Jane E. Marshall

Three-dimensional echocardiographic reconstruction of the mitral valve, with implications for the diagnosis of mitral valve prolapse.

Mitral valve prolapse has been diagnosed by two-dimensional echocardiographic criteria with surprising frequency in the general population, even when preselected normal subjects are examined. In most of these individuals, however, prolapse appears in the apical four-chamber view and is absent in roughly orthogonal long-axis views. Previous studies of in vitro models with nonplanar rings have shown that systolic mitral annular nonplanarity can potentially produce this discrepancy. However, to prove directly that apparent leaflet displacement in a two-dimensional view does not constitute true displacement above the three-dimensional annulus requires reconstruction of the entire mitral valve, including leaflets and annulus. Such reconstruction would also be necessary to explore the complex geometry of the valve and to derive volumetric measures of superior leaflet displacement. A technique was therefore developed and validated in vitro for three-dimensional reconstruction of the entire mitral valve. In this technique, simultaneous real-time acquisition of images and their spatial locations permits reconstruction of a localized structure by minimizing the effects of patient motion and respiration. By applying this method to 15 normal subjects, a coherent mitral valve surface could be reconstructed from intersecting scans. The results confirm mitral annular nonplanarity in systole, with a maximum deviation of 1.4 +/- 0.3 cm from planarity. They directly show that leaflets can appear to ascend above the mitral annulus in the apical four-chamber view, as they did in at least one view in all subjects, without actual leaflet displacement above the entire mitral valve in three dimensions, thereby challenging the diagnosis of prolapse by isolated four-chamber view displacement in otherwise normal individuals. This technique allows us to address a uniquely three-dimensional problem with high resolution and provide new information previously unavailable from the two-dimensional images. This new appreciation should enhance our ability to ask appropriate clinical questions relating mitral valve shape and leaflet displacement to clinical and pathologic consequences.

Myocardial Injury and Ventricular Dysfunction Related to Training Levels Among Nonelite Participants in the Boston Marathon

Background— Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results— We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler–derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, >60% of participants had increased cTnT >99th percentile of normal (>0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (≥0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL (P<0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r=−0.70, P<0.001) and inversely with training mileage (r=−0.71, P<0.001). Compared with athletes training >45 miles/wk, athletes who trained ≤35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16±5% versus 25±4%, P<0.001), myocyte injury (cTnT 0.09 versus <0.01 ng/mL, P<0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P<0.001). Conclusions— Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.

Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction.

OBJECTIVES The aim of this study was to evaluate whether chronic heart failure (HF) therapy guided by concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is superior to standard of care (SOC) management. BACKGROUND It is unclear whether standard HF treatment plus a goal of reducing NT-proBNP concentrations improves outcomes compared with standard management alone. METHODS In a prospective single-center trial, 151 subjects with HF due to left ventricular (LV) systolic dysfunction were randomized to receive either standard HF care plus a goal to reduce NT-proBNP concentrations ≤1,000 pg/ml or SOC management. The primary endpoint was total cardiovascular events between groups compared using generalized estimating equations. Secondary endpoints included effects of NT-proBNP-guided care on patient quality of life as well as cardiac structure and function, assessed with echocardiography. RESULTS Through a mean follow-up period of 10 ± 3 months, a significant reduction in the primary endpoint of total cardiovascular events was seen in the NT-proBNP arm compared with SOC (58 events vs. 100 events, p = 0.009; logistic odds for events 0.44, p = 0.02); Kaplan-Meier curves demonstrated significant differences in time to first event, favoring NT-proBNP-guided care (p = 0.03). No age interaction was found, with elderly patients benefitting similarly from NT-proBNP-guided care as younger subjects. Compared with SOC, NT-proBNP-guided patients had greater improvements in quality of life, demonstrated greater relative improvements in LV ejection fraction, and had more significant improvements in both LV end-systolic and -diastolic volume indexes. CONCLUSIONS In patients with HF due to LV systolic dysfunction, NT-proBNP-guided therapy was superior to SOC, with reduced event rates, improved quality of life, and favorable effects on cardiac remodeling. (Use of NT-proBNP Testing to Guide Heart Failure Therapy in the Outpatient Setting; NCT00351390).

Hydrodynamic compression of the right atrium: a new echocardiographic sign of cardiac tamponade.

The relationship of right atrial inversion, a previously undescribed cross-sectional echocardiographic sign, to the presence of cardiac tamponade was examined. We studied 127 patients with moderate or large pericardial effusions. Cardiac tamponade was present in 19 and absent in 104. Four patients with equivocal tamponade were excluded from analysis. Right atrial inversion was present in 19 of 19 patients with cardiac tamponade and 19 of 104 without cardiac tamponade (sensitivity, 100%; specificity, 82%; predictive value, 50%). The degree of inversion as quantitated by the area-corrected curvature did not improve the ability to discriminate between patients with and without cardiac tamponade. However, consideration of the duration of inversion by the right atrial inversion time index (duration of inversion/cardiac cycle length) and an empirically derived cut-off of 0.34 did improve the specificity and predictive value (100% and 100%, respectively) without a significant loss of sensitivity (94%). We conclude that right atrial inversion, particularly if prolonged, is a useful echocardiographic marker of cardiac tamponade that may be of particular diagnostic value when the clinical picture is unclear.

Proximal Jet Size by Doppler Color Flow Mapping Predicts Severityof Mitral Regurgitation: Clinical Studies

Background Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation. Methods and Results In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results we...

New Locus for Autosomal Dominant Mitral Valve Prolapse on Chromosome 13 Clinical Insights From Genetic Studies

Background—Mitral valve prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. To date, 2 MVP loci have been described, but the defective genes have yet to be discovered. In the present study, we analyzed a large family segregating MVP, and identified a new locus, MMVP3. This study and others have enabled us to explore mitral valve morphological variations of currently uncertain clinical significance. Methods and Results—Echocardiograms and blood samples were obtained from 43 individuals who were classified by the extent and pattern of displacement. Genotypic analyses were performed with polymorphic microsatellite markers. Evidence of linkage was obtained on chromosome 13q31.3-q32.1, with a peak nonparametric linkage score of 18.41 (P<0.0007). Multipoint parametric analysis gave a logarithm of odds score of 3.17 at marker D13S132. Of the 6 related individuals with mitral valve morphologies not meeting diagnostic criteria but resembling fully developed forms, 5 carried all or part of the haplotype linked to MVP. Conclusions—The mapping of a new MVP locus to chromosome 13 confirms the observed genetic heterogeneity and represents an important step toward gene identification. Furthermore, the genetic analysis provides clinical lessons with regard to previously nondiagnostic morphologies. In the familial context, these may represent early expression in gene carriers. Early recognition of gene carriers could potentially enhance the clinical evaluation of patients at risk of full expression, with the ultimate aim of developing interventions to reduce progression.

A Locus for Autosomal Dominant Mitral Valve Prolapse on Chromosome 11p15.4

Mitral valve prolapse (MVP) is a common cardiovascular abnormality in the United States, occurring in approximately 2.4% of the general population. Clinically, patients with MVP exhibit fibromyxomatous changes in one or both of the mitral leaflets that result in superior displacement of the leaflets into the left atrium. Although often clinically benign, MVP can be associated with important accompanying sequelae, including mitral regurgitation, bacterial endocarditis, congestive heart failure, atrial fibrillation, and even sudden death. MVP is genetically heterogeneous and is inherited as an autosomal dominant trait that exhibits both sex- and age-dependent penetrance. In this report, we describe the results of a genome scan and show that a locus for MVP maps to chromosome 11p15.4. Multipoint parametric analysis performed by use of GENEHUNTER gave a maximum LOD score of 3.12 for the chromosomal region immediately surrounding the four-marker haplotype D11S4124-D11S2349-D11S1338-D11S1323, and multipoint nonparametric analysis (NPL) confirms this finding (NPL=38.59; P=.000397). Haplotype analysis across this region defines a 4.3-cM region between the markers D11S1923 and D11S1331 as the location of a new MVP locus, MMVP2, and confirms the genetic heterogeneity of this disorder. The discovery of genes involved in the pathogenesis of this common disease is crucial to understanding the marked variability in disease expression and mortality seen in MVP.

Can a Teaching Intervention Reduce Interobserver Variability in LVEF Assessment: A Quality Control Exercise in the Echocardiography Lab

OBJECTIVES This study sought to determine whether a formalized teaching intervention could reduce the interobserver variability (IOV) in visual estimation of left ventricular ejection fraction (LVEF) within a group of sonographers and physicians with a spectrum of experience. BACKGROUND Precise and reliable echocardiographic assessment of LVEF is necessary for clinical decision-making and minimizing duplicative testing. Skill in the visual estimation of LVEF varies depending on experience and is critical for corroborating EF quantification. IOV may also lead to inconsistency if multiple readers are assessing the EF on serial exams. METHODS Fourteen cases of 2-dimensional echocardiograms were shown to 25 participants who estimated the EF based on a complete assessment of LV wall motion including parasternal, short-axis, apical, and subcostal views. The cases represented a spectrum of EF range, image quality, and clinical context. Following the initial interpretations, participants underwent a teaching intervention involving tutorial review of reference cases and group discussion of each case with determination of the EF guided by quantitative measure (biplane Simpson method). Three months after the teaching intervention, 14 new cases were shown to the 25 participants following the same methodology. RESULTS IOV was quantified before and after the teaching intervention with the use of a 3-factor, nested analysis of variance. The factors were: observer, patient, and pre- and post-intervention (time). The analysis of variance showed that the intervention reduced the IOV for the 25 readers between the pre- and post-intervention assessments (F = 2.8, p = 0.007). The IOV decreased from ± 14% EF prior to intervention to ± 8.4% EF following intervention (a 40% reduction in IOV). CONCLUSIONS In a large echocardiography laboratory with a wide range of training levels and experience, a simple, formalized teaching intervention can successfully diminish IOV of LVEF assessment. This intervention provides not only discrete quality measures, but also serves as a practical tool to document and improve quality of reporting, potentially reducing clinical inefficiencies and repeat testing.

Effects of prolonged transesophageal echocardiographic imaging and probe manipulation on the esophagus—An echocardiographic-pathologic study

Transesophageal echocardiography is being increasingly utilized in the operating room and intensive care and ambulatory settings. However, to date no data are available concerning possible trauma of the transesophageal echocardiographic technique to the esophagus due to probe insertion, manipulation or direct ultrasound energy transmission. To test the hypothesis that transesophageal manipulations caused no traumatic or thermal injury to the esophageal mucosa, 12 animals were studied with continuous transesophageal echocardiography for a period of variable duration (mean 4.6 h +/- 51 min). The study group consisted of four monkeys (mean weight 5.7 +/- 0.6 kg and eight mongrel dogs (mean weight 29.8 +/- 1.4 kg). The eight dogs were studied during right heart bypass with full heparinization for 6.6 +/- 0.2 h, whereas the four monkeys were studied for 60 to 90 min in the absence of cardiopulmonary bypass and anticoagulation. Immediately after completion of transesophageal echocardiography in each case, the esophagus was entirely excised. Detailed macroscopic and microscopic examination of the esophagus revealed no significant mucosal or thermal injury. This preliminary animal study suggests that transesophageal echocardiography is safe for the esophageal mucosa in animals as small as 5 kg in weight, despite prolonged use and in the presence of systemic anticoagulation.

Echocardiographic detection of left main coronary artery obstruction.

Advances in two-dimensional echocardiography have improved the prospects of using this technique to detect left main coronary artery (LMCA) obstruction. Using an echocardiograph that had digital gray scale, a 3-MHz transducer and strobe freeze-frame capability and reviewing recordings on an off-line videotape-videodisc analyzer, we retrospectively examined the LMCA in 72 patients who underwent coronary cineangiography. Angiography showed 50% or greater LMCA obstruction in seven patients. All seven had high-intensity echoes in the walls of the LMCA. The high-intensity echoes were irregularly located in the artery and partially occluded it. The LMCA could frequently be recorded proximal and distal to the obstruction. A blinded observer reviewed 28 randomly selected patients from this group and correctly identified the four patients with LMCA obstruction. There was one true and two questionable false-positive diagnoses. In a prospective study of 31 patients, two independent observers correctly identified the three patients with LMCA obstruction. There were no false negatives, and one observer had one false positive. All of the false positives were in patients with proximal left anterior descending coronary artery obstructions. Echocardiography may be a practical means of identifying patients with the LMCA obstruction.