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To date, the role of CPET (cardiopulmonary exercise testing) for risk stratification in elderly patients with HF (heart failure) with depressed or preserved ventricular function has not been evaluated. In the present study, we analysed whether CPET is useful in predicting outcome in this population. A total of 220 NYHA (New York Heart Association) class I-III patients with HF > or =70 years of age [median age, 75 years; 23% had NYHA class III; and 59% had preserved ventricular systolic function (left ventricular ejection fraction > or =40%)] performed maximal CPET (peak expiratory exchange ratio >1.00). Median peak oxygen uptake was 11.9 ml.kg(-1) of body weight.min(-1), median VE/VCO(2) slope (slope of the minute ventilation/carbon dioxide production ratio) was 33.2 and 45% had an EVR (enhanced ventilatory response) to exercise (VE/VCO(2) slope > or =34). During 19 months of follow-up, 94 patients (43%) met the combined end point of death and hospital admission for worsening HF, arrhythmias or acute coronary syndromes. By Cox multivariable analysis, a creatinine clearance of <50 ml/min {HR (hazard ratio), 1.657 [95% CI (confidence interval), 1.055-2.602]} and EVR [HR, 1.965 (95% CI, 1.195-3.231)] were the best predictors of outcome, while ventricular function had no influence on prognosis. In conclusion, in elderly patients with HF, a steeper VE/VCO(2) slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high-risk population, commonly not considered in exercise testing guidelines.

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90-520] pg/mL. Mean LVEF was 33 +/- 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO(2) slope) averaged 35 +/- 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO(2) slope >35) was found in 67 patients (43%). During 759 +/- 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO(2) slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.

Aim: To assess safety and feasibility of cardiopulmonary exercise test (CPX) in elderly patients with chronic heart failure (CHF) and left ventricular dysfunction., Methods and Results: We analysed 395 cardiopulmonary exercise tests (CPXs) performed in 227 clinically stable patients with CHF [mean age 76 years, males 70%, mean New York Heart Association (NYHA) class 2.2 +/- 0.5] and impaired left ventricular function (mean ejection fraction 43 +/- 12%). Ninety-eight out of 395 CPXs (25%) were performed in patients older than 80 years. A standard bicycle exercise ramp protocol was used, with increments of 10 W/min. An expiratory exchange ratio (RER) >or= 1.05 at the peak of CPX was considered as the index of maximal exercise. Average workload was 65 +/- 23 W. No adverse reactions were observed, although one test was stopped for non-sustained ventricular tachycardia. The main reasons for stopping were exhaustion (50%), dyspnoea (30%), maximal predicted heart rate (17%), orthopaedic problems (2.5%) and significant ST segment depression (0.5%). In the overall cohort, 80% of patients achieved an RER >or= 1.05 and, in 56% of them, the RER was >or= 1.15. The anaerobic threshold (AT) was detectable in 80% of CPXs, and mean oxygen consumption (VO2) at AT was 9 +/- 6 ml/kg per min, whereas mean peak VO2 was 11 +/- 3 ml/kg per min. In the cohort of patients aged > 80 years, 71% reached an RER >or= 1.05 and 47% reached an RER >or= 1.15. In these older patients, AT was detectable in 68% of CPXs performed, and the mean peak VO2 was 10 +/- 3 ml/kg per min., Conclusions: In elderly patients with CHF, the CPX is safe, feasible and able to provide basic information for individual risk assessment. These findings potentially extend the indications of CPX, which is currently applied to selected middle-aged patients with CHF, to the elderly population.

Aim: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2)., Methods: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35., Results: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01)., Conclusions: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.

Exercise electrocardiography (ECG) is of limited usefulness in hypertensive patients, whereas pharmacologic stress echocardiography can provide diagnostic and prognostic information. The aim of this study was to compare the prognostic value of clinical data, exercise ECG, and pharmacologic stress echocardiography in hypertensive patients with chest pain and to identify the best strategy for their risk stratification. Three hundred sixty-seven hypertensive patients (189 men, age 61 +/- 9 years) with chest pain of unknown origin underwent exercise ECG and pharmacologic stress echocardiography (237 with dipyridamole and 130 with dobutamine) and were followed up for 31 +/- 24 months. Positive exercise ECG (ST-segment shift of > or =1 mm at 80 ms after the J point) and stress echocardiography (new wall motion abnormalities) were found in 130 (35%) and 86 (23%) patients, respectively. During follow-up, there were 13 deaths and 16 myocardial infarctions. Additionally, 43 patients underwent coronary revascularization and were censored accordingly. Of 12 clinical, electrocardiographic, and echocardiographic variables analyzed, a positive result of stress echocardiography was the only multivariate predictor of either death (hazard ratio [HR] 4.7, 95% confidence interval [CI] 1.5 to 14.5, p = 0.007) or hard events (death, myocardial infarction) (HR 4.1, 95% CI 1.8 to 9.3, p = 0.0009). Using an interactive stepwise procedure, stress echocardiography provided additional prognostic information to clinical evaluation and exercise ECG. However, the negative predictive value of the 2 tests was similarly (p = NS) high in assessing 4-year event-free survival. In conclusion, a negative exercise electrocardiographic test identifies low-risk hypertensive patients with chest pain and should be the first-line approach for risk stratification. In contrast, positive exercise ECG is unable to distinguish between patients with different levels of risk. In this case, stress echocardiography provides strong and incremental prognostic power over clinical and exercise electrocardiographic data.

Objective: To assess the prognostic value of stress echocardiography as an adjunct to exercise electrocardiography in patients with uncomplicated acute myocardial infarction., Design: 496 patients underwent a maximum exercise ECG and pharmacological stress echocardiography (406 dobutamine and 90 dipyridamole) within 15 days of uncomplicated acute myocardial infarction and were followed for a mean of 25 months (range 1-74 months) for reinfarction, unstable angina, and cardiac death. Patients undergoing revascularisation were omitted., Results: Exercise ECG was positive in 162 patients (32.6%) and low threshold positive (< 100 W) in 91 (18%). Stress echocardiography was positive in 239 patients (48%) (194 with dobutamine and 45 with dipyridamole stress). The agreement between the two tests was 63% (kappa = 0.24, 95% confidence interval 0.15 to 0.33). Sixty nine spontaneous events occurred (14 cardiac deaths, 26 reinfarctions, and 29 with unstable angina requiring hospital admission), and 126 patients underwent revascularisation (39 coronary angioplasty and 87 bypass surgery). By receiver operating characteristic curve analysis, stress echocardiography provided incremental prognostic information compared with clinical data. A low threshold positive exercise ECG was associated with a worse outcome, but there was a fivefold increase in risk in patients with positive stress echocardiography who also had a high threshold (> 100 W) positive exercise ECG. Event-free survival of patients with both tests positive was significantly less than in patients with only one positive test or with both tests negative., Conclusions: Stress echocardiography provides additional prognostic information after uncomplicated acute myocardial infarction, but the greatest gain is found in patients with a high threshold positive exercise ECG.

Dobutamine stress echocardiography (DSE) accurately detects viable myocardium and residual ischemia in patients with acute myocardial infarction (AMI). The prognostic interaction of viability and ischemia has not been completely clarified in these patients. This study assesses the long-term effect of viability, ischemia, or their combination on survival in patients with AMI and mildly impaired left ventricular (LV) function. Four hundred eleven patients (age 57 +/- 9 years) underwent predischarge DSE (up to 40 microg/kg/min plus atropine if needed) after uncomplicated AMI and were prospectively followed for 23 months (range 1 to 78). According to DSE findings, patients were divided into 4 groups: viability only, ischemia only, combination of viability and ischemia, and scar. Adverse outcome occurred in 64 patients: 34 patients had hard events (9 cardiac deaths, 25 nonfatal AMI) and 30 patients had unstable angina requiring hospitalization. The combination of viability and ischemia, diabetes mellitus, and non-Q-wave AMI were significant predictors of all events at univariate and multivariate analysis. The same variables were also univariate predictors of hard events, but multivariate analysis indicated only the combination of viability and ischemia and diabetes as independent predictors. The event-free survival of patients with combined viability and ischemia was significantly lower (hazard ratio 3 [95% confidence interval 1.8 to 11]) compared with patients with ischemia only. Thus, viability and ischemia show a significant adverse prognostic interaction in patients with AMI and preserved LV function.

The aim of our study was to compare the prognostic value of stress echocardiography and exercise electrocardiography after uncomplicated non-Q-wave acute myocardial infarction in a series of 68 consecutive patients. Our data show that stress echocardiography and exercise electrocardiography offer similar prognostic information after uncomplicated non-Q-wave AMI.

Unlabelled: Recent reports suggest a relationship between ECG changes and myocardial viability during dobutamine stress echocardiography in patients with myocardial infarction. The aim of the study was to analyze the predictive value of T-wave normalization and ST segment elevation during low- (10 mucg/Kg/m') and high-dose (40 mucg/Kg/m') dobutamine stress test for late spontaneous recovery of function in patients with a first uncomplicated Q-wave myocardial infarction., Methods: Seventy eight consecutive patients (59 +/- 9 yrs; males = 67; anterior MI = 41, inferoposterior MI = 37 pts) underwent baseline 2D echo and dobutamine stress test at 9 +/- 2 days from onset of symptoms and they were free of cardiac events during the first three months after myocardial infarction. T-wave normalization (negative T-wave becoming > or = 1 mm upright in > or = 2 leads) and ST segment elevation (> or = 0.1 mm in > or = 2 leads) at low- and high-dose dobutamine infusion were compared with an improvement of contractility in the infarct area detected echocardiographically at three months. A wall motion score decrease in infarct area > or = 2 was the criterion for recovery of contractility., Results: ST segment elevation occurred in 19/78 patients at low dose (24%) and in 45/78 patients at high dose (58%). Late recovery of contractility in the infarct area was observed in 38/78 patients (49%). The positive and negative predictive values of ST segment elevation for late recovery of contractility were, respectively, 63-56% at low dose and 47-48% at high dose. A baseline negative T-wave in > or = 2 leads was present in 56 patients, and 27 (48%) showed recovery of contractility at three months. T-wave normalization occurred in 14 patients at low-dose (25%) and in 29 patients at high-dose dobutamine infusion (52%). The positive and negative predictive values of T-wave normalization were, respectively, 71-59% at low dose and 62-67% at high dose. Both ECG markers were present in 10/56 patients at low dose and in 19 patients at high dose. The positive and negative predictive values, respectively, were 70-57% at low dose and 58-57% at high dose. At univariate analysis, neither the ECG changes alone nor their combination during dobutamine stress testing were shown to be significant predictors of recovery of function., Conclusions: Our study demonstrates that in patients with a first uncomplicated Q-wave myocardial infarction, the T-wave normalization and/or the ST segment elevation occurring during early dobutamine stress testing are not reliable predictors of late spontaneous recovery of contractility in the infarct area.

Prevalence and prognostic significance of painful and silent ischemia detected by exercise electrocardiography (ECG) and dobutamine stress echocardiography (DSE) were evaluated in 407 consecutive patients recovering from acute myocardial infarction. Painful ischemia assessed by both tests was not associated with different clinical characteristics of patients; on the other hand, it identified a higher risk subgroup compared with silent ischemia during exercise ECG but not during DSE.

Resting and stress echocardiography is a 'one-stop shop', which enables a wide range of information to be collected on resting function, myocardial viability, and induced ischaemia, all of which are useful for prognostic stratification. Large scale, multicentre, prospectively collected data show the prognostic failure of resting function and inducible ischaemia, both independently and combined, which are especially effective in predicting cardiac death. The GISSI data show that the increment of risk as a result of reduction in ventricular function has a hyperbolic trend, with a relatively moderate increase in mortality for ejection fraction values between 50 and 30%, but with marked increases below 30%. The EPIC data show that the 1-year risk of cardiac death is as low as 2% in patients with negative dipyridamole stress echocardiography: it doubles if the test is positive at a high dose, and is almost four times higher if it is positive at a low dose. In the field of prognostic stratification, in the absence of carefully controlled studies, the choice between coronary angiography as the only essential study, or use of a non-invasive test to discriminate access to catheterization currently reflect alternate philosophical approaches rather than scientifically based decisions. In the invasive approach, stress echocardiography offers relief from the vicious circle of chest pain-coronary angiography revascularization. In the non-invasive and physiological approach, stress echo is capable of offering, in one sitting, an insight into the main determinants of survival: function, viability, and ischaemia.

Backgrounds: The aim of the study was to assess the relative prognostic accuracy of dobutamine echocardiography (TED) vs maximal bicycle exercise electrocardiography (TE) in patients with proven coronary artery disease., Methods: One hundred and thirty consecutive patients (70 patients with uncomplicated recent myocardial infarction, 19 asymptomatic patients with previous myocardial infarction and 41 patients with stable angina pectoris and previous myocardial infarction or previous myocardial revascularization procedure) underwent TED (incremental dobutamine infusion: 5 to 40 ncg/kg/min, continued with atropine 0.25 to 1 mg iv if necessary) and TE on different days and in random order. Criteria for positivity were: new or worsening regional dyssynergy for TED; ST segment shift > or = 1 mm from baseline for TE. End points were defined as spontaneous events (cardiac death, myocardial infarction and unstable angina) and total events (spontaneous events plus myocardial revascularization procedures)., Results: During 15.4 +/- 7.9 (range 1-33) months of follow-up, 33 events occurred: cardiac death (1), myocardial infarction (4) unstable angina (21) myocardial revascularization (7). Sensitivity, specificity, positive and negative predictive value, prognostic accuracy were similar for TED and TE (P = NS). Cumulative event-free survival curves as a function of TED and TE results were both statistically significant. A Cox stepwise regression analysis identified TED positivity obtained without atropine administration as the best predictor of spontaneous and total events (Odds ratio 5.33 and 4.38, respectively). Cumulative survival curves obtained by the combination of TED and TE results were statistically different (P < 0.05 and P < 0.001 for spontaneous and total events, respectively) and showed a poor clinical outcome in patients with both tests or only TED positive. TED correctly predicted clinical outcome in 24/39 patients in whom there was disagreement between the two tests., Conclusions: In patients with proven coronary artery disease, TED and TE have a similar accuracy for predicting clinical outcome. Where a discrepancy is seen between the two tests, TED appears to have a slightly higher prognostic value.