Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities.

BACKGROUND: The combination of fenfluramine and phentermine was a widely used obesity treatment before the withdrawal of fenfluramine for an association with heart valve regurgitation. The prevalence and clinical significance of regurgitation among patients treated with these medications has yet to be fully established. METHODS AND RESULTS: To evaluate the potential association between the duration of treatment and the prevalence of heart valve abnormalities, we examined 1163 patients who had taken fenfluramine-phentermine and 672 control patients who had not taken the drug combination within 5 years. Mild or greater aortic regurgitation was present in 8.8% of treated patients and 3.6% of control patients (P<0.001). Moderate or greater mitral regurgitation was present in 2.6% of treated patients and 1.5% of control patients (P=0.18). The adjusted odds ratio compared with controls of aortic regurgitation of mild or greater severity increased according to duration of treatment: 90 to 180 days, 1.5 (P=0.23); 181 to 360 days, 2.4 (P=0.002); 361 to 720 days, 4.6 (P<0.001); >720 days, 6.2 (P<0.001). CONCLUSIONS: This is the largest study to demonstrate a relation between the length of treatment with fenfluramine-phentermine and the prevalence of valvular abnormalities. These findings suggest that valvular abnormalities in patients who took fenfluramine-phentermine primarily involve those who had taken these medications for >6 months and predominantly results in mild aortic regurgitation. The valve regurgitation identified by this study was not accompanied by significant differences in cardiovascular symptoms nor physical findings other than a higher prevalence of heart murmurs.

Effect of dobutamine stress echocardiography on mitral regurgitation.

OBJECTIVES: This study was performed to examine the effect of dobutamine stress echocardiography on mitral regurgitation and to test the hypothesis that mitral regurgitation will increase in patients with an ischemic response. BACKGROUND: New or worsening mitral regurgitation during stress testing has been proposed as a marker of ischemia. However, it is unclear whether ischemia induced by dobutamine is associated with mitral regurgitation because the hemodynamic effects of dobutamine may vary with regard to mitral regurgitation, depending on left ventricular function and maximal dose attained. METHODS: Dobutamine stress echocardiography was performed in 102 consecutive patients with suspected or known coronary artery disease. Color flow Doppler was used to determine the presence and change in mitral regurgitation at baseline and peak dobutamine infusion (up to 40 micrograms/kg body weight per min). The mitral regurgitation color flow Doppler area was semiquantitatively graded as mild (< 4 cm2), moderate (4 to 8 cm2) or severe (> 8 cm2). Patients were assigned to ischemic and nonischemic groups according to the dobutamine stress echocardiographic results. RESULTS: The two groups achieved the same maximal dose and demonstrated similar blood pressure and heart rate responses to dobutamine infusion. Only two patients developed new mitral regurgitation during dobutamine infusion, and both had a normal dobutamine echocardiographic result. More patients without ischemia had no mitral regurgitation compared with patients with ischemia. There was an insufficient number of patients with coronary angiographic data to determine the effects of mitral regurgitation on the sensitivity and specificity of dobutamine stress echocardiography. Of 23 patients with a rest ejection fraction < 50%, 61% had an improvement in mitral regurgitation grade compared with 25% of patients with a rest ejection fraction > or = 50% (p < 0.02). CONCLUSIONS: These data indicate that although dobutamine infusion often improves mitral regurgitation in patients with left ventricular dysfunction during stress echocardiography, it does not induce or worsen mitral regurgitation in those who demonstrate an ischemic response. Future studies are necessary, with large numbers of patients, to determine the effects of mitral regurgitation on the sensitivity and specificity of dobutamine stress echocardiography.

Real-time orthogonal mode scanning of the heart. I. System design.

A necessary percursor to real-time three-dimensional echocardiographic imaging is the ability to obtain multiple planes of acoustic data simultaneously. A new ultrasound imaging technique facilitates the display of two real-time orthogonal B-mode images (O-mode). The O-mode technique uses a novel two-dimensional transducer and system processor to interrogate the two perpendicular planes simultaneously, yielding sector arcs that share one origin. It permits simultaneous display of two sector arcs on a single monitor either side by side or in a two-dimensional projection designed to convey the three-dimensional nature of the acoustic data. Clinical results from the first 50 patients undergoing O-mode evaluation indicate that image quality in the two simultaneously obtained planes is equal to that of a single plane when the system is operating in its conventional format. These data confirm the feasibility of real-time multiplane imaging. The system design offers the potential for the future addition of more simultaneous planes and, thus, the possibility of real-time three-dimensional ultrasound imaging.

Subvalvular left ventricular pseudoaneurysm after mitral valve replacement: two-dimensional echocardiographic findings.

Disruption of the posterior mitral anulus is a rare complication of mitral valve replacement that may result in subvalvular left ventricular pseudoaneurysm formation. Such pseudoaneurysm formation was easily recognized by two-dimensional echocardiography in a 54 year old man 3 years after his second mitral valve replacement. The finding was confirmed by cineangiography and direct surgical inspection. Recognition of this rare complication of mitral valve replacement has therapeutic importance because surgical correction is necessary.

In vitro color flow, pulsed and continuous wave Doppler ultrasound masking of flow by prosthetic valves.

On the hypothesis that Doppler ultrasound fails to penetrate prosthetic valves, an in vitro flow simulation system was constructed in a large water tank. Conventional pulsed, continuous wave and Doppler color flow systems were used to detect flow in tubing placed diagonally within the water and maintained by a continuous pump. After control periods of flow detection within the tubing, six different prosthetic valves were interposed on a stage between the transducer and the tubing. In comparison with control measurements, detection of flow within the tubing was impossible when the Doppler beam traversed the central occluding ball of the Starr-Edwards Silastic prosthesis by any modality. Marked reduction in the detection of the Doppler signal was noted for the Starr-Edwards stellite prosthesis with only slight improvement in the ability to detect the flow signals through the central occluding discs of the Björk-Shiley, Hall-Kastor and St. Jude valves. In distinction to the other valves, the ability of Doppler ultrasound to detect flow behind the cusps of the Carpentier-Edwards heterograft was similar to that during the control period. An understanding of flow masking should improve the clinical utility of Doppler methods for investigating prosthetic valve dysfunction.

Utility of echocardiography in the management of patients with penetrating missile wounds of the heart.

Nine consecutive patients with penetrating missile wounds of the heart were evaluated by M-mode and two-dimensional echocardiography for localization of retained missile fragments noted to be moving in synchrony with the heart by fluoroscopy. Echocardiography precisely located all 12 moving fragments: 2 in the pericardium, 5 in the anterior right ventricular wall, 3 in the free left ventricular wall, 1 in the interventricular septum and 1 in the right posterior atrioventricular groove. Five patients had echocardiographic evidence of pericardial effusion and only one manifested a wall motion abnormality, indicating that direct myocardial perforation does not always result in detectable intrapericardial bleeding or asynergy. Localization of the missile fragments to be in danger of endocardial perforation, in danger of eroding the right coronary artery and creating a clinically unsuspected membranous ventricular septal defect led directly to surgical intervention in three different patients. In all three, intraoperative echocardiography quickly localized the missile fragments and significantly reduced patient cardiopulmonary bypass time. In the remaining six patients, localization of missile fragments well within the myocardium with no danger of erosion led to decisions against surgical removal.

The safety of contrast echocardiography: report of the Committee on Contrast Echocardiography for the American Society of Echocardiography.

The results of a survey of 363 physicians performing echocardiography were evaluated to assess the relative safety of contrast echocardiography. Fifteen physicians reported a variety of transient side effects, including neurologic and respiratory symptoms. Although contrast echocardiography appeared to carry some risk for side effects, that risk was low (0.062%) and no residual side effects or complications were observed. In view of the significant benefits reported for contrast echocardiography, it appears to remain a valuable technique that is safer than currently available alternative diagnostic modalities. However, during contrast echocardiography, precautions should be taken to prevent the injection of visible amounts of air, especially in patients with a right to left shunt or arterial catheters.

Ultrasound diagnosis of pseudoaneurysm and contiguous ventricular septal defect complicating inferior myocardial infarction.

Two patients with recent inferior myocardial infarction were found by two-dimensional and Doppler echocardiography to have both an inferior wall pseudoaneurysm and a contiguous rupture of the posterior ventricular septum. The pseudoaneurysm was not suspected clinically in either patient. In one patient, a complex or dissecting septal rupture was visualized in detail. To our knowledge, the combined defect has not previously been diagnosed during life by noninvasive methods.

Relation of quantitative coronary lesion measurements to the development of exercise-induced ischemia assessed by exercise echocardiography.

To assess the relation of quantitative measures of coronary stenoses to the development of exercise-induced regional wall motion abnormalities, 34 patients with isolated, single vessel coronary artery lesions and normal wall motion at rest underwent exercise echocardiography and quantitative angiography on the same day. Although all 11 patients with a visually estimated stenosis greater than or equal to 75% had an ischemic response and 10 (91%) of 11 patients with a less than or equal to 25% visually estimated stenosis had a normal response by exercise echocardiography, among 12 patients with a visually estimated stenosis of 50%, 6 (50%) had an ischemic response and 6 (50%) had a normal exercise echocardiogram. Quantitative measurements of stenosis severity distinguished patients with ischemic (group 1) from normal (group 2) exercise echocardiographic responses as follows: minimal luminal diameter (mm), group 1 1.0 +/- 0.4 versus group 2 1.7 +/- 0.4, p less than 0.0001; minimal cross-sectional area (mm2), group 1 0.9 +/- 0.6 versus group 2 2.5 +/- 1.1, p less than 0.0001; percent diameter stenosis, group 1 68.3 +/- 14.2 versus group 2 42.2 +/- 12.1, p less than 0.0001; and percent area stenosis, group 1 87.5 +/- 7.8 versus group 2 64.8 +/- 15.9, p less than 0.0001. These data validate the utility of exercise echocardiography by demonstrating that 1) coronary stenosis severity measured by quantitative angiography is closely related to wall motion abnormalities detected by exercise echocardiography, and 2) exercise echocardiography can be used as a noninvasive means to assess the physiologic significance of coronary artery lesions.

Opacification and border delineation improvement in patients with suboptimal endocardial border definition in routine echocardiography: results of the Phase III Albunex Multicenter Trial.

OBJECTIVES: This study was designed to assess the safety and efficacy of intravenously administered sonicated human serum albumin for enhancing echocardiographic delineation of the left ventricular endocardium and improving assessment of wall motion in patients with incomplete depiction of noncontrast echocardiography. BACKGROUND: Echocardiographic regional wall motion analysis is impaired by incomplete endocardial definition in as many as 10% of patients. Sonicated human serum albumin is a stable contrast material that, unlike other agents, opacifies the left ventricle when administered intravenously. METHODS: One hundred seventy-five patients were enrolled at eight centers on the basis of incomplete echocardiographic endocardial depiction. Sonicated 5% human serum albumin, a stable preparation of air-filled microspheres (size range 1 to 10 microns), was administered intravenously in divided doses: 0.08 ml/kg body weight in all patients, followed by 0.14 and 0.08 ml/kg or a single dose of 0.22 ml/kg, depending on the result of the initial dose. Investigators and independent reviewers blinded to the protocol scored the echocardiograms for degree of left ventricular opacification and improvement of endocardial border depiction. RESULTS: Overall, 81% of patients had at least moderate left ventricular chamber opacification with at least one contrast dose, and endocardial definition was improved in 83%. In the subgroup with inadequate left ventricular opacification from the initial dose, a second, larger dose (0.22 ml/kg) improved endocardial depiction in 64%. No significant side effects occurred. CONCLUSIONS: In patients with incomplete echocardiographic endocardial definition, sonicated human serum albumin is a safe, effective contrast agent that, when administered intravenously, produces left ventricular chamber opacification, improves endocardial depiction and enhances regional wall motion analysis.

The utility of transesophageal echocardiography and Doppler color flow imaging in patients undergoing cardiac valve surgery.

To assess the value of intraoperative transesophageal echocardiography during cardiac valve surgery, 154 consecutive patients who had a valve operation in conjunction with pre- and postcardiopulmonary bypass transesophageal imaging were studied. Prebypass imaging yielded unsuspected findings that either assisted or changed the planned operation in 29 (19%) of the 154 patients. Imaging immediately after bypass revealed unsatisfactory operative results that necessitated immediate further surgery in 10 (6%) of the 154 patients. Postbypass left ventricular dysfunction, prompting administration of inotropic agents, was identified in 13 patients (8%). Transesophageal echocardiography proved most useful when both two-dimensional and Doppler color flow imaging were employed in patients undergoing a mitral valve operation, where surgical decisions based on echocardiographic results were made in 26 (41%) of 64 cases. Postbypass echocardiographic findings identified patients at risk for an adverse postoperative outcome. Of 123 patients whose postbypass valve function was judged to be satisfactory, 18 (15%) had a major postoperative complication and 6 (5%) died, whereas of 7 patients with moderate residual valve dysfunction, 6 (86%) had a postoperative complication and 3 (43%) died (p less than 0.05 for both). Likewise, of 131 patients with preserved postbypass left ventricular function, 12 (9%) had a major complication and 7 (5%) died, whereas of 23 patients with reduced ventricular function, 17 (73%) had a postoperative complication and 6 (26%) died (p less than 0.05 for both). These data indicate that intraoperative transesophageal echocardiography is useful in formulating the surgical plan, assessing immediate operative results and identifying patients with unsatisfactory results who are at increased risk for postoperative complications.

Report of the Council on Scientific Affairs: ultrasonic imaging of the heart: report of the Ultrasonography Task Force.

The use of ultrasonography in cardiology has progressed so dramatically that not only is anatomic information available but information can also be derived about cardiac hemodynamics. Applications range from intravascular ultrasonic imaging of coronary atherosclerosis to predictions of the severity of fetal valvular pulmonic stenosis detected in utero. We reviewed cardiac ultrasonography as utilized in B-mode imaging, pulsed and continuous-wave spectral Doppler, and Doppler color flow mapping. We reviewed specialized areas, including stress echo for wall motion analysis, valvular and congenital heart disease applications, and new applications in intraoperative, transesophageal, contrast echography, coronary imaging, and fetal echocardiography. Finally, future applications of quantitative flow mapping and intraluminal and interventional ultrasonography were considered along with the required technological advances.

Echo-Doppler in the diagnosis and management of congenital heart disease.

Advancements in echo-Doppler technology now provide the capability for both high-quality anatomic imaging as well as the assessment of cardiac flows and hemodynamics. Given these capabilities, and the potentially complex nature of all congenital heart lesions, echo-Doppler is well suited for the diagnostic assessment of congenital heart disease. As a noninvasive, reliable, and relatively inexpensive tool, it is well suited for the longitudinal follow-up of patients with treated and untreated congenital heart lesions. Recent experience with intraoperative imaging has indicated that direct epicardial echo-Doppler examination provides clinically useful information for the surgeon treating congenital heart lesions. Echo-Doppler examination continues to evolve into a primary modality for the recognition, evaluation, and treatment of congenital heart disease.

Cardiac involvement in myotonic muscular dystrophy.

Cardiac illness in myotonic muscular dystrophy (MyD) is infrequent, but subclinical cardiac involvement in MyD is very common (found in 42 of 46 subjects) and may be responsible for sudden death. In this series, we found ECG abnormalities in 72%, left ventricular dysfunction in 70%, mitral valve prolapse in 37%, and sudden death in 4%. Four deaths during the study period were due to acute left ventricular failure, one to sepsis and respiratory insufficiency, and one was unexplained. We did not find ominous bradyarrhythmias or atrioventricular block, evidence of congestive heart failure, noninvasive evidence of coronary artery disease, or any correlation of type or amount of cardiac involvement with any clinical parameter such as age, sex, or severity of systemic dystrophy. We feel tachyarrhythmias may play as important a role in sudden death of myotonic muscular dystrophy subjects as bradyarrhythmias, and coronary artery disease in addition to cardiac dystrophy may produce arrhythmias and myocardial dysfunction in myotonic muscular dystrophy. In addition, some subjects have an unusual form of resting left ventricular dysfunction which improves with exercise. The most important problem in the clinical management of myotonic muscular dystrophy subjects is sudden death, and the solution does not appear to be empiric ventricular pacing. Our recommendations for prophylaxis of sudden death in myotonic muscular dystrophy are noninvasive investigation of coronary artery disease in subjects with significant risk factors, with angiography and surgery if indicated: detailed evaluation of syncopal and presyncopal events, including electrophysiologic testing, with pacemaker or antiarrhythmic drug therapy if indicated; and consideration of ventricular pacing of asymptomatic subjects if severe bradycardia or marked intraventricular conduction delay develops during follow-up, serial 12-lead ECGs. The documentation of tachyarrhythmias during sudden death and syncopal episodes in myotonic muscular dystrophy subjects makes ventricular pacing alone an uncertain modality for prevention of sudden death in subjects with only mildly lengthened PR or QRS intervals, and suggests a combination of pacemaker and antiarrhythmic drug therapy for the myotonic muscular dystrophy subject with syncope of no apparent cause.

Dynamic cardiac imaging using a focused, phased-array ultrasound system.

A two-dimensional ultrasound imaging system capable of producing high resolution, cross-sectional images of the heart in real-time has been developed. This system relies upon phased-array principles to rapidly steer and focus the ultrasound beam through the cardiac structures under investigation. A hand-held, linear array of 24 transducers is manipulated on the anterior chest wall to image various cardiac structures. Images of high line density are presented in selectable sector arcs to a maximum of 90 degrees. This imaging system has proved particularly useful for the detection of a variety of left ventricular and cardiac valvular disease.

Etiology of large pericardial effusions.

PURPOSE: To determine the effectiveness of the preoperative evaluation and overall diagnostic efficacy of subxiphoid pericardial biopsy with fluid drainage in patients with new, large pericardial effusions. DESIGN: A prospective interventional case series of consecutive patients admitted with new, large pericardial effusions. PATIENTS AND METHODS: Fifty-seven of 75 consecutive patients admitted to a university tertiary-care center and a university-affiliated Veterans Administration Medical Center with new, large pericardial effusions were studied over a 20-month period. Each patient was assessed by a comprehensive preoperative evaluation followed by subxiphoid pericardiotomy. The patients' tissue and fluid samples were studied pathologically and cultured for aerobic and anaerobic bacteria, fungi, mycobacteria, mycoplasmas, and viruses. RESULTS: A diagnosis was made in 53 (93%) patients. The principle diagnoses consisted of malignancy in 13 (23%) patients; viral infection in 8 (14%) patients; radiation-induced inflammation in 8 (14%) patients; collagen-vascular disease in 7 (12%) patients; and uremia in 7 (12%) patients. No diagnosis was made in four (7%) patients. A variety of unexpected organisms were cultured from either pericardial fluid or tissue: cytomegalovirus (three), Mycoplasma pneumoniae (two), herpes simplex virus (one), Mycobacterium avium-intracellulare (one), and Mycobacterium chelonei (one). The pericardial fluid yielded a diagnosis in 15 (26%) patients, 11 of whom had malignant effusions. The examination of pericardial tissue was useful in the diagnosis of 13 (23%) patients, 8 of whom had an infectious agent cultured. Of the 57 patients undergoing surgery, the combined diagnostic yield from both fluid and tissue was 19 patients (33%). CONCLUSIONS: A systematic preoperative evaluation in conjunction with fluid and tissue analysis following subxiphoid pericardiotomy yields a diagnosis in the majority of patients with large pericardial effusions. This approach may also result in the culturing of "unusual" infectious organisms from pericardial tissue and fluid.

Evaluation of the left ventricle with two dimensional echocardiography.

Two dimensional echocardiography, because of its wide field of view, has been shown to be superior to the M mode approach for ultrasonic evaluation of the left ventricle. The use of this technique for determination of ventricular volume estimates and detection of asynergy has been promising but is limited by compromised image quality found in many patients with ischemic heart disease. Because it supplies cross-sectional information about the ventricular chamber and wall thickness simultaneously, this new technique lends itself to the anatomic localization of changes in regional performance that accompany ischemic heart disease. It allows simultaneous study of regional dynamic changes in chamber circumference, wall thickness and motion characteristics that give practical information on coronary artery disease and acute myocardial infarction.

Interatrial shunting in atrial septal aneurysm.

Adequate contrast 2-dimensional (2-D) echocardiograms were recorded in 13 to 16 patients with typical 2-D findings of atrial septal aneurysm. Five patients were referred for detection of intracardiac source of emboli after embolic stroke and 11 were evaluated for suspicion of valvular or other forms of heart disease. Contrary to findings of previous clinical studies, all 13 patients had 2-D evidence of right-to-left atrial level shunting. These findings represent the first clinical evidence of a high prevalence of atrial shunting in patients with atrial septal aneurysm.

Intraoperative echocardiography in congenital heart disease surgery: preliminary report on a current study.

CLINICAL PERSPECTIVE: The first prospective trial in which both echocardiography and Doppler color flow imaging (echo-DCFI) are used routinely during surgery for congenital heart lesions has been undertaken at Duke Medical Center. Precardiopulmonary bypass (CPB) echo-DCFI examinations have revealed previously unsuspected cardiac findings in several of the patients. These examinations have influenced the surgical course in some way in many of the cases. Post-CPB ultrasound evaluation of the quality of the surgical repairs alone has resulted in immediate additional corrective surgery in several patients, most of whom then left the operating room with an optimum repair.

Pericardial effusion after intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction.

The effect of thrombolytic therapy on the frequency, time course and sequelae of pericardial effusion after myocardial infarction are unknown. A prospective, serial, 2-dimensional echocardiographic study of patients with myocardial infarction who received recombinant tissue-type plasminogen activator (rt-PA) was undertaken to address this issue. The study population comprised 52 of the 112 patients enrolled in the first Thrombolysis and Angioplasty in Myocardial Infarction trial at Duke University Medical Center. Enrollment in the serial echocardiography protocol was determined by equipment and support staff availability. Complete echocardiographic studies were performed within 90 minutes after initiation of thrombolytic therapy (day 0), and on days 1, 3 and 6. Patients undergoing serial echocardiography did not differ in demographic or clinical characteristics from those who did not. Pericardial effusion was present in 3 of 38 patients (8%) at day 0, in 2 of 44 (5%) at day 1, in 8 of 43 (19%) at day 3, and in 10 of 42 (24%) at day 6. By day 6, 3 of 10 pericardial effusions were moderate in size, 1 of 10 was large and the remainder were small. No patients developed echocardiographic or hemodynamic signs of cardiac tamponade. The prevalence and time course of pericardial effusion among patients with acute myocardial infarction who received rt-PA in this study are similar to observations reported in earlier studies in which patients did not receive thrombolytic therapy. Adverse sequelae of pericardial effusion after thrombolytic therapy are rare.