Natural history of valvular regurgitation using side-by-side echocardiographic analysis in anorexigen-treated subjects.

In 1997, the US Food and Drug Administration (FDA) reported valvular regurgitation (aortic regurgitation [AR] mild or greater and/or mitral regurgitation [MR] moderate or greater) in 32.8% of patients treated with anorexigens. This study sought to determine the natural history of valvular regurgitation in patients who were included in the FDA's original report. This was a nonrandomized, natural history study of these subjects. Cohort I consisted of 155 of 186 patients (83%) who were reported to the FDA. Cohort II consisted of a similar group of 311 patients who were not included. Initial echocardiograms were obtained for medical indications before the study initiation, and study echocardiograms were standardized and obtained at 3-month intervals. Level III echocardiographers performed blinded, side-by-side comparison of the first and last study echocardiograms at a core laboratory. Cohorts I and II consisted of predominantly female, middle-aged, obese subjects. At enrollment, patients in cohorts I and II had mild or greater AR (17.9%, 13.5%) and moderate or greater MR (3.3%, 4.0%), respectively, which was less than in the FDA's report. At follow-up, there were no statistically significant changes in the degree of valvular regurgitation in either cohort when the first and last study echocardiograms were read side by side. In conclusion, this natural history follow-up study demonstrates that MR and AR in long-term anorexigen-treated patients was less than reported to the FDA, did not progress, and remained echocardiographically stable during the 10-month duration of the study.

Usefulness of tissue doppler and color M-mode indexes of left ventricular diastolic function in predicting outcomes in systolic left ventricular heart failure (from the ADEPT study).

The prognostic values of tissue Doppler imaging and color M-mode diastolic indexes were studied in 225 patients who had symptomatic systolic heart failure in the ADEPT study. The primary end point of death, transplantation, or hospitalization due to heart failure occurred in 65 patients and was independently predicted by shorter deceleration time, lower ratio of pulmonary vein systolic to diastolic velocity, and increasing levels of the ratios of early transmitral velocity to early annular velocity or velocity of propagation. For the ratio of early transmitral velocity to early annular velocity, this prediction was additive to deceleration time. Newer diastolic indexes provide an independent prediction of clinical outcomes.

Combination of pulsed-wave Doppler and real-time three-dimensional color Doppler echocardiography for quantifying the stroke volume in the left ventricular outflow tract.

Real-time three-dimensional (3-D) color Doppler echocardiography (RT3D) is capable of quantifying flow. However, low temporal resolution limits its application to stroke volume (SV) measurements. The aim of the present study was, therefore, to develop a reliable method to quantify SV. In animal experiments, cross-sectional images of the LV outflow tract were selected from the RT3D data to calculate peak flow rates (Q(p3D)). Conventional pulsed-wave (PW) Doppler was performed to measure the velocity-time integral (VTI) and the peak velocity (V(p)). By assuming that the flow is proportional to the velocity temporal waveform, SV was calculated as alpha x Q(p3D) x VTI/V(p), where alpha is a temporal correction factor. There was an excellent correlation between the reference flow meter and RT3D SV (mean difference = -1. 3 mL, y = 1. 05 x -2. 5, r = 0. 94, p < 0. 01). The new method allowed accurate SV estimations without any geometric assumptions of the spatial velocity distributions.

Salvage of nondiagnostic transthoracic echocardiograms on patients in intensive care units with intravenous ultrasound contrast.

Transthoracic echocardiography (TTE) is often technically difficult on patients in intensive care units. Contrast echocardiography can improve left ventricular wall visualization and the assessment of regional and global left ventricular wall motion. Our study undertook to determine what proportion of nondiagnostic TTE studies on patients in intensive care units could be salvaged (i.e., converted to diagnostic studies) with contrast. Ninety-two patients with nondiagnostic TTEs had a repeat study after contrast. Using predefined criteria, 51% of studies were salvaged with contrast. Female gender emerged as the only factor associated with less likelihood of salvaging a study.

Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function.

OBJECTIVES: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF). BACKGROUND: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone. METHODS: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function. RESULTS: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001). CONCLUSIONS: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.

Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice.

Cardiac hypertrophy and heart failure remain leading causes of death in the United States. Many studies have suggested that, under stress, myocardium releases factors triggering protein synthesis and stimulating myocyte growth. We identified and cloned myotrophin, a 12-kDa protein from hypertrophied human and rat hearts. Myotrophin (whose gene is localized on human chromosome 7q33) stimulates myocyte growth and participates in cellular interaction that initiates cardiac hypertrophy in vitro. In this report, we present data on the pathophysiological significance of myotrophin in vivo, showing the effects of overexpression of cardio-specific myotrophin in transgenic mice in which cardiac hypertrophy occurred by 4 weeks of age and progressed to heart failure by 9-12 months. This hypertrophy was associated with increased expression of proto-oncogenes, hypertrophy marker genes, growth factors, and cytokines, with symptoms that mimicked those of human cardiomyopathy, functionally and morphologically. This model provided a unique opportunity to analyze gene clusters that are differentially up-regulated during initiation of hypertrophy versus transition of hypertrophy to heart failure. Importantly, changes in gene expression observed during initiation of hypertrophy were significantly different from those seen during its transition to heart failure. Our data show that overexpression of myotrophin results in initiation of cardiac hypertrophy that progresses to heart failure, similar to changes in human heart failure. Knowledge of the changes that take place as a result of overexpression of myotrophin at both the cellular and molecular levels will suggest novel strategies for treatment to prevent hypertrophy and its progression to heart failure.

Myeloperoxidase and plasminogen activator inhibitor 1 play a central role in ventricular remodeling after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) results in LV dilation, a major cause of congestive heart failure and sudden cardiac death. Ischemic injury and the ensuing inflammatory response participate in LV remodeling, leading to myocardial rupture and LV dilation. Myeloperoxidase (MPO), which accumulates in the infarct zone, is released from neutrophils and monocytes leading to the formation of reactive chlorinating species capable of oxidizing proteins and altering biological function. We studied acute myocardial infarction (AMI) in a chronic coronary artery ligation model in MPO null mice (MPO(-/-)). MPO(-/-) demonstrated decreased leukocyte infiltration, significant reduction in LV dilation, and marked preservation of LV function. The mechanism appears to be due to decreased oxidative inactivation of plasminogen activator inhibitor 1 (PAI-1) in the MPO(-/-), leading to decreased tissue plasmin activity. MPO and PAI-1 are shown to have a critical role in the LV response immediately after MI, as demonstrated by markedly delayed myocardial rupture in the MPO(-/-) and accelerated rupture in the PAI-1(-/-). These data offer a mechanistic link between inflammation and LV remodeling by demonstrating a heretofore unrecognized role for MPO and PAI-1 in orchestrating the myocardial response to AMI.

Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography.

BACKGROUND: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall-motion analysis. Interpretation of dobutamine stress echocardiography is observer-dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. METHODS AND RESULTS: Twenty-nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5-3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. CONCLUSION: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.