Leanne Short

Echocardiographic detection of early diabetic myocardial disease

OBJECTIVES We sought to determine whether disturbances of myocardial contractility and reflectivity could be detected in diabetic patients without overt heart disease and whether these changes were independent and incremental to left ventricular hypertrophy (LVH). BACKGROUND Left ventricular (LV) dysfunction is associated with diabetes mellitus, but LVH is common in this population and the relationship between diabetic LV dysfunction and LVH is unclear. METHODS We studied 186 patients with normal ejection fraction and no evidence of CAD: 48 with diabetes mellitus only (DM group), 45 with LVH only (LVH group), 45 with both diabetes and LVH (DH group), and 48 normal controls. Peak strain and strain rate of six walls in apical four-chamber, long-axis, and two-chamber views were evaluated and averaged for each patient. Calibrated integrated backscatter (IB) was assessed by comparison of the septal or posterior wall with pericardial IB intensity. RESULTS All patient groups (DM, DH, LVH) showed reduced systolic function compared with controls, evidenced by lower peak strain (p < 0.001) and strain rate (p = 0.005). Calibrated IB, signifying myocardial reflectivity, was greater in each patient group than in controls (p < 0.05). Peak strain and strain rate were significantly lower in the DH group than in those in the DM alone (p < 0.03) or LVH alone (p = 0.01) groups. CONCLUSIONS Diabetic patients without overt heart disease demonstrate evidence of systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH.

Prediction of Mortality by Exercise Echocardiography A Strategy for Combination With the Duke Treadmill Score

Background—In studies generally involving short follow-up, exercise echocardiography has been shown to predict composite end points. We sought to study the prediction of mortality with this test and to devise a strategy for combination with standard exercise testing. Methods and Results—Clinical, exercise testing, and echocardiographic data were collected in 5375 patients (aged 54±14 years, 3880 men) undergoing exercise echocardiography. The Duke treadmill score was derived from the results of treadmill exercise testing. Resting left ventricular (LV) function and the presence and severity of ischemia were interpreted by expert observers. Follow-up at 10.6 years (mean 5.5±1.9 years) was complete in 5211 patients (97%). The Duke score classified 59% of patients as low risk, 39% as intermediate risk, and 2% as high risk. Resting LV dysfunction was present in 1445 patients (27%), and the exercise echocardiogram was abnormal in 2525 patients (47%). Death occurred in 649 patients (12%). Over the first 6 years of follow-up, those with normal exercise echocardiograms had a mortality of 1% per year. Ischemia was an independent predictor of mortality. In sequential Cox models, the predictive power of clinical data was strengthened by adding the Duke score, resting LV function, and the results of exercise echocardiography. Exercise echocardiography was able to substratify patients with intermediate-risk Duke scores into groups with a yearly mortality of 2% to 7%. Conclusions—A normal exercise echocardiogram confers a low risk of death, and positive results are an independent predictor of death; ischemia is incremental to other data. This test may be particularly useful in patients with intermediate-risk Duke treadmill scores.

Prediction of Mortality Using Dobutamine Echocardiography

OBJECTIVES We sought to find out whether dobutamine echocardiography (DbE) could provide independent prediction of total and cardiac mortality, incremental to clinical and angiographic variables. BACKGROUND Existing outcome studies with DbE have examined composite end points, rather than death, over a relatively short follow-up. Clinical and stress data were collected in 3,156 patients (age 63 +/- 12 years, 1,801 men) undergoing DbE. Significant stenoses (>50% diameter) were identified in 70% of 1,073 patients undergoing coronary angiography. Total and cardiac mortality were identified over nine years of follow-up (mean 3.8 +/- 1.9). Cox models were used to analyze the effect of ischemia and other variables, independent of other determinants of mortality. RESULTS The dobutamine echocardiogram was abnormal in 1,575 patients (50%). Death occurred in 716 patients (23%), 259 of whom (8%) were thought to have died from cardiac causes. Patients with normal DbE had a total mortality of 8% per year and a cardiac mortality of 1% per year over the first four years of follow-up. Ischemia and the extent of abnormal wall motion were independent predictors of cardiac death, together with age and heart failure. In sequential Cox models, the predictive power of clinical data alone (model chi-square 115) was strengthened by adding the resting left ventricular function (model chi-square 138) and the results of DbE (model chi-square 181). In the subgroup undergoing coronary angiography, the power of the model was increased to a minor degree by the addition of coronary anatomy data. CONCLUSIONS Dobutamine echocardiography is an independent predictor of death, incremental to other data. While a normal dobutamine echocardiogram predicts low risk of cardiac death (on the order of 1% per year), this risk increases with the extent of abnormal wall motion at rest and stress.

Application of tissue Doppler to interpretation of dobutamine echocardiography and comparison with quantitative coronary angiography.

The main limitation of dobutamine echocardiography (DE) is its subjective interpretation. We sought to reduce the need for expert interpretation by developing a quantitative approach to DE using myocardial Doppler velocity (MDV) in 242 patients undergoing DE. In 128 patients with a normal dobutamine echocardiogram, the normal range was designed to give a specificity of 80%. The accuracy of this range was investigated in 114 consecutive patients who underwent coronary angiography within 2 months of DE. A standard dobutamine echocardiographic protocol was used, with MDV gathered from color tissue Doppler at rest and peak stress. Wall motion at these stages was scored by experienced observers using a 16-segment model and MDV was measured off-line. Sensitivity and specificity of wall motion scoring and MDV were obtained by comparison with angiographic evidence of disease, defined as stenosis > 50% of the coronary artery diameter. The normal range in tethered segments (septum, anteroseptum, and inferior) was > or = 7 cm/s in the basal segments and > or = 5 cm/s in the midsegments. In the free wall (anterior, lateral, and posterior), the cutoff was > or = 6 cm/s in the base and > or = 4 cm/s in the midventricle. Of 114 patients undergoing angiography, 84 (75%) had significant stenoses, and the sensitivity of wall motion scoring and MDV were 88% and 83%, respectively, with specificities of 81% and 72% (p = NS). The accuracy was similar overall (86% vs 80%), as well as in each vascular territory. These data suggest that a fully quantitative interpretation of DE using site-specific normal ranges of tissue Doppler, which account for regional variations of base-apex function, is feasible and equivalent in accuracy to expert wall motion scoring.

Relationship of ventricular longitudinal function to contractile reserve in patients with mitral regurgitation

BACKGROUND Latent left ventricular (LV) dysfunction in patients with valvular or myocardial disease may be identified by loss of contractile reserve (CR) at exercise echocardiography. Contraction in the LV longitudinal axis may be more sensitive than radial contraction to minor disturbances of LV function. We sought to determine whether tissue Doppler measurement of longitudinal function could be used to identify CR. METHODS Exercise echocardiography was performed in 86 patients (20 women, age 53 +/- 18 years), 72 with asymptomatic or minimally symptomatic mitral regurgitation, and 14 normal controls. Pulsed-wave tissue Doppler imaging (DTI) was used to measure maximum annular systolic velocity at rest and stress. Inducible ischemia was excluded by analysis of wall motion by an experienced observer. CR was defined by >or=5% improvement of stress compared with rest ejection fraction (EF). Exercise capacity was assessed from expired gas analysis. RESULTS CR was present in 34 patients with mitral regurgitation (47%); peak EF in patients with and without CR was 74% +/- 11% versus 54% +/- 15% (P <.0001). CR could not be predicted by resting EF, volumes or sphericity, and DTI measurement of base-apex function was the only resting echocardiographic parameter to distinguish between patients with and without CR (10 +/- 2 vs 8 +/- 2 cm/s, P <.03). This parameter showed greater differences after stress (14 +/- 4 vs 11 +/- 3 cm/s, P <.001). Patients with CR showed lower peak DTI than controls, as well as lower exercise capacity and EF response to exercise. In a multiple linear regression model, rest DTI (P =.03) was an independent correlate of contractile reserve. The other correlates were age (P <.0001), resting (P <.0001) and peak end-systolic volume (P =.01), and resting (P <.0001) and peak end-diastolic volume (P <.0001); the model r(2) was 0.93 (P <.001). CONCLUSION In the absence of regional LV dysfunction, measurement of longitudinal axis function by DTI may be a marker of CR.

Assessment of regional long-axis function during dobutamine echocardiography

Echocardiographic analysis of regional left ventricular function is based upon the assessment of radial motion. Long-axis motion is an important contributor to overall function, but has been difficult to evaluate clinically until the recent development of tissue Doppler techniques. We sought to compare the standard visual assessment of radial motion with quantitative tissue Doppler measurement of peak systolic velocity, timing and strain rate (SRI) in 104 patients with known or suspected coronary artery disease undergoing dobutamine stress echocardiography (DbE). A standard DbE protocol was used with colour tissue Doppler images acquired in digital ciné-loop format. Peak systolic velocity (PSV), time to peak velocity (TPV) and SRI were assessed off-line by an independent operator. Wall motion was assessed by an experienced reader. Mean PSV, TPV and SRI values were compared with wall motion and the presence of coronary artery disease by angiography. A further analysis included assessing the extent of jeopardized myocardium by comparing average values of PSV, TPV and SRI against the previously validated angiographic score. Segments identified as having normal and abnormal radial wall motion showed significant differences in mean PSV (7.9 +/- 3.8 and 5.9 +/- 3.3 cm/s respectively; P < 0.001), TPV (84 +/- 40 and 95 +/- 48 ms respectively; P = 0.005) and SRI (-1.45 +/- 0.5 and -1.1 +/- 0.9 s(-1) respectively; P < 0.001). The presence of a stenosed subtending coronary artery was also associated with significant differences from normally perfused segments for mean PSV (8.1+/-3.4 compared with 5.7+/-3.7 cm/s; P < 0.001), TPV (78 +/- 50 compared with 92 +/- 45 ms; P < 0.001) and SRI (-1.35 +/- 0.5 compared with -1.20 +/- 0.4 s(-1); P = 0.05). PSV, TPV and SRI also varied significantly according to the extent of jeopardized myocardium within a vascular territory. These results suggest that peak systolic velocity, timing of contraction and SRI reflect the underlying physiological characteristics of the regional myocardium during DbE, and may potentially allow objective analysis of wall motion.

Prediction of mortality in patients without angina: Use of an exercise score and exercise echocardiography

Background Exercise testing has limited efficacy for identifying coronary artery disease (CAD) in the absence of anginal symptoms. Exercise echocardiography is more accurate than standard exercise testing, but its efficacy in this situation has not been defined. We sought to identify whether the Duke treadmill score or exercise echocardiography (ExE) could be used to identify risk in patients without anginal symptoms . Methods We studied 1859 patients without typical or atypical angina, heart failure, or a history or ECG evidence of infarction or CAD, who were referred for ExE, of whom 1832 (age 51±15 years, 944 men) were followed for up to 10 years. The presence and extent of ischaemia and scar were interpreted by expert reviewers at the time of the original study. Results Exercise provoked significant (>0.1mV) ST segment depression in 215 patients (12%), and wall motion abnormalities in 137 (8%). Seventy-eight patients (4%) died before revascularization, only 17 from known cardiac causes. The independent predictors of death were age (RR 1.1, p<0.0001), smoking, Duke treadmill score (RR 0.9, p<0.0001) and resting LV dysfunction (RR 1.9, p<0.04), but did not include ischaemia at ExE. Echocardiography was not predictive of outcome in subgroups with an intermediate or high risk Duke score, nor in patients with two or more risk factors. Conclusions Patients without anginal symptoms have a low mortality, especially from cardiac causes. If such individuals undergo exercise testing and a resting echocardiogram, exercise echocardiography does not offer additional prognostic information.

Usefulness of quantitative echocardiographic techniques to predict recovery of regional and global left ventricular function after acute myocardial infarction

The left ventricular response to dobutamine may be quantified using tissue Doppler measurement of myocardial velocity or displacement or 3-dimensional echocardiography to measure ventricular volume and ejection fraction. This study sought to explore the accuracy of these methods for predicting segmental and global responses to therapy. Standard dobutamine and 3-dimensional echocardiography were performed in 92 consecutive patients with abnormal left ventricular function at rest. Recovery of function was defined by comparison with follow-up echocardiography at rest 5 months later. Segments that showed improved regional function at follow-up showed a higher increment in peak tissue Doppler velocity with dobutamine therapy than in nonviable segments (1.2 +/- 0.4 vs 0.3 +/- 0.2 cm/s, p = 0.001). Similarly, patients who showed a >5% improvement of ejection fraction at follow-up showed a greater displacement response to dobutamine (6.9 +/- 3.2 vs 2.1 +/- 2.3 mm, p = 0.001), as well as a higher rate of ejection fraction response to dobutamine (9 +/- 3% vs 2 +/- 2%, p = 0.001). The optimal cutoff values for predicting subsequent recovery of function at rest were an increment of peak velocity >1 cm/s, >5 mm of displacement, and a >5% improvement of ejection fraction with low-dose dobutamine.

Usefulness of clinical risk markers and ischemic threshold to stratify risk in patients undergoing major noncardiac surgery

The risk of cardiac events in patients undergoing major noncardiac surgery is dependent on their clinical characteristics and the results of stress testing. The purpose of this study was to develop a composite approach to defining levels of risk and to examine whether different approaches to prophylaxis influenced this prediction of outcome. One hundred forty-five consecutive patients (aged 68 +/- 9 years, 79 men) with >1 clinical risk variable were studied with standard dobutamine-atropine stress echo before major noncardiac surgery. Risk levels were stratified according to the presence of ischemia (new or worsening wall motion abnormality), ischemic threshold (heart rate at development of ischemia), and number of clinical risk variables. Patients were followed for perioperative events (during hospital admission) and death or infarction over the subsequent 16 +/- 10 months. Ten perioperative events occurred in 105 patients who proceeded to surgery (10%, 95% confidence interval [CI] 5% to 17%), 40 being cancelled because of cardiac or other risk. No ischemia was identified in 56 patients, 1 of whom (1.8%) had a perioperative infarction. Of the 49 patients with ischemia, 22 (45%) had 1 or 2 clinical risk factors; 2 (9%, 95% CI 1% to 29%) had events. Another 15 patients had a high ischemic threshold and 3 or 4 risk factors; 3 (20%, 95% CI 4% to 48%) had events. Twelve patients had a low ischemic threshold and 3 or 4 risk factors; 4 (33%, 95% CI 10% to 65%) had events. Preoperative myocardial revascularization was performed in only 3 patients, none of whom had events. Perioperative and long-term events occurred despite the use of beta blockers; 7 of 41 beta blocker-treated patients had a perioperative event (17%, 95% CI 7% to 32%); these treated patients were at higher anticipated risk than untreated patients (20 +/- 24% vs 10 +/- 19%, p = 0.02). The total event rate over late follow-up was 13%, and was predicted by dobutamine-atropine stress echo results and heart rate response.

A randomized trial of aggressive lipid reduction for improvement of myocardial ischemia, symptom status, and vascular function in patients with coronary artery disease not amenable to intervention

PURPOSE To determine the effects of aggressive lipid lowering on markers of ischemia, resistance vessel function, atherosclerotic burden, and symptom status in patients with symptomatic coronary artery disease. METHODS Sixty consecutive patients with coronary artery disease that was unsuitable for revascularization were assigned randomly to either usual therapy of lipids for patients with a low-density lipoprotein (LDL) cholesterol target level <116 mg/dL, or to a more aggressive lipid-lowering strategy involving up to 80 mg/d of atorvastatin, with a target LDL cholesterol level <77 mg/dL. The extent and severity of inducible ischemia (by dobutamine echocardiography), vascular function (brachial artery reactivity), atheroma burden (carotid intima-media thickness), and symptom status were evaluated blindly at baseline and after 12 weeks of treatment. RESULTS After 12 weeks of treatment, patients in the aggressive therapy group had a significantly greater decrease in mean (+/- SD) LDL cholesterol level than those in the usual care group (29 +/- 38 mg/dL vs. 7 +/- 24 mg/dL, P = 0.03). Patients in the aggressive therapy group had a reduction in the number of ischemic wall segments (mean between-group difference of 1.3; 95% confidence interval: 0.1 to 2.0; P = 0.04), flow-mediated dilatation (mean between-group difference of 5.9%; 95% confidence interval: 2.5% to 9.4%; P = 0.001), and angina score after 12 weeks. There were no significant changes in atherosclerotic burden in either group. CONCLUSION Patients with symptomatic coronary artery disease who are treated with aggressive lipid lowering have improvement of symptom status and ischemia that appears to reflect improved vascular function but not atheroma burden.