Stress-induced cardiomyopathy and psychological wellbeing 1 year after an acute event.

Stress cardiomyopathy (SCM) typically presents similar symptoms to acute myocardial infarction (AMI). However, these symptoms differ when it comes to a transient and completely reversible myocardial dysfunction, which is frequently precipitated by acute stressful events, occurring in the absence of plaque rupture and coronary thrombosis. The purpose of this study was to investigate health-related quality of life (HRQL) and emotional burden subsequent to cardiac events in SCM patients. Thirty-seven SCM patients were compared with 37 matched AMI patients. All selected patients were assessed for HRQL and psychological distress at baseline and 1-year after the acute event. After controlling for covariates, scores on the Psychological General Well Being Index indicated that depressed mood had increased in both groups, but the increase for SCM patients was greater than for AMI patients. The AMI group displayed greater decreases than the SCM in physical quality of life and in total cardiac-related health quality of life. The percentage of patients with psychological distress increased significantly more in the SCM group than in the AMI group, and it made no difference whether the triggering event was emotional or physical. Our results suggest that, despite the more favorable medical prognosis of SCM patients, their cardiac condition being transient and resolving completely in few weeks, the psychological impact associated with their condition is more negative 1 year later than in the case of AMI patients whose medical prognosis is less favorable, and this difference is independent of type of trigger event.

Type D personality is associated with the development of stress cardiomyopathy following emotional triggers.

BACKGROUND: Stress cardiomyopathy (SCM) can be triggered by emotional events. Recently, type D personality has been established as an independent predictor of acute cardiac adverse events. PURPOSE: We sought to examine whether type D personality can be identified in SCM patients. METHODS: A case-control study with 37 SCM patients, 37 myocardial infarction (AMI) patients, who both experienced emotional triggering, and 37 SCM patients without emotional triggers was performed. The DS14 and Interview for Recent Life Events were administered. RESULTS: Twenty-eight (76 %) SCM emotional trigger patients were categorized as type D compared with 13 (43 %) SCM patients without emotional trigger and 12 (32 %) AMI patients (p < 0.001). SCM patients with emotional triggers had higher scores on the social inhibition subscale than the other patient groups. CONCLUSIONS: The present study highlights the possible link between type D, with a specific key role for social inhibition component, and increased biological reactivity to acute emotional stress.

Prognostic implication of appropriateness criteria for pharmacologic stress echocardiography performed in an outpatient clinic [corrected].

BACKGROUND: Although appropriateness criteria for stress echocardiography have been developed to deliver high-quality care, the prognostic impact of these criteria remains undefined. Therefore, we sought to assess the prognostic implication of the American College of Cardiology/American Society of Echocardiography appropriateness criteria for pharmacological stress echo in a cohort of ambulatory patients. METHODS AND RESULTS: The study population consisted of 1552 ambulatory patients who underwent pharmacological (752 dobutamine, 800 dipyridamole) stress echo for the evaluation of known (n=549) or suspected (n=1003) coronary artery disease at a single cardiology center. Patients were followed up for a median of 36 months. Indications were determined for consecutive studies by 2 reviewers and categorized as follows: 984 (63%) patients had appropriate, 145 (9%) uncertain, and 423 (27%) inappropriate indication for stress echo. Ischemia was present in 15% of patients with appropriate, 8% of those with uncertain, and 5% of those with inappropriate indication (P<0.0001). During follow-up, 146 events (89 deaths, 57 nonfatal infarctions) occurred. Annual event rate associated with appropriate, uncertain, and inappropriate study was 3.1%, 3.8%, and 1.3%, respectively. The abnormal test result in patients with appropriate, uncertain, and inappropriate study was associated with 5.0%, 5.6%, and 1.8% annual event rate, respectively, exerting an independent value only in the appropriate and uncertain subset. CONCLUSIONS: Inappropriate indication for pharmacological stress echo is common, being documented in about 1 of 4 patients evaluated in an ambulatory setting, and is associated with lower rate of positive results and better survival as compared with appropriate and uncertain indication.

Is viability still viable after the STICH trial?

Stunning and hibernation represent two different forms of tissue viability identifiable in acute coronary syndromes and chronic ischaemic cardiomyopathy, respectively. Functional recovery occurs spontaneously with myocardial stunning, while it generally follows revascularization in case of hibernating myocardium. Low-dose dobutamine stress echocardiography is an accurate modality for identifying myocardial stunning and provides important information on ventricular remodelling after both systemic thrombolysis and primary angioplasty. In patients with conservatively treated infarction, the prognostic significance of viability by dobutamine stress echocardiography correlates with residual pump function. Substantial contractile reserve is predictive of favourable outcome in patients with poor but not in those with preserved or slightly reduced left ventricular function. Non-invasive assessment of coronary flow reserve with transthoracic Doppler echocardiography of the left anterior descending coronary artery allows to distinguish between necrotic and stunned myocardium and predicts ventricular remodelling following primary angioplasty. Resting echocardiographic examination can provide information on hibernating myocardium. In particular, systolic thickening <7 mm, restrictive filling pattern, and high end-systolic volume are predictive of no viability. Compared with nuclear imaging, dobutamine stress echocardiography is more specific for predicting functional recovery, less expensive, more generally available and radiation-free. A large body of evidence collected over the years demonstrates the favourable prognostic impact of revascularizing extensive myocardial territories which are found viable at dobutamine stress echocardiography in patients with ischaemic cardiomyopathy. The prognostic implications of viability-guided revascularization have been clearly established in both diabetic and non-diabetic patients. However, the prognostic value of myocardial viability has been questioned by the results of the STICH trial that did not demonstrate any advantage of survival in the patients with a large extent of myocardial viability undergoing revascularization. Is the end of a paradigm that deeply influenced clinical practice so far or just a neutral result that can be ignored due to the several limitations of study design? In the present review, we will address the main advantages and limitations of ultrasounds for the evaluation of myocardial viability and try to demonstrate that viability is still viable.

Integrating stress-related ventricular functional and angiographic data in preventive cardiology: a unified approach implementing a Bayesian network.

BACKGROUND: Identification of key factors associated with the risk of adverse cardiovascular events and quantification of this risk using multivariable prediction algorithms are among the major advances made in preventive cardiology and cardiovascular epidemiology. METHODS: In the present paper, we examined clinical predictors of adverse cardiovascular events among 228 individuals with symptoms suggestive of coronary artery disease (CAD) undergoing functional (stress echocardiography) and anatomical (coronary angiography) assessment of CAD. Particularly, we evaluate the possibility to integrate simple measures that have known prognostic value and more recently discovered predictors of risk, such as stress-related ventricular function data and angiographic data, in a unique model implementing a Bayesian network (BN). Moreover, we compared the performance of BN and the covariates hierarchy with those obtained from logistic regression model and from a set of alternative tools becoming popular in various clinical settings, including random forest classification tree analysis, artificial neural networks and support vector machine. RESULTS: Network graph and results coming from sensitivity analysis, where variables are ranked according to the gain they provided in variance reduction, seem have an easily intuitive lecture: variables that are measure of ventricular disfunction or of the extent of CAD show a greater impact in predicting event. On the other hand, anamnestic data such as diabetes, dyslipidaemia, hypertension, smoke habits, which are related to the outcome throughout a process of intermediate variables, per se have a small role in outcome prediction. BNs are able to explain a relevant part of variance (70%) and have discrimination ability superior or comparable with those to random forest classification tree analysis, artificial neural networks and support vector machine. DISCUSSION: Despite the complexity of interactions, model obtained implementing a BN seems to be able to adequately describe the relationships existing among the analysed variables. BN, being able to predict scenarios in which new variables can be incorporated as health process evolves, can measure individual's risks for adverse cardiovascular events, providing a permanent second opinion to the medical practitioner and assisting diagnostic and therapeutic process.

Prognostic implication of stress echocardiography in 6214 hypertensive and 5328 normotensive patients.

Aims To compare the prognostic implication of stress echocardiography (SE) in a large cohort of hypertensive and normotensive patients with known or suspected coronary artery disease (CAD). The relative prognostic meaning of the SE result in hypertensive and normotensive patients remains to be addressed. Methods and results The study group was formed by 11 542 patients (6214 hypertensive patients; 5328 normotensive patients) who underwent exercise (n= 686), dobutamine (n= 2524), or dipyridamole (n= 8332) SE for evaluation of known (n= 4563) or suspected (n= 6979) CAD. Patients were followed up for a median of 25 months (1st quartile, 7; 3rd quartile, 57). Ischaemia on SE (new wall motion abnormality) was detected in 3209 (28%) patients. During follow-up, 1587 events (924 deaths, 663 non-fatal infarctions) occurred. Patients (n= 2764) undergoing revascularization were censored. The annual event rate was 7.0% in hypertensive and 5.7% in normotensive patients (P = 0.02) with known CAD, and 3.7% in hypertensive and 2.4% in normotensive patients (P< 0.0001) with suspected CAD. Ischaemia on stress echo, resting wall motion abnormality (RWMA), age, male sex, and diabetes mellitus were multivariable prognostic predictors in both patient groups. Analysing data according to the interaction of prognostically important echocardiographic covariates, such as ischaemia on SE and RWMA, an effective risk assessment was obtained in hypertensive as well as normotensive patients. The annual event rate was markedly higher in hypertensive than in normotensive patients with no ischaemia and no RWMA (2.5 and 1.7%, P = 0.0001). Finally, the incremental prognostic value of inducible ischaemia over clinical evaluation and resting left ventricular function was greater in hypertensive than in normotensive patients both with known and suspected CAD. Conclusion The SE result allows an effective prognostication in hypertensive and normotensive patients. However, a non-ischaemic test predicts better survival in normotensive than in hypertensive patients with no RWMA.

Understanding coronary atherosclerosis in relation to obesity: is getting the distribution of body fatness using dual-energy X-ray absorptiometry worth the effort? A novel perspective using Bayesian Networks.

AIM: A relative excess of fat in the upper body region has been proven to be associated with increased coronary artery disease (CAD) risk. Dual-energy X-ray absorptiometry (DXA) is probably the most accurate and precise method available to study fat regional distribution and to directly measure total body fat and lean soft tissue mass. However, while several studies have investigated the abilities of obesity anthropometric measures in predicting CAD, only few studies have evaluated DXA as CAD predictor; particularly, a comparison between a model including information coming from anthropometric measurements and a model in which fat is precisely measured by DXA, is still lacking. In order to verify if CAD severity, as measured by Gensini score, is better predicted when a prognostic model includes DXA measurements rather than anthropometric measures, we compared performance obtained by two Bayesian Networks (BNs) including standard anthropometric measures and DXA, respectively. METHODS: Data come from 58 consecutive patients, 79% of them having suspected and 21% known CAD. Two BNs were implemented: input variables include anamnestic information, biochemical data and obesity measures. In the first model (BN1) obesity was measured by body mass index and waist-to-hip ratio, while in the second one (BN2) it is quantified by DXA-derived parameters. RESULTS: Network graphs and results coming from sensitivity analysis show that in both models lipoproteins and biomarkers of inflammation act as proximal node, while obesity (independently of the chosen measure) appears to be a distal node acting by the intermediation of other variables. Both models show high predictive abilities, the mean percentage classification errors being, respectively, 14.13 and 18.87. CONCLUSIONS: In our study, the BN predictive ability is slightly superior when obesity is measured using anthropometric data instead of DXA measurements. The reason probably relies on the fact that in the BN the obesity role in predicting CAD is mediated by the action of other factors that appear to be more directly influencing the outcome. Thus, the necessity to dispose of a perfect measure becomes less compulsory and the huge effort to precisely estimate body composition with complex methods as DXA could be avoided when using expert system such as BN as predictive tool.

Impact of advanced exercise ECG analysis on cost of coronary artery disease management.

BACKGROUND: Conventional analysis of exercise electrocardiogram (EX-ECG) has limited accuracy. This study aims to evaluate the potential impact of improving EX-ECG accuracy on costs of diagnosis and number of misdiagnoses of coronary artery disease (CAD). METHODS: A decision-tree model was simulated including sequential application of diagnostic procedures for suspected CAD. The model was structured in two main branches (presence or absence of CAD). A probabilistic sensitivity analysis was then performed for several combinations of improvement in test sensitivity and specificity. RESULTS: A clear trend in cost reduction was observed at improving EX-ECG specificity (about 8-8.5 million dollars, corresponding to a 5.6-7.6% reduction according to the prevalence level). Wrong diagnoses counted for 9-13% of test. Improvements in test parameters lead to reductions in wrong diagnoses, especially when increasing specificity (8.8-12.5%). CONCLUSIONS: A proper improvement in EX-ECG sensitivity and specificity would have a relevant impact on the costs of CAD management, while reducing the number of misdiagnoses.

Stress echocardiography for the risk stratification of patients following coronary bypass surgery.

OBJECTIVES: The aim of the study was to assess the prognostic value of stress echocardiography after surgical revascularization. METHODS: We evaluated 500 (100 women) patients who had undergone exercise or pharmacological SE after a median of 69 months after coronary artery by-pass grafting (CABG). Of these, 351 (70%) complained of symptoms suggestive of ischemic origin while 149 (30%) were tested for asymptomatic progression of the disease. RESULTS: SE was positive for ischemia in 196 (39%) patients. During a median follow-up of 25 months, 61 patients died, 33 had a nonfatal myocardial infarction, and 112 underwent late (>3 months) revascularization. Multivariable Cox' regression analysis indicated age (HR=1.04; 95% CI 1.01-1.06; p<0.003), and peak WMSI (HR=3.07; 95% CI 1.96-4.81; p=0.0001) as independent predictors of hard (total mortality and myocardial infarction) events. SE information provided a significant improvement in predictive power of the statistical model (chi-square increase 34%, p<0.0001 for hard and 91%, p<0.0001 for major events, respectively). Survival analysis showed ischemia at SE to be associated with significantly higher hard and major event rate in both symptomatic and asymptomatic patients. DISCUSSION: SE represents an effective tool for the risk stratification of patients with previous CABG independently of the presence of symptoms suggestive of ischemic origin.

Prognostic implications of stress-induced transient ischemic dilation of the left ventricle in patients with systolic dysfunction and fixed perfusion defects.

PURPOSE: To verify whether stress-induced transient ischemic dilation (TID) of the left ventricle may help refine prognostic assessment of patients with resting systolic dysfunction and fixed perfusion defects. METHODS: Two hundred seventy patients with resting ejection fraction

Assessing functional mitral regurgitation with exercise echocardiography: rationale and clinical applications.

Secondary or functional mitral regurgitation (FMR) represents an increasing feature of mitral valve disease characterized by abnormal function of anatomically normal leaflets in the context of the impaired function of remodelled left ventricles. The anatomic and pathophysiological basis of FMR are briefly analyzed; in addition, the role of exercise echocardiography for the assessment of FMR is discussed in view of its relevance to clinical practice.

Non-invasive risk stratification of coronary artery disease: an evaluation of some commonly used statistical classifiers in terms of predictive accuracy and clinical usefulness.

OBJECTIVE: To compare different prediction models for assessing outcome of patients undergoing non-invasive risk stratification of suspected or known coronary artery disease. METHODS: Six statistical classifiers and data mining models were applied to the prospective data bank of two different institutions. Of these, one represented the training (n = 2777) and the other one the test (n = 2679) set, each set consisting of usual clinical and stress echo information of patients followed-up for the combined endpoint of all-cause mortality and non-fatal acute coronary syndromes. The following models were used: Logistic regression, Generalized Additive Model, Projection Pursuit Regression, Linear Discriminant Analysis, Quadratic Discriminant Analysis and Artificial Neural Networks. Models were selected using the Akaike Information Criterion and compared in terms of accuracy and Negative Predictive Value, overall Misclassification Rate and ROC Area Under Curve. RESULTS: During a median follow-up of 31 months, 573 events occurred: 271 in the training and 302 in the test set respectively. All models selected the same subset of covariates as significantly associated with the outcome. The comparison of model performance showed that: (1) Quadratic Discriminant Analysis and Artificial Neural Networks provided a worse prediction of outcome than models more closely bonded to the hypothesis of linearity of the covariates effect; (2) overall predictive capability of the best performing models was excellent (>90% and >85% for training and test set respectively); and (3) there was a substantial lack of agreement among model indications in the individual patient. CONCLUSIONS: The selection of variables and predictive models are not independent processes and may affect the performance of risk scoring systems or algorithms designed to transfer general prognostic rules into clinical practice. Thus, caution must be used in translating model prediction into strict clinical indications.

Impact of gender on risk stratification by stress echocardiography.

OBJECTIVE: To compare the prognostic value of stress echocardiography results in men and women with known and suspected coronary artery disease. METHODS: We analyzed the data of 8737 patients (5529 men and 3208 women) who underwent stress echocardiography (exercise in 523 patients, dipyridamole in 6227 patients, dobutamine in 1987) for evaluating known (n=3857) or suspected (n=4880) coronary artery disease. Patients were followed up for the occurrence of overall mortality or nonfatal myocardial infarction. RESULTS: During a median follow-up of 25 months, 1218 cardiac events (693 deaths and 525 infarctions) occurred. Moreover, 2263 patients (1731 men [31%] and 532 women [17%]; P<.0001) underwent coronary revascularization and were censored. Stress echocardiography results added prognostic information to that of clinical findings and resting wall motion score index in men and women with both known and suspected coronary artery disease. In patients with known coronary artery disease, women had a higher (P=.01) event rate than men in the presence of ischemia. The annual event rate was worse for nondiabetic women (P=.007) but not diabetic women; age had a neutral prognostic effect in the 2 sexes. In patients with suspected coronary artery disease, men without ischemia had a higher (P<.0001) event rate than women. The annual event rate was worse in men aged less than 65 years (P<.0001) or more than 65 years (P=.04), and those with (P=.03) or without (P<.0001) diabetes. CONCLUSION: Prognosis is at least comparable in men and women with ischemia and in those with coronary artery disease and no ischemia at stress echocardiography. In these clinical settings, availability for major procedures should be similar for both genders.

Information on center characteristics as costs' determinants in multicenter clinical trials: is modeling center effect worth the effort?

OBJECTIVES: Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. METHODS: To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). RESULTS: The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. CONCLUSIONS: This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.

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.

Direct stenting after thrombus removal before primary angioplasty in acute myocardial infarction.

OBJECTIVES: To verify whether direct stenting (DS) after thrombus removal during primary angioplasty (PPCI) in patients with ST-elevation acute myocardial infarction (STEMI) can improve myocardial reperfusion and prevent distal embolization compared to conventional stent implantation. BACKGROUND: Both mechanical removal and DS reduce thrombus dislodgment and improve microcirculatory reperfusion during PPCI. However, the additional effect of DS after thrombus removal has not been definitely assessed. METHODS: The DEAR-MI study included 148 consecutive STEMI patients who were randomly assigned to undergo or not thrombus aspiration before PPCI. For the purpose of the present study, we interrogated the DEAR-MI data bank to compare the occurrence of complete (>70%) ST-segment resolution (STR), myocardial blush grade (MBG)-3, no-reflow, and angiographic embolization in patients treated and untreated with DS. RESULTS: Clinical and angiographic characteristics were similar in the two groups. Comparing DS and no-DS groups, complete STR was found in 67% versus 51% (P = 0.08), MBG-3 in 86% versus 49% (P < 0.001), no-reflow in 1% versus 14% (P < 0.01), angiographic embolization in 3% versus 19% (P < 0.01), TIMI flow-3 in 89% versus 70% (P < 0.01), and the corrected TIMI frame count was 16.2 versus 18.8 (P < 0.05). Among patients undergoing thrombus aspiration, the odds ratio of DS for MBG-3 and distal embolization was 4 (95% CI 1-16.6) and 0.10 (95% CI 0.01-0.93), respectively. At multivariable analysis, thrombus aspiration (P < 0.001) and DS (P < 0.05) independently predicted MBG-3, while thrombus aspiration was the only independent predictor of DS. CONCLUSIONS: DS during PPCI reduces distal embolization and improves myocardial reperfusion. This effect is significantly more relevant after thrombus aspiration.

Truncal fat determined by dual-energy X-ray absorptiometry is an independent predictor of coronary artery disease extension.

BACKGROUND: Controversy prevails regarding the existence of a correlation between the severity of coronary artery disease (CAD) and the extent and distribution of obesity. PURPOSE: To assess the correlation between total fat, truncal fat (TF), and lean mass, obtained with dual-energy X-ray absorptiometry (DEXA) and standard anthropomorphic indices (body mass index, waist circumference, waist-to-hip ratio) and to verify whether DEXA indices can predict the extent and severity of CAD. MATERIALS AND METHODS: Fifty-eight patients (19 females) consecutively referred for coronary angiography underwent physical examination and DEXA assessment of body composition. RESULTS: Of the 58 patients enrolled, 22 were overweight and 13 were obese. Significant CAD was found in 39 (67%) patients. DEXA-derived total mass and fat mass enabled us to distinguish overweight from obese patients (P<0.005), whereas just TF mass correlated with the number of diseased vessels after adjusting for body mass index, sex, age, and smoking habit (odds ratio, 8.68; 95% confidence interval: 1.02-74.10). CONCLUSION: TF determined by DEXA is independently related with CAD extension.

Survival models for cost data: the forgotten additive approach.

The usage of the Aalen additive approach is proposed to model cost data. Using a Monte Carlo simulation, in a wide set of scenarios, we showed that the Aalen model is performing well and can be a reasonable alternative to the standard Gamma regression models. In addition, with reference to the COSTAMI trial data, we highlighted the ability of the Aalen model to offer additional information about the relationships between costs and specific covariates, as compared with standard regression techniques.