Echocardiographic predictors of adverse clinical events in children with dilated cardiomyopathy: a prospective clinical study.

OBJECTIVES: To compare tissue Doppler (TD) velocities between patients with dilated cardiomyopathy (DCM) and normal controls and to determine whether TD velocities, Tei index, right ventricular fractional area change, and left ventricular ejection fraction (LVEF) predict adverse clinical outcomes in children with DCM. METHODS: Prospective evaluation of children with DCM. RESULTS: 54 children with DCM and 54 age and sex matched control group participants were studied. Mitral inflow velocities were similar for both groups except for decreased mitral deceleration time in patients with DCM. Systolic and diastolic TD velocities at the mitral annulus (septal and lateral sides) and tricuspid annulus were significantly reduced in children with DCM compared with controls (p < 0.001 for each). By multivariate analysis, after adjustment for Tei index and right ventricular fractional area change, decreased LVEF and tricuspid velocity during early diastole (Ea) were predictors of the primary end point (PEP), a composite end point consisting of need for hospitalisation or the outcome transplantation or death. Tricuspid Ea velocity < 8.5 cm/s had 87% specificity and 60% sensitivity for reaching the PEP. LVEF < 30% had 68% specificity and 74% sensitivity for the PEP. Combined LVEF < 30% and tricuspid Ea < 11.5 cm/s had 100% specificity and 44% sensitivity for the PEP. CONCLUSIONS: Children with DCM have significantly lower TD velocities than normal controls. In such cases, lower LVEF (< 30%) is more sensitive but less specific than lower tricuspid Ea velocities (< 8.5 cm/s) in predicting which patients are at risk of hospitalisation, transplantation, or death.

Intracardiac echocardiographic measurement of left ventricular volume.

We tested the utility of intracardiac echocardiography (ICE) in measuring left ventricular (LV) volume. In 4 normal dogs, a 10-F percutaneous sheath was placed inside the LV along its major axis. An ICE catheter (9 F, 9 MHz) was then inserted through the sheath into the LV. The ICE catheter was pulled back in 1-mm intervals starting from the apex, and 2-D tomographic images were continuously acquired. Subsequently, the ICE catheter was replaced in the LV by a conductance catheter to measure single-beat volume signals. Stroke volume was determined by thermodilution for validation. All measurements were made in each dog while pacing the atrium at two different cycle lengths (range=300-500 ms). The endocardium was segmented in the ICE images throughout the cardiac cycle, and LV volume was computed by integrating multiple segments (range=55-70 mm). We found that ICE accurately reconstructed LV 3-D anatomy. Stroke volume by ICE was in excellent agreement with thermodilution (error = 3.8+/-3.0%, r = 0.99, n = 8). Morphology of LV volume signals correlated well with instantaneous volume signals derived by conductance (r=0.93, n=8). In conclusion, ICE accurately reconstructs LV anatomy and volume throughout the cardiac cycle in the normal heart. This approach could facilitate interventional diagnostic and therapeutic procedures.

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.

Myocardial viability: recent developments in detection and clinical significance.

The long-term prognosis of patients with ischemic cardiomyopathy is highly variable, depending on the extent of myocardial viability and the success and completeness of the revascularization techniques used. Other important factors include left ventricular function, extent of coronary artery disease (CAD), and patient age. Chronic left ventricular dysfunction in ischemic cardiomyopathy is the result of a mixture of scarred as well as hibernating myocardium. In fact, most patients have both scarring and hibernation in different regions. Transmural biopsies of dysfunctional segments reveals that recovery of function is inversely proportional to the extent of fibrosis and that endocardial fibrosis extending over 30% of the myocardial thickness precludes recovery of function.Nagueh et al. [1] evaluated the relation of contractile reserve and thallium uptake in hibernating myocardium to myocardial structure in humans. The authors found that segments with postoperative functional recovery had more wall thickening at low-dose dobutamine echocardiography (DE), higher thallium uptake, and less fibrosis (2.0 vs 28%) than those segments without recovery. Also, segments with viability on DE had less fibrosis, less vimentin and fibronectin, more glycogen, and higher thallium uptake, than those segments without viability. Importantly, segments viable by single-photon emission computed tomography (SPECT) and DE had significantly less fibrosis (1%) than those viable by only one of the two techniques. In this review, we discuss recent developments in the detection of myocardial viability, including echocardiography, nuclear cardiac imaging, magnetic resonance imaging (MRI), and other techniques.

Echocardiographic evaluation of mitral regurgitation.

Accurate evaluation of mitral regurgitation (MR) severity remains a challenging task in clinical cardiology. The importance of proper quantification of regurgitation cannot be underestimated because a delayed decision to replace or repair a defective valve may lead to worsening ventricular function and increased perioperative and long-term mortality. In this review we discuss both recent developments in the quantification of MR as well as new insights into the pathophysiology and progression of this lesion.

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.

Decreased expression of tumor necrosis factor-alpha and regression of hypertrophy after nonsurgical septal reduction therapy for patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Nonsurgical septal reduction therapy (NSRT) is a novel therapeutic strategy for patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the clinical benefits of this technique appear to be clear, the structural and functional changes that lead to improvements in cardiac function are not completely defined. In these studies, we sought to define the effect of NSRT on myocardial function as well as various markers of hypertrophy including the expression of tumor necrosis factor (TNF)-alpha, a cytokine capable of producing fibrosis, left ventricular hypertrophy (LVH), and cardiomyopathy. METHODS AND RESULTS: We performed endomyocardial biopsies of the RV side of the septum and echocardiograms on 15 HOCM patients at baseline and after successful NSRT. Comparative analysis on paired myocardial samples were performed to determine the effects of NSRT on LVH, end-diastolic volume and chamber stiffness, myocyte size, collagen content, and TNF-alpha levels. At baseline, myocardial TNF-alpha levels were increased in all patients. After NSRT, myocyte size, collagen content, and TNF-alpha were significantly decreased. These changes were accompanied by an increase in left ventricular volumes and a reduction in LVH and chamber stiffness. CONCLUSIONS: We suggest that pressure overload in HOCM patients contributes to the development of hypertrophy. These data provide the initial experimental evidence to suggest that TNF-alpha may play a pathogenetic role in the hypertrophy of pressure overload.

Stress echocardiography in the diagnosis of coronary artery disease.

Stress echocardiography (SE) is currently a widely accepted method for the diagnostic and prognostic assessment of coronary artery disease. This article reviews new concepts in SE, such as new stress techniques, new methods of endocardial border detection, strain, tissue Doppler velocities, and others. Although some of these techniques are in their infancy, we believe that they will become widely accepted.

Regression of left ventricular hypertrophy after nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy.

BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular hypertrophy (LVH) in the absence of increased external load. Recently, nonsurgical septal reduction therapy (NSRT) with intracoronary ethanol has been introduced to treat severely symptomatic patients with outflow tract obstruction. Its long-term effects on LV mass, however, are unknown. METHODS AND RESULTS: The LV size, function, and outflow tract gradient of 26 HOCM patients (53+/-15 years old) who underwent NSRT were assessed by echocardiography at baseline and 1 and 2 years after the procedure. LVH was evaluated by wall thickness of individual myocardial segments, planimetered myocardial area, and mass. The outflow gradient decreased from 36+/-6 mm Hg before NSRT to 0+/-3 mm Hg at 2 years (P<0.001), with patients experiencing symptomatic improvement (P<0.05). LV end-diastolic and end-systolic dimensions increased significantly at both 1 and 2 years (P<0.001). All parameters of LVH showed evidence of regression. LV mass decreased (301+/-78 g at baseline, 223+/-5 g at 1 year, and 190+/-58 g at 2 years; P<0.01), with the 2-year reduction in mass related to infarct size and the acute reduction in outflow tract gradient (r=0.48, P<0.05 and r=0.63, P<0.01, respectively). CONCLUSIONS: NSRT results in LV remodeling that is characterized by an increase in LV size and a decrease in the extent of LVH.

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

Echocardiographic insights into the mechanisms of relief of left ventricular outflow tract obstruction after nonsurgical septal reduction therapy in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: We sought to evaluate the mechanisms by which nonsurgical septal reduction therapy (NSRT) reduces left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM) both acutely and on a long-term basis. BACKGROUND: NSRT reduces LVOT obstruction in patients with HOCM and leads to symptomatic improvement. The mechanisms involved, however, are not well studied. METHODS: An initial group of 30 HOCM patients (age 46 +/- 17, 16 women) who underwent NSRT had echocardiographic studies performed at baseline and six months after the procedure. Measurements included LVOT diameter, end-diastolic distance between the anterior mitral leaflet and interventricular septum, septal base function and the angle between LV systolic flow and the protruding mitral leaflets. In addition, pulse Doppler recordings at a point 2.5 cm apical to the mitral valve were acquired and analyzed for peak and mean ejection velocity, peak acceleration rate and the ratio of acceleration time to ejection time (AT/ET). RESULTS: Significant changes were observed after the procedure, with widening in the LVOT, thinning and akinesis of the septal base, decrease in the angle between LV systolic flow and the protruding mitral leaflets, a decrease in peak acceleration rate and an increase in AT/ET. All of these variables had significant relations with the decrease in LVOT obstruction (r = 0.5 to 0.79, p < 0.01). These correlations were then evaluated in a test group of 15 patients who underwent echocardiographic examinations at baseline, acutely in the catheterization laboratory with ethanol injection and at six weeks post NSRT. Acute changes in peak acceleration rate (r = 0.65) and AT/ET (r = 0.73) related significantly (p < 0.01) to the decrease in LVOT obstruction with ethanol. At six weeks, changes similar to those noted in the initial group were observed in LVOT geometry, the angle between LV systolic flow and the protruding mitral leaflets, peak acceleration rate and AT/ET. In both populations combined, these parameters accounted for 72% to 77% of the variance in gradient reduction. CONCLUSIONS: Changes in LV ejection dynamics and septal base function account in part for the acute relief of LVOT gradient after NSRT. The long-term relief of obstruction is dependent on remodeling of LVOT as well as the changes in LV ejection.

Hemodynamic determinants of the mitral annulus diastolic velocities by tissue Doppler.

OBJECTIVES: Our goal was to identify the hemodynamic determinants of the mitral annulus (MA) diastolic velocities by tissue Doppler. BACKGROUND: The MA diastolic velocities are promising indexes of left ventricular (LV) diastolic function. However, their hemodynamic determinants have not yet been evaluated. METHODS: Ten adult mongrel dogs underwent left atrial (LA) and LV pressure measurements by Millar catheters while tissue Doppler was applied to record the MA diastolic velocities at the septal and lateral comers. Conventional transmitral flow was also obtained. Left atrial and LV pressures were modified utilizing fluid administration and caval occlusion, whereas dobutamine and esmolol were used to change LV and LA relaxation. Left ventricular filling pressures were altered during different lusitropic states to evaluate for the possible interaction of preload and LV relaxation on the early diastolic velocity (Ea). RESULTS: In the majority of dogs, a positive significant relation was observed between Ea and the transmitral pressure gradient (r = 0.57, p = 0.04). The Ea had strong correlations with tau (r = -0.83, p < 0.001), LV -dP/dt (r = 0.8, p < 0.001) and minimal LV pressure (r = -0.76, p < 0.01). However, there was no relation between Ea and the transmitral pressure gradient in experimental stages where tau >50 ms. Furthermore, the late diastolic velocity at both corners of the MA had significant positive relations with LA dP/dt (r = 0.67, p < 0.01) and LA relaxation (r = 0.73, p < 0.01) but an inverse correlation with LV end-diastolic pressure (r = -0.53, p = 0.01). CONCLUSIONS: Left ventricular relaxation, minimal pressure and preload determine Ea while late diastolic velocity determinants include LA dP/dt, LA relaxation and LV end-diastolic pressure.

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.

Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up.

OBJECTIVE: The objective of this study is to evaluate the one-year outcome of the first 50 patients who underwent nonsurgical septal reduction for symptomatic hypertrophic obstructive cardiomyopathy at our institution. BACKGROUND: Left ventricular outflow tract obstruction is an important determinant of clinical symptoms in patients with hypertrophic obstructive cardiomyopathy. Nonsurgical septal reduction is a new therapy that has been shown to result in left ventricular outflow tract gradient reduction and resolution of symptoms immediately after the procedure and on midterm follow-up. METHODS: Fifty patients with hypertrophic obstructive cardiomyopathy who underwent nonsurgical septal reduction at our institution and completed 1-year follow-up are described. Complete history, physical examination, two-dimensional echocardiography with Doppler and exercise treadmill testing have been analyzed. RESULTS: The mean age of the study group was 53 +/- 17 years. All patients had refractory symptoms before enrollment. Ninety-four percent had class III or IV New York Heart Association class symptoms at baseline compared to none at 1 year (p < 0.001). The exercise duration increased by 136 s at 1 year (p < 0.021). Only 20% of patients were either receiving beta-blockers or calcium-channel blockers on follow-up. The resting left ventricular outflow tract gradient decreased from 74 +/- 23 mm Hg to 6 +/- 18 mm Hg (p < 0.01) and from 84 +/- 28 mm Hg to 30 +/- 33 mm Hg (p < 0.01) in patients with dobutamine-provoked gradient at one year. These changes are associated with decreased septal thickness and preserved systolic function. CONCLUSION: Nonsurgical septal reduction therapy is an effective therapy for symptomatic patients with hypertrophic obstructive cardiomyopathy with persistence of the favorable outcome up to one year after the procedure.

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.