Hypertrophic obstructive cardiomyopathy masked by tako-tsubo syndrome: a case report.

Introduction. Left ventricular outflow obstruction might be part of the pathophysiological mechanism of Tako-tsubo cardiomyopathy. This obstruction can be masked by Tako-tsubo cardiomyopathy and diagnosed only by followup. Case Presentation. A 70-year-old female presented with Tako-tsubo cardiomyopathy and masked obstructive hypertrophic cardiomyopathy at presentation. Conclusion. Tako-tsubo cardiomyopathy typically presents like an acute MI and is characterized by severe, but transient, regional left ventricular systolic dysfunction. Prompt evaluation of the coronary status is, therefore, mandatory. The prognosis under medical treatment of heart failure symptoms and watchful waiting is favourable. Previous studies showed that LVOT obstruction might be part of the pathophysiological mechanism of TCM. This paper supports this theory. However, TCM may also mask any preexisting LVOT obstruction.

Prediction of global left ventricular function after bypass surgery in patients with severe left ventricular dysfunction. Impact of pre-operative myocardial function, perfusion, and metabolism.

AIMS: Previous studies have compared the accuracy of various tests of viability for the prediction of recovery of regional left ventricular function; global left ventricular recovery has been less well studied, although it has important prognostic and functional ramifications. We sought to identify the relative contribution of ischaemia, regional and global contractile reserve, perfusion and metabolic function to changes in left ventricular volumes and global function after coronary artery bypass surgery in patients with severe left ventricular dysfunction. METHODS AND RESULTS: Dipyridamole stress Rb-82, fluorodeoxyglucose positron emission tomography and low and high-dose dobutamine-atropine stress echocardiography were obtained in 66 patients with left ventricular impairment. Myocardial segments were considered viable if ischaemia or either metabolic or contractile reserve were present, on positron emission tomography or dobutamine echocardiography. Resting left ventricular function was reassessed after surgery (mean 10+/-3 weeks) in the 59 patients who had not suffered a major peri-operative event; functional improvement was defined by a 5% increment of ejection fraction. Myocardial viability was found in 37 (63%) patients using positron emission tomography and in 42 (71%) patients using dobutamine echocardiography; post-operative functional improvement was noted in 28 (47%) patients. In univariate analyses, predictors of global post-operative functional recovery included: the extent of viability according to positron emission tomography [OR (odds ratio): 2.08 for each additional viable segment, 95% CI (confidence interval): 1.33-3. 25, P=0.001] or dobutamine echocardiography (OR: 2.06 for each additional viable segment, 95% CI: 1.28-3.30, P=0.003) and the increase in ejection fraction with low-dose dobutamine (OR: 1.9 for each 1% increase in ejection fraction with low dose dobutamine, 95% CI 1.39-2.61, P<0.0001). In a multivariate model which included evidence of viability by either technique, and change in ejection fraction with low-dose dobutamine echocardiography, only change in ejection fraction with low-dose dobutamine echocardiography was predictive of post-operative left ventricular functional recovery (adjusted OR: 1.81, 95% CI: 1.30-2.52, P=0.0005). CONCLUSION: Among patients with severe left ventricular dysfunction who are referred for surgical revascularization, the overall accuracies of positron emission tomography and dobutamine echocardiography for the prediction of post-operative myocardial recovery are comparable. However, the strongest predictor of overall improvement of post-operative left ventricular function is an increase of ejection fraction with a low-dose dobutamine infusion.

Correlation of preoperative myocardial function, perfusion, and metabolism with postoperative function at rest and stress after bypass surgery in severe left ventricular dysfunction.

Previous studies of dobutamine echocardiography (DE) and positron emission tomography (PET) showed similar accuracy for predicting improvement in resting wall motion after revascularization, although limited direct comparative data are available. We sought to compare the relative accuracy of detecting contractile reserve, ischemia, perfusion, and myocardial metabolism for predicting functional recovery after coronary bypass surgery in 94 consecutive patients (aged 63+/-11 years) with chronic coronary disease and depressed left ventricular function (ejection fraction 28+/-5%). PET imaging comprised rest and dipyridamole stress myocardial perfusion images, with fluorodeoxyglucose to define metabolism-perfusion mismatch. A standard dobutamine-atropine stress was used, with evaluation of low- and peak-dose echocardiographic responses. Regional function was assessed after 13+/-16 weeks at rest in 68 patients who underwent isolated coronary bypass operation without evidence of perioperative infarction, and at rest and stress in a subgroup of 29 patients. Concordance between methods for evaluating abnormal segments (ischemic, viable, and scar) and accuracy of both tests for predicting improvement in regional function were identified. Concordance between PET and DE for identifying viable or nonviable myocardium was 63% using a 16-segment model. For predicting improved resting function after surgery, the sensitivity of PET (84%) was superior to DE (69%, p<0.001), but DE was more specific (78% vs. 37%, p<0.0001) and more accurate (75% vs. 53%, p<0.001) in predicting recovery at rest. Analysis of postoperative recovery of segmental function during stress also showed the specificity of DE to exceed that of PET (89% vs. 32%, p<0.001). The accuracy of DE was enhanced by evaluation of function during stress (86%, p<0.001), but this was not altered with PET (52%, p = NS). Thus, PET is more sensitive than DE in predicting functional recovery, but DE is more specific than PET. Evaluation of left ventricular functional recovery during stress may be preferable to assessment at rest.

Intraoperative transesophageal echocardiography in minimally invasive cardiac valve surgery.

The minimally invasive procedure is a new surgical technique that uses a small sternal incision. Because of limited surgical exposure, removal of intracavitary air and visual assessment of cardiac function are not possible. We studied the utility of intraoperative transesophageal echocardiography (IOE) before and after cardiopulmonary bypass in 112 patients (mean age 53.1 +/- 15.2 years, 74 males) who underwent minimally invasive valvular surgery. Surgical procedures included 52 isolated mitral valve procedures (49 repairs, 3 prostheses), 58 isolated aortic valve procedures (16 repairs, 26 prostheses, 16 homografts), and 2 combined aortic and mitral valve repairs. Prepump IOE was useful to confirm valve dysfunction and assist determination of arterial cannulation site. Postpump IOE identified intracardiac air in all patients, which was defined as extensive in 58 (52%) cases. Postoperatively, new left ventricular dysfunction was noted in 22 (20%) patients, more often in the group with extensive air by IOE (17 [30%] of 58 patients) compared with those without extensive air (5 [10%] of 54 patients, P =.01). Second pump runs were required in 7 (6%) of 112 patients: 3 cases of residual aortic regurgitation, 1 case of residual mitral regurgitation, and 3 cases with new ventricular dysfunction. No deaths occurred. We conclude that IOE is essential in minimally invasive valvular surgery because it detects problems that require immediate remedy. IOE allows real-time assessment of ventricular filling, ventricular and valvular function, and intracardiac air.

Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability.

OBJECTIVES: The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND: Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS: Sixty three patients (51 men, age 66+/-9 years) with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS: Patients had wall motion abnormalities in 83+/-18% of LV segments. A mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS: In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

Prognosis of patients with vascular disease after clinical evaluation and dobutamine stress echocardiography.

BACKGROUND: Coronary disease is an important cause of long-term morbidity in patients needing major vascular surgery. We sought to assess the efficacy of preoperative clinical evaluation and the detection of inducible ischemia for prediction of immediate and long-term cardiac outcomes of patients undergoing vascular surgery. METHODS: In 233 patients undergoing vascular procedures, we assessed risk clinically on the basis of Eagle's criteria. Dobutamine echocardiography was performed with a standard protocol and results were classified as showing ischemia, scar, or a normal response. Patients were observed perioperatively, and late follow-up (28 +/- 13 months) was completed in all surgical survivors. A composite end point of cardiac death, myocardial infarction, and unstable and progressive angina requiring late revascularization was used to judge event-free survival. RESULTS: Of 233 patients undergoing preoperative dobutamine echocardiography, 39 (17%) had inducible ischemia and 36 (15%) had scar. Perioperative events occurred in 8 patients (3%). None of the patients with ischemia had perioperative events, reflecting the effect of revascularization in 9 patients. Late events occurred in 36 patients; ischemia on preoperative stress testing was a predictor of these events even after adjusting for clinical variables and left ventricular dysfunction (relative risk = 3.3; 95% confidence interval 1.6 to 6.8; P =.001). The association of ischemia with clinical predictors was associated with incrementally worse outcome. CONCLUSION: In addition to perioperative assessment, the combined use of clinical and dobutamine echocardiographic evaluation may stratify the risk of late cardiac events.

Diagnostic and prognostic implications of left ventricular cavity obliteration response to dobutamine echocardiography.

Left ventricular (LV) cavity obliteration during dobutamine echocardiography (DE) indicates a vigorous inotropic response to stress. Such a response may suggest the absence of coronary artery disease (CAD), but a small LV cavity may also preclude recognition of wall motion abnormalities. We sought to determine the frequency, correlates, accuracy, and prognostic value of the LV cavity obliteration response in 336 consecutive patients who underwent coronary angiography within 1 year of DE. Cavity obliteration was defined by contact of the opposite walls in the apical views during DE, and ischemia by detection of a new or worsening wall motion abnormality. Sensitivity was based on comparison with coronary anatomy in 220 patients without prior revascularization. The prognostic implications of cavity obliteration were examined by follow-up of 324 patients (96%) over 23 +/- 9 months for death, myocardial infarction, and late revascularization. Cavity obliteration was present in 86 of the 336 DE studies (26%). Baseline and stress hemodynamics were not predictive of cavity obliteration, which was associated with LV hypertrophy and female gender (p <0.0001), and inversely related to LV systolic dysfunction and use of angiotensin-converting enzyme inhibitors or diuretics (p <0.02). The sensitivity of DE was less in patients with cavity obliteration than the remainder, especially in single vessel (46% vs 92%, p <0.001) but also in multivessel CAD (73% vs 95%, p = 0.01). Irrespective of DE and angiographic results, cavity obliteration was a negative predictor for cardiac events (RR 0.42, 95% confidence interval [CI] 0.21 to 0.87, p = 0.02) and death (RR 0.14, 95% CI 0.02 to 1.09, p = 0.06). Even after exclusion of patients with LV dysfunction, cavity obliteration was an independent predictor of freedom from events (RR 0.41, 95% CI 0.19 to 0.88, p = 0.02). Thus, LV cavity obliteration is a frequent response to DE, which compromises the sensitivity of DE but is correlated paradoxically with a favorable clinical outcome.

Cardiac outcomes in coronary patients with submaximum dobutamine stress echocardiography.

This study evaluated the prediction of cardiac events (cardiac death, myocardial infarction, unstable angina, or late myocardial revascularization) in patients with submaximum responses to dobutamine stress, defined by attainment of <85% age-predicted heart rate. Of 1,772 patients undergoing dobutamine echocardiography over a 2-year period, 425 had a submaximum heart rate response. After exclusion of patients treated with beta-adrenoceptor blocking agents, 255 patients formed the study group. In these patients, the test was terminated after administration of the maximum dose of 40 microg/kg/min of dobutamine with atropine (end of protocol, n = 186), severe angina, ischemic ST-segment changes, or intolerable side effects (n = 69). Dobutamine-induced changes (ischemia, viability, or both) were detected in 46 patients, involving ischemia in 133 segments, viability in 23, and ischemia and viability in 16 segments. Patients were followed for an interval of 28 +/- 17 months; 5 (1.2%) were lost to follow-up. Of the medically treated patients, cardiac events occurred in 73 of 228 (31%), including cardiac death in 25 (11%), nonfatal myocardial infarction in 11 (4.8%), severe unstable angina in 35 (15%), and late revascularization in 2 (0.9%). Cardiac events occurred in 11 of 30 (36%) with inducible abnormalities, and 62 of 198 without inducible abnormalities (31%, p = NS). Thus, cardiac event rates are high in patients with inadequate chronotropic responses to dobutamine stress, irrespective of whether stress-induced changes are detected. A negative dobutamine echocardiogram at submaximum heart rate should be considered nondiagnostic.

Influence of gender on physiologic response and accuracy of dobutamine echocardiography.

Dobutamine echocardiography (DE) has been shown to be safe, feasible, and accurate for identification of coronary artery disease (CAD) in mixed populations. The purpose of this study was to examine gender differences in physiologic response and accuracy of DE. We studied 2,886 consecutive DEs, performed in 2,748 patients, 1,209 of whom (44%) were women. A standard incremental protocol (5 to 40 microg/kg/min in 3-minute stages) was followed by atropine and/or an additional stage with 50 microg/kg/min, if the heart rate response was inadequate. Hemodynamic and echocardiographic findings were recorded at each stage. Three hundred sixty-nine patients without previous cardiac intervention (including 135 women) also underwent cardiac catheterization within 1 year of DE. Significant coronary stenoses (defined angiographically as >50% diameter) were present in 67% of women and 65% of men, of whom 55% and 65%, respectively, had multivessel disease. Women had a higher baseline heart rate (76 +/- 13 vs 73 +/- 14 beats/min, p <0.0001), and showed a more rapid increase in heart rate at low dose, with a higher age-predicted maximum heart rate at peak. This led to test termination at target heart rate but a submaximum dose in 22% of women versus 15% of men (p <0.0001) and less frequent administration of atropine (29% vs 34%, p <0.01). Dose-limiting side effects (8% vs 7%) and submaximum heart rate responses (14% vs 17%) were comparable in men and women. Even after the exclusion of negative DE at submaximal heart rate responses, the overall sensitivity was significantly lower in women than men (78% vs 88%, p <0.05), both for single (72% vs 78%, p <0.05) and for multivessel disease (82% vs 93%, p <0.05). The low specificity in both genders (55% vs 46%) probably reflected post-test referral bias. Thus, physiologic responses to dobutamine stress are comparable in men and women, except for a more rapid heart rate response in women, but the accuracy of DE for diagnosis of CAD in women is less than in men.

Evolution of dobutamine echocardiography protocols and indications: safety and side effects in 3,011 studies over 5 years.

OBJECTIVES: This study sought to document the safety of dobutamine stress echocardiography as it has evolved at a single center and to define predictors of adverse events. BACKGROUND: The indications and protocol for dobutamine stress testing have evolved over 5 years of clinical use, but the influence of these changes on the safety and side effects of the test is undefined. METHODS: Over 5 years, 3,011 consecutive dobutamine stress studies were performed in 2,871 patients, using an incremental protocol from 5 to 40 micrograms/kg body weight per min in 3-min stages, followed by atropine or an additional stage with 50 micrograms/kg per min, if required. Clinical data were gathered prospectively, and hemodynamic and echocardiographic findings were recorded at each stage, including recovery. Dobutamine echocardiography was defined as positive for ischemia in the presence of new or worsening wall motion abnormalities; in the absence of ischemia, failure to attain 85% of age-predicted maximal heart rate was identified as a nondiagnostic result. RESULTS: Studies were performed for risk assessment (70%) and symptom evaluation (30%); over the study period, there was an increment in the use of dobutamine echocardiography for preoperative evaluation. Most tests (n = 2,194 [73%]) were terminated due to attainment of peak dose with achievement of target heart rate (> 85% maximal age-predicted heart rate); 455 patients (15%) failed to achieve > 85% maximal predicted heart rate despite maximal doses of dobutamine and atropine. The protocol was stopped prematurely in 230 patients (7.6%) because of side effects, including ventricular (n = 27 [0.9%]) and supraventricular rhythm disorders (n = 22 [0.7%]), severe hypertension (n = 24 [0.8%]) and hypotension or left ventricular outflow tract obstruction (n = 112 [3.8%]). Noncardiac symptoms, such as headache, nausea or anxiety, caused early test termination in 45 patients (1.6%). The remaining tests were stopped because of severe chest pain (n = 106 [3.5%]) or severe ischemia by echocardiography (n = 26 [0.9%]). Serious complications occurred in nine patients, including sustained ventricular tachycardia in five, myocardial infarction in one and other conditions in three requiring hospital admission (sustained supraventricular tachycardia, hypotension, suspected myocardial infarction), but neither ventricular fibrillation nor death occurred. Independent predictors of serious complications could not be defined. Over 5 years, higher dose protocols and more frequent use of atropine have raised the number of diagnostic protocols from 59% to 80%, without increasing the incidence of major side effects. CONCLUSIONS: Despite the use of more aggressive protocols and alterations of the indications for testing to include sicker patients, major side effects are a rare complication of dobutamine echocardiography.

Purification and characterization of a novel human 15 kd cholesterol crystallization inhibitor protein in bile.

Crystallization-inhibiting proteins can explain longer nucleation times associated with bile from gallstone-free subjects as compared with bile from patients with cholesterol gallstones. We partially characterized and examined the crystallization inhibitory potency of a newly purified 15 kd human biliary protein. Gallbladder bile was passed through an anti-apolipoprotein A-I (apo A-I) immunoaffinity column to extract lipid-associated proteins. The bound fraction was separated by 30 kd ultrafiltration. Sodium dodecyl sulfate-polyacrylamide gel electrophesis (SDS-PAGE) was performed under nonreducing and reducing conditions. Cholesterol crystallization activity was tested in a photometric cholesterol crystal growth assay. Isoelectric focusing was performed by using a standard gel. The purified 15 kd protein was subjected to N-terminal amino acid sequencing. Although the whole apo A-I-bound fraction contained a variety of proteins and lipids, its 30 kd filtrate yielded a nearly pure 15 kd protein with only minor contamination from apo A-1. Amino acid sequencing showed that the protein was unique. Enzymatic deglycosylation revealed no evidence for glycosylation. At a protein concentration of 10 micrograms/ml, crystallization time was delayed as compared with control and apo A-I, and final crystal mass was reduced to 75% of control. Its isoelectric point was 6.1 without isoforms. Under nonreducing conditions, the protein formed a 30 kd dimer and a 60 kd tetramer. We conclude that this protein is a novel potent biliary crystallization inhibitor protein.