Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

A t(2;19)(p13;p13.2) in a giant invasive cardiac lipoma from a patient with multiple lipomatosis.

Cardiac lipomas occur infrequently but account for a significant portion of rare cardiac tumors. Common cutaneous lipomas have previously been associated with rearrangements of chromosome band 12q15, which often disrupt the high-mobility-group protein gene HMGIC. In this report, we describe the cytogenetic analysis of an unusual giant cardiac lipoma that exhibited myocardial invasion in a patient with a history of multiple lipomatosis (cutaneous lipoma, lipomatous gynecomastia, lipomatous hypertrophy of the interatrial septum, and dyslipidemia). Cytogenetic studies of cells derived from the cardiac lipoma demonstrated no abnormalities of chromosome 12, but did reveal a t(2;19)(p13;p13.2). A liposarcoma-derived oncogene (p115-RhoGEF) previously mapped to chromosome 19 and the low-density lipoprotein receptor gene (LDLR) previously mapped to chromosome band 19p13 were evaluated to determine whether they were disrupted by this translocation. Fluorescence in situ hybridization analyses assigned p115-RhoGEF to chromosome 19 in bands q13.2-q13.3 and mapped the LDLR to chromosome arm 19p in segment 13.2, but centromeric to the t(2;19) breakpoint. Thus, these genes are unlikely to be involved in the t(2;19)(p13;p13.2). Further studies of the regions of chromosomes 2 and 19 perturbed by the translocation in this unusual infiltrating cardiac lipoma will identify gene(s) that participate in adipocyte growth and differentiation and may provide insight into syndromes of multiple lipomatosis.

Left ventricular geometry and function preceding neurally mediated syncope.

BACKGROUND: Neurally mediated syncope has been associated with increased left ventricular (LV) fractional shortening (FS) during tilt testing, which is consistent with the hypothesis that the stimulation of LV mechanoreceptors leads to reflex hypotension and/or bradycardia. However, FS does not represent true LV contractility because of its dependence on afterload and preload. METHODS AND RESULTS: To elucidate the role of increased contractility in the mediation of neurally mediated syncope, we compared echocardiographic measures of LV performance corrected for end-systolic stress (ESS) in 21 patients (13 women and 8 men) with unexplained syncope who had either positive (n=10) or negative (n=11) responses to a tilt-table test. Two-dimensional echocardiographic LV imaging was performed at baseline and during the initial 5 minutes of upright tilt. In the supine position, both groups had similar LV end-diastolic volume indexes, stroke volumes, FS, circumferential ESS, and afterload-independent measures of LV performance (stress-corrected midwall and FS). However, after 5 minutes of upright tilt, patients who subsequently had a positive test had a lower stroke volume, lower stress-corrected midwall shortening, and endocardial FS. The tilt-positive group also had a greater fall in ESS and FS early during upright tilt. CONCLUSIONS: Reduced ESS, LV volume, and chamber function during initial upright tilt are associated with a subsequent positive tilt response in patients with unexplained syncope. These data suggest that if paradoxic activation of LV mechanoreceptors has a role in mediating neurally mediated syncope, it is not triggered by LV hypercontractility or increased systolic wall stress during the initial period of upright tilt.

Echocardiographic and survival studies in mice undergoing endotoxic shock: effects of genetic ablation of inducible nitric oxide synthase and pharmacologic antagonism of platelet-activating factor.

Evidence implicating inducible nitric oxide synthase (iNOS) in the alterations of cardiac function characteristic of septic shock has come mostly from studies on anesthetized animals, isolated hearts, cultured myocytes, or hosts treated with pharmacologic inhibitors that lack complete specificity for iNOS. Platelet-activating factor (PAF) can participate in the induction of iNOS and has also been implicated in cardiac dysfunction in sepsis. The present studies assessed cardiac function in a model of sepsis in awake mice in which the gene for iNOS was either normal or selectively disrupted. Mice of each genotype were treated with parenteral fluids or with a highly specific antagonist of PAF. Endotoxic shock was induced by challenge with bacterial lipopolysaccharide (LPS) after priming with heat-killed Propionobacterium acnes. Wild-type mice increased stroke volume and cardiac output in response to LPS. These changes were absent in iNOS-deficient mice. When treated with parenteral fluids, LPS-challenged wild-type and iNOS-deficient mice both had a marked reduction in cardiac output. Antagonism of PAF had no effect on echocardiographic indices in wild-type mice, but selectively overcame the bradycardia and reduced cardiac output elicited by fluid administration in LPS-shocked, iNOS-deficient mice. Thus, there are major cardiovascular effects of PAF that are shared by rather than mediated by iNOS. Neither complete iNOS deficiency nor antagonism of PAF improved survival, whether tested as single or combined intervention. On the contrary, complete deficiency of iNOS was detrimental to survival. Finally, we tested the hypothesis that iNOS deficiency might improve survival if the deficiency were specific but partial. For this, we used mice with one normal and one disrupted gene for iNOS. No survival advantage was evident for these iNOS heterozygotes. Thus, partial or complete inhibition of iNOS, with or without antagonism of PAF, afforded no evident benefit beyond the previously demonstrated reduction in hypotension. Finally, these studies demonstrate that echocardiography preceded by acclimatization is feasible in unanesthetized mice, a finding which should expand the value of genetically manipulated animals for analysis of cardiac function.

Relations of diastolic left ventricular filling to systolic chamber and myocardial contractility in hypertensive patients with left ventricular hypertrophy (The PRESERVE Study).

Abnormalities of left ventricular (LV) diastolic filling and stress-corrected midwall shortening (MWS) have been described in hypertensive patients with normal ejection fraction (EF). However, whether stress-corrected MWS parallels LV diastolic filling better than EF does remains uncertain. Blood pressure, body mass index, echocardiographic LV mass and LV geometry, EF and stress-corrected MWS, LV diastolic filling (peak E- and A-wave velocities, E-wave deceleration time, and atrial filling fraction) were evaluated in 212 hypertensive patients with LV hypertrophy enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement study. LV structure, geometry, as well as LV diastolic filling, were compared between patients with reduced EF (<55%, n = 39, 18%) and those with normal EF (>55%) as well as between patients with reduced stress-corrected MWS (<89.2%, n = 31, 15%) and those with normal stress-corrected MWS (>89.2%). Patients with reduced EF had higher LV mass, eccentric LV geometry, and higher heart rate than those with normal EF, although they did not differ in age, blood pressure, or body mass index. LV filling pattern was also similar in those 2 groups. Patients with reduced stress-corrected MWS had higher atrial filling fraction, body mass index, heart rate, LV mass, and concentric geometry than those with normal stress-corrected MWS. Atrial filling fraction was negatively associated with stress-corrected MWS, but not with EF in multivariate models, independently of age, gender, heart rate, and body mass index. Thus, in hypertensive patients with LV hypertrophy, abnormal LV diastolic filling is more closely related to impaired myocardial contractility than to LV chamber EF.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121.

A gene therapy strategy involving direct myocardial administration of an adenovirus (Ad) vector encoding the vascular endothelial growth factor 121 cDNA (Ad(GV)VEGF121.10) has been shown to be capable of "biological revascularization" of ischemic myocardium in an established porcine model [Mack, C.A. (1998). J. Thorac. Cardiovasc. Surg. 115, 168-177]. The present study evaluates the local and systemic safety of this therapy in this porcine ischemia model and in normal mice. Myocardial ischemia was induced in Yorkshire swine with an ameroid constrictor 21 days prior to vector administration. Ad(GV)VEGF121.10 (10(9) or 10(10) PFU), Ad5 wild type (10(9) PFU), AdNull (control vector with no transgene; 10(9) PFU), saline, or no injection (naive) was administered in 10 sites in the ischemic, circumflex distribution of the myocardium. Toxicity was assessed by survival, serial echocardiography, blood analyses, and myocardial and liver histology at 3 and 28 days after vector administration. All pigs survived to sacrifice, except for one animal in the Ad(GV)VEGF121.10 (10(10) PFU) group, which died as a result of oversedation. Echocardiograms of Ad(GV)VEGF121.10-treated pigs demonstrated no differences in pericardial effusion, mitral valve regurgitation, or regional wall motion compared with control pigs. Intramyocardial administration of Ad(GV)VEGF121.10 included only minimal myocardial inflammation and necrosis, and no hepatic inflammation or necrosis. Only a mild elevation of the white blood cell count was encountered on day 3, which was transient and self-limited in the Ad(GV)VEGF121.10 group as compared with the saline-treated animals. As a measure of inadvertent intravascular administration of vector, normal C57/BL6 mice received intravenous Ad(GV)VEGF121.10 (10(4), 10(6), 5 x 10(7), or 10(9) PFU), AdNull (5 x 10(7) or 10(9) PFU), or saline. Toxicity was assessed by survival, blood analyses, and organ histology at 3 and 7 days after vector administration. A separate group of C57/BL6 mice received intravenous AdmVEGF164 (Ad vector encoding the murine VEGF164 cDNA), Ad(GV)VEGF121.10, AdNull (10(8) PFU each group), or saline to assess duration of expression and safety of a homologous transgene. All mice survived to sacrifice except for 40% of the mice in the highest (10(9) PFU; a dose more than 10(3)-fold higher by body weight than the efficacious dose in pigs) Ad(GV)VEGF121.10 dose group, which died on days 5-6 after vector administration. The only differences seen in the blood analyses between treated and control mice were in the very high Ad(GV)VEGF121.10 dose group (10(9) PFU), which demonstrated an anemia as well as an increase in alkaline phosphatase when compared with all other treatment groups. Hepatic VEGF levels by ELISA in AdmVEGF164-treated mice did not persist beyond 14 days after vector administration, suggesting that persistent expression of a homologous VEGF gene transferred with an Ad vector is not a significant safety risk. Although this is not a chronic toxicity study, these data demonstrate the safety of direct myocardial administration of Ad(GV)VEGF121.10, and support the potential use of this strategy to treat human myocardial ischemia.

Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart.

OBJECTIVES: Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, can be delivered to targeted tissues by means of a replication-deficient adenovirus (Ad) vector. We hypothesized that direct administration of Ad vector expressing the VEGF121 complementary deoxyribonucleic acid (AdGVVEGF121.10) into regions of ischemic myocardium would enhance collateral vessel formation and improve regional perfusion and function. METHODS: Yorkshire swine underwent thoracotomy and placement of an Ameroid constrictor (Research Instruments & MFG, Corvallis, Ore.) on the circumflex coronary artery. Three weeks later, myocardial perfusion and function were assessed by single photon emission computed tomography imaging (SPECT) with 99mTc-labeled sestamibi and by echocardiography during rest and stress. AdGVVEGF121.10 (n = 7) or the control vector, AdNull (n = 8), was administered directly into the myocardium at 10 sites in the circumflex distribution (10(8) pfu/site). Four weeks later, these studies were repeated and ex vivo angiography was performed. RESULTS: SPECT imaging 4 weeks after vector administration demonstrated significant reduction in the ischemic area at stress in AdGVVEFG121.10-treated animals compared with AdNull control animals (p = 0.005). Stress echocardiography at the same time demonstrated improved segmental wall thickening in AdGVVEGF121.10 animals compared with AdNull control animals (p = 0.03), with AdGVVEGF121.10 animals showing nearly normalized function in the circumflex distribution. Collateral vessel development assessed by angiography was also significantly greater in AdGVVEGF121.10 animals than in AdNull control animals (p = 0.04), with almost complete reconstitution of circumflex filling in AdGVVEGF121.10 animals. CONCLUSIONS: An Ad vector expressing the VEGF121 cDNA induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardial perfusion and function. Such a strategy may be useful in patients with ischemic heart disease in whom complete revascularization is not possible.

Channel patency and neovascularization after transmyocardial revascularization using an excimer laser: results and comparisons to nonlased channels.

BACKGROUND: Transmyocardial revascularization (TMR) has emerged as a promising treatment for ischemic heart disease in patients who are not candidates for coronary bypass surgery or angioplasty. Controversy exists, however, as to whether the use of laser energy is critical for TMR channel patency. We therefore compared by histologic assessment the outcome of lased channels with nonlased channels 30) days after TMR, using a low energy, short-pulse, fiberoptic excimer laser. METHODS AND RESULTS: In each of six sheep, 36 1-mm TMR channels (9 mJ; 240 Hz; 1.55 cm advance/s) were placed in the anterior wall of the left ventricle, and 12 1-mm nonlased channels were created in adjacent segments by advancing the fiberoptic through the left ventricular wall with the laser inactivated. Of the 36 lased channels, 56+/-7.3% were identifiable, and 100% of those identifiable appeared to represent a "channel derivative" with evidence of an endothelialized lumen, whereas none of the nonlased channels had evidence of channel patency. Lased channels had a marked neovascular response (graded on a 0-3 scale) compared with nonlased channels (2.5+/-0.1 versus 1.0+/-0.1; P<.05). Echocardiography performed 1 and 30 days after TMR demonstrated normal global and regional left ventricular function in all animals. Creatinine phosphokinase myocardial band fractions were not significantly increased after TMR. CONCLUSIONS: TMR using the excimer laser results in increased evidence of channel derivatives and neovascularization compared with nonlased channels while preserving normal ventricular function. These findings suggest that laser energy may be an important component of TMR strategy.

Estimation of left ventricular chamber and stroke volume by limited M-mode echocardiography and validation by two-dimensional and Doppler echocardiography.

This study has been designed to improve estimation of stroke volume from linear left ventricular (LV) dimensions measured by M-mode echocardiography, in symmetrically contracting ventricles. In experimental studies, the ratio of LV epicardial long/short axes "Z" is about 1.3. We measured systolic and diastolic epicardial long and short axes by 2-dimensional echocardiography in 115 adults with widely varying LV short-axis dimensions (LV end-diastolic dimension = 3.95 to 8.3 cm). In a learning series of 23 normotensive and 27 hypertensive subjects, Z(diastole) was 1.3 +/- 0.1 and Z(systole) = 1.2 +/- 0.1, similar to findings in experimental animals. Regression equations were developed by comparing LV volumes by M-mode and 2-dimensional echocardiography. In a test series (65 subjects), LV volumes were calculated using separate regression equations for end-diastolic volume ([LV end-diastolic dimension] 4.765 - 0.288 x posterior wall thickness]) and for end-systolic volume ([LV end-systolic dimension] [4.136 - 0.288 x posterior wall thickness]). Because the term 0.288 x wall thickness was only about 8% of the first term between brackets, the average wall thickness in the learning series was substituted in the Z-volume formulas applied to the test series: end-diastolic volume = (4.5 x [LV end-diastolic dimensions]2) and end-systolic volume = (3.72 x [LV end-diastolic dimension]2). The mean relative error produced with this simplified method was 0.9%. in diastole and 1.4% in systole. Compared with Teichholz' M-mode volume method, Z-derived end-diastolic volume in the test series was equally well related to 2-dimensional volumes (both r = 0.88), with a better intercept (1.5 vs -23 ml, p <0.001) and a slope closer to the identity line (1.1 vs 1.4). Similar results were found for systolic volumes. In a second test series of 1,721 American Indian participants in the Strong Heart Study without mitral regurgitation or segmental LV wall motion abnormalities, Doppler-derived LV stroke volume (70 +/- 14 ml/beat) was similarly predicted by the Z-derived method (r = 0.65, 70 +/- 11 ml/beat) and Teichholz formulas (r = 0.64, 72 +/- 13 ml/beat), but Z-derived volumes had a regression line significantly closer to the identity line (p <0.005). Thus, LV chamber and stroke volumes can be determined from M-mode LV diameters over a wide range of LV sizes and in epidemiologic as well as clinical populations. The performance of this new method appears better than that obtained using the Teichholz formula, with a formula that is easy to handle and makes calculation of LV volumes by pocket calculator possible, even from limited echocardiographic studies.

Assessment of left ventricular function by meridional and circumferential end-systolic stress/minor-axis shortening relations in dilated cardiomyopathy.

Echocardiographic meridional wall stress-endocardial shortening relations provide estimates of left ventricular (LV) contractility that do not uniformly detect myocardial dysfunction despite severe symptoms in dilated cardiomyopathy. To improve detection of myocardial dysfunction in patients with congestive heart failure (CHF) due to dilated cardiomyopathy, echocardiographic meridional and circumferential end-systolic stress were related to endocardial and midwall shortening in 42 patients (95% dead within a mean of 22 months) with dilated cardiomyopathy and 140 normal subjects. A method to estimate LV long-axis dimension from M-mode minor-axis epicardial measurements was developed in a separate series of 115 subjects. Endocardial shortening to meridional wall stress relation identified 31 of 42 CHF patients falling below the 95% normal confidence interval of the reference population; use of midwall shortening decreased this number to 26 (p = NS). The use of circumferential wall stress identified 39 of 42 patients with subnormal endocardial LV shortening and 41 of 42 patients with depressed midwall performance (p < 0.01 vs use of meridional stress). The circumferential/meridional wall stress ratio was 2.6 +/- 0.5 in normal subjects and 1.3 +/- 0.2 in CHF patients (p < 0.0001). Thus, use of circumferential end-systolic stress as the measure of afterload improves the detection of myocardial dysfunction by stress/shortening relations in patients with CHF. The ratio between the 2 stresses decreases with more spherical LV shape. Midwall and endocardial shortening measurements are equivalent in the setting of thin LV walls as occurs in dilated cardiomyopathy.

Regression of left ventricular hypertrophy as a surrogate end-point for morbid events in hypertension treatment trials.

OBJECTIVE: To assess whether regression of left ventricular hypertrophy (LVH) can be used as a surrogate end-point for morbid events in hypertension treatment trials. DESIGN AND METHODS: Statistical, epidemiologic and treatment trial literature was reviewed to identify the criteria that should be met by a surrogate end-point and to determine whether these criteria are met by existing data on the regression of LVH. RESULTS: Relevant criteria include: (1) a consistent relationship between LVH and subsequent morbid events; (2) prediction of lower or higher complication rates by LVH regression or progression; (3) evidence that the relationship between LVH regression/progression and morbidity/mortality is consistent in different populations and with different treatments; and (4) demonstration of a quantitative relationship that allows prediction of a change in clinical risk from a measured change in LVH. The results of seven electrocardiographic and 10 echocardiographic studies with a total of about 20000 subjects have shown consistently higher risks of morbid events in subjects with than without LVH (odds ratios 1.4-5.4). The available data (four studies, 1145 subjects) suggest that morbid events will occur in a higher proportion of subjects in whom LVH progresses (13-59%) rather than regresses (7-12%). However, the latter data are derived almost entirely from white subjects, predominantly male, with incomplete knowledge of interim treatment and blood pressure in most instances; no information on the mathematical relationship between change in LVH and subsequent morbidity and mortality is yet available. CONCLUSIONS: A strict definition of the information required to establish a fully adequate surrogate end-point for morbid events in antihypertensive has been partially but not completely satisfied. The consistent relationship between baseline LVH and subsequent morbid events and the initial evidence of a parallelism between LVH change and prognosis need to be supplemented by additional studies that examine the latter relationship in diverse populations under varied treatments, and which examine the quantitative relationship between measured change in LVH and the subsequent rates of morbid events. Additional data will come from ongoing treatment trials (approximately 12 000 subjects) and observational studies (approximately 8000 subjects) with serial assessments of LVH.

Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector.

BACKGROUND: Direct myocardial gene transfer is a mordality that involves the introduction of genetic information into myocardial tissue to achieve a therapeutic effect. This study was designed to characterize the temporal and spatial limits of gene expression and to determine the safety of direct myocardial gene transfer in a large animal model using replication-deficient adenovirus vectors. METHODS: Mongrel dogs underwent left thoracotomy and direct myocardial injections (100 microL/injection) of adenovirus vectors (10(9) pfu) carrying the DNA for the reporter enzyme chloramphenicol acetyl transferase or the angiogenic protein vascular endothelial growth factor. Two to 14 days after vector administration, regional protein expression was evaluated in myocardium and distant organs. Left ventricular function, assessed by echocardiography, and routine hematologic and biochemical indices were evaluated before and after vector administration. RESULTS: Peak levels of chloramphenicol acetyl transferase activity were detected 2 days after vector administration, and levels above baseline persisted for at least 14 days. Local chloramphenicol acetyl transferase activity was detected at distances at least as far as 1.5 cm from the site of injection. Chloramphenicol acetyl transferase activity in distant organs was less than 0.1% of that in injected myocardium 7 days after vector administration. Localized expression of vascular endothelial growth factor was achieved for up to 7 days after a single vector administration. Cardiac function and laboratory values were unchanged during the study. CONCLUSIONS: Adenovirus-mediated direct myocardial gene transfer can be accomplished safely in a large animal model, providing high levels of protein expression in a greater spatial distribution than previously reported, with minimal transfection of distant organs. Sustained and localized expression of a potent angiogenic mediator has been accomplished, which may provide an innovative strategy to stimulate angiogenesis in ischemic myocardium.

Transesophageal echocardiography to diagnose and demonstrate resolution of an acute massive pulmonary embolus.

A 54-yr-old man presented with acute respiratory failure and hemodynamic collapse. Acute massive pulmonary embolus was confirmed with visualization of the thrombus by transesophageal echocardiography. Successful resolution after thrombolysis was confirmed by a repeat study. Transesophageal echocardiography can be used for both diagnosis and assessment of therapy in select cases of acute massive pulmonary embolism.

Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves.

To determine whether aortic root dilation associated with a bicuspid aortic valve occurs independently of valvular hemodynamic abnormality, aortic root dimensions were measured by two-dimensional echocardiography in 83 adults with a functionally normal (n = 19), mildly regurgitant (n = 26), severely regurgitant (n = 27) or stenotic (n = 11) bicuspid aortic valve and compared with findings in normal subjects matched for age and gender. Aortic root measurements were made at four levels: anulus, sinuses of Valsalva, supraaortic ridge and proximal ascending aorta. Seventy-one percent of patients with a bicuspid aortic valve were men. When compared with control subjects, all hemodynamic subgroups showed a significantly larger aortic root size at three levels: sinuses of Valsalva, supraaortic ridge and proximal ascending aorta (p less than 0.05 to p less than 0.001). The prevalence of aortic root enlargement among all hemodynamic subgroups ranged from 9% to 59% at the level of the anulus, 36% to 78% at the sinuses, 47% to 79% at the supraaortic ridge and 50% to 64% in the ascending aorta. Thus, there is a high prevalence of aortic root enlargement in patients with a bicuspid aortic valve that occurs irrespective of altered hemodynamics or age. These findings support the hypothesis that bicuspid aortic valve and aortic root dilation may reflect a common developmental defect.