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Biomedical subjects

M G St John Sutton

Publications and source records attributed to M G St John Sutton.

At least 19 recordsLinked to original sources

Prognostic value of two-dimensional echocardiography and N-terminal proatrial natriuretic peptide following an acute myocardial infarction. Assessment of baseline values (2-7 days) and changes at 3 months in patients with a preserved systolic function.

AIMS: The purpose of this prospective, observational study was to evaluate the relationship of left ventricular volumes, systolic function and plasma N-terminal proatrial natriuretic peptide (Nt-proANP) to cardiac morbidity and mortality in post-myocardial infarction patients with left ventricular ejection fraction > or =40%. METHODS AND RESULTS: Two-dimensional echocardiographic recordings and Nt-proANP measurements were obtained in 834 patients who survived acute myocardial infarction. Patients were examined at 2-7 days and 3 months after the index infarction and followed up for 24 months. All measurements of left ventricular volumes, ejection fraction and Nt-proANP were performed in core laboratories. During follow-up 102 patients sustained one or more incidents of the combined primary end-point: cardiac death (n=11), recurrent infarction (n=55) or heart failure requiring hospitalization or treatment with an ACE inhibitor and a diuretic (n=52). Using Cox proportional hazards model, baseline Nt-proANP predicted these events (chi-square 25.3, P<0.0001), while baseline echo volumes and ejection fraction did not. During the subsequent 3-24 month period, 51 patients suffered a primary end-point: cardiac death (n=9), recurrent infarction (n=29), heart failure (n=21). An increase in left ventricular end-systolic volume was the strongest predictor for adverse events (chi-square 19.1, P<0.0001), especially for heart failure. Individual changes in Nt-proANP did not predict cardiac events, whereas both echocardiographic variables and Nt-proANP measured at 3 months had a prognostic impact on subsequent cardiac events (3-24 months). CONCLUSIONS: In post-myocardial infarction patients with preserved left ventricular function (left ventricular ejection fraction > or =40%) baseline Nt-proANP, but not echocardiographic left ventricular volumes predicted adverse cardiac events. Early changes in left ventricular volumes and ejection fraction from baseline to 3 months had a further prognostic impact on subsequent events (3-24 months).

Aged↗

Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium.

BACKGROUND: After acute myocardial infarction, regional myocardial wall strains and stresses change and a complex cellular and biochemical response is initiated to remodel the ventricle. This study tests the hypothesis that changes in regional ventricular wall strains affect regional collagen accumulation and collagenase activity. METHODS: Fourteen sheep had acute anteroapical infarction that progressively expands into left ventricular aneurysm within 8 weeks. In 7 sheep, infarct expansion was restrained by prior placement of mesh over the area at risk. Fourteen days after infarction, and after hemodynamic and echocardiographic measurements, animals were euthanized for histology, measurements of hydroxyproline, matrix metalloproteinase-1 (MMP-1 or collagenase) and MMP-2 (gelatinase) activity, as well as collagen type I and III in infarcted, borderzone, and remote myocardium. RESULTS: Restraining infarct expansion does not change collagen content or MMP-1 or MMP-2 activity in the infarct, but significantly increases the ratio of collagen I/III. In borderzone and remote myocardium infarct, restraint significantly increases collagen content and significantly reduces MMP-1 activity. MMP-2 activity is reduced (p = 0.059) in borderzone myocardium only. Between groups, the ratio of type I/III fibrillar collagen does not change in borderzone myocardium. CONCLUSIONS: Fourteen days after acute myocardial infarction, restraining infarct expansion increases collagen accumulation in borderzone and remote myocardium, which may prevent expansion of hypocontractile, fully perfused "remodeling myocardium" adjacent to the infarct. This study demonstrates that changes in regional myocardial wall strain alter the cellular and biochemical processes involved in postinfarction ventricular remodeling.

Animals↗

Right ventricular dysplasia in an asymptomatic young man: an uncommon case with biventricular involvement and no known family history.

A 33-year-old man had cardiomegaly on a routine x-ray examination. He was asymptomatic with no history of infarction, syncope, or palpitations. There was no family history of congenital heart disease or sudden death. Two-dimensional transthoracic echocardiography demonstrated marked enlargement of the right atrium and ventricle with severely depressed right and left ventricular function that was consistent with right ventricular dysplasia. The patient was treated with an angiotensin-converting enzyme inhibitor and did well for 6 months, but then developed symptomatic left-sided congestive heart failure. Short-term improvement was obtained with intravenous inotropic therapy, but he continued to have progressive symptoms of heart failure. Approximately 7 months after his initial presentation, the patient underwent orthotopic heart transplantation for intractable congestive heart failure. Pathologic examination of the explanted heart established the diagnosis of right ventricular dysplasia with left ventricular involvement. This is an uncommon presentation of right ventricular dysplasia with biventricular involvement and no known family history.

Adult↗

Structural determinants of aortic regurgitation in type A dissection and the role of valvular resuspension as determined by intraoperative transesophageal echocardiography.

Disruption of the aortic root by dissection often produces significant aortic regurgitation (AR). Resuspension of the native valve usually reestablishes competence. The mechanisms of this complex process are poorly understood. We used intraoperative transesophageal echocardiography to characterize the in vivo aortic root structure of type A aortic dissection and the changes brought about by native valve resuspension. Intraoperative transesophageal echocardiograms were obtained from 34 patients with type A dissection and aortic resuspension between January 1990 and April 1997. The severity of AR, aortic root diameter, circumference of the aortic annulus, percentage of the annulus dissected, and presence of leaflet prolapse were assessed in multiple planes. Preoperatively, AR of varying degree was present in 25 patients (73%). Multivariate analysis revealed that preoperative AR was most related to percentage of the annulus dissected (p<0.0001) and less related to root diameter (p<0.01). Leaflet prolapse was predicted by percent aortic annulus dissected (p <0.0001). After resuspension, annular dissection and leaflet prolapse were no longer present. Postoperative AR was significantly decreased from preoperative AR (p<0.0001) and was considered trace to mild. Although postoperative root diameter and annular circumference decreased (p<0.001), individual reductions in AR did not correlate with individual changes in root diameter or annular circumference. The degree of dissection of the valve annulus is the most significant determinant of leaflet prolapse and AR severity. Overall size of the aortic root also contributes to AR. Surgical resuspension significantly decreases root size, but its primary benefit is restoration of the structural integrity of the aortic annulus.

Aortic Dissection↗

Pheochromocytoma crisis, cardiomyopathy, and hemodynamic collapse.

Pheochromocytoma is a notorious clinical entity. Although suspicion is aroused by severe hypertension in young patients, this sign is often absent. We present a case in which early absence of hypertension and nonspecific signs and symptoms led to failure of prompt diagnosis. The delay proved fatal when the patient developed fulminant pheochromocytoma crisis. This case illustrates a variety of clinical features seen from the vantage of the evolution of the disease as it went unrecognized. The patient's course underscores the importance of familiarity with the gamut of manifestations for timely diagnosis, and the priority of the latter given the looming risk of overwhelming complications.

Acute Disease↗

Effect of systemic sclerosis on left ventricular long-axis motion and left ventricular mass assessed by magnetic resonance.

The aim of this study was to assess the effect of scleroderma on left ventricular mass and subendocardial function using cardiovascular magnetic resonance (CMR) to determine parameters reflecting early dysfunction from fibrosis. Fifteen patients with a history of scleroderma had left ventricular mass measured with standard techniques and regional subendocardial contractile function assessed using myocardial velocity mapping in the basal short-axis plane with long-axis sensitized velocity mapping. Peak myocardial velocities in systole and diastole were measured to reflect systolic and diastolic function. The variance in the regional myocardial velocity, was determined as a parameter of function heterogeneity around the ventricle. The results were compared with 19 healthy volunteers without a history of cardiovascular disease. In 10 patients, pulmonary transfer factor was measured using a single-breath helium dilution technique. The duration of scleroderma correlated with left ventricular mass (r = 0.7, p < 0.05), the coefficient of variation of velocity (r = 0.63, p < 0.05), and inversely with the mean left ventricular diastolic long-axis velocity (r = -0.63, p < 0.05). There was also a correlation between left ventricular diastolic long-axis velocity and the pulmonary transfer factor (r = 0. 7, p < 0.05). Trends suggested differences between control subjects and scleroderma patients for mean systolic (64 vs. 49 mm/sec, p = 0.09) and diastolic (90 vs. 72 mm/sec, p = 0.07) velocities, as well as velocity variance (26 vs. 33, p = 0.09). In conclusion, there is a relationship between duration of scleroderma and both left ventricular mass and diastolic function, which may result from increased myocardial fibrosis. Trends suggest absolute differences in functional values with control subjects that reflect impaired diastolic and systolic function, with greater regional heterogeneity that is consistent with nonuniform collagen deposition, but a larger sample size is required to confirm this. CMR should be explored further as a technique for monitoring myocardial involvement in scleroderma noninvasively.

Adult↗

Left ventricular remodelling in post-myocardial infarction patients with left ventricular ejection fraction 40-50% vs 25-39%. Influence of nisoldipine treatment? An echocardiographic substudy from the DEFIANT II study.

OBJECTIVE: Left ventricular (LV) remodelling following acute myocardial infarction has generally been studied in patients with LV ejection fraction (EF) < 40%, and it has been shown that this process can be attenuated by ACE inhibitors. Little is known regarding LV remodelling in patients with LVEF > or = 40% or the effects of treatment in this patient cohort. The DEFIANT II study (Doppler Flow and Echocardiography in Functional cardiac insufficiency) included 542 post-infarction patients with LVEF 25-50% without overt heart failure within 13 days following acute myocardial infarction (AMI). They were then randomized to nisoldipine coat-core (CC) or placebo and followed up for 6 months. DESIGN: Two-dimensional echoes were obtained after 8 (5-13) days and 6 months following AMI. SETTING: LV end diastolic (ED) and end systolic (ES) volumes (V) were calculated in 503 patients with technically satisfactory paired echoes using the biplabe method of discs in a core laboratory. SUBJECTS: Group A. 217 patients with baseline EF 40-50%, of whom 112 were randomized to nisoldipine and 104 to placebo (one patient was taken off study medication). Group B. 286 patients with EF 25-39%, of whom 145 were randomized to nisoldipine and 141 to placebo. RESULTS: LVEDV was 175 (+/-45) ml in Group A vs 203 (+/-49) ml in Group B (p = 0.001) at baseline and 184 (+/-48) ml vs 213 (+/-56) ml (p = 0.001), respectively, at 6 months. LVESV at baseline was 97 (+/-42) ml in Group A vs 133 (+/-37) ml in Group B (p = 0.001), and 106 (+/-34) ml vs 134 (+/-45) ml (p = 0.001) at 6 months, respectively. The increase of LVESV was 9 (+/-29) ml in Group A vs 2 (+/-35) ml in Group B (p = 0.007). LVEF decreased by 2 (+/-6)% in Group A vs an increase of 3 (+/-6)% in Group B (p = 0.001). Treatment with nisoldipine had no influence on LV volumes in either of the two groups or in the total study group. CONCLUSION: LV dilatation 6 months following AMI in patients with EF 40-50% was similar in end diastole, but more pronounced in end systole vs patients with EF 25-39%. LV remodelling did not change significantly after nisoldipine treatment.

Adult↗

The fen-phen finale: a study of weight loss and valvular heart disease.

OBJECTIVE: To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. RESEARCH METHODS AND PROCEDURES: Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuous-wave Doppler examinations. RESULTS: At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 + 10.0%, which was significantly (p<0.001) smaller than their 1-year loss of 17.1 +/- 8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 +/- 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 +/- 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. DISCUSSION: Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.

Adult↗

Sustained-release calcium channel antagonists in cardiovascular disease: pharmacology and current therapeutic use.

Calcium channel antagonists are a heterogeneous group of drugs with differing cardiovascular effects, and are effective in the treatment of hypertension and angina pectoris. A number of these agents are available in a sustained-release formulation. These formulations produce a gradual and sustained drop in peripheral vascular resistance, thereby avoiding reflex sympathetic stimulation, and thus may avoid the deleterious effects that have been reported with short-acting preparations. The results of a number of trials with sustained-release calcium channel antagonists have been reported recently, and the results are promising. Currently they can be recommended for use in patients with hypertension or stable angina which cannot be controlled with other agents. They have been shown to be at least safe when used in patients with left ventricular systolic dysfunction, and may be useful in certain subsets of patients with heart failure. The empirical use of calcium channel antagonists in unstable angina and acute myocardial infarction is not supported by the currently available data. Several large trials with sustained-release formulations are ongoing, which may alter treatment recommendations in the future.

Acute Disease↗

Diagnosis in adolescents and adults with congenital heart disease. Prospective assessment of individual and combined roles of magnetic resonance imaging and transesophageal echocardiography.

BACKGROUND: The inability to obtain complete diagnoses with transthoracic echocardiography in many adults with congenital heart disease provided the incentive to evaluate prospectively the individual and combined roles of magnetic resonance imaging (MRI) and transesophageal echocardiography (TEE) as "second-line" techniques for unresolved diagnostic problems. METHODS AND RESULTS: Eighty-five patients were studied; 81 had MRI with a 0.5-T magnet to obtain spin-echo images, cine-MRI, and flow-velocity maps. Seventy-nine patients had TEE (37 biplane). A simple score (range, 0 to 1) was used for quantification of the results of MRI and TEE alone, for their comparison (in the 75 patients who had both), and for assessment of their combination. MRI, TEE, or their combination achieved a score of at least 0.75 in 18 of 25 diagnostic categories. A summary of the scores showed that for intracardiac anatomy. MRI scored 0.34, TEE scored 0.71 (P < .0001), and MRI plus TEE scored 0.84 (P < .003); for extracardiac anatomy, MRI scored 0.76, TEE scored 0.23 (P < .0001), and MRI plus TEE scored 0.84 (P = NS); and for hemodynamics and function, MRI scored 0.58, TEE scored 0.41 (P < .05), and MRI plus TEE scored 0.67 (P = NS). Total scores were MRI, 0.52; TEE, 0.50 (P = NS); and MRI plus TEE, 0.80 (P < .0001). MRI and TEE were inadequate for collateral and coronary arteries and pulmonary vascular resistance. Cine-MRI and flow-velocity maps comprised 43% of the MRI scores. Biplane TEE was better than single plane (scores of 0.59 versus 0.42, P < .0001). CONCLUSIONS: MRI and TEE are important and complementary "second-line" investigations for congenital heart disease. Analysis of their performance in a wide range of diagnostic categories provides guidelines for their judicious application. Where both are available, diagnostic catheterizations are either obviated or simplified.

Adolescent↗

Calculation of aortic regurgitation orifice area by Doppler echocardiography: an application of the continuity equation.

The evaluation of aortic regurgitation by current echocardiographic techniques has been qualitative and load-dependent. The area of the regurgitant orifice, which is theoretically independent of haemodynamic conditions, has not been determined non-invasively. In 20 patients with various degrees of aortic regurgitation, this area was determined by use of the continuity equation applied during diastole. The velocity-time integrals were determined at the supravalvar (VTIs) and regurgitant orifice (VTIj) levels by pulsed and continuous wave Doppler respectively. The cross sectional area at the supravalvar level (As) was also measured by cross sectional echocardiography. The regurgitant orifice is given by: (As x VTIs)/VTIj. Other non-invasive measurements of the aortic regurgitation severity were also recorded: (a) an overall echo score (1-5+) given blindly by two echocardiographers, (b) the maximal proximal jet width by colour Doppler, (c) left ventricular end systolic and end diastolic volumes and left ventricular mass. The regurgitant area ranged from 0.25 to 1.7 cm2 and this area accorded with the overall echo score and the maximal proximal jet width measured by colour Doppler. The aortic regurgitation orifice area can be calculated non-invasively and it may be a quantitative measure of the severity of aortic regurgitation.

Adult↗

Assessment of valvular heart disease with Doppler echocardiography.

The addition of Doppler principles to two-dimensional echocardiography has revolutionized the noninvasive evaluation of valvular heart disease. Doppler techniques allow precise measurements of blood flow velocity at different locations in the heart and great vessels, so that many aspects of hemodynamics can now be measured noninvasively. These techniques are particularly useful for the quantitative assessment of valvular stenosis; both valve areas and transvalvular gradients may be determined. Doppler echocardiography (particularly with color flow mapping) is also useful for the qualitative assessment of valvular regurgitation. By understanding the uses and limitations of Doppler echocardiography, physicians may now confidently follow up patients with mild or moderate valvular disease with serial noninvasive studies, avoiding the risks of cardiac catheterization in many patients.

Blood Flow Velocity↗

Peak left ventricular pressure during percutaneous aortic balloon valvuloplasty: clinical and echocardiographic correlations.

Peak left ventricular pressure during balloon inflation was measured in 20 patients who underwent balloon valvuloplasty for severe aortic stenosis to define the determinants of ventricular pressure development in response to increased loading conditions. The peak left ventricular pressure ranged from 150 +/- 5 to 386 +/- 22 mm Hg (mean +/- SD), was reproducible in each patient with each balloon inflation (mean coefficient of variation 7.8%) and correlated with concurrent echocardiographic measurements of ejection fraction (r = 0.89, p = 0.0001) and mass/volume ratio in systole (r = 0.91, p = 0.0001) or diastole (r = 0.88, p = 0.0001). Thirteen patients with class II or more severe congestive heart failure had lower values for peak left ventricular pressure than did those without failure (225 +/- 46 versus 305 +/- 45 mm Hg, p = 0.002), whereas no difference in rest left ventricular systolic pressure was seen between the two groups. The measurement of peak left ventricular pressure was inversely related to rest mean circumferential end-systolic wall stress (r = 0.52, p = 0.046). Thus, peak left ventricular systolic pressure measured during aortic valvuloplasty in humans correlates closely with traditional measures of left ventricular function. This measurement, which previously has been obtained only in experimental animal studies, is a simple and reproducible hemodynamic index that may provide new insights in studies of ventricular function and congestive heart failure in aortic stenosis.

Adult↗

Doppler echocardiographic study of the frequency and severity of aortic regurgitation in hypertrophic cardiomyopathy.

Aortic regurgitation (AR) has been reported sporadically in hypertrophic cardiomyopathy (HC) but neither its frequency nor severity has been determined. Thirty-one consecutive patients with HC were evaluated by Doppler echocardiography over a 2-year period. Twenty-nine had echocardiographically normal aortic cusps and participated in the study; 2 had calcified aortic valves and were excluded. AR of grade I to grade II severity was demonstrated in 9 of 29 (31%) patients. Patients were divided into 2 groups: group 1 (n = 9) with AR and group 2 (n = 20) without AR. Group 1 patients were significantly older than group 2 patients (73 +/- 7 vs 60 +/- 17 years, p less than 0.05) and had larger end-diastolic (4.5 +/- 0.5 vs 4.0 +/- 0.7 cm, p less than 0.01) and end-systolic (2.7 +/- 0.4 vs 2.3 +/- 0.4, p less than 0.02) left ventricular dimensions. Left ventricular wall thickness, degree of asymmetric septal hypertrophy and left ventricular fractional shortening were similar in the 2 groups. Mitral regurgitation was more common in group 1 (100% vs 35%, p less than 0.005), although there were no differences in left atrial size between the 2 groups. The HC patients were compared with a control group of 23 normal subjects of similar age. There was no mitral regurgitation or AR in the normal subjects. Thus, nearly one-third of patients with HC had mild AR by Doppler. The AR most probably results from high-velocity systolic blood flow causing microscopic damage to the valve cusps.

Adult↗

Comparison of echocardiographic methods for assessment of left ventricular shortening and wall stress.

M-mode echocardiographic measurement of left ventricular fractional shortening and meridional wall stress has been used extensively alone and in combination to describe left ventricular systolic function. To determine whether the improved dimensional information afforded by two-dimensional echocardiography might result in shortening and stress calculations yielding a different view of left ventricular function, we compared two-dimensional and M-mode echocardiograms in 69 subjects (19 normal, 13 with aortic stenosis, 22 with aortic regurgitation and 15 with congestive cardiomyopathy). Fractional shortening was greater with M-mode than with two-dimensional echocardiography in all subjects, especially in those with cardiomyopathy (p less than 0.05). In aortic stenosis, two-dimensional shortening, at 24 +/- 5%, was reduced (p less than 0.05 versus normal), but M-mode shortening, at 34 +/- 5%, was not. M-mode estimates of meridional stress were higher than two-dimensional values, again especially in cardiomyopathy. Two-dimensional echocardiography enabled determination of long- and short-axis ratios, circumferential stress and the ratio of circumferential to meridional stresses. Circumferential stress was elevated in aortic stenosis at 302 +/- 65 X 10(3) dynes/cm2, suggesting afterload excess as the cause for the observed reduction in two-dimensional shortening. The more spherical cardiomyopathic hearts had a meridional to circumferential stress ratio closer to 1, such that use of meridional stress alone would overestimate effective afterload. It is concluded that M-mode and two-dimensional echocardiographic analyses of left ventricular shortening and stress produce different results. Two-dimensional echocardiographic methods may enhance the assessment of ventricular function, especially in patients with aortic stenosis and cardiomyopathy.

Adult↗

Relationship of cardiac chamber volume to baroreflex activity in normal humans.

The objectives of this study were to examine the effect of incremental lower body negative pressure (LBNP) on cardiac chamber volume and assess the relationship between cardiac chamber volume and baroreflex activation of the neurohormonal axis. Accordingly, echocardiographic determination of cardiac chamber volume and neurohormonal responses were studied in 14 normal subjects during incremental LBNP. LBNP -10 mm Hg decreased left atrial diameter and left ventricular systolic volume index, but did not alter heart rate, systolic or pulse pressure, or stroke volume. During LBNP -10 mm Hg, plasma norepinephrine levels increased, suggesting activation of the sympathetic nervous system. LBNP -40 mm Hg caused a significant decrease in left atrial diameter and left ventricular systolic, diastolic, and stroke volume indices. During LBNP -40 mm Hg, heart rate increased, and systolic and pulse pressure fell. With this more negative level of LBNP, norepinephrine, angiotensin II, aldosterone, and arginine vasopressin concentrations and PRA all increased. The findings that left atrial diameter decreased and plasma norepinephrine concentration increased during LBNP -10 mm Hg suggest that the sympathetic nervous system is sensitive to changes in atrial receptor activity. At higher levels of LBNP (-40 mm Hg), activation of the renin-angiotensin system and release of vasopressin were associated with a fall in left ventricular diastolic volume as well as a decrease in the pressure input to the arterial baroreceptors. Under this condition, the differential contribution of the cardiopulmonary and arterial baroreceptors to the regulation of the renin-angiotensin system and vasopressin release cannot be distinguished.

Adult↗

Dynamic three-dimensional reconstruction of the left ventricle from two-dimensional echocardiograms.

Using an open chest canine model, a method was developed for three-dimensional reconstruction of the contracting left ventricle from two-dimensional echocardiograms, which is applicable to intraoperative studies in humans. A mechanically held 5 MHz transducer was used to record parallel high resolution cross-sectional images with precise spatial registration. Myocardial borders were tracked manually and entered into a computer system. Regional filling and interpolation routines were applied to reconstruct the endocardial and epicardial surfaces of the ventricle. The myocardium can be displayed as a translucent, shaded three-dimensional solid surrounding the ventricular cavity. One or both surfaces can be rotated about any axis, sectioned through any plane and viewed in motion through systole and diastole. Studies before and after left anterior descending coronary artery occlusion showed the three-dimensional extent of abnormal left ventricular cavity and myocardial deformation. Quantitative examination of regions of interest permits the analysis of global and regional volumetric and myocardial thickness changes throughout the cardiac cycle. Thus, open chest three-dimensional echocardiography provides a powerful tool for the quantitative physiologic investigation of the left ventricle.

Animals↗