Novel parameters of global and regional mitral annulus geometry in man: comparison between normals and organic mitral regurgitation, before and after mitral valve repair.

AIMS: The mitral annulus (MA) saddle shape is complex but vital for a normal functioning mitral apparatus. Although conventional parameters of MA geometry such as area and height are helpful, they fall short of describing its complex regional geometry. METHODS AND RESULTS: In this prospective study, novel parameters of MA curvature and torsion were derived from three-dimensional (3D) transoesophageal echocardiography. These quantitative indices were computed in 15 patients with normal valves (age 53 ± 8 years) and in 15 patients with organic significant mitral regurgitation (MR, age 66 ± 11 years), before and after mitral valve repair (MVR). The MA was traced and modelled in mid- and end-systole. Curvature and torsion were computed at 500 points across the MA to derive regional and global indices. Overall, patients with organic MR presented the smallest global curvature and torsion; this decrease in curvature and torsion reflects a loss of tonicity of the MA tissue. These changes were largely corrected with MVR surgery, to higher values, compared with normals. The regional analysis revealed similar trends. The maximal MA curvature was found to be at the MA 'anterior horn', whereas the MA 'posterior horn' had the lowest curvature values. CONCLUSION: Novel MA parameters of curvature and torsion can be computed from 3D echocardiography and provide quantitative characteristics of dynamic regional MA geometry. In patients with organic MR, the reduced regional and global curvatures improve following surgical MVR. These quantitative parameters may help further refine the quantitative description of MA geometry in various mitral valve pathologies and after MVR.

Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to compare the hemodynamic efficacy of nonsurgical septal reduction therapy (NSRT) by intracoronary ethanol with standard therapy (surgical myectomy) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical septal reduction therapy has gained interest as a new treatment modality for patients with drug-refractory symptoms of HOCM; however, its benefits in comparison to surgery are unknown. METHODS: Forty-one consecutive NSRT patients at Baylor College of Medicine with one-year follow-up were compared with age- and gradient-matched septal myectomy patients at the Mayo Clinic. All patients had left ventricular outflow obstruction with a resting gradient > or =40 mm Hg and none had concomitant procedures. RESULTS: There were no baseline differences in New York Heart Association class, severity of mitral regurgitation, use of cardiac medications or exercise capacity. One death occurred during NSRT because of dissection of the left anterior descending artery. At one year, all improvements in both groups were similar. After surgical myectomy, more patients were on medications (p < 0.05) and there was a higher incidence of mild aortic regurgitation (p < 0.05). After NSRT, the incidence of pacemaker implantation for complete heart block was higher (22% vs. 2% in surgery; p = 0.02). However, seven of the nine pacemakers in the NSRT group were implanted before a modified ethanol injection technique and the use of contrast echocardiography. CONCLUSIONS: Nonsurgical septal reduction therapy resulted in a significantly higher incidence of complete heart block, but the risk was reduced with contrast echocardiography and slow ethanol injection. Surgical myectomy resulted in a significantly higher incidence of mild aortic regurgitation. Nonsurgical septal reduction therapy, guided by contrast echocardiography, is an effective procedure for treating patients with HOCM. The hemodynamic and functional improvements at one year are similar to those of surgical myectomy.

Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography.

OBJECTIVES: We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND: Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time. METHODS: One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM w ere assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS: In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%,respectively) with the highest accuracy (86%). CONCLUSIONS: The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

Tissue Doppler imaging consistently detects myocardial abnormalities in patients with hypertrophic cardiomyopathy and provides a novel means for an early diagnosis before and independently of hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the absence of LVH. We tested whether humans with FHCM also consistently showed reduced myocardial TD velocities, irrespective of LVH. METHODS AND RESULTS: We performed 2D and Doppler echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were positive for various mutations but did not have LVH, and 30 age- and sex-matched controls (all adults; 77% women). LV wall thickness and mass were significantly greater in FHCM subjects (P<0.01 versus those without LVH and controls). There were no significant differences in 2D echocardiographic, mitral, and pulmonary venous flow indices between mutation-positives without LVH and controls. In contrast, systolic and early diastolic TD velocities were significantly lower in both mutation-positives without LVH and in FHCM patients than in controls (P<0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of 93% for identifying mutation-positives without LVH. CONCLUSIONS: Myocardial contraction and relaxation velocities, detected by TD imaging, are reduced in FHCM, including in those without LVH. Before and independently of LVH, TD imaging is an accurate and sensitive method for identifying subjects who are positive for FHCM mutations.

Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is a genetic disease characterized by cardiac hypertrophy, myocyte disarray, interstitial fibrosis, and left ventricular (LV) dysfunction. We have proposed that hypertrophy and fibrosis, the major determinants of mortality and morbidity, are potentially reversible. We tested this hypothesis in beta-myosin heavy chain-Q(403) transgenic rabbits. METHODS AND RESULTS: We randomized 24 beta-myosin heavy chain-Q(403) rabbits to treatment with either a placebo or simvastatin (5 mg. kg(-1). d(-1)) for 12 weeks and included 12 nontransgenic controls. We performed 2D and Doppler echocardiography and tissue Doppler imaging before and after treatment. Demographic data were similar among the groups. Baseline mean LV mass and interventricular septal thickness in nontransgenic, placebo, and simvastatin groups were 3.9+/-0.7, 6.2+/-2.0, and 7.5+/-2.1 g (P<0.001) and 2.2+/-0.2, 3.1+/-0.5, and 3.3+/-0.5 mm (P=0.002), respectively. Simvastatin reduced LV mass by 37%, interventricular septal thickness by 21%, and posterior wall thickness by 13%. Doppler indices of LV filling pressure were improved. Collagen volume fraction was reduced by 44% (P<0.001). Disarray was unchanged. Levels of activated extracellular signal-regulated kinase (ERK) 1/2 were increased in the placebo group and were less than normal in the simvastatin group. Levels of activated and total p38, Jun N-terminal kinase, p70S6 kinase, Ras, Rac, and RhoA and the membrane association of Ras, RhoA, and Rac1 were unchanged. CONCLUSIONS: Simvastatin induced the regression of hypertrophy and fibrosis, improved cardiac function, and reduced ERK1/2 activity in the beta-myosin heavy chain-Q(403) rabbits. These findings highlight the need for clinical trials to determine the effects of simvastatin on cardiac hypertrophy, fibrosis, and dysfunction in humans with hypertrophic cardiomyopathy and heart failure.

Deceleration time in ischemic cardiomyopathy: relation to echocardiographic and scintigraphic indices of myocardial viability and functional recovery after revascularization.

BACKGROUND: In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. METHODS AND RESULTS: Forty patients with ischemic cardiomyopathy underwent (201)Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 microg. kg(-1). min(-1)) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE (r=0.72), scar perfusion defect by SPECT (r=-0.69), and the change in ejection fraction (DeltaEF) after surgery (r=0.77) (all P:<0.01). DT >150 ms effectively identified (sensitivity 79%, specificity 81%) patients with DeltaEF >/=5%. The population was divided into 2 groups according to DT: group 1 (DT >150 ms, n=21) and group 2 (DT

Variants of trophic factors and expression of cardiac hypertrophy in patients with hypertrophic cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) exhibit variable expression of left ventricular hypertrophy (LVH), a major determinant of mortality and morbidity, which is partly due to the diversity of causal mutations, genetic background (modifier genes), and probably environmental factors. We determined association of functional variants of tumor necrosis factor (TNF)- alpha, interleukin-6 (IL6), insulin-like growth factor-2 (IGF2), transforming growth factor- beta 1 (TGFB1), and aldosterone synthase (CYP11B2) genes, all previously implicated in cardiac hypertrophy, with the severity of LVH in patients with HCM. Two-dimensional echocardiography was performed and demographic variables were recorded in 142 genetically independent patients. Indices of LVH including interventricular septal thickness (IVST), left ventricular mass index (LVMI), and LVH score were measured/calculated. TNF-alpha-308G/A, IL6-174G/C, IGF2 820G/A, TGFB1-509C/T, and CYP11B2-344T/C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were identified by the presence of specific electrophoretic patterns and their distributions were according to the Hardy-Weinberg equilibrium. Demographic variables were not significantly different among the genotypes. Subjects with the AA genotype of TNF-alpha (n=8) were approximately 13 years younger at the time of clinical diagnosis. Despite a younger age, they had a greater mean LVMI than those with the GG (n=94) or GA (n=33) genotypes (191.8+/-59.5 v 139.1+/-47.3 v 132.1+/-34.3, respectively, P=0.004). TNF-alpha-308G/A genotypes accounted for 6.0% of variability of LVMI (P=0.002). Mean IVST, LVEDD, and LVH score were not significantly different. Variants of IL6, IGF2, TGFB1, and CYP11B2 were not associated with indices of LVH. The uncommon allele of TNF-alpha-308G/A polymorphism, known to produce more TNF- alpha, was associated with greater LVMI and clinical diagnosis at a younger age in patients with HCM. Functional variants of other trophic factors, previously implicated in cardiac hypertrophy, were not associated with the indices of LVH. These results suggest that TNF-alpha is a modifier gene for HCM.

Altered adrenergic receptor density in myocardial hibernation in humans: A possible mechanism of depressed myocardial function.

BACKGROUND: Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. METHODS AND RESULTS: Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. alpha- and ss-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compared with normal segments and were most pronounced in those without contractile reserve (P:<0.001). Similar findings were observed if recovery of function or scintigraphic uptake was analyzed as a marker for viability. No significant relation between either ARD or BRD and percent myocardial fibrosis was noted (r=0.37 and -0.39, respectively). CONCLUSIONS: Thus, graded and reciprocal changes in alpha- and ss-adrenergic receptor densities occur in viable, hibernating myocardium and may account in part for the observed depression in resting myocardial function and preserved contractile reserve in this entity.

Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. METHODS AND RESULTS: M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type beta-myosin heavy chain-arginine(403) (n=14), and mutant beta-myosin heavy chain-glutamic acid(403) (n=24) transgenic rabbits. Mean septal thicknesses were 2.0+/-0.3, 2.0+/-0.25, and 2.75+/-0.3 mm in the 3 groups, respectively (P:=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P:<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45+/-2.2 versus 10.8+/-2.3 cm/s in nontransgenic and 9. 0+/-0.76 cm/s in wild-type; P:<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. CONCLUSIONS: Myocardial contraction and relaxation were reduced in the mutant beta-myosin heavy chain-glutamic acid(403) transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans.

OBJECTIVES: We sought to evaluate the relation of segmental tissue Doppler (TD) velocities to both the regional amount of interstitial fibrosis and the myocyte beta-adrenergic receptor density in humans. BACKGROUND: The systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) acquired by TD are promising new indexes of left ventricular function. However, their structural and functional correlates in humans are still unknown. METHODS: Ten patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsy at the time of coronary bypass surgery (two biopsies per patient for a total of 20 specimens). The specimens were analyzed for percent interstitial fibrosis and beta-adrenergic receptor density. RESULTS: Normal segments (n = 8) had a higher beta-adrenoceptor density (2,280 +/- 738 vs. 1,373 +/- 460, p = 0.03) and a lower amount of interstitial fibrosis (13 +/- 3.3% vs. 28 +/- 11.5%, p = 0.002) than dysfunctional segments (n = 12). Myocardial systolic velocity and Em were also significantly higher (9.5 +/- 2.7 vs. 5.9 +/- 1.8 cm/s, p = 0.025 and 11.3 +/- 2.8 vs. 6.4 +/- 2.1 cm/s, p = 0.002, respectively) in normal segments. A significant relationship was present between Em and the beta-adrenergic receptor density (r = 0.78, p < 0.001) and percent interstitial fibrosis (r = -0.7, p = 0.0026), which together accounted for 81% of the variance observed in Em. Likewise, a significant relationship was present between Sm and the beta-adrenergic receptor density (r = 0.68, p < 0.001) and the percent interstitial fibrosis (r = -0.66, p = 0.004) and together accounted for 62% of the variance observed in Sm. CONCLUSIONS: Systolic myocardial velocity and Em are strongly dependent on both the number of myocytes and the myocardial beta-adrenergic receptor density.

End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography.

OBJECTIVES: The study assessed whether end-diastolic wall thickness (EDWT), measured with echocardiography, is an important marker of myocardial viability in patients with suspected myocardial hibernation, and it compared this index to currently established diagnostic modalities of dobutamine stress echocardiography (DSE) and rest-redistribution thallium-201 (T1-201) scintigraphy. BACKGROUND: Because myocardial necrosis is associated with myocardial thinning, preserved EDWT may provide a simple index of myocardial viability that is readily available from the resting echocardiogram. METHODS: Accordingly, 45 patients with stable coronary artery disease and ventricular dysfunction underwent rest 2D echocardiograms, DSE and rest-redistribution T1-201 tomography before revascularization and a repeat resting echocardiogram > or =2 months later. RESULTS: Global wall motion score index decreased from 2.38 +/- 0.73 to 1.94 +/- 0.82 after revascularization (p < 0.001). Thirty-eight percent of severely dysfunctional segments recovered resting function. Compared to segments without recovery of resting function, those with recovery had greater EDWT (0.94 +/- 0.18 cm vs. 0.67 +/- 0.22 cm, p < or = 0.0001) and a higher T1-201 uptake (78 +/- 13% vs. 59 +/- 21%; p < 0.0001). An EDWT >0.6 cm had a sensitivity of 94% and specificity of 48% for recovery of function. Similarly, a T1-201 maximal uptake of > or =60% had a sensitivity of 91% and specificity of 50%. Receiver operating characteristic curves for prediction of recovery of regional and global function were similar for EDWT and maximum T1-201 uptake. Combination of EDWT and any contractile reserve during DSE for recovery of regional function improved the specificity to 77% without a significant loss in sensitivity (88%). CONCLUSIONS: End-diastolic wall thickness is an important marker of myocardial viability in patients with suspected hibernation, and it can predict recovery of function similar to T1-201 scintigraphy. Importantly, a simple measurement of EDWT < or =0.6 cm virtually excludes the potential for recovery of function and is a valuable adjunct to DSE in the assessment of myocardial viability.

Estimation of mean right atrial pressure using tissue Doppler imaging.

Sixty-two patients underwent simultaneous right atrial pressure measurement and Doppler echo including tissue Doppler to evaluate the utility of this technique in the estimation of right ventricular filling pressure. Mean right atrial pressure related weakly to the ratio of tricuspid peak early inflow velocity to annular early diastolic velocity (r = 0.75, p <0.0001), with a mean difference between Doppler and catheter pressures of 0.3 +/- 3.7 mm Hg.

Changes in left ventricular filling and left atrial function six months after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The purpose of this study was to evaluate changes in left ventricular (LV) filling, left atrial (LA) volumes and function six months after nonsurgical septal reduction therapy (NSRT) for hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Patients with HOCM frequently have enlarged left atria, which predisposes them to atrial fibrillation. Nonsurgical septal reduction therapy results in significant reduction in left ventricular outflow tract (LVOT) obstruction and symptomatic improvement. However, its effect on LV passive filling volume, LA volumes and function is not yet known. METHODS: Thirty patients with HOCM underwent treadmill exercise testing as well as 2-dimensional and Doppler echocardiography before and six months after NSRT. Data included clinical status, exercise duration, LVOT gradient, mitral regurgitant (MR) volume, LV pre-A pressure and LA volumes. Left atrial ejection force and kinetic energy (KE) were computed noninvasively and were compared with 12 age-matched, normal subjects. RESULTS: New York Heart Association (NYHA) class was lower and exercise duration was longer (p < 0.05) six months after NSRT. The LVOT gradient, MR volume and LV pre-A pressure were all significantly reduced. HOCM patients had larger atria, which had a higher ejection force and KE, compared with normal subjects (p < 0.01). After NSRT, LV passive filling volume increased (p < 0.01), whereas LA volumes, ejection force and KE decreased (p < 0.01). Reduction in LA maximal volume was positively related to changes in LV pre-A pressure (r = 0.8, p < 0.05) and MR volume (0.4, p < 0.05). Changes in LA ejection force were positively related to changes in LA pre-A volume (r = 0.7, p < 0.01) and KE (r = 0.81, p < 0.01). The increase in exercise duration paralleled the increase in LV passive filling volume (r = 0.85, p < 0.05). CONCLUSIONS: Nonsurgical septal reduction therapy results in an increase in LV passive filling volume and a reduction in LA size, ejection force and KE.

Assessment of myocardial viability with stress echocardiography.

Over the past two decades, there has been an increased realization that systolic myocardial dysfunction, outside of the setting of acute ischemia, does not necessarily imply irreversible myocardial injury. Echocardiographic techniques, particularly dobutamine stress echocardiography, have emerged as important diagnostic modalities that can identify residual viable myocardium in patients following acute myocardial infarction and in those with suspected myocardial hibernation. Dobutamine echocardiography can also help risk stratify patients with coronary artery disease and depressed ventricular function and identify patients who would benefit best from revascularization procedures.

Desmin mutation responsible for idiopathic dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy, of which approximately 20% of cases are familial (FDCM), is a primary myocardial disorder characterized by ventricular dilatation and impaired systolic function. It is a common cause of heart failure and the need for cardiac transplantation. Although 6 chromosomal loci responsible for autosomal dominant FDCM have been mapped by linkage analysis, none of these genes have been identified. By use of the candidate-gene approach, actin was identified recently as being responsible for dilated cardiomyopathy. Considerable evidence suggests desmin, a muscle-specific intermediate filament, plays a significant role in cardiac growth and development. METHODS AND RESULTS: To determine whether a defect of desmin induces dilated cardiomyopathy, 44 probands with FDCM underwent clinical evaluation and DNA analysis. Diagnostic criteria, detected by echocardiography, consisted of ventricular dimension of >/=2.7 cm/m(2) with an ejection fraction

Relation of the contractile reserve of hibernating myocardium to myocardial structure in humans.

BACKGROUND: Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure. METHODS AND RESULTS: We evaluated 20 patients with coronary disease (64+/-13 years old, ejection fraction 28+/-7.5%) with DE (up to 40 micrograms . kg(-1). min(-1)), rest-redistribution (201)Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%, P<0.001), higher thallium uptake (69% versus 48%, P=0.03), and less interstitial fibrosis (2% versus 28%, P<0.001). Quantitative angiographic parameters did not predict recovery of function. Segments with DE viability (contractile reserve and/or ischemia) had less fibrosis (2.7% versus 28%, P<0.001), less vimentin and fibronectin (both P<0.01), more glycogen (P=0.016), and higher thallium uptake (64% versus 35.5%, P<0.05) than those without viability. Viable segments by both DE and thallium had less fibrosis (1%) than those viable by 1 of the 2 techniques (9%) or not viable by both (28%, P=0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis (r=-0.83, P<0.01). CONCLUSIONS: Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.

Simultaneous multisite mapping of the right and the left atrial septum in the canine intact beating heart.

BACKGROUND: The spread of activation between the right atrium (RA) and left atrium (LA), particularly along the right and left aspects of the interatrial septum, is not clear. METHODS AND RESULTS: Basket-shaped catheters carrying 64 electrodes were deployed into both the RA and LA of 10 dogs. Position and orientation of the baskets were determined by fluoroscopy and echocardiography. Basket unipolar electrograms were simultaneously recorded in each dog during sinus rhythm, right ventricular pacing, and pacing of the right septum through the basket in the superior and inferior regions. Isochrone maps depicting all aspects of the atria, including the septum, were compared. During sinus rhythm and superior right septal pacing, wave fronts propagated predominantly from superior to inferior regions on both the right and left septum. However, activation of the left septum was delayed compared with the right septum. During right ventricular pacing and inferior right septal pacing, activation of the septum was discordant; 1 wave front propagated rapidly on the right septum from inferior to superior regions, whereas 2 opposing wave fronts originated on the left septum in both the superior and inferior regions. The left septum was activated predominantly by the superior wave front. Activation of the left septum was completed in a significantly shorter time during pacing of the right septum in the inferior region compared with the superior region. CONCLUSIONS: In dogs, activation of the right and left aspects of the interatrial septum is discordant. Electrical connections are present between the RA and LA in regions superior as well as inferior to the septum.

Supine bicycle versus post-treadmill exercise echocardiography in the detection of myocardial ischemia: a randomized single-blind crossover trial.

OBJECTIVES: We sought to determine the comparative accuracy of supine bicycle exercise echocardiography (SBE) and posttreadmill exercise echocardiography (TME) in detecting myocardial ischemia in patients with known or suspected coronary artery disease (CAD). BACKGROUND: Supine bicycle echocardiography and TME have been used for evaluation of CAD. However, the comparative accuracy of these modalities in the detection of ischemia in the same patients is not known. METHODS: Seventy-four patients (age 59 +/- 9 years [mean +/- SD]) referred for evaluation of coronary disease underwent SBE (starting at 25 to 50 W with 25-W increment every 3 min) and post-TME (Bruce protocol) in a random sequence. Digitized images at baseline and maximal exercise were interpreted in a random and blinded fashion. RESULTS: Maximal heart rate was higher during TME, whereas systolic blood pressure was higher during SBE, resulting in a similar double product. At quantitative angiography (n = 67), 57 patients had coronary stenosis (>50%). During SBE, ischemia was detected in 47 patients compared with 38 patients by TME (p < 0.001). Wall motion score index at maximal exercise was higher with SBE than with TME (1.48 +/- 0.51 vs. 1.38 +/- 0.43; p < 0.001). The extent of myocardial ischemia (number of ischemic segments) was higher during SBE compared with TME (3.3 +/- 3.4 vs. 2.3 +/- 2.9 segments; p = 0.004), whereas severity of abnormal wall motion was similar. The sensitivity of SBE and TME for CAD was 82% and 75% with a specificity of 80% and 90%, respectively. Image quality was similar with both techniques. Patients and sonographers favored SBE over TME. CONCLUSIONS: During SBE and TME exercise, patients achieve a similar double product. During SBE, however, the detection of ischemia is more frequent and more extensive which, along with patient and sonographer preference, makes supine bicycle exercise a valuable stress echocardiographic modality.

Usefulness of transthoracic echocardiography in detecting significant prosthetic mitral valve regurgitation.

To identify the transthoracic echo-Doppler (TTE) variables most predictive of significant mitral regurgitation (MR) of mechanical prosthetic valves, TTE and trans-esophageal echo (TEE) studies were independently reviewed in 57 patients (mean age [+/-SD] 59+/-12.5 years) undergoing both studies within 2+/-3 days. Several 2-dimensional and Doppler hemodynamic variables from the TTE studies were derived. Prosthetic MR was significant (moderate or severe) by TEE in 20 patients, whereas mild or no MR was seen in 37 patients. The best univariate predictors of significant MR by TTE were peak velocity of mitral inflow, mean gradient, tricuspid regurgitation velocity, isovolumic relaxation time, and ratio of time velocity integral of mitral inflow to time velocity integral in the left ventricular outflow (TVI(MV)/TVI(LVO)). Peak mitral velocity and TVI(MV)/TVI(LVO) were the best predictors of significant MR and performed similarly (area under the receiver-operating characteristic curve: 0.97 for both). A peak velocity of > or =1.9 m/s was 90% sensitive and 89% specific for significant prosthetic MR, whereas a TVI(MV)/TVI(LVO) > or =2.5 had a sensitivity and specificity of 89% and 91%, respectively. A decision tree was constructed to assess the conditional probabilities of having significant MR given all the possible outcomes of the 2 best predictors. None of the patients with peak velocity < 1.9 m/s and TVI(MV)/TVI(LVO) <2.5 by TTE had significant MR. Conversely, all patients with peak velocity > or =1.9 m/s and TVI(MV)/TVI(LVO) > or =2.5 had significant MR. The use of more complex algorithms did not further improve the results. Thus, measurements of hemodynamic Doppler variables on TTE examination can accurately identify a large number of patients without significant prosthetic MR, thereby reducing the need for further investigation with TEE.