarction (AMI) or previous MI (67%). DIP-E was positive in 28/61 (46%) and negative in 33/61 (54%) patients. Additional echo positivity was obtained in 18/33 (54%) patients after ATRO. Coronary arteriography was normal in 6 patients (10%); 1-vessel CAD was diagnosed in 28 (46%), 2-vessel CAD in 16 (26%) and 3-vessel CAD in 11 (18%) cases. The sensitivity for CAD diagnosis was 49% (27/55) for DIP-E and 84% (46/55) for DIP-E + ATRO (p<0.001). Specificity was 83% and 80%, respectively. Diagnostic accuracy increased from 52% to 83% (p<0.001). The better diagnostic accuracy of DIP-E was mainly related to the significant increase in sensitivity of the combined test in patients with 1-vessel CAD (from 46% to 75%) (p<0.005). At quantitative coronary evaluation, compared to patients with positive DIP-E + ATRO or negative DIP-E + ATRO test, patients with positive DIP-E had a higher mean % diameter stenosis: 80±13% vs 72±24% and 65±36%, respectively. Peak heart rate was significantly higher after the addition of ATRO vs basal and DIP alone in patients with a positive DIP-E + ATRO test. The addition of ATRO to DIP increases diagnostic accuracy of DIP-E particularly in patients with less severe extent of CAD; ATRO may be considered as a useful routine procedure for increasing diagnostic value of DIP-E test.     

Spiramycin Treatment of Toxoplasma gondii Infection in Pregnant Women Impairs the Production and the Avidity Maturation of T. gondii-Specific Immunoglobulin G Antibodies

The aim of the study was to evaluate the influence of treatment with spiramycin on the increase of immunoglobulin G (IgG) titers and IgG avidity indexes (AI) in pregnant women with seroconversion from the beginning of therapy until delivery and after delivery. This group was compared with adult patients with recently acquired untreated toxoplasmosis. One hundred four samples from 32 pregnant women with seroconversion for toxoplasmosis and/or very low IgG AI were followed from the beginning of therapy with spiramycin until delivery. Twenty-nine women were further followed some months after delivery and interruption of therapy. Thirty-eight samples from 16 untreated, nonpregnant patients were evaluated as the control group. The Toxoplasma gondii-specific IgG antibody and the T. gondii-specific IgG AI were significantly delayed in pregnant women receiving therapy compared to nonpregnant, untreated controls, and the findings were consistent with the results of assays from two different manufacturers. The T. gondii-specific IgG AI increased in pregnant women after they gave birth. Avidity maturation is delayed during pregnancy and treatment, and low-avidity antibodies in pregnant women within 3 to 4 months cannot be taken as a sign of infection.After infection, the specific immunoglobulin G (IgG) antibody response matures by the selection of clones of B cells producing antibodies with increasingly higher avidities against a specific antigen from the invading microorganism. In Toxoplasma gondii infections, specific IgM may be present for a long time (14-17), and measurement of the T. gondii-specific IgG avidity index (AI) is the best method to determine the time of infection (24) and is a further development of the differential agglutination assay (3, 27).The original method developed by Hedman et al. (4, 5) used serial dilutions tested in enzyme immunoassays with and without 6 M urea, but automated assays calculate the IgG AI from two single measurements with and without urea (22). This introduces uncertainty, although experiments with only two serum sample dilutions showed excellent agreement with IgG AI measurements obtained with four serial serum sample dilutions (9).A persistent, low IgG AI poses a diagnostic problem, at least in some pregnant women receiving treatment during pregnancy (21).The observation that Toxoplasma gondii-specific IgG maturation is delayed in treated pregnant women compared to nontreated, nonpregnant individuals has been reported in two previous studies, which found significantly delayed IgG maturation in treated individuals (13, 26).The maturation of the IgG response varies between individuals and may take months in pregnant, treated women, for whom one study found that a low IgG AI persisted up to 9 months postinfection (20). In a study of T. gondii-infected pregnant women identified prospectively through prenatal screening, one study found that 2 out of 73 women had IgG AI above 0.2 before 20 weeks of gestation, but many continued to have low IgG AI even a year after infection. It is assumed that all women were treated during pregnancy (7).One problem with different findings in different studies is the lack of standardization of the T. gondii-specific IgG AI assay (12).We report here that treatment of T. gondii infection may influence IgG production and avidity maturation in pregnant women, which was evaluated by two commercial methods.     

Non invasive estimation of mean right atrial pressure utilizing the 2D-Echo transverse diameter of the left hepatic vein

Aim of our study was to assess if the 2D-Echo transverse diameter of the left hepatic vein (LHV) obtained from the subcostal approach is correlated with invasive mean right atrial pressure (RAP). Thirty-two consecutive patients with acute myocardial infarction were studied by simultaneous 2D-Echo and right heart catheterization. LHV could be adequately imaged in 90% of patients. Mean RAP values at catheterization ranged from 0 to 15mmHg (mean 6±3.5 mmHg). A correlation was found between mean RAP and LHV diameter calculated after inspiration (r=0.81, SEE=1.54 mm, slope=0.71,p< 0.001) as well as after expiration (r=0.82, SEE=1.32mm, slope=0.62,p< 0.001) or during post-expiratory apnoea (r=0.85, SEE=1.3 mm, slope=0.71,p< 0.001). Moreover, percent increments of LHV diameter correlated well with percent changes of mean RAP during rapid infusion of 250–500 cc of saline in 4 patients (r=0.98,p< 0.001).Thus, the 2D-Echo LHV diameter is a feasible measurement that seems to correlate well with invasive mean RAP over a wide range of mean RAP values in patients with myocardial infarction; the changes in LHV diameter correlate well with the percent increase in central venous pressure obtained with saline infusion. Underestimation of invasive RAP occurs when mean RAP value exceeds 12 mmHg and can be explained by limited venous compliance. However these preliminary results suggest that this method may represent a valid alternative to obtain a non invasive estimate of mean RAP with 2D-Echocardiography.     

The role of echocardiography and pulsed Doppler in the congenital absence of the pericardium. Description of 2 cases

Congenital absence of the left pericardium, partial or complete, is an uncommon cardiac defect. Most patients affected by this abnormality are asymptomatic. Usually it is suspected on the basis of a chest X-ray showing a normal sized cardiac shadow projecting entirely to the left of the spine. Computed axial tomography confirmed the absence of the left pericardium detecting the interposition of the left lung between the ascending aorta and main pulmonary artery. The M-mode, two-dimensional, and Doppler-cardiographic findings of complete congenital absence of the left pericardium are described in two cases. Imaging seems to be not specific for this abnormality; however in both cases pulsed Doppler detected mild tricuspid and pulmonic valve regurgitation.     

Noninvasive estimation of both systolic and diastolic pulmonary artery pressure from Doppler analysis of tricuspid regurgitant velocity spectrum in patients with chronic heart failure

Background Noninvasive estimation of pulmonary artery systolic and diastolic pressures usually requires the investigation of both tricuspid and pulmonary regurgitant jets and an estimate of right atrial pressure. A new, noninvasive method to obtain pulmonary diastolic pressure (based on the hemodynamic demonstration that right ventricular systolic pressure and pulmonary artery diastolic pressure are equal at the time of pulmonary valve opening) from the analysis of tricuspid regurgitation alone has been described in a small cohort of patients. We sought to verify the accuracy of this method in a large population of patients with heart failure. Methods An estimate of pulmonary artery diastolic pressure was obtained by transposing the pulmonary opening time (from the onset of the R wave on the electrocardiographic tracing to the beginning of pulmonic forward flow on Doppler examination) onto the tricuspid regurgitant velocity curve and calculating the pulmonary artery diastolic pressure value as the pressure gradient between the right ventricle and right atrium at this time. The study group included 86 consecutive patients (64 men, aged 52 ± 11 years) with heart failure (New York Heart Association class ≥II, 94%) who were in stable clinical condition with a chiefly idiopathic (57%), ischemic (24%), or other form (13%) of dilated cardiomyopathy. Noninvasive, right-sided pressures were compared with invasive measurements obtained during right heart catheterization performed within 24 hours. The Bland and Altman graphic method was used together with the calculation of the Lin concordance correlation coefficient and its 95% CI to assess the agreement between hemodynamic and echocardiographic measurements. Results Catheter-derived pulmonary artery systolic pressure ranged from 8 to 119 mm Hg (mean 42 ± 21 mm Hg), pulmonary artery diastolic pressure from 1 to 59 mm Hg (mean 20 ± 11 mm Hg), and right atrial pressure from −5 to 20 mm Hg (mean 6 ± 5 mm Hg). Tricuspid regurgitation was detected in 75 of 86 patients (87%). Pulmonary artery systolic pressure ranged from 13 to 110 mm Hg (mean 44 ± 21 mm Hg); the pressure gradient between the right ventricle and right atrium at time t of the pulmonary valve opening on the tricuspid regurgitation velocity curve was measurable in 70 of 75 (93%) cases and ranged from 3.5 to 64 mm Hg (mean 22 ± 11 mm Hg). Good agreement was observed not only for pulmonary artery systolic pressure but also for pulmonary artery diastolic pressure, based on the analysis of the tricuspid regurgitation velocity jet, with a slight difference between measurements (−1.8 and 0.1, respectively), no evident pattern of point scattering, and a high concordance correlation coefficient that was elicited by the virtually total overlapping of lines on the graph. Overall results were not significantly different whether patients with depressed right ventricular function (right ventricular ejection fraction ≤35%), with a tricuspid regurgitation grade ≥2 and atrial fibrillation were included in the analysis. Conclusions The narrow paired difference for the estimate of pulmonary artery systolic pressure and the even better difference for pulmonary artery diastolic pressure using the tricuspid regurgitation velocity curve analysis indicates that this new method reliably estimates invasive right-sided pressures over a wide range of pressure values in patients with heart failure. The overall good correlation with invasive values indicates that Doppler examination of tricuspid regurgitation alone may provide a simple and comprehensive new method for the noninvasive evaluation of right ventricular and pulmonary hemodynamics in patients with heart failure. (Am Heart J 2002;144:1087-94.)