Prognostic implications of intraventricular conduction defects in patients undergoing stress echocardiography for suspected coronary artery disease

PURPOSE: To investigate the prognostic implications of conduction defects in subjects without proven coronary artery disease who had been referred for stress echocardiography. METHODS: The study sample consisted of 1230 patients (574 men and 656 women; mean [+/- SD] age, 63 +/- 10 years) who underwent stress echocardiography with dipyridamole (n = 780) or dobutamine (n = 450) to evaluate suspected coronary artery disease. A summary wall motion score (on a 1 to 4 scale) was calculated. Patients were followed for a mean of 41 +/- 27 months; mortality was the only endpoint. RESULTS: Four hundred and twenty patients (34%) had intraventricular conduction defects on a resting electrocardiogram (173 with complete left bundle branch block, 98 with isolated right bundle branch block, 43 with right bundle branch block with left anterior hemiblock, and 106 with left anterior hemiblock). Ischemia at stress echo (new or worsening of preexisting wall motion abnormality) was found in 250 patients (20%). There were 56 deaths during follow-up; 138 patients underwent revascularization and were censored. Multivariate predictors of mortality were resting wall motion score index (hazard ratio [HR] = 6.0 per unit increase; 95% confidence interval [CI]: 2.3 to 16; P <0.0001), ischemia at stress echo (HR = 3.9; 95% CI: 2.2 to 6.7; P <0.0001), age >65 years (HR = 3.2; 95% CI: 1.7 to 5.9; P <0.0001), hypertension (HR = 1.8; 95% CI: 1.1 to 3.2; P = 0.03), and right bundle branch block with left anterior hemiblock (HR = 3.7; 95% CI: 1.8 to 7.5; P <0.0001). The other three forms of intraventricular conduction defects (left bundle branch block, isolated complete right bundle branch block, and left anterior hemiblock) were not associated with mortality in multivariate analyses, or among the 980 patients who did not have ischemia. CONCLUSION: Right bundle branch block with left anterior hemiblock is an independent predictor of mortality in patients with suspected coronary artery disease undergoing stress echocardiography, whereas isolated right bundle branch block is associated with outcomes similar to those observed in patients with no conduction defects.     

Prediction of mortality in patients with left ventricular hypertrophy by clinical,exercise stress,and echocardiographic data

OBJECTIVES: This study evaluated the clinical, exercise stress test, and echocardiographic predictors of mortality and cardiac events in patients with left ventricular hypertrophy (LVH). BACKGROUND: Left ventricular hypertrophy is associated with an increased risk of cardiovascular morbidity and mortality. METHODS: Symptom-limited treadmill exercise echocardiography was performed for evaluation of coronary artery disease in 483 patients (age, 66 +/- 11 years; 281 men) with LVH. End points during follow-up were all-cause mortality and hard cardiac events (cardiac death and nonfatal myocardial infarction [MI]). RESULTS: Forty-six patients died and 14 had nonfatal MI. The cumulative mortality rate was higher in patients with abnormal exercise echocardiography (3% vs. 0.4% at one year, 11.7% vs. 3.7% at three years, and 18.3% vs. 9.5% at five years, p < 0.001). In a sequential multivariate analysis model of clinical, exercise test, and rest and exercise echocardiographic data, incremental predictors of mortality were workload (hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3 to 0.9), rate pressure product (HR, 0.7; 95% CI, 0.5 to 0.9), left ventricular (LV) mass index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase ejection fraction (EF) with exercise (HR, 2.1; 95% CI, 1.1 to 3.8). Predictors of cardiac events were history of coronary artery bypass grafting (HR, 2.6; 95% CI, 1.2 to 5.4), lower exercise rate-pressure product (HR, 0.6; 95% CI, 0.5 to 0.8), resting wall motion score index (HR, 1.4; 95% CI, 1.1 to 1.8), and failure to increase EF with exercise (HR, 3.3; 95% CI, 1.6 to 6.9). CONCLUSIONS: In patients with LVH, LV mass index and EF response to exercise are independent predictors of mortality, incremental to clinical and exercise test data and resting LV function. A normal exercise echocardiogram predicts a relatively low mortality rate during the following three years.     

Long-term prediction of mortality in elderly persons by dobutamine stress echocardiography

BACKGROUND: Dobutamine stress echocardiography (DSE) was shown to provide incremental prognostic information. However, its role in the prediction of mortality in elderly persons is not well defined. We assessed the value of DSE in the prediction of mortality and hard cardiac events during long-term follow-up in patients older than 65 years. METHODS: We studied 1434 patients >65 years old (mean age 72 +/- 3 years) who underwent DSE for evaluation of coronary artery disease. Ischemia was defined as new or worsening wall motion abnormalities. Follow-up events were total mortality and hard cardiac events (cardiac mortality and nonfatal myocardial infarction). Multivariable Cox regression analysis was used to identify the independent predictors of follow-up events. RESULTS: Ischemia was detected in 675 patients (47%). Five hundred six patients (35%) had a normal study, and 253 (18%) had fixed wall motion abnormalities. During a mean follow-up of 6.5 years, 532 (37%) deaths occurred, of which 249 (17%) were due to cardiac causes. A nonfatal myocardial infarction occurred in 45 patients (3%). Independent predictors of all-cause mortality in a multivariate analysis model were age (hazard ratio [HR] 1.06; 95% confidence interval [CI], 1.05-1.08), male sex (HR 1.5; 95% CI, 1.2-1.8), hypertension (HR 1.2; 95% CI, 1.1-1.4), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.4; 95% CI, 1.1-1.8), rest wall motion abnormalities (HR 1.07; 95% CI, 1.06-1.09), and ischemia (HR 1.3; 95% CI, 1.1-1.6). Independent predictors of hard cardiac events were age (HR 1.07; 95% CI, 1.05-1.09), male sex (HR 1.3; 95% CI, 1.1-1.7), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.6; 95% CI, 1.2-2.2), rest wall motion abnormalities (HR 1.13; 95% CI, 1.12-1.16), and ischemia (HR 2.1; 95% CI, 1.5-2.8). CONCLUSION: DSE provides independent prognostic information to predict all-cause mortality and hard cardiac events in elderly patients.     

Prediction of mortality in patients with right bundle branch block referred for pharmacologic stress echocardiography

Right bundle branch block (RBBB) is independently associated with all-cause mortality in patients referred for noninvasive evaluation of coronary artery disease. However, further stratification of risk in these patients has not been specifically addressed. The aim of this study was to risk stratify patients with RBBB who were referred for stress echocardiography. The study population was comprised of 343 patients (267 men; age 66 ± 9 years) with RBBB who underwent pharmacologic stress echocardiography (231 dipyridamole, 112 dobutamine) for evaluation of suspected or known coronary artery disease. Overall mortality was the only end point. Stress echocardiography was positive for ischemia in 109 patients (32%). During follow-up (38 ± 32 months), 36 deaths occurred. Seventy-three patients underwent revascularization and were censored. Ischemia at stress echocardiography (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.5 to 5.5, P = 0.002), left anterior fascicular block (LAFB) (HR 2.8, 95% CI 1.4 to 5.6, P = 0.002), age>65 years (HR 2.1, 95% CI 1.0 to 4.3, P = 0.047), and wall motion score index at rest (HR 2.5, 95% CI 1.0 to 6.5, P = 0.057) were multivariate predictors of mortality. On the basis of stress echocardiographic result and presence and/or absence of LAFB, 3 levels of risk were identified: (1) low-risk, in cases of no ischemia and no LAFB (49% of the entire study population); (2) intermediate-risk, in cases of ischemia or LAFB only; and (3) high-risk, in cases of ischemia and LAFB. Clinical data, electrocardiography at rest, and stress echocardiographic results can provide effective stratification of risk in patients with RBBB.     

Safety, feasibility, and prognostic implications of pharmacologic stress echocardiography in 1482 patients evaluated in an ambulatory setting

BACKGROUND: The outpatient prognostic assessment of coronary artery disease (CAD) by exercise electrocardiography has limitations, including the feasibility of the test and its low positive predictive value in several clinical conditions. In the current study we investigated the safety, feasibility, and prognostic value of pharmacologic stress echocardiography in a large cohort of ambulatory patients. METHODS: The study group was made of 1482 ambulatory patients (969 men, aged 60 +/- 10 years) who underwent stress echocardiography with either dipyridamole (n = 846) or dobutamine (n = 636) for evaluation of suspected or known stable CAD.The pretest likelihood of CAD was intermediate (<70%) in 709 patients and high (> or =70%) in 773 patients. RESULTS: There was no complication during the dipyridamole test, whereas 2 ischemia-dependent, sustained ventricular tachycardias occurred during the dobutamine test. Limiting side effects were observed in 2% of dipyridamole and in 3% of dobutamine stresses. The echocardiogram was positive in 459 patients. During a mean follow-up of 28 +/- 24 months, 58 patients died, 33 had a nonfatal myocardial infarction, and 158 underwent early (< or =3 months) and 64 late (>3 months) revascularization. Multivariate predictors of hard events (death, infarction) were positive echocardiographic results (hazard ratio [HR] 2.9) and resting wall motion score index (WMSI) (HR 2.3). In considering major events (death, infarction, late revascularization) as end points, positive echocardiographic result (HR 4.3), scar (HR 2.2), and resting WMSI (HR 1.7) were independent prognostic predictors. The 5-year survival rates for the ischemic and nonischemic groups were, respectively, 80% and 91% (HR 3.6, 95% confidence interval [CI] 3.8-8.4; P <.0001) considering hard cardiac events and 65% and 88% (HR 2.6, 95% CI 2.1-5.9; P <.0001) considering major events. Multivariate predictors of major events were positive echocardiographic results (HR 8.2) and male sex (HR 2.5) for the intermediate-risk group and positive echocardiographic results (HR 2.9), resting WMSI (HR 1.8), and prior Q-wave myocardial infarction (HR 1.8) for the high-risk group. CONCLUSIONS: Pharmacologic stress echocardiography is safe, highly feasible, and effective in prognostic assessment of ambulatory patients when both a general population and groups selected on the basis of pretest likelihood of CAD are analyzed. It represents a valid complementary tool to exercise electrocardiography for prognostic purposes in outpatients.     

Prognostic power of dobutamine echocardiography after uncomplicated acute myocardial infarction in the elderly

STUDY OBJECTIVES: To assess the prognostic value of dobutamine-atropine stress echocardiography (DSE) after uncomplicated acute myocardial infarction (AMI) in elderly patients. DESIGN: We analyzed 59 consecutive patients (42 men) aged > or = 70 years (mean +/- SD age, 75 +/- 4 years) who underwent DSE within 10 days after uncomplicated AMI. DSE was carried out following the standard protocol. Five myocardial responses were considered: (1) negative, (2) sustained improvement of contractility, (3) biphasic response (initial improvement followed by worsening), (4) worsening of contractility in the infarcted area, and (5) worsening at a distance. RESULTS: Mean follow-up duration was 13 +/- 8 months. Twenty-one patients had an event: cardiac death (n = 5), myocardial infarction (n = 1), heart failure (n = 1), unstable angina (n = 10), and revascularization (n = 4). Clinical and stress echocardiographic variables previously related to adverse prognosis were entered in Cox regression analysis, and the predictors of impaired outcome were inducible ischemia during DSE (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.77 to 4.99; p < 0.001) and resting wall motion score index (WMSI) > 1.6 (HR, 1.68; 95% CI, 1.02 to 2.77; p = 0.04). After excluding revascularization procedures and considering only spontaneous events, the following predictors were found: ischemia during DSE (HR, 2.95; 95% CI, 2.78 to 3.12; p < 0.001) and resting WMSI > 1.6 (HR, 2.53; 95% CI, 1.30 to 4.93; p = 0.006). CONCLUSIONS: Inducible ischemia during DSE within 10 days after uncomplicated AMI predicts an impaired outcome in the elderly.     

Exercise echocardiography for the prognostic stratification of patients with low pretest probability of coronary artery disease.

PURPOSE: The aim of this study was to determine whether exercise echocardiography provides incremental data for risk stratification of patients with a low pretest probability of coronary artery disease. PATIENTS AND METHODS: The study included patients referred for exercise echocardiography whose probability of coronary artery disease was 25% or less. We calculated an exercise wall motion score index (on a 1-5 scale), an indicator of the extent and severity of exercise-induced abnormalities. The primary outcomes of the study were subsequent cardiac events (cardiac death and nonfatal myocardial infarction). RESULTS: We studied 571 men and 1047 women; their mean (+/- SD) age was 55 +/- 13 years. During a median follow-up of 3 years, there were 19 cardiac events (6 cardiac deaths and 13 nonfatal myocardial infarctions); an additional 37 patients underwent coronary revascularization. In a multivariate analysis of clinical, exercise electrocardiographic, and echocardiographic parameters, exercise wall motion score index (hazard ratio [HR] = 2.1 per 0.5 units; 95% confidence interval [CI]: 1.3 to 3.4), and age (HR = 2.0 per decade; 95% CI: 1.2-2.8) were independently associated with the risk of cardiac events. Although exercise echocardiographic variables contributed significantly (P = 0.01) to a model of the risk of adverse events, only 9 (47%) of the 19 patients with cardiac events were identified by an abnormal exercise echocardiogram. CONCLUSION: Among patients with low pretest probability of coronary artery disease by clinical criteria, exercise echocardiography identifies some, but not all, patients at risk of future events. Because of the low event rate, routine application of exercise echocardiography in a patient with a low pretest probability does not appear to be cost-effective and therefore cannot be recommended.     

Exercise-electrocardiography and/or pharmacological stress echocardiography for non-invasive risk stratification early after uncomplicated myocardial infarction. A prospective international large scale multicentre study.

AIMS: The aim of the present study was to assess the relative prognostic value of clinical variables, the exercise electrocardiography test and the pharmacological stress echocardiography test either with dipyridamole or dobutamine early after a first uncomplicated acute myocardial infarction in a large, multicentre, prospective study. METHODS AND RESULTS: Seven hundred and fifty-nine in-hospital patients (age=56+/-10 years) with a recent and first clinical uncomplicated myocardial infarction, with baseline echocardiographic findings of satisfactory quality, an interpretable ECG and able to exercise underwent a resting 2D echocardiogram, a pharmacological stress test with either dipyridamole or dobutamine and an exercise electrocardiography test at a mean of 10 days from the infarction; they were followed-up for a median of 10 months. During the follow-up, there were 13 deaths, 23 non-fatal myocardial infarctions and 59 re-hospitalizations for unstable angina. When all spontaneous events were considered, with multivariate analysis, the difference between the wall motion score index at rest and peak stress (delta wall motion score index), and exercise duration were independent predictors of future spontaneous events (relative risk 7.2; 95% CI=2.73-19.1; P=0.000; relative risk 1.1, 95% CI=1.02-1.18; P=0.008, respectively). Kaplan-Meier survival estimates showed a better outcome for those patients with a negative pharmacological stress echocardiography test compared to patients with low dose positivity (94.7 vs 74.8%, P=0.000). CONCLUSION: Stress echocardiography tests provide stronger information than historical and exercise electrocardiography test variables. Pharmacological echocardiography as well as the exercise ECG is able to predict all spontaneously occurring events when the presence as well as the timing, severity, and extension of stress-induced wall motion abnormalities are considered.     

The stress echo prognostic gender gap.

AIMS: To investigate whether myocardial ischaemia elicitable during pharmacological stress echocardiography portends different prognosis in men and women.METHODS AND RESULTS: The study group was made by 1733 patients (941 men, 792 women) who underwent dipyridamole (n=1008) or dobutamine (n=725) stress echo for evaluation of known or suspected coronary artery disease. An ischaemic response was found in 460 patients (308 men, 152 women). Considering the whole ischaemic population, women were older (P<0.0001) and more likely to have hypertension (P=0.02) and hypercholesterolaemia (P=0.04) than men. No difference in age and risk factors was evidenced between the two sexes in the subset of 203 patients with ischaemia and suspected coronary artery disease. During follow-up (25 +/- 24 months for the ischaemic and 37 +/- 25 months for the non-ischaemic sample), there were 113 cardiac events (45 deaths and 68 infarctions) and 232 revascularizations. Revascularization rate in ischaemic population was similar in both sexes (P=0.36). Multivariate predictors of cardiac events in the whole ischaemic group were resting WMSI (HR=2.7, 95% CI 1.3--3.3;P=0.0050), female gender (HR=2.2, 95% CI 1.2--3.7;P=0.0062), age > or = l65 years (HR=1.9, 95% CI=1.0--3.6;P=0.0427), and Delta WMSI (HR=2.1, 95% CI=1.0--3.7;P=0.0447). Female gender (HR=2.7, 95% CI 1.1--6.3;P=0.0233) was the only independent prognostic predictor in patients with ischaemia and suspected coronary artery disease. Five-year infarction-free survival was 82% in men and 71% in women in the whole ischaemic population (P=0.0041) as well as in the ischaemic group with suspected coronary artery disease (CAD) (P=0.0175). In the non-ischaemic sample resting WMSI (HR=4.8), history of myocardial infarction (HR=2.5), and hypercholesterolaemia (HR=1.8) were independent predictors of outcome at multivariate analysis, whilst the gender had no prognostic importance.Conclusions: Our results show that female gender is an independent predictor of cardiac events in patients with myocardial ischaemia induced by pharmacological stress echocardiography.     

New bundle branch block after coronary artery bypass grafting--evaluation by CK-MB isoenzyme analysis and transoesophageal echocardiography

Twelve patients with a new complete bundle branch block after coronary artery bypass grafting underwent transoesophageal echocardiography (TEE). The results of TEE were compared with the pre-operative ventriculography, CK-MB isoenzyme time-release curves and clinical course. In eight patients with transient right bundle branch block or bifascicular block, low CK-MB activities and an uncomplicated postoperative course, transoesophageal echocardiography showed no new segmental wall motion abnormalities apart from a paradoxical septal movement in five. A persistent right or left bundle branch block was associated with either elevated isoenzyme activities, transoesophageal echocardiographic evidence of new segmental wall motion disturbance or both in four patients. One patient died because of fatal arrhythmia and one suffered from a prolonged low cardiac output syndrome. A transient bundle branch block is usually a benign electrocardiographic finding. In case of a persistent bundle branch block associated with elevated CK MB isoenzymes, new left ventricular wall motion disturbances indicating a peri-operative myocardial injury are easily detected by transoesophageal echocardiography.     

Clinical and prognostic implications of angina pectoris developing during dobutamine stress echocardiography in the absence of inducible wall motion abnormalities

This study assessed the incidence, clinical correlates, and prognostic significance of angina during dobutamine stress echocardiography (DSE) in patients who did not have inducible wall motion abnormalities. We studied 2,117 patients (61 +/- 13 years of age; 1,149 men) who underwent large-dose DSE and had no new or worsening wall motion abnormalities during DSE. Follow-up events were hard cardiac events (cardiac death or nonfatal myocardial infarction) and myocardial revascularization. Angina was induced in 217 patients (10%) during stress. DSE was normal in 1,198 patients (57%), whereas 919 patients (43%) had fixed wall motion abnormalities. During a mean follow-up of 5.5 +/- 3.7 years, 143 patients (7%) died of cardiac causes and 78 (4%) had nonfatal myocardial infarction. Patients who developed angina during DSE were more likely to have a history of exertional angina (64% vs 16%, p <0.001) and had a higher wall motion score index at rest (1.29 +/- 0.5 vs 1.17 +/- 0.4, p = 0.01) compared with patients who did not have angina. Annual hard cardiac event rates were 2.2% in patients who had dobutamine-induced angina (DIA) and 2.1% in patients who did not (p = NS). Myocardial revascularization was performed more frequently in patients who had DIA than in those who did not (39% vs 14%, p <0.0001). In Cox's regression model, independent predictors of hard events were age (RR 1.03, 95% confidence interval [CI] 1.02 to 1.04), male gender (RR 1.6, 95% CI 1.1 to 2.2), smoking (RR 1.5, 95% CI 1.1 to 2.9), and wall motion score index at rest (RR 2.6, 95% CI 1.8 to 3.8). In conclusion, in patients who do not have ischemia by echocardiographic criteria during DSE, inducible angina pectoris is associated with a high incidence of revascularization during follow-up. However, the hard cardiac event rate does not differ in patients who develop DIA from those who do not.     

Prognostic value of treadmill exercise echocardiography

INTRODUCTION AND OBJECTIVES: Exercise echocardiography (EE) is useful for diagnosing coronary disease, but little is known about its value for risk stratification. We aimed to determine: a) whether data from EE supplemented clinical data and data from exercise testing and resting echocardiography in predicting cardiac events; and b)whether the number and location of abnormal regions and their responses to exercise influenced risk stratification. PATIENTS AND METHOD: The 2,436 patients referred for EE were followed up for 2.1+/-1.5 years. Some 120 serious cardiovascular events (i.e., non-fatal myocardial infarction or cardiovascular death) occurred before revascularization. RESULTS: In 1203 patients (49%), EE gave abnormal results. There were 89 events in patients with an abnormal result (7.3%) and 31 in those with a normal result (2.5%; P<.0001). Multivariate analysis of clinical data, and data from exercise testing, resting echocardiography, and EE showed that male sex (RR=1.7; 95% CI, 1.1-2.8; P=.02), metabolic equivalents or METs (RR=0.9; 95% CI, 0.86-0.98; P=.01), peak heart rate x blood pressure (RR= 0.9;95% CI, 0.9; P=.002), resting wall motion score index (RR=2.5; 95% CI, 1.5-4.1; P<.0001), and number of abnormal regions at peak exercise (RR=1.4; 95% CI, 1.2-1.7; P<.0001) were independently associated with the risk of a serious event (final model chi2, 170; incremental P<.0001). The same variables, excluding sex, were independently associated with cardiovascular death (final model chi2, 169; incremental P=.01). CONCLUSIONS: Exercise echocardiography supplements clinical data and data from exercise testing and resting echocardiography in patients with known or suspected coronary artery disease.     

Complete bundle branch block as an independent predictor of all-cause mortality: report of 7,073 patients referred for nuclear exercise testing

PURPOSE: Complete left bundle branch block is a well-established independent risk factor for mortality, but the prognostic importance of right bundle branch block is unclear. We determined whether left and right bundle branch block was associated with all-cause mortality risk after adjustment for potential confounders, including clinical, exercise, and nuclear scintigraphic variables. SUBJECTS AND METHODS: We studied 7,073 adults who were referred for symptom-limited nuclear exercise testing. Patients with heart failure or pacemakers were excluded. The presence or absence of bundle branch block was determined from resting electrocardiograms. The main outcome measure was all-cause mortality during a mean of 6.7 years of follow-up. RESULTS: One hundred ninety patients (3%) had complete right bundle branch block, and 150 (2%) had complete left bundle branch block. There were 825 deaths (12%). Mortality was greater in patients with complete right bundle branch block (24% [46 of 190]) or left bundle branch block (24% [36 of 150]) than in those without these findings (11% [779 of 6,883 and 789 of 6,923, respectively]; both P <0.0001). After adjustment for potential confounders, right bundle branch block was as strong an independent predictor of mortality (hazard ratio [HR] 1.5; 95% confidence interval [CI]: 1.1 to 2.1; P = 0.007) as left bundle branch block (HR 1.5; 95% CI: 1.0 to 2.0; P = 0.017). Incomplete right bundle branch block was not associated with mortality. CONCLUSION: Complete right and left bundle branch block are independent predictors of all-cause mortality risk even after adjustment for exercise capacity, nuclear perfusion defects, and other risk factors.     

The additive prognostic value of wall motion abnormalities and coronary flow reserve during dipyridamole stress echo.

AIMS: The aim of the study was to evaluate the prognostic value of Doppler echocardiographic-derived coronary flow reserve (CFR) over regional wall motion in patients with known or suspected coronary artery disease (CAD) undergoing dipyridamole echocardiography test (DET). METHODS AND RESULTS: In a prospective, multicentre, observational study, we evaluated 1145 patients (702 males; 64 +/- 11 years) who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echo with CFR evaluation of LAD by Doppler. DET was positive for regional wall motion abnormalities in 291 (25%) and negative in 854 (74%) patients. Mean CFR was 2.2 +/- 0.5. At individual patient analysis 702 patients had normal (CFR > 2.0) and 443 had abnormal CFR on LAD. During a median follow-up of 27 months, 109 events occurred: 16 deaths, 17 non-fatal myocardial infarctions, 76 re-hospitalizations for unstable angina. The 30 months infarction-free survival showed the best outcome for those patients with negative DET by wall motion criteria and normal CFR and the worst outcome for patients with positive DET by wall motion and abnormal CFR (99 vs. 68%, P < 0.001). At multivariable analysis, CFR on LAD [hazard ratio (HR) 2.4, 95% CI 1.1-5.4, P = 0.030], medical therapy at time of testing (HR 2.8, 95% CI 1.2-6.6, P = 0.022), DET positivity for regional wall motion abnormalities (HR 3.6, 95% CI 1.5-8.7, P = 0.000), and angina on effort (HR 6.3, 95% CI 2.7-14.8, P = 0.000) were independent prognostic predictors of hard cardiac events. CONCLUSION: In patients with known or suspected CAD, DET result by wall motion criteria and CFR are additive and complementary for the identification of patients at risk of experiencing hard events.     

Comparison of heart rate reserve versus 85% of age-predicted maximum heart rate as a measure of chronotropic response in patients undergoing dobutamine stress echocardiography

The role of heart rate (HR) reserve (HRR) in the risk stratification of patients who undergo dobutamine stress echocardiography is not well defined. This study evaluated 1,323 patients (mean age 63 +/- 13 years, 47% men) who underwent dobutamine stress echocardiography. Abnormal stress echocardiographic results were defined as those with stress-induced ischemia. HRR was defined as [(peak HR - HR at rest)/(220 - age - HR at rest)] x 100, with HRR <70% defined as low. Follow-up data (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 16) and cardiac death (n = 58) were obtained. HRR risk stratified patients into normal and abnormal subgroups (event rate 1.1%/year vs 4.2%/year, p <0.0001) and further risk stratified patients into normal (adjusted HR 1 [reference] vs 2.88, p = 0.04) and abnormal (adjusted HR 4.17 vs 10.09, p <0.0001) stress echocardiography groups. Low HRR (relative risk [RR] 2.15, 95% confidence interval [CI] 1.23 to 4.01, p = 0.013) was an independent predictor of cardiac event even after controlling for standard cardiovascular risk factors, other stress electrocardiographic variables, and stress echocardiographic variables. Low HRR (chi-square 32) was superior to 85% maximum predicted HR (MPHR; chi-square 18) and provided incremental value over stress echocardiography and 85% MPHR (global chi-square increased from 48.3 to 54 to 61.3, p <0.0001) in a model consisting of stress echocardiography, MPHR, and HRR. In conclusion, HRR can further risk stratify patients who undergo dobutamine stress echocardiography and provides independent and incremental prognostic value over standard cardiovascular risk factors and also independent of echocardiographic myocardial ischemia and left ventricular dysfunction and is superior to 85% MPHR. In the setting of low HRR, normal stress echocardiographic results are prognostically less benign, whereas abnormal stress echocardiographic results are prognostically more malignant.     

Usefulness of stress echocardiography for risk stratification of patients after percutaneous coronary intervention

The prognostic value of stress echocardiography in patients with previous percutaneous coronary intervention (PCI) remains undefined. The aim of this study was to investigate the prognostic implication of stress echocardiography after PCI. The study group comprised 1,063 patients (794 men, 65 +/- 10 years of age) who underwent stress echocardiography with exercise (n = 105), dipyridamole (n = 780), or dobutamine (n = 178) after a median of 10 months from a successful PCI. Of these patients, 616 (58%) complained of chest pain and 447 (42%) were asymptomatic. Stress echocardiogram was positive for inducible ischemia in 328 patients (31%). During a median follow-up of 20 months, there were 167 events (61 deaths, 106 infarctions). Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.09, p <0.0001), wall motion score index at rest (HR 3.91, 95% CI 2.19 to 6.99, p <0.0001), and ischemia at stress echocardiography (HR 1.82, 95% CI 1.05 to 3.16, p = 0.03). Five-year mortalities were 20% in patients with and 9% in those without ischemia (p = 0.006). Independent predictors of hard events were ischemia at stress echocardiography (HR 3.82, 95% CI 2.75 to 5.29, p <0.0001), age (HR 1.02, 95% CI 1.01 to 1.04, p = 0.009), wall motion score index at rest (HR 1.98, 95% CI 1.30 to 3.02, p = 0.002), multivessel disease at time of PCI (HR 1.45, 95% CI 1.05 to 2.02, p = 0.02), and female gender (HR 1.44, 95% CI 1.03 to 2.01, p = 0.03). Five-year hard event rates were 53% in patients with and 16% in those without ischemia (p <0.0001). Stress echocardiographic positivity added prognostic information to clinical and at-rest echocardiographic parameters in symptomatic and asymptomatic patients. Moreover, it identified a subset of patients at higher risk of developing hard events independent of the subtending coronary anatomy (multivessel or single vessel disease). In conclusion, stress echocardiography is effective in risk-stratifying patients with previous PCI. In particular, inducible ischemia is a strong and independent predictor of mortality and hard events.     

The prevalence and prognosis of unrecognized myocardial infarction and silent myocardial ischemia in patients undergoing major vascular surgery

OBJECTIVE: The aim of this study is to determine the prevalence and prognosis of unrecognized myocardial infarction (MI) and silent myocardial ischemia in vascular surgery patients. METHODS: In a cohort of 1092 patients undergoing preoperative dobutamine stress echocardiography and noncardiac vascular surgery, unrecognized MI was determined by rest wall motion abnormalities in the absence of a history of MI. Silent myocardial ischemia was determined by stress-induced wall motion abnormalities in the absence of angina pectoris. Beta blockers and statins were noted at baseline. During follow-up (mean: 6+/-4 years), all-cause mortality and major cardiac events (cardiac death or nonfatal MI) were noted. RESULTS: The prevalence of unrecognized MI and silent myocardial ischemia was 23 and 28%, respectively. Both diabetes and heart failure were important predictors of unrecognized MI and silent myocardial ischemia. During follow-up, all-cause mortality occurred in 45% and major cardiac events in 23% of patients. In multivariate analysis, unrecognized MI and silent myocardial ischemia were significantly associated with increased risk of mortality [hazard ratio (HR), 1.86; 95% confidence interval (CI), 1.53-2.25 and HR, 1.74; 95% CI, 1.46-2.06, respectively] and major cardiac events (HR, 2.15; 95% CI, 1.59-2.92 and HR, 1.86; 95% CI, 1.43-2.41, respectively). In patients with unrecognized MI, beta-blockers and statins were significantly associated with improved survival. Statins improved survival in patients with silent myocardial ischemia. CONCLUSIONS: In patients undergoing major vascular surgery, unrecognized MI and silent myocardial ischemia are highly prevalent (23 and 28%) and associated with increased long-term mortality and major cardiac events.     

Early low-dose dobutamine echocardiography predicts late functional recovery after thrombolyzed acute myocardial infarction

BACKGROUND: This study was undertaken to evaluate the ability of predischarge low-dose dobutamine echocardiography to predict late left ventricular functional recovery after thrombolyzed acute myocardial infarction. METHODS AND RESULTS: Low-dose dobutamine echocardiography was performed in 54 patients 4 +/- 2 days after acute myocardial infarction treated with thrombolysis. Follow-up resting echocardiography was carried out in 49 of these patients at a mean of 18 +/- 6 months later. Viability was defined as recovery of myocardial function at follow-up, expressed as an improvement of wall motion of at least 1 grade or more in at least 2 contiguous infarct zone segments. In 24 of the 49 patients (group I), wall motion at follow-up improved in comparison with the early resting echocardiographic study (1.72 +/- 0.29 vs 1.37 +/- 0.34, P <.001). In the remaining 25 patients (group II), no wall motion enhancement was seen at follow-up (1.57 +/- 0.38 vs 1.58 +/- 0.36, NS). In 22 of the 24 patients in group I, early low-dose dobutamine echocardiography showed improvement in the wall motion score index compared with baseline resting measurements (1.72 +/- 0.29 vs 1.44 +/- 0.24, P <.001). The positive and negative predictive value of early low-dose dobutamine echocardiography to predict functional recovery was 76% and 92%, respectively. CONCLUSION: Predischarge low-dose dobutamine echocardiography is an accurate tool for detecting viable myocardium and predicting late left ventricular recovery after acute myocardial infarction treated with thrombolysis.     

Prognostic significance of impairment of heart rate response to exercise: impact of left ventricular function and myocardial ischemia

OBJECTIVES: The goal of this research was to study the association between heart rate (HR) response to exercise and the risk of death and myocardial infarction (MI) after adjustment for left ventricular (LV) function and myocardial ischemia. BACKGROUND: Chronotropic incompetence during exercise testing is associated with increased mortality. It is unknown whether LV dysfunction or ischemia accounts for this. METHODS: We studied 3,221 patients (age 59 +/- 12 years; 1,701 men) who underwent treadmill exercise echocardiography. We considered two markers of chronotropic incompetence: 1) failure to achieve 85% of the maximal predicted HR, and 2) low (<0.8) chronotropic index. The independent association between HR response and end points was evaluated by an adjusted risk (AR) model, which included clinical parameters, ejection fraction, and the severity of ischemic wall motion abnormalities. RESULTS: Target HR was not achieved in 495 (15%) patients. Low chronotropic index was observed in 793 (25%) patients. There were 129 deaths (41 cardiac) during a median follow-up of 3.2 years. Myocardial infarction occurred in 65 patients. Low chronotropic index was associated with cardiac death (AR, 1.54; 95% confidence interval [CI], 1.18 to 2.04; p = 0.002) and MI (AR, 1.37; 95% CI, 1.09 to 1.69; p = 0.007). Failure to achieve 85% of maximal predicted HR was associated with increased mortality (AR, 1.49; 95% CI, 1.02 to 2.22; p = 0.04) and cardiac death (AR, 2.13; 95% CI, 1.10 to 4.17; p = 0.03). CONCLUSIONS: Impaired chronotropic response to exercise is associated with increased mortality and cardiac events even after adjusting for LV function and the severity of exercise-induced myocardial ischemia.     

Left atrial enlargement and NT-proBNP as predictors of sudden cardiac death in patients with heart failure

AIMS: The identification of valuable markers of sudden cardiac death (SCD) in patients with established HF remains a challenge. We sought to assess the value of clinical, echocardiographic and biochemical variables to predict SCD in a consecutive cohort of patients with heart failure (HF) due to systolic dysfunction. METHODS: A cohort of 494 patients with established HF had baseline echocardiographic and NT-proBNP measurements and were followed for 942+/-323 days. RESULTS: Fifty patients suffered SCD. Independent predictors of SCD were indexed LA size>26 mm/m2 (HR 2.8; 95% CI 1.5-5.0; p=0.0007), NT-proBNP>908 ng/L (HR 3.1; 95% CI 1.5-6.7; p=0.003), history of myocardial infarction (HR 2.3; 95% CI 1.3-4.1; p=0.007), peripheral oedema (HR 2.1; 95% CI 1.1-3.9; p=0.02), and diabetes mellitus (HR 1.9; 95% CI 1.1-3.3; p=0.03). NYHA functional class, left ventricular ejection fraction and glomerular filtration rate were not independent predictors of SCD in this cohort. Notably, the combination of both LA size>26 mm/m2 and NT-proBNP>908 ng/L increased the risk of SCD (HR 4.3; 95% CI 2.5-7.6; p<0.0001). At 36 months, risk of SCD in patients with indexed LA size26 mm/m2 and NT-proBNP>908 ng/L reached 25% (p<0.0001). CONCLUSIONS: Among HF patients, indexed LA size and NT-proBNP levels are more useful to stratify risk of SCD than other clinical, echocardiographic or biochemical variables. The combination of these two parameters should be considered for predicting SCD in patients with HF.