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.

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.

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.

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.

Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy.

BACKGROUND: Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS: Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS: LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.

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

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.

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.

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.

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.

Pathologic correlates of aortic plaques, thrombi and mobile "aortic debris" imaged in vivo with transesophageal echocardiography.

OBJECTIVES: This study sought to evaluate the pathologic correlates of aortic atheromas, thrombi and mobile "aortic debris" imaged in vivo by transesophageal echocardiography (TEE). BACKGROUND: Atherosclerotic plaques with various complexity, thrombi and debris are frequently identified by TEE during imaging of the aorta. However, pathologic data to characterize these lesions imaged in vivo are lacking. METHODS: Intraoperative TEE was performed prospectively in 31 patients undergoing repair of aortic aneurysm or dissection. TEE was used to guide the surgeon to mark aortic areas of interest that were sent for pathologic examination. A four-point scoring system was used for both TEE and pathologic evaluation to grade the degree of involvement of the aortic wall with atheroma. Ultrasound video intensity of the aortic wall lesions was measured and compared with quantitative measures of wall composition at pathologic examination. The presence of thrombi and mobile aortic debris by TEE was noted and compared with pathologic findings. RESULTS: Histologic-TEE correlations were possible in 62 aortic segments. There was 73% exact agreement between TEE and pathologic grading. Discrepancies were mostly in the inability of TEE to detect superficial ulcerations. However, separation of normal aorta and minimal intimal thickening (grades I and II) from more complex atheromas (grades III and IV) was observed in 93%. For identification of thrombus, TEE had a sensitivity of 91% (29 of 32 segments) and a specificity of 90% (27 of 30 segments). Mobile aortic debris were identified in six aortic segments and were confirmed at pathologic examination to be thrombi. Ultrasound video intensity increased with worsening complexity of atheroma and related significantly to aortic plaque composition at pathologic evaluation (r = 0.80, p < 0.0001). Ultrasound intensity of thrombi and mobile debris was similar and was lower than that of complex atheromas. CONCLUSIONS: Thus, in the evaluation of aortic pathologic segments, TEE can assess aortic plaque complexity and identify thrombus formation, findings that may have important therapeutic implications.

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.

Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures.

OBJECTIVES: This investigation was designed 1) to assess whether the early diastolic velocity of the mitral annulus (Ea) obtained with Doppler tissue imaging (DTI) behaves as a preload-independent index of left ventricular (LV) relaxation; and 2) to evaluate the relation of the mitral E/Ea ratio to LV filling pressures. BACKGROUND: Recent observations suggest that Ea is an index of LV relaxation that is less influenced by LV filling pressures. METHODS: One hundred twenty-five study subjects were classified into three groups according to mitral E/A ratio, LV ejection fraction (LVEF) and clinical symptoms: 34 asymptomatic subjects with a normal LVEF and an E/A ratio > or =1; 40 with a normal LVEF, an E/A ratio <1 and no heart failure symptoms (impaired relaxation [IR]); and 51 with heart failure symptoms and an E/A ratio >1 (pseudonormal [PN]). Ea was derived from the lateral border of the annulus. A subset of 60 patients had invasive measurement of pulmonary capillary wedge pressure (PCWP) simultaneous with Doppler echocardiographic DTI. RESULTS: Ea was reduced in the IR and PN groups compared with the group of normal subjects: 5.8 +/- 1.5 and 5.2 +/- 1.4 vs. 12 +/- 2.8 cm/s, respectively (p < 0.001). Mean PCWP (20 +/- 8 mm Hg) related weakly to mitral E (r = 0.68) but not to Ea. The E/Ea ratio related well to PCWP (r = 0.87; PCWP = 1.24 [E/Ea] + 1.9), with a difference between Doppler and catheter measurements of 0.1 +/- 3.8 mm Hg. CONCLUSIONS: Ea behaves as a preload-independent index of LV relaxation. Mitral E velocity, corrected for the influence of relaxation (i.e., the E/Ea ratio), relates well to mean PCWP and may be used to estimate LV filling pressures.

Differentiating thrombus from pannus formation in obstructed mechanical prosthetic valves: an evaluation of clinical, transthoracic and transesophageal echocardiographic parameters.

OBJECTIVES: We sought to determine the clinical and echocardiographic parameters that differentiate thrombus from pannus formation as the etiology of obstructed mechanical prosthetic valves. BACKGROUND: Distinction of thrombus from pannus on obstructed prosthetic valves is essential because thrombolytic therapy has emerged as an alternative to reoperation. METHODS: We analyzed clinical, transthoracic and transesophageal echocardiography (TEE) data in 23 patients presenting with 24 obstructed prosthetic valves and compared the findings to pathology at surgery. RESULTS: Fourteen valves had thrombus and 10 had pannus formation. Patients with thrombus had a shorter duration from time of valve insertion to malfunction, shorter duration of symptoms, but similar New York Heart Association functional class at the time of operation. Patients with thrombus had a lower rate of adequate anticoagulation (21% vs. 89%; p=0.0028). Pannus formation was more common in the aortic position (70% vs. 21%; p=0.035). Abnormal prosthetic valve motion was detected by TEE in all cases with thrombus formation but in 60% with pannus (p=0.0198). Thrombi were larger than pannuses (total length 2.8+/-2.47 cm vs. 1.17+/-0.43 cm; p=0.038). This was mostly due to extension of thrombi into the left atrium in prosthetic mitral valves. Thrombi appeared as a soft mass on the valve in 92% of cases, whereas 29% of pannuses had a soft echo density (p= 0.007). Ultrasound video intensity ratio, derived as the videointensity of the mass to that of the prosthetic valve, was lower in the thrombus group (0.46+/-0.14 vs. 0.71+/-0.17, p=0.006). A videointensity ratio of <0.70 had a positive predictive value of 87% and a negative predictive value of 89% for thrombus. Duration from onset of symptoms to reoperation of <1 month separated thrombus from pannus formation. The best objective clinical parameter for prediction of thrombus was inadequate anticoagulation, whereas the best TEE parameters were qualitative and quantitative ultrasound intensity of the mass. The presence of either inadequate anticoagulation or a soft mass by TEE improved the predictive power of either parameter alone and was similar to that of ultrasound videointensity ratio. CONCLUSIONS: Duration of symptoms, anticoagulation status and qualitative and quantitative ultrasound intensity of the mass obstructing a mechanical prosthetic valve can help differentiate pannus formation from thrombus and may therefore be of value in refining the selection of patients for thrombolytic therapy of prosthetic valve obstruction.

Identification of hibernating myocardium: comparative accuracy of myocardial contrast echocardiography, rest-redistribution thallium-201 tomography and dobutamine echocardiography.

OBJECTIVES: We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 microg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation. BACKGROUND: Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated. METHODS: Eighteen patients (aged [+/- SD] 57 +/- 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated > or = 6 weeks after revascularization. RESULTS: Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 +/- 14% to 45 +/- 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65). CONCLUSIONS: In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.

Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia.

OBJECTIVES: We sought to determine the effects of nicotine patch therapy, when used to promote smoking cessation, on myocardial ischemia in patients with coronary artery disease. BACKGROUND: Nicotine patches substantially increase quit rates among cigarette smokers, but their safety in patients with myocardial ischemia who are attempting to quit smoking is unknown. METHODS: This is a prospective study using exercise thallium-201 single-photon emission computed tomography (SPECT) to assess serial changes in the total and ischemic myocardial perfusion defect size at baseline while patients were smoking and during treatment with 14- and 21-mg nicotine patches. Entry criteria required that patients 1) smoked > or = 1 pack of cigarettes per day; 2) had known coronary artery disease; and 3) had myocardial ischemia (i.e., > or = 5% reversible perfusion defect) on SPECT. All patients performed symptom-limited treadmill exercise, and the baseline SPECT study served as its own control. We interpreted and computer quantified the SPECT images with no knowledge of the testing sequence. RESULTS: Thirty-six of the 40 enrolled patients had exercise SPECT at baseline and during treatment with at least 14-mg nicotine patches. These patients had an initial perfusion defect size of 17.5 +/- 10.6% while smoking an average of 31 +/- 11 cigarettes per day for 40 +/- 12 years. A significant reduction in the total perfusion defect size (p < 0.001) was observed from baseline (17.5 +/- 10.6%) to treatment with 14-mg (12.6 +/- 10.1%) and 21-mg (11.8 +/- 9.9%) nicotine patches. This reduction occurred despite an increase in treadmill exercise duration (p < 0.05) and higher serum nicotine levels (p < 0.001). There was a significant correlation between the reduction in defect size and exhaled carbon monoxide levels (p < 0.001) because patients reduced their smoking by approximately 74% during the trial. CONCLUSIONS: Nicotine patches, when used to promote smoking cessation, significantly reduce the extent of exercise-induced myocardial ischemia as assessed by exercise thallium-201 SPECT.

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.

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.

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.