Carolyn K. Landolfo

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.

Real-time volumetric echocardiography: the technology and the possibilities.

The heart is a dynamic organ with complexities in its shape. As such, it places special demands on three‐dimensional techniques for reconstruction. Real‐time volumetric echocardiography, which is based on phased array and parallel processing principles to enhance line density within a scan volume, provides rapid image acquisition. We introduce the principle, potential clinical importance, current limitations, and future of volumetric imaging methods.

A Comparison of Mechanical and Laser Transmyocardial Revascularization for Induction of Angiogenesis and Arteriogenesis in Chronically Ischemic Myocardium

OBJECTIVES The purpose of the present study was to compare the use of a mechanical transmyocardial implant (TMI) device with transmyocardial laser revascularization (TMR) for induction of therapeutic angiogenesis and arteriogenesis in the chronically ischemic heart. BACKGROUND Prior experimental studies have demonstrated evidence for neovascularization after both mechanical and laser transmyocardial revascularization, although a long-term comparison of the two techniques has not been performed. METHODS Using an established model of chronic hibernating myocardium, mini-swine underwent 90% proximal left circumflex (LCx) coronary artery stenosis. One month later, baseline positron emission tomography (PET) and dobutamine stress echocardiography (DSE) were performed to quantitate regional myocardial blood flow (MBF) and function. Animals then underwent TMR with a holmium:yttrium-aluminum-garnet (holmium:YAG) laser (n = 5), TMI (n = 5), or sham redo-thoracotomy (n = 5). In the TMR group, the entire LCx region was treated with transmural laser channels at a density of 1/cm(2). Transmyocardial implants were placed transmurally at a similar density in the LCx region of the TMI group. Six months later, the PET and DSE studies were repeated, and the animals were euthanized. RESULTS Six months after TMR, there was a significant increase over baseline in resting MBF to the lased LCx region (68.9 +/- 4.6% vs. 89.3 +/- 3.0% reference non-ischemic septal segments; p < 0.001). This increased MBF was accompanied by a significant improvement in LCx regional wall motion during peak dobutamine stress (p = 0.04). Compared with baseline, there was no change in LCx region MBF six months after either TMI (72.9 +/- 4.8% vs. 85.7 +/- 3.4%; p = 0.10) or sham redo-thoracotomy (75.6 +/- 4.6% vs. 80.1 +/- 5.0%; p > 0.2). Likewise, there was no significant change in rest or stress wall motion by DSE six months postoperatively in either group. Overall vascular density was increased only in the TMR-treated regions six months postoperatively. The difference between groups was most notable for a twofold increase in the number of small arterioles seen in the lased (4.4 +/- 0.3 arterioles per high power field; p < 0.001 vs. both TMI and sham) compared with TMI (2.2 +/- 0.2) and sham (1.9 +/- 0.2)-treated regions. CONCLUSIONS Mechanical transmyocardial revascularization with a TMI device does not appear to promote physiologically significant angiogenesis or arteriogenesis in the chronically ischemic porcine heart and cannot be recommended for clinical trials at this time. Infrared laser-mediated injury mechanisms may be important for inducing therapeutic neovascularization with direct myocardial revascularization techniques.

Is chronically dysfunctional yet viable myocardium distal to a severe coronary stenosis hypoperfused

BACKGROUND Controversy exists regarding the perfusion status of chronically dysfunctional yet viable myocardium. Studies investigating the pathophysiology of this condition have reached different conclusions, with some suggesting that myocardial blood flow (MBF) in these regions is normal at rest with regional dysfunction resulting from repetitive stress-induced ischemia (stunned myocardium), whereas others have proposed that MBF is chronically reduced at rest (hibernating myocardium). However, adequately powered experimental studies investigating this question in an appropriate animal model using clinically available techniques have not been performed. Based on the mixed results of prior studies, we hypothesized that these chronically dysfunctional yet viable regions may actually represent a mixture of hibernation and stunning. Consequently, the purpose of this study was to quantitatively determine the distribution of MBF in left ventricular regions with chronically impaired resting function but preserved viability in a large population of animals with single-vessel coronary stenosis in an attempt to further elucidate the mechanism(s) responsible for chronic, reversible myocardial dysfunction. METHODS Fifty-two adult mini-swine with 90% proximal left circumflex (LCx) stenosis underwent dynamic positron emission tomography (PET) with 13N-ammonia and 18F-fluorodeoxyglucose and dobutamine stress echocardiography (DSE) (5 to 40 microg/kg/min) 1 month after stenosis creation. Values of MBF and FDG uptake by PET and wall motion score index (WMSI) by DSE were compared using a standard 16-segment model. RESULTS Of 312 possible LCx segments seen on PET, 303 (97.1%) were visualized by DSE. Of the 303 LCx segments, 279 (92.1%) had rest dysfunction (WMSI > or = 2) by DSE. One hundred eighty-two segments (60.1%) had decreased (< 85% reference) MBF at rest with preserved to increased (> 60% reference) FDG uptake and were classified as hibernating. Ninety-two segments (30.4%) had preserved MBF (> or = 85% reference) and were classified as stunned. Five segments (1.7%) with reduced (< or = 60% reference) FDG uptake by PET and akinesis or dyskinesis at rest (WMSI > or = 3) and no contractile reserve were considered infarcted. Hibernating segments had significantly higher FDG uptake at rest (360.7+/-48.3 vs 212.3+/-17.7% septal values; p < 0.001) than stunned segments consistent with greater resting ischemia. Likewise, mean rest WMSI was also worse in hibernating versus stunned segments (2.35+/-0.04 vs 2.13+/-0.04; p < 0.001). There was no difference in the percentage of hibernating versus stunned segments exhibiting contractile reserve during dobutamine infusion (55.5 vs 63.7%; p = 0.4), indicating similar degrees of viability. CONCLUSIONS Myocardial hibernation and stunning appear to frequently coexist in regions served by a stenotic coronary vessel. Hibernating regions appear to have greater resting ischemia based on higher values of FDG uptake and greater resting dysfunction. Reversible left ventricular dysfunction in the setting of chronic coronary artery disease is likely due to a combination of these two mechanisms.

A novel approach to the diagnosis of left atrial appendage thrombus using contrast echocardiography and power Doppler imaging

BACKGROUND Transesophageal echocardiography is performed routinely among patients with atrial fibrillation (AF) in order to exclude left atrial appendage (LAA) thrombus prior to cardioversion. Because assessment for LAA thrombus is dependent upon the experience of the operator and is therefore subjective, there remains a subset of patients in whom the diagnosis may not be definitive. The purpose of this report is to present a novel technique which may aid in the confirmation and/or exclusion of LAA thrombus using contrast echocardiography (CE) and power Doppler (PD) imaging. METHODS TEE imaging of the LAA appendage was performed in 3 patients. By visual inspection, the presence of the thrombus was absent (patient one), equivocal (patient two) and definite (patient three). Contrast echocardiography with Definity and power Doppler imaging was performed to aid in the confirmation and/or exclusion of thrombus in these 3 patients. RESULTS CE alone was useful in confirming the absence and presence of LA thrombus determined by visual inspection in patients one and three, respectively. CE in conjunction with PD imaging was useful in identifying the presence of LAA thrombus (by showing a filling defect and the absence of flow in the tip) in the patient with equivocal results by visual inspection CONCLUSION Contrast echocardiography alone may be useful in confirming and/or excluding the presence of LAA thrombus among patients with AF. CE with PD imaging provides incremental information in aiding in the diagnosis when the conventional images are equivocal.

Heart Failure in the Older Hypertensive Patient

The prevalence of heart failure is 4,900,000 and is rising (1). The prevalence of heart failure progressively increases with aging (Fig. 1). The incidence is 550,000 and approaches 10 per 1000 people after age 65 years. The annual rate for new and recurrent heart events is displayed in Fig. 2. Data from the Framingham Heart Study suggest that the incidence of heart failure has declined in women, but not men (2). At age 40 years, the lifetime risk of developing heart failure is about 20%. Mortality from heart failure is grim, with 20% of patients dying within 1 year (Fig. 3).