Siu-Sun Yao

Practical applications in stress echocardiography: Risk stratification and prognosis in patientswith known or suspected ischemic heart disease

OBJECTIVES The purpose of this study was to define appropriate parameters for risk stratification and prognosis in patients undergoing stress echocardiography. BACKGROUND Stress echocardiography is an established technique for the diagnosis of coronary artery disease. However, current data on risk stratification of patients undergoing stress echocardiography are limited. METHODS We evaluated 1,500 patients (59 +/- 13 years old; 51% male) undergoing stress echocardiography (34% with treadmill exercise and 66% with dobutamine). Resting left ventricular ejection fraction (EF) and regional wall motion were assessed by the consensus of two echocardiographers. Follow-up (mean 2.7 +/- 1.0 years) for confirmed non-fatal myocardial infarction (n = 31) and cardiac death (n = 44) were performed. RESULTS By univariate analysis, both the peak wall motion score index (WMSI) (p < 0.0001) and EF (p < 0.0001) were significant predictors of cardiac events. Peak WMSI effectively risk stratified patients into low (0.9%/year), intermediate (3.1%/year), and high (5.2%/year) risk groups (p < 0.0001). A threshold of 45% EF provided further risk stratification of all WMSI groups. By multivariate logistic regression analysis, peak WMSI (relative risk [RR] 2.1, 95% confidence interval [CI] 1.0 to 4.4; p = 0.04) and EF (RR 1.0, 95% CI 0.9 to 1.0; p = 0.01) were both predictors of cardiac events. CONCLUSIONS Stress echocardiography yields prognostic information for risk stratification of patients with known or suspected ischemic heart disease. A normal stress echocardiographic study (peak WMSI = 1.0) confers a benign prognosis (0.9%/year cardiac event rate). Peak WMSI >1.7 and EF < or =45% are independent markers of patients at high risk of an adverse clinical outcome.

Standing and Exercise Doppler Echocardiography in Obstructive Hypertrophic Cardiomyopathy: The Range of Gradients with Upright Activity

BACKGROUND The ideal provocative maneuver in patients with hypertrophic cardiomyopathy (HCM) is a subject of ongoing investigation. Standing is a fundamental activity of daily life. This study examined acquisition of standing, Valsalva, and post-exercise left ventricular outflow tract gradients in HCM. METHODS Rest supine, standing, and post-Valsalva gradients were measured in 98 consecutive patients with HCM who were referred for outpatient echocardiography. In 53 (54%) of the 98 patients, symptom-limited treadmill exercise was also performed, with gradients measured immediately after in the supine position. RESULTS Fifty-six (57%) of the 98 patients had resting gradient<30 mm Hg and would thus be characterized as nonobstructive at rest. In the 98 patients, median gradients were 25 mm Hg at rest (range 0-205 mm Hg), increasing to 44 mm Hg after standing (range 0-309 mm Hg), an increase of 76%, and were again higher after Valsalva, 64 mm Hg (range 0-256 mm Hg) (P<.001). In the 53 patients who had gradient assessed after exercise, they were higher still, 100 mm Hg (range 0-256 mm Hg) (P<.001). In 29 patients (30%), standing provoked a higher gradient than Valsalva. CONCLUSION Although standing increased gradients by 76%, it is not as potent a provocative maneuver as Valsalva or treadmill exercise. Nevertheless, standing is recommended as a physiologic provocative maneuver. In some patients standing may guide therapy; in others, the standing and exercise gradient provide a correct appreciation of the range of physiologically experienced gradients during daily upright activity.

Cardioprotection with beta‐blockers: myths, facts and Pascal’s wager

Beta‐blockers were documented to reduce reinfarction rate more than 3 decades ago and subsequently touted as being cardioprotective for a broad spectrum of cardiovascular indications such as hypertension, diabetes, angina, atrial fibrillation as well as perioperatively in patients undergoing surgery. However, despite lowering blood pressure, beta‐blockers have never shown to reduce morbidity and mortality in uncomplicated hypertension. Also, beta‐blockers do not prevent heart failure in hypertension any better than any other antihypertensive drug class. Beta‐blockers have been shown to increase the risk on new onset diabetes. When compared with nondiuretic antihypertensive drugs, beta‐blockers increase all‐cause mortality by 8% and stroke by 30% in patients with new onset diabetes. Beta‐blockers are useful for rate control in patients with chronic atrial fibrillation but do not help restore sinus rhythm or have antifibrillatory effects in the atria. Beta‐blockers provide symptomatic relief in patients with chronic stable angina but do not reduce the risk of myocardial infarction. Adverse effects of beta‐blockers are common including fatigue, dizziness, depression and sexual dysfunction. However, beta‐blockers remain a cornerstone in the management of patients having suffered a myocardial infarction and for patients with heart failure. Thus, recent evidence argues against universal cardioprotective properties of beta‐blockers but attest to their usefulness for specific cardiovascular indications.

Prognostic Implications of Stress Echocardiography and Impact on Patient Outcomes: An Effective Gatekeeper for Coronary Angiography and Revascularization

BACKGROUND Stress echocardiography is an established technique for diagnosis, risk stratification, and prognosis in patients with known or suspected coronary artery disease. The ability of stress echocardiography to predict clinical outcomes, such as coronary angiography and revascularization, has not been reported previously. The purpose of this study was to evaluate the clinical outcomes of coronary angiography, revascularization, and cardiac events in patients undergoing stress echocardiography. METHODS A total of 3121 patients (mean age, 60 + or - 13 years; 48% men) undergoing stress echocardiography (41% treadmill, 59% dobutamine) were assessed. Follow-up (mean, 2.8 + or - 1.1 years) for subsequent coronary angiography, revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]), and confirmed hard events (nonfatal myocardial infarction or cardiac death) was obtained. RESULTS Stress echocardiographic results were normal (peak wall motion score index [pWMSI], 1.0) in 66% and abnormal (pWMSI > 1.0) in 34% of patients. The pWMSI effectively risk-stratified patients into low-risk (pWMSI, 1.0; 0.8% per year), intermediate-risk (pWMSI, 1.1-1.7; 2.6% per year), and high-risk (pWMSI >1.7; 5.5% per year) groups for future cardiac events (P < .0001). Early coronary angiography (30 days following stress echocardiography) was performed in only 35 patients (1.7%) with normal stress echocardiographic results and 267 patients (25.5%) with abnormal stress echocardiographic results (P < .0001). Late coronary revascularization (2 years following stress echocardiography) occurred in 80 patients (PCI, 2.8%; CABG, 1.1%) with pWMSI values of 1.0, 123 patients (PCI, 13.5%; CABG, 7.3%) with pWMSI values of 1.1 to 1.7, and 102 patients (PCI, 12.7%; CABG, 9.6%) with pWMSI values > 1.7. Multivariate logistic regression analysis identified pWMSI as a predictor of coronary angiography (relative risk, 2.04; 95% confidence interval, 1.67-2.5), revascularization (relative risk, 1.91; 95% confidence interval, 1.68-2.17), and cardiac events (relative risk, 2.45; 95% confidence interval, 2.09-2.88) (all P values < .0001). Patients with markedly abnormal stress echocardiographic results (pWMSI > 1.7) had a significantly higher cardiac event rate in those who did not undergo coronary revascularization (9.6% per year vs 2.9% per year, P < .05). CONCLUSIONS Stress echocardiography is an effective gatekeeper for coronary angiography and revascularization. Stress echocardiographic results influence clinical decision making in higher risk patients with significantly increased referral to coronary angiography and revascularization. Patients with markedly abnormal stress echocardiographic results (pWMSI > 1.7) were most likely to benefit from coronary revascularization.

Assessment of myocardial viability with dobutamine stress echocardiography in patients with ischemic left ventricular dysfunction.

The noninvasive assessment of myocardial viability has proved clinically useful for distinguishing hibernating and/or stunned myocardium from irreversibly injured myocardium in patients with chronic ischemic heart disease or recent myocardial infarction, with marked regional and/or global left ventricular (LV) dysfunction. Noninvasive techniques utilized for the detection of viability in asynergic myocardial regions include positron emission tomographic imaging of residual metabolic activity, single photon emission tomography (SPECT) of radioisotope uptake with thallium‐201, low‐dose dobutamine echocardiography assessment of inotropic reserve and myocardial contrast echocardiography for evaluation of microvascular integrity. Of these techniques, dobutamine stress echocardiography is a safe, widely available and relatively inexpensive modality for the identification of myocardial viability for risk stratification and prognosis. Low‐dose dobutamine response can accurately predict improvement of dysfunctional yet viable myocardial regions, and thus identify a subset of patients whose LV function will improve following successful coronary revascularization.

Risk Stratification and Prognosis in Octogenarians Undergoing Stress Echocardiographic Study

Background: The prognostic value of stress echocardiography (SE) for the diagnosis and risk stratification of coronary artery disease in octogenarians is not well defined. Methods: Follow‐up of 5 years (mean 2.9 ± 1.0 years) for confirmed nonfatal myocardial infarction (n = 17) and cardiac death (n = 37) was obtained in 335 patients, age ≥80 years (mean age 84 ± 3 years, 44% male), undergoing SE (33% treadmill, 67% dobutamine). Left ventricular (LV) regional wall motion was assessed by a consensus of two echocardiographers and scored as per standard five‐point scale, 16‐segment model of wall motion analysis. Ischemic LV wall segment was defined as deterioration in the thickening and excursion during stress (increase in wall‐motion score index (WMSI) ≥1). Results: By univariate analysis, inducible ischemia (chi‐square = 38.4, P < 0.001), left ventricular ejection fraction (chi‐square = 41.2, P < 0.001), a history of previous myocardial infarction (chi‐square = 22.3, P < 0.01), hypertension (chi‐square = 33, P < 0.01), and age (chi‐square = 27.7, P < 0.01) were significant predictors of future cardiac events. WMSI, an index of inducible ischemia, provided incremental prognostic information when forced into a multivariable model where clinical and rest echocardiography variables were entered first. WMSI effectively stratified octogenarians into low‐ and high‐risk groups (annualized event rates of 1.2 versus 5.8%/year, P < 0.001). Conclusions: Stress echocardiography yields incremental prognostic information in octogenarians and effectively stratifies them into low‐ and high‐risk groups. Precise therapeutic decision making in very elderly patients should incorporate combined clinical and stress echocardiography data.

Prognostic value of stress echocardiogram in patients with angiographically significant coronary artery disease.

The purpose of this study was to evaluate the prognostic value of stress echocardiography in patients with angiographically significant coronary artery disease (CAD). Two hundred sixty patients (mean age 63 ± 10 years, 58% men) who underwent stress echocardiography (41% treadmill, 59% dobutamine) and coronary angiography within 3 months and without intervening coronary revascularization were evaluated. All patients had significant CAD as defined by coronary stenosis ≥70% in major epicardial vessels or branches (45% had single-vessel disease, and 55% had multivessel disease). The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Patients with abnormal results on stress echocardiography were defined as those with stress-induced ischemia (increase in wall motion score of ≥1 grade). Follow-up (3.1 ± 1.2 years) for nonfatal myocardial infarction (n = 23) and cardiac death (n = 6) was obtained. In patients with angiographically significant CAD, stress echocardiography effectively risk stratified normal (no ischemia, n = 91) in contrast to abnormal (ischemia, n = 169) groups for cardiac events (event rate 1.0%/year vs 4.9%/year, p = 0.01). Multivariate logistic regression analysis identified multivessel CAD (hazard ratio 2.53, 95% confidence interval 1.16 to 5.51, p = 0.02) and number of segments in which ischemia was present (hazard ratio 4.31, 95% confidence interval 1.29 to 14.38, p = 0.01) as predictors of cardiac events. A Cox proportional-hazards model for cardiac events showed small, significant incremental value of stress echocardiography over coronary angiography (p = 0.02) and the highest global chi-square value for both (p = 0.004). In conclusion, in patients with angiographically significant CAD, (1) normal results on stress echocardiography conferred a benign prognosis (event rate 1.0%/year), and (2) stress echocardiographic results (no ischemia vs ischemia) added incremental prognostic value to coronary angiographic results, and (3) stress echocardiography and coronary angiography together provided additive prognostic value, with the highest global chi-square value.

Prediction of Myocardial Infarction Versus Cardiac Death by Stress Echocardiography

BACKGROUND The echocardiography literature to date has considered cardiac death and myocardial infarction (MI) as a combined end point. The purposes of the present study were to evaluate the differential prognosis of nonfatal MI versus cardiac death in patients undergoing stress echocardiography and to effectively risk stratify patients using the appropriate combination of functional, ischemic, and infarction data. METHODS The authors evaluated 3,259 patients (mean age, 59 +/- 13 years; 48% men) undergoing stress echocardiography. Follow-up (mean, 2.8 +/- 1.1 years) for confirmed nonfatal MI (n = 91) and cardiac death (n = 105) was obtained. RESULTS Multivariate analysis showed that the strongest predictor of cardiac death was a low ejection fraction (chi(2) = 37.3, P < .0001), and the strongest predictor of nonfatal MI was the extent of ischemia (chi(2) = 12.3, P < .0001). The relationship between ejection fraction and cardiac death rate was an exponential curve (y = 16.91e(-0.50x); r = -0.99, P < .0001). Among patients with ejection fractions > 30% (the low-risk to intermediate-risk groups), peak wall motion score index (WMSI) was able to further risk stratify patients into a very low risk group (peak WMSI = 1.0; cardiac death rate, 0.26% per year) and a higher risk group (peak WMSI > 1.7; cardiac death rate, 2.56% per year). However, patients with ejection fractions < 30% had high cardiac death risk regardless of peak WMSI category. CONCLUSIONS In patients referred for stress echocardiography, the integration of functional information (on the basis of ejection fraction) and ischemic and infarction data (on the basis of WMSI) effectively risk stratifies patients for the outcome-specific end points of cardiac death and nonfatal MI.

Assessment of myocardial viability: an effective gatekeeper for coronary revascularization?

Heart failure is an emerging worldwide epidemic. In the USA alone, there are an estimated 4.8 million Americans with heart failure, 10% of persons aged 70 years or greater and 400,000 new cases annually [1]. Heart failure is the most common diagnosis in hospitalized patients aged 65 years and older. There is an exceedingly high mortality rate associated with heart failure; approximately 50% of patients diagnosed with heart failure will be dead within 5 years. As the population ages, with more cardiac patients living longer with their disease, the opportunity for developing heart failure increases. The economic costs of heart failure are substantial with an estimated US

PROGNOSTIC IMPLICATIONS OF SUBMAXIMAL (<85p MPHR) STRESS ECHOCARDIOGRAPHY

23.2 billion society costs per year in the USA. Coronary artery disease (CAD) is the most common cause of left ventricular (LV) systolic dysfunction leading to heart failure [2]. It was previously thought that loss of myocardial contractility after myocardial infarction was caused by the destruction of myocardium and the development of irreversible scarring. With the subsequent development of coronary artery bypass grafting (CABG), clinical observations showed that in some individuals, the function of hypo or akinetic segments could improve following revascularization [3]. The contractile regional dysfunction seen in patients may be either transient (stunning) or prolonged (hibernation). In reality, the spectrum of myocardial dysfunction is probably a continuum extending from myocardial ischemia to programmed cell death and apoptosis. A proportion of patients with heart failure will confer viability by symptomatic angina or ischemia demonstrated by myocardial perfusion imaging [4]. However, most patients with LV systolic dysfunction due to CAD have a heterogeneous mixture of stunned, hibernating and scarred myocardium in various proportions. Given many considerations, it is clear that patients with heart failure due to CAD should pursue treatment options to prevent future coronary events. These therapies include treatment of heart failure, myocardial ischemia, and myocardial stunning and hibernation. Standard treatment of patients with heart failure due to LV systolic dysfunction include angiotensin-converting enzyme (ACE) inhibitors, angiotensinreceptor blockers, β-blockers and aldosterone antagonists [5–8]. Many cardiologists, and some guidelines [9], recommend evaluating patients with CAD and heart failure to identify patients suitable for coronary revascularization, although this strategy is not evidence based. It is often believed that the presence of viable but dysfunctional myocardium is an indication for revascularization, although very few patients with heart failure undergo viability testing.