Colin Case

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.

Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease

Objectives: To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). Patients: 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Main outcome measures: Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. Results: According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p  =  0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p  =  0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. Conclusions: In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.

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.

Incremental Value of Strain Rate Analysis as an Adjunct to Wall-Motion Scoring for Assessment of Myocardial Viability by Dobutamine Echocardiography A Follow-Up Study After Revascularization

Background— Assessment of myocardial viability based on wall-motion scoring (WMS) during dobutamine echocardiography (DbE) is difficult and subjective. Strain-rate imaging (SRI) is quantitative, but its incremental value over WMS for prediction of functional recovery after revascularization is unclear. Methods and Results— DbE and SRI were performed in 55 stable patients (mean age, 64±10 years; mean ejection fraction, 36±8%) with previous myocardial infarction. Viability was predicted by WMS if function augmented during low-dose DbE. SR, end-systolic strain (ESS), postsystolic strain (PSS), and timing parameters were analyzed at rest and with low-dose DbE in abnormal segments. Regional and global functional recovery was defined by side-by-side comparison of echocardiographic images before and 9 months after revascularization. Of 369 segments with abnormal resting function, 146 showed regional recovery. Compared with segments showing functional recovery, those that failed to recover had lower low-dose DbE SR, SR increment (ΔSR), ESS, and ESS increment (ΔESS) (each P<0.005). After optimal cutoffs for the strain parameters were defined, the sensitivity of low-dose DbE SR (78%, P=0.3), ΔSR (80%, P=0.1), ESS (75%, P=0.6), and ΔESS (74%, P=0.8) was better though not significantly different from WMS (73%). The specificity of WMS (77%) was similar to the SRI parameters. Combination of WMS and SRI parameters augmented the sensitivity for prediction of functional recovery above WMS alone (82% versus 73%, P=0.015; area under the curve=0.88 versus 0.73, P<0.001), although specificities were comparable (80% versus 77%, P=0.2). Conclusions— The measurement of low-dose DbE SR and ΔSR is feasible, and their combination with WMS assessment improves the sensitivity of viability assessment with DbE.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation

Objective: To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR). Design: Cohort study. Setting: Regional cardiac centre. Patients and outcome measures: LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events (cardiac death, heart failure, and new atrial fibrillation) were documented. Results: CR was present in 45 patients (CR+) and absent in 26 patients (CR−). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR− patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p  =  0.006) and postoperative LV dysfunction (EF < 50%) persisted in five patients, all in the CR− group. Event-free survival was lower in surgically treated patients without CR (p  =  0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated. Conclusions: Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.

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.

High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest

This trial compared blinded 10 mg aliquots of adrenaline with placebo in 194 cardiac arrest patients treated in hospital using American Heart Association guidelines. In-hospital and out-of-hospital arrests were included. Of the 339 eligible patients a large proportion (145 (45%)) were not randomised and received open 1 mg aliquots of adrenaline. This group is also analysed. Supervising physicians gave significant preference for males, patients with no previous cardiac history and without multiple organ disease to be given open 1 mg adrenaline. Patients in asystole at the time of consideration for entry were preferentially placed in the trial group (114 (69%) vs. 170 (88%)) and patients in ventricular fibrillation were preferentially given open 1 mg adrenaline (31 (21%) vs. 24 (12%) P < 0.03). The most beneficial rhythm changes which led to survival were sinus rhythm and ventricular tachycardia. Analysis of rhythm changes resulting from the dosing showed a significant (P = 0.01) change to a beneficial rhythm with 10 mg adrenaline but not for 1 mg adrenaline or placebo. This was not reflected by an improvement in immediate survival. No significant differences in immediate survival (IS) or hospital discharge (HD) exists between open 1 mg adrenaline (IS 14 (9.7%), HD 3 (2%)) or the 10 mg adrenaline (IS 9 (9.6%), HD 0) vs. placebo (IS 7 (7%), HD 0) trial arms. Patients reaching the point of use of adrenaline have a uniformly poor immediate survival (8.8%) and hospital discharge rate (0.9%). Dosing with 10 mg or 1 mg adrenaline does not influence outcome compared with placebo.

Does renal failure cause an atherosclerotic milieu in patients with end-stage renal disease?☆

PURPOSE Atherosclerotic vascular disease is the main cause of morbidity and mortality in patients with end-stage renal disease, but the independent contribution of renal failure rather than associated risk factors is unclear. We sought to examine the relative contribution of these factors to the severity of atherosclerosis by measuring intima-medial thickness and brachial artery reactivity in uremic patients and controls. SUBJECTS AND METHODS Cardiovascular risk factors, including lipid and homocysteine levels, were evaluated in 213 patients (69 on hemodialysis, 60 on peritoneal dialysis, and 82 nonuremic controls). High-resolution B-mode ultrasonography with automated off-line analysis was used to measure the intima-medial thickness in the common carotid artery and to measure the lumen diameter of the brachial artery at rest, during reactive hyperemia, and after sublingual nitroglycerine. The correlations of risk factors with intima-medial thickness and brachial reactivity were examined using a general linear regression model. RESULTS Patients with renal failure had a greater mean (+/- SEM) maximum intima-medial thickness than controls (0.83 +/- 0.02 mm versus 0.70 +/- 0.02 mm, P < 0.05), but the brachial artery response to reactive hyperemia was not significantly different between the renal failure patients and the control group (4.7% +/- 6.1% versus 6.1% +/- 8.6% dilatation, P > 0.05). The uremic state was an independent predictor of intima-medial thickness (r2 = 0.16, P < 0.001) but not of brachial artery reactivity (P = 0.99). CONCLUSION The atherosclerotic burden in patients with renal failure, as indicated by an increased intima-medial thickness, may reflect effects of uremia that are independent of cardiovascular risk factors.

Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice

BACKGROUND Patients with known or suspected coronary disease are often investigated to facilitate risk assessment. We sought to examine the cost-effectiveness of strategies based on exercise echocardiography and exercise electrocardiography. METHODS AND RESULTS We studied 7656 patients undergoing exercise testing; of whom half underwent exercise echocardiography. Risk was defined with the Duke treadmill score for those undergoing exercise electrocardiography alone, and by the extent of ischaemia by exercise echocardiography. Cox proportional hazards models, risk adjusted for pretest likelihood of coronary artery disease, were used to estimate time to cardiac death or myocardial infarction. Costs (including diagnostic and revascularisation procedures, hospitalisations, and events) were calculated, inflation-corrected to year 2000 using Medicare trust fund rates and discounted at a rate of 5%. A decision model was employed to assess the marginal cost effectiveness (cost/life year saved) of exercise echo compared with exercise electrocardiography. Exercise echocardiography identified more patients as low-risk (51% vs 24%, p<0.001), and fewer as intermediate- (27% vs 51%, p<0.001) and high-risk (22% vs 4%); survival was greater in low- and intermediate-risk and less in high-risk patients. Although initial procedural costs and revascularisation costs (in intermediate-high risk patients) were greater, exercise echocardiography was associated with a greater incremental life expectancy (0.2 years) and a lower use of additional diagnostic procedures when compared with exercise electrocardiography (especially in lower risk patients). Using decision analysis, exercise echocardiography ( in 2615/life year saved) was more cost effective than exercise electrocardiography. CONCLUSION Exercise echocardiography may enhance cost-effectiveness for the detection and management of at risk patients with known or suspected coronary disease.