Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound

Two-dimensional (2-D) planimetry is limited by the technical demands, time, and observer variability required to locate the minimal orifice area, limiting the confident clinical reporting of mitral valve area (MVA). In 27 consecutive patients, MVA was determined independently by 2 observers using the conventional 2-D method and a new 3-D-guided method. Using a matrix-array probe, the valve was visualized in a long-axis view and a cursor steered to intersect the leaflet tips and provide a perpendicular short-axis plane viewed side-by-side. Two-dimensional and 3-D-guided methods allowed planimetry in 24 patients. Consistent with better orifice localization, 3-D guidance eliminated the overestimation of internal orifice diameters in the planimetered short-axis view relative to the limiting diameter defined by the long-axis view (for 3-D guidance, 0.73 +/- 0.20 vs 0.73 +/- 0.21 cm, p = 0.98, vs 0.90 +/- 0.27 cm in the 2-D short-axis view, p <0.01). Accordingly, mean values for the smallest orifice area by 3-D guidance were less than by 2-D imaging (1.4 +/- 0.5 vs 1.5 +/- 0.5 cm(2), p <0.01), changing the clinical severity classification in 11 of 24 patients (46%). The 2-D method also overestimated MVA relative to 3-D guidance compared with Doppler pressure halftime and (n = 6) Gorlin areas. Phantom studies verified no differences in resolution for the 2 acquisition modes. Three-dimensional guidance reduced intraobserver variability from 9.8% to 3.8% (SEE 0.14 to 0.06 cm(2), p <0.01) and interobserver variability from 10.6% to 6.1% (SEE 0.15 to 0.09 cm(2), p <0.02). In conclusion, matrix-array technology provides a feasible and highly reproducible direct 3-D-guided method for measuring the limiting mitral orifice area.     

Relation between coronary "steal" and contractile function at rest in collateral-dependent myocardium of humans with ischemic heart disease.

BACKGROUND: We tested the hypothesis that rest asynergy in collateral-dependent myocardium correlates with coronary steal. METHODS AND RESULTS: PET with [13N]ammonia measured myocardial blood flow and flow reserve in 15 patients with symptomatic chronic ischemic heart disease. Coronary angiography assessed stenosis severity and collateral blood supply. Echocardiography or contrast ventriculography evaluated regional wall motion. Collateral-dependent segments with normal flow at rest and supplied by coronary vessels having /=0.15 mL. min-1. g-1 versus rest. Blood flow at rest in asynergic, collateral-dependent segments with steal (1.15+/-0.35 mL. min-1. g-1) exceeded (P<0.0001) that of asynergic segments without steal (0.81+/-0.24) and those with normal contraction (0.77+/-0.18). Although the flow reserve ratio of segments with normal contraction (1.8+/-0.8) exceeded that of asynergic ones with (0.6+/-0.1) or without (1.3+/-0.4) steal, overlap was great. Correlation between basal contraction and flow reserve ratio in collateral-dependent myocardium was significant but weak (r=0.45, P<0.001). However, segments demonstrating "steal" with adenosine manifested asynergy in 22 of 23 collateral-dependent segments versus 24 of 39 nonsteal segments (chi2=7.10, P<0.01). CONCLUSIONS: Although myocardial flow reserve in collateral-dependent segments with normal contraction exceeded that of asynergic segments, overlap was great. However, in patients with angina or congestive heart failure, left ventricular segments demonstrating steal with adenosine almost always exhibit asynergy at rest. Thus, coronary steal may play an important role in the pathogenesis of chronic contractile impairment at rest, whereas simple reduction of flow reserve may be less important in selected patients.     

Mutations in promoter region of thrombomodulin and venous thromboembolic disease

The present study was designed to analyze the thrombomodulin proximal promoter region spanning nucleotides -293 to -12 to search for polymorphisms that could modify thrombomodulin gene expression in patients with venous thromboembolic disease. The study population comprised 205 patients and 394 healthy subjects of similar age and sex distribution. No polymorphisms and only 1 point mutation (G-33A) were found. The G-33A mutation was present at the heterozygous state in 2 patients and in 1 control. Being more frequent in the patients (0.97%) than in the controls (0.25%), the G-33A mutation might be a risk factor for venous thrombosis. To investigate the effect of this mutation on the thrombomodulin promoter activity, the proximal promoter region of the gene (bearing or not bearing the G-33A mutation) was inserted into a promotorless expression vector, upstream of the firefly luciferase gene, and transiently transfected into EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation mildly decreased the promoter activity. This study confirms that abnormalities of the thrombomodulin proximal promoter are not frequent in patients with venous thromboembolism.     

Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II 'reactive site' deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation.     

Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy

OBJECTIVES

We tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow.

BACKGROUND

Whether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial.

METHODS

Positron emission tomography (PET) ¹³N-ammonia was used to measure myocardial blood flow in combination with ¹⁸F-fluorodeoxyglucose (¹⁸FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo.

RESULTS

Regional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood flow in normal regions was 1.14 ± 0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48 ± 0.15; N = 8 patients) and nonviable (0.45 ± 0.14; N = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67 ± 0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients.

CONCLUSIONS

Reduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow.     

Progressive changes in ventricular structure and function during the year after acute myocardial infarction.

To investigate the long-term changes in left ventricular structure and function after myocardial infarction, 51 patients with a first myocardial infarction (17 anterior, 23 inferior, and 11 non-Q wave) were studied by two-dimensional echocardiography at the time of entry into the hospital, at 3 months, and 1 year after infarction. The left ventricular endocardial surface was reconstructed from these echocardiograms, and the endocardial surface area (ESA) index (in cm2/m2) and area of abnormal wall motion (AWM in cm2) were quantitated. Despite different trends in the ESA index between entry and 3-month values in those with and without early infarct expansion, a decrease in the ESA index from 3 months to 1 year was noted in anterior and non-Q wave infarctions (anterior with early expansion: 96.3 +/- 8.6 to 81.5 +/- 4.2 cm2/m2, p less than 0.05; anterior without early expansion: 59.7 +/- 2.0 to 54.7 +/- 2.0 cm2/m2, p less than 0.01; non-Q wave: 64.1 +/- 3.5 to 57.9 +/- 4.4 cm2/m2, p less than 0.01). The mean decline in ESA from 3 months to 1 year of 8.9 +/- 2.5 cm2 was independent of initial infarct size. Regional function, as represented by the area of AWM, was also improved but the timing of the improvement was related to the location and size of the infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiopulmonary Resuscitation Feedback: A Comparison of Device-Measured and Self-Assessed Chest Compression Quality

BackgroundHigh-quality cardiopulmonary resuscitation is the foundation of cardiac arrest care. Guidelines specify chest compression depth, recoil, and rate, but providers often fail to achieve these targets. Furthermore, providers are largely unable assess the quality of their own or other peoples’ chest compressions. Chest compression feedback devices can improve chest compression quality; their use is endorsed internationally, but they remain largely absent in clinical care.This article analyzes preclinical data collected during a quality improvement project. It describes provider demographics and perceptions about their chest compression quality and correlates them to measured chest compression quality, compares clinician perception of chest compressions to objective measures, and describes the effect of feedback on compression quality.MethodsClinicians were recruited from 2 metropolitan emergency departments. A questionnaire was used to assess participants’ levels of training and experience. A before-and-after assessment of chest compression quality was performed using a Laerdal CPRmeter 2 and a CPR mannequin. Pretest measures of chest compression quality were made by covering the device screen thereby blinding providers to feedback; repeat measures were then collected from the same participants but unblinded to feedback. Provider charecteristic were collected by survey. Correlations between blinded chest compression quality and provider charecteristics; the reliability of providers estimated compared to measured quality; and the effects of feedback on chest compression quality were assessed using Pearsons correlations, Cohens κ, and paired t testing.Results84 participants were assessed. The mean years of certification were 11.74. Ninty-five percent of the providers self-assessed as more experienced than novice and 81% reported performing cardiopulmonary resuscitation at least occasionally. The frequency of performing chest compressions was correlated with self-assessed skill (r = 0.58, P < .001). However, self-assessed skill was only weakly correlated with chest compression quality (r = 0.29, P = .01) and not at all with the frequency of performing chest compressions or years of certification. There was no agreement between self-assessed and device-measured chest compression depth (κ = ?0.10, P = 0.11), recoil (κ = ?0.14, P = .03), or rate (κ = 0.06, P =.30). The overall quality of compressions improved by 16.9%; the percentage of chest compressions achieving target depth by 3.58%; recoil by 22.82%; and rate by 23.66% with feedback. A total of 97.6% of the staff rated chest compression feedback helpful.ConclusionsOur findings suggest that participants’ demographics were not correlated with chest compression quality and that providers cannot reliably assess chest compression quality. The data also demonstrate that with minimal training, feedback can significantly improve chest compression quality.     

HLA-G haplotype structure shows good conservation between different populations and good correlation with high,normal and low soluble HLA-G expression

HLA-G molecule has considerable impact in various clinical fields, therefore many studies attempted to predict its expression based on HLA-G genotype. These studies have focused on polymorphisms in either the coding region or in one of the two untranslated regions (UTR) of the gene. The aim of our study was to determine if HLA-G haplotype defined based on SNPs 5′ and 3′UTR could be used to predict soluble HLA-G expression in unstimulated individuals. Our findings showed that HLA-G haplotype structure was well conserved between distant populations and that the defined haplotypes were correlated with high, normal and low HLA-G soluble secretors. In conclusion, we showed that this genotyping strategy based on the use of a few selected SNPs rather than isolated SNP analysis allows reliable HLA-G expression in all populations. This strategy could be useful in a number of clinical settings, e.g., predicting graft compatibility immunogenetic laboratories.