Carolyn L Donovan

Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients.

OBJECTIVES The purpose of this prospective study was to examine the role of echocardiography in patients with Staphylococcus aureus bacteremia (SAB). BACKGROUND The reported incidence of infective endocarditis (IE) among patients with SAB varies widely. Distinguishing patients with uncomplicated bacteremia from those with IE is therapeutically and prognostically important, but often difficult. METHODS One hundred-three consecutive patients undergoing both transthoracic (TTE) echocardiography and transesophageal (TEE) echocardiography were prospectively evaluated. All patients presented with fever and > or = 1 positive blood culture and were followed up for 12 weeks. RESULTS Although predisposing heart disease was present in 42 patients (41%), clinical evidence of infective endocarditis (IE) was rare (7%). TTE revealed anatomic abnormalities in 33 patients, but vegetations in only 7 (7%), and was considered indeterminate in 19 (18%). TEE identified vegetations in 22 patients (aortic valve in 5, mitral valve in 9, tricuspid valve in 4, catheter in 2 and pacemaker in 2, abscesses in 2, valve perforation in 1 and new severe regurgitation in 1; 26 total [25%]). Using Duke criteria for the diagnosis of IE, definite IE was present in 26 patients (25%). Clinical findings and predisposing heart disease did not distinguish between patients with and without IE. The sensitivity of TTE for detecting IE was 32%, and the specificity was 100%. The addition of TEE increased the sensitivity to 100%, but resulted in one false positive result (specificity 99%). TEE detected evidence of IE in 19% of patients with a negative TTE and 21% of patients with an indeterminate TTE. At follow-up, cure of staphylococcal infection occurred in a similar percentage of patients with and without IE (77% and 75%, respectively). However, death due to sepsis was significantly more likely among patients with IE (4 of 26 [15%]) than among those without IE (2 of 77 [3%]) (p = 0.03). CONCLUSIONS Our results suggest that IE is common among patients admitted to the hospital with SAB and is associated with an increased risk of death due to sepsis. TEE is essential to establish the diagnosis and to detect associated complications. Therefore, the test should be considered part of the early evaluation of patients with SAB.

Two-dimensional and dobutamine stress echocardiography in the preoperative assessment of patients with end-stage liver disease prior to orthotopic liver transplantation.

Orthotopic liver transplantation is an established therapy for end-stage liver disease. This study evaluated the range of cardiovascular abnormalities in patients undergoing evaluation for orthotopic liver transplantation and determined the prognostic implications of abnormal echocardiographic features, including ischemia during dobutamine stress echocardiography, in predicting postoperative cardiac events. Two-dimensional echocardiography was performed in 190 patients for assessment of left ventricular function, valvular pathology, and pulmonary hypertension. Dobutamine stress echocardiography was performed in 165 patients for evaluation of inducible ischemia. Contrast echocardiography for detection of intrapulmonary shunting was performed in 125 patients at rest and in 99 during dobutamine stress. Left ventricular dysfunction, significant valvular regurgitation, and inducible ischemia were identified in <1O% of patients. Pulmonary hypertension, left ventricular hypertrophy and > or = moderate intrapulmonary shunting were present in 12%, 16%, and 26% of patients, respectively. Severe intrapulmonary shunting predicted death prior to transplantation (P=0.01). Of the 71 transplanted patients, major perioperative events included global left ventricular dysfunction in four patients and myocardial infarction in one patient with normal coronary arteries. No preoperative echocardiographic parameters, including ischemia on dobutamine echocardiography, predicted these perioperative events. No cardiac events related to obstructive coronary artery disease occurred in the 154 patients without ischemia on dobutamine stress echocardiography. The majority of patients with end-stage liver disease, including those with alcoholic cirrhosis, have normal cardiac function on two-dimensional echocardiography. Severe intrapulmonary shunting portends a poor prognosis in patients awaiting transplantation. A negative dobutamine stress echocardiogram appears useful in excluding patients at risk for perioperative cardiac events related to obstructive coronary artery disease.

Improvement in inducible ischemia during dobutamine stress echocardiography after transmyocardial laser revascularization in patients with refractory angina pectoris.

OBJECTIVES The purpose of this ongoing study is to determine whether transmyocardial laser revascularization (TMLR) can lessen inducible ischemia and improve contractile reserve in patients with refractory angina pectoris. BACKGROUND TMLR is an emerging surgical technique for the treatment of myocardial ischemia and angina pectoris not amenable to conventional percutaneous or surgical revascularization. Objective data documentating a reduction in ischemia during noninvasive stress testing after TMLR are rare. METHODS Fifteen patients with severe coronary artery disease unsuitable for treatment with standard revascularization techniques were studied with dobutamine stress echocardiography (DSE) before TMLR. Of the 12 patients who underwent TMLR, DSE was repeated at 3 months postoperatively in 11 patients and at 6 months in 9 patients. Stress echocardiograms were analyzed for inducible ischemia, with calculation of the wall motion score index (WMSI). Heart rate and dobutamine dose achieved at peak stress were also assessed as indexes of stress tolerance. RESULTS Compared with that before TMLR, wall motion at rest for all myocardial segments did not change significantly after TMLR, although there was a mild improvement in the WMSI of the lased myocardial regions ([mean +/- SD] 1.64 +/- 0.34 after vs. 1.78 +/- 0.34 before TMLR, p < 0.05). Overall WMSI at peak stress improved markedly after TMLR (1.70 +/- 0.30 after vs. 2.06 +/- 0.31 before TMLR, p < 0.002), with the improvement in WMSI limited to the lased segments only (1.47 +/- 0.31 after vs. 2.15 +/- 0.34 before TMLR, p < 0.0004). The improvement in WMSI with stress resulted primarily from a decrease in the percentage of ischemic segments (47% before vs. 23% after TMLR, p < 0.0008), with no change in the percentage of infarcted segments (23% before vs. 26% after TMLR). Heart rate (83 +/- 5 beats/min before vs. 102 +/- 21 beats/min after TMLR, p = 0.01) and dobutamine infusion rate (26 +/- 9 micrograms/kg body weight per min before vs. 34 +/- 9 micrograms/kg per min after TMLR) achieved at peak stress also increased postoperatively, consistent with improved stress tolerance. The reduction in ischemic wall motion abnormalities and improved stress tolerance persisted at 6 months, without evidence of further improvement or deterioration of function over time. CONCLUSIONS TMLR performed in patients with refractory angina pectoris reduces ischemic wall motion abnormalities and improves stress-induced tolerance during dobutamine echocardiography. These beneficial effects persist up to 6 months postoperatively.

Assessment of Regional Wall Motion Abnormalities with Real-Time 3-Dimensional Echocardiography

Accurate characterization of regional wall motion abnormalities requires a thorough evaluation of the entire left ventricle (LV). Although 2-dimensional echocardiography is frequently used for this purpose, the inability of tomographic techniques to record the complete endocardial surface is a limitation. Three-dimensional echocardiography, with real-time volumetric imaging, has the potential to overcome this limitation by capturing the entire volume of the LV and displaying it in a cineloop mode. The purpose of this study was to assess the feasibility of using real-time 3-dimensional (RT3D) echocardiography to detect regional wall motion abnormalities in patients with abnormal LV function and to develop a scheme for the systematic evaluation of wall motion by using the 3-dimensional data set. Twenty-six patients with high-quality 2-dimensional echo images and at least 1 regional wall motion abnormality were examined with RT3D echocardiography. For 2-dimensional echocardiography, wall motion was analyzed with a 16-segment model and graded on a 4-point scale from normal (1) to dyskinetic (4), from which a wall motion score index was calculated. Individual segments were then grouped into regions (anterior, inferoposterior, lateral, and apical) and the number of regional wall motion abnormalities was determined. The RT3D echocardiogram was recorded as a volumetric, pyramid-shaped data set that contained the entire LV. Digital images, consisting of a single cardiac cycle cineloop, were analyzed off-line with a computerized display of the apical projection. Two intersecting orthogonal apical projections were simultaneously displayed in cineloop mode, each independently tilted to optimize orientation and endocardial definition. The 2 planes were then slowly rotated about the major axis to visualize the entire LV endocardium. Wall motion was then graded in 6 equally spaced views, separated by 30 degrees, yielding 36 segments per patient. A higher percentage of segments were visualized with 2-dimensional versus RT3D echocardiography (97% vs 83%, respectively, P <.001). With the use of the 2-dimensional echocardiographic results as the standard, RT3D echocardiography detected 55 (96%) of 57 regional wall motion abnormalities. Analysis of the RT3D echocardiograms resulted in 3 false-negative and 5 false-positive findings. The total number of regional wall motion abnormalities was correctly classified by RT3D echocardiography in 19 (73%) of 26 patients. RT3D echocardiography detected 11 of 13 anterior, 19 of 20 inferoposterior, 9 of 9 lateral, and 15 of 15 apical wall motion abnormalities. An excellent correlation was found between the 2 techniques for assessment of the regional wall motion score index (r = 0.89, P <.001). This initial clinical study demonstrates the feasibility and potential advantages of RT3D echocardiography for the assessment of regional LV function. Compared with 2-dimensional echocardiography, this new method permits recording of the entire LV in a single beat, allowing the extent and location of the regional wall motion abnormalities to be determined.

Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia

BACKGROUND The mechanism of clinical improvement after transmyocardial laser revascularization (TMR) is unknown. One hypothesis holds that TMR causes increased myocardial perfusion through neovascularization. This study sought to determine whether angiogenesis occurs after TMR in a porcine model of chronic myocardial ischemia. METHODS Six miniature pigs underwent subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, dobutamine stress echocardiography and positron emission tomography were performed to document ischemic, viable myocardium. The animals then underwent TMR and were sacrificed 6 months later for histologic and immunohistochemical analysis. RESULTS Histologic analysis of the lased left circumflex region demonstrated many hypocellular areas filled with connective tissue representing remnant TMR channels. Histochemical staining demonstrated a highly disorganized pattern of neovascularization consistent with angiogenesis located predominantly at the periphery of the channels. Immunohistochemical analysis confirmed the presence of endothelial cells within neovessels. Vascular density analysis revealed a mean of 29.2+/-3.6 neovessels per high-power field in lased ischemic myocardium versus 4.0+/-0.3 (p<0.001) in nonlased ischemic myocardium. CONCLUSIONS This study provides evidence that neovascularization is present long term in regions of ischemic, viable myocardium after TMR. Angiogenesis may represent the mechanism of clinical improvement after TMR.

Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and excimer lasers.

BACKGROUND Transmyocardial laser revascularization (TMR) is an emerging treatment for end-stage coronary artery disease. A variety of lasers are currently available to perform the procedure, although their relative efficacy is unknown. The purpose of this study was to compare changes in myocardial blood flow and function 6 months after TMR with holmium:yttrium-aluminum-garnet (holmium:YAG), carbon dioxide (CO2), and xenon chloride excimer lasers in a model of chronic ischemia. METHODS Miniswine underwent subtotal (90%) left circumflex coronary stenosis. Baseline positron emission tomography and dobutamine stress echocardiography were performed to document hibernating myocardium in the left circumflex coronary artery distribution. Animals were then randomized to sham redo-thoracotomy (n = 5) or TMR using a holmium:YAG (n = 5), CO2 (n = 5) or excimer (n = 5) laser. Six months postoperatively, the positron emission tomography and dobutamine stress echocardiography studies were repeated and the animals sacrificed. RESULTS In animals undergoing TMR with holmium: YAG and CO2 lasers, a significant improvement in myocardial blood flow to the lased left circumflex regions was seen. No significant change in myocardial blood flow was seen in sham- or excimer-lased animals. There was a significant improvement in regional stress function of the lased segments 6 months postoperatively in animals undergoing holmium:YAG and CO2 laser TMR that was consistent with a reduction in ischemia. There was no change in wall motion in sham- or excimer-lased animals. Significantly greater neovascularization was observed in the holmium:YAG and CO2 lased regions than with either the sham procedure or excimer TMR. CONCLUSIONS Transmyocardial laser revascularization with either holmium:YAG or CO2 laser improves myocardial blood flow and contractile reserve in lased regions 6 months postoperatively. These changes were not seen following excimer TMR or sham thoracotomy, suggesting that differences in laser energy or wavelength or both may be important in the induction of angiogenesis.

An experimental model of chronic myocardial hibernation

BACKGROUND Hibernating myocardium describes persistently impaired ventricular function at rest caused by reduced coronary blood flow. However, a realistic animal model reproducing this chronic ischemic state does not exist. The purpose of this study was to explore whether chronic low-flow hibernation could be produced in swine. METHODS Miniswine underwent 90% stenosis of the left circumflex coronary artery. Positron emission tomography and dobutamine stress echocardiography were performed 3 and 30 days (n = 6) or 14 days (n = 4) after occlusion to evaluate myocardial blood flow and viability. Triphenyl tetrazolium chloride assessed percent infarction. Electron microscopy was used to identify cellular changes characteristic of hibernating myocardium. RESULTS Positron emission tomography (13N-labeled-ammonia) 3 days after occlusion demonstrated a significant reduction in myocardial blood flow in the left circumflex distribution. This reduced flow was accompanied by increased glucose use (18F-fluorodeoxyglucose), which is consistent with hibernating myocardium. Thirty days after occlusion, positron emission tomography demonstrated persistent low flow with increased glucose use in the left circumflex distribution. Dobutamine stress echocardiography 3 days after occlusion demonstrated severe hypocontractility at rest in the left circumflex region. Regional wall motion improved with low-dose dobutamine followed by deterioration at higher doses (biphasic response), findings consistent with hibernating myocardium. The results of dobutamine stress echocardiography were unchanged 30 days after occlusion. Triphenyl tetrazolium chloride staining (n = 6) revealed a mean of 8% +/- 2% infarction of the area-at-risk localized to the endocardial surface. Electron microscopy (n = 4) 14 days after occlusion demonstrated loss of contractile elements and large areas of glycogen accumulation within viable cardiomyocytes, also characteristic of hibernating myocardium. CONCLUSIONS Chronic low-flow myocardial hibernation can be reproduced in an animal model after partial coronary occlusion. This model may prove useful in the study of the mechanisms underlying hibernating myocardium and the use of therapies designed to improve blood flow to the heart.

Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium

BACKGROUND Transmyocardial laser revascularization (TMR) has been demonstrated effective for relieving angina, although prior studies have yielded inconsistent results regarding postoperative myocardial perfusion and function. This study evaluated long-term changes in myocardial perfusion and contractile reserve after TMR in a model of hibernating myocardium. METHODS Miniswine had subtotal left circumflex coronary artery occlusion to reduce resting blood flow to 10% of baseline. After 2 weeks in the low-flow state, positron emission tomography and dobutamine stress echocardiography were performed to document ischemic, viable (hibernating) myocardium in the left circumflex distribution. Animals then had sham redo thoracotomy (n = 4) or TMR (n = 6). Six months later the positron emission tomography and dobutamine stress echocardiography studies were repeated. RESULTS Myocardial blood flow in the left circumflex distribution as measured by positron emission tomography was significantly reduced in all animals after 2 weeks in the low-flow state. In animals that had TMR, there was significant improvement in myocardial blood flow to the lased regions 6 months postoperatively. No significant change in myocardial blood flow was seen in sham animals at 6 months. Dobutamine stress echocardiography after 2 weeks of low-flow demonstrated severe hypocontractility at rest in the left circumflex region of all animals, with a biphasic response to dobutamine consistent with hibernating myocardium. In animals that had TMR, there was a trend toward improved resting function and significantly improved regional stress function in the lased segments 6 months postoperatively, consistent with a reduction in ischemia. Global left ventricular wall motion at peak stress improved significantly as well. There was no change in wall motion 6 months postoperatively in sham-operated animals. CONCLUSIONS This study found improvements in myocardial perfusion and regional and global contractile reserve 6 months after TMR in a porcine model of hibernating myocardium. This improved perfusion and function likely accounts for the clinical benefits of the procedure.

Perioperative morbidity and mortality after transmyocardial laser revascularization: incidence and risk factors for adverse events

OBJECTIVES The purpose of this study was to describe the incidence and spectrum of perioperative cardiac and noncardiac morbidity and mortality after transmyocardial laser revascularization (TMR) and to identify predictors of these adverse clinical events. BACKGROUND Clinical studies have demonstrated the efficacy of TMR for relieving angina pectoris, although no study to date has specifically addressed the associated perioperative morbidity and mortality. METHODS Between October 1995 and August 1997, 34 consecutive patients with end-stage coronary artery disease (CAD) underwent isolated TMR. The majority of patients (94%) had class III or IV angina pectoris, and two patients (6%) had unstable symptoms preoperatively. Patient records were reviewed for fatal and nonfatal adverse cardiac and noncardiac events. RESULTS Perioperative death occurred in two patients (5.9%) due to cardiogenic shock complicating acute myocardial infarction. Perioperative cardiac morbidity occurred in 16 patients (47.1%); noncardiac morbidity was seen in 12 patients (35.3%). Preoperative unstable angina was the only variable predictive of perioperative death (p = 0.005). Cardiac (p = 0.005) and noncardiac (p < 0.001) morbidity rates were significantly higher for the initial 15 patients undergoing the procedure. Other predictors of perioperative complications included lack of postoperative treatment with a furosemide infusion (p < or = 0.04) and preoperative unstable angina (p = 0.05). CONCLUSIONS Perioperative mortality in patients undergoing isolated TMR is low. Transmyocardial laser revascularization patients are at higher risk for adverse perioperative cardiac and noncardiac events, likely reflecting the lack of immediate benefit from the procedure in the setting of severe CAD. These patients merit vigilant surveillance for adverse events and aggressive medical management in the perioperative period.

Early postoperative changes in regional systolic and diastolic left ventricular function after transmyocardial laser revascularization: a comparison of holmium:YAG and CO2 lasers.

OBJECTIVES The purpose of this study was to determine the short-term effects of transmyocardial laser revascularization (TMR) on regional left ventricular systolic and diastolic function, myocardial blood flow (MBF) and myocardial water content (MWC). BACKGROUND Clinical studies of TMR have noted a significant incidence of cardiac complications in the early postoperative period. However, the early post-treatment effects of laser therapy on the myocardium and their potential contribution to postoperative cardiac morbidity are unknown. METHODS Swine underwent holmium:yttrium-aluminum-garnet (holmium:YAG) (n = 12) or carbon dioxide (CO2) (n = 12) laser TMR. Regional systolic function for the lased and nonlased regions was quantitated using preload recruitable work area (PRWA) and regional diastolic function with the ventricular stiffness constant alpha. RESULTS Preload recruitable work area was significantly decreased in the lased regions both 1 (59.8+/-13.0% of baseline, p = 0.02) and 6 h (64.2+/-9.4% of baseline, p = 0.02) after holmium:YAG TMR. This decreased PRWA was associated with a significant reduction in MBF to the lased regions (13.2% reduction at 1 h, p = 0.02; 18.4% decrease at 6 h post-TMR, p = 0.01). These changes were not seen after CO2 laser TMR. A significant increase in MWC (1.4+/-0.3% increase with holmium:YAG, p = 0.004; 1+/-0.2% increase with CO2, p = 0.002) and alpha (217.4+/-44.2% of baseline 6 h post-holmium:YAG TMR, p = 0.05; 206+/-36.7% of baseline 6 h post-CO2 TMR, p = 0.03) was seen after TMR with both lasers. CONCLUSIONS In the early postoperative setting, impaired regional systolic function in association with regional ischemia is seen after TMR with a holmium:YAG laser. Both holmium:YAG and CO2 lasers are associated with increased MWC and impaired diastolic relaxation in the lased regions. These changes may explain the significant incidence of early postoperative cardiac morbidity. The impact of these findings on anginal relief and long-term outcome are not known.