Cost of strategies after myocardial infarction (COSTAMI)

A multicentre, international, randomized trial for cost-effective discharge after uncomplicated myocardial infarction

Alessandro Desideria,*, Paolo Maria Fiorettib, Lauro Cortigianic, Dario Gregorid, Claudio Colettae, Carlo Vignaf, Francesco Totag, Riccardo Rambaldih, Jeroen Baxi, Leopoldo Celegonj, Riccardo Bigik and Eugenio Picanol on behalf of the COSTAMI (Cost of Strategies After Myocardial Infarction) Trial Investigators

a Cardiovascular Research Foundation, Castelfranco Veneto, Italy
b IRCAB Foundation, Udine, Italy
c Campo di Marte Hospital, Lucca, Italy
d IRCAB Foundation, Udine, Italy
e Santo Spirito Hospital, Roma, Italy
f IRCCS General Hospital, San Giovanni Rotondo, Italy
g General Hospital, Bari, Italy
h General Hospital, Bentivoglio, Italy
i University Medical Center, Leiden,The Netherlands
j Cardiovascular Research Foundation, Castelfranco Veneto, Italy
k Cardiovascular Research Foundation, Castelfranco Veneto, Italy
l CNR Institute of Clinical Physiology, Pisa, Italy

* Corresponding author: Alessandro Desideri, MD, FESC, FACC, Cardiovascular Research Foundation, S. Giacomo Hospital, 31033 Castelfranco Veneto (TV), Italy. Tel.: +39-0423-732300; fax: +39-0423-732301
E-mail address: aldesi{at}tin.it

Received 17 February 2003; revised 9 May 2003; accepted 21 May 2003


    Abstract
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 
Aims Risk stratification after uncomplicated acute myocardial infarction is mostly applied by either symptom-limited post discharge exercise electrocardiography or pre-discharge submaximal exercise test. Aim of the present study was to determine if early pharmacological stress echocardiography and discharge within 24 hours of the test in cases without induced myocardial ischemia leads to lower costs and similar clinical outcome during 1 year follow up when compared to clinical evaluation and exercise electrocardiography after discharge.

Methods and results Four-hundred fifty-eight patients from 10 participating centers with a recent uncomplicated myocardial infarction were randomized to pharmacological stress echocardiography on day 3–5 followed by early discharge in the case of negative test result (early discharge strategy) (n=233) or clinical evaluation with hospital discharge on day 7–9 and symptom-limited post-discharge exercise electrocardiography at 2–4 weeks after myocardial infarction (usual care strategy) (n=225). At 1 year follow up there were 63 events (4 deaths, 9 non fatal reinfarctions, 50 chest pains requiring hospitalization) in patients randomized to early discharge, and 69events (6 deaths, 13 reinfarctions, 50 chest pains requiring hospitalization) in usual care (p=ns). Total median individual costs calculated on the basis of hospitalizations, investigations and interventions during 1 year follow up were 3561 for early discharge strategy vs 3850 for usual care strategy (p<0.05).

Conclusions Early pharmacological stress echocardiography followed by early discharge in case of negative test result gives similar clinical outcome and lower costs after uncomplicated myocardial infarction than clinical evaluation and delayed post-discharge symptom-limited exercise electrocardiography.

Key Words: Myocardial Infarction • early discharge • cost-benefit analysis

Management of the postinfarct patient after initial stabilization has changed in the last decade, aiming at the most cost-effective strategy. Length of hospital stay has been identified as the most important determinant of cost1and an early discharge of uncomplicated cases has been advocated to reduce the economical burden of care. In spite of these premises, only retrospective analysis of large trials2have shown that patients with an uncomplicated course after the acute phase of a myocardial infarction (MI) can be safely discharged on day 3 to 4 and no prospective controlled clinical trials have focused on the issue of the safety and the economical value of a strategy based on early non invasive risk stratification followed by discharge in this population.

We performed an international, multicentre, prospective, randomized trial to compare an early discharge strategy based on stress echocardiography to standard care based on clinical evaluation and post-discharge exercise electrocardiography (ECG) as contemplated by current guidelines;3the primary end-point was to identify the most cost-effective strategy during a 12 month follow-up.


    1. Methods
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 
1.1. Patients
Between January 1998, and August 2000, we investigated 458 patients from 10 General Hospitals, eight in Italy and two in Turkey. The Trial protocol was approved by the local ethics committees of participating centres.

Patients were uncomplicated MIs admitted within 24h of the onset of symptoms. MI was confirmed by a rise and fall of cardiac enzymes (creatine kinase and creatine kinase MB isoenzyme) of at least twice the upper limit of the reference range, within 12h of admission. An eligible uncomplicated MI was defined as follows: (1) No recurrent ischaemic chest pain (with documented electrocardiographic changes) lasting 5min or longer and occurring at least 24h after hospital admission, (2) No clinical and/or radiographic evidence of heart failure, (3) No major arrhythmias and (4) Echocardiographic left ventricular (LV) ejection fraction at rest >40% on day 3. Exclusion criteria were: age >75 years, serious arrhythmias (ventricular fibrillation, ventricular tachycardia requiring DC shock, fixed atrio-ventricular blocks of second or third degree), left bundle branch block, pericarditis, insufficient acoustic window, poor short-term prognosis because of concomitant disease.

1.2. Study design
The study patients gave informed, written consent and were randomly assigned to a study group within 72h from the onset of symptoms according to the adaptive-allocative procedure, a randomization scheme which maximized the probability of balance between the treatment groups within the medical centres and with respect to each of the following variables used for stratification: age, previous MI, use of thrombolytics, ST-segment depression on the electrocardiogram obtained at entry and anterior location of the infarct. The allocation sequence was generated by the statistics team in the central lab (IRCAB Foundation, Udine, Italy). The random allocation sequence was concealed by numbered envelopes until interventions wereassigned.

Patients were enrolled and randomly assigned to early discharge or usual care strategy by the local investigators. Early discharge strategy consisted of early (day 3 up to day 5 in case of organizational problems) use of pharmacological stress echocardiography and immediate subsequent discharge in case of a negative result of test. Usual care strategy was based on clinical evaluation with no stress before discharge and a symptom-limited exercise ECG at 2–3 weeks after discharge, according to present guidelines.3

1.2.1. Pharmacological stress- echocardiography
The stress echo of first choice was dipyridamole stress; dobutamine stress was performed in the case of contraindication to dipyridamole. Patients were instructed to avoid coffee, tea or cola within 8h before the tests. Dipyridamole. Two-dimensional echocardiography was performed on day 3–5, without withdrawing the medical therapy, at rest and in combination with dipyridamole infusion (0.84mg/kg over 10min). The test was interrupted by aminophilline (up to 240mg) at the 15th minute in the case of negative test result or when a clear dyssynergy appeared. Dobutamine. Dobutamine was infused in 3-min dose increments, starting from 5mcg/kg/min up to 40mcg/kg/min. Infusion was stopped as soon as criteria for positivity were reached during the test. Metoprolol (up to 5mg) was given intravenously to reverse the effects of dobutamine. Diagnostic end-points. Positivity of the test was based on the detection of a transient ventricular dyssynergy of contraction, which was absent or of a lesser degree in the baseline examination. Diagnostic end-points, apart from development of dyssynergy, were: peak drug dose; achievement of conventional non-echocardiographic ‘ischaemic’ end-points (severe chest pain and/or ST segment shift >2mV). The test was also stopped, in the absence of diagnostic end-points, for one of the following reasons: (1) intolerable symptoms; (2) limiting asymptomatic side effects, consisting of hypertension (systolic blood pressure >220mmHg, diastolic blood pressure >120mmHg), hypotension (30mmHg decrease in blood pressure), severe supraventricular or ventricular arrhythmias. Echocardiographic analysis. Two-dimensional echocardiographic monitoring was performed throughout and up to 5min after the stop of drug infusion. The left ventricular wall was divided into 16 segments; segmental wall motion was graded as follows: 1=normal, 2=hypokinetic, 3=akinetic, 4=dyskinetic. A wall motion score index (WMSI), obtained dividing the sum of individual segment scores by the number of visualized segments, was calculated at baseline and at peak drug infusion. A test result was considered positive for ischaemia when the wall motion score increased by one or more points in two or more adjacent segments as compared to resting echo. Akinesia becoming diskinesia was not be considered as sign of ischaemia.4The ejection fraction was calculated on a single plane according to the area-length method. Reading of echocardiograms was performed on site by the local investigators. The enrolling centres passed a quality control performed according to criteria previously utilized in EPIC5and EDIC6multicentre studies to guarantee a homogeneous interpretation in stress echo reading.

1.2.2. Exercise ECG
All patients performed a symptom limited exercise ECG, on medical therapy at 2–3 weeks after discharge. Initial work load was 25W, with 25W increments every 2min. Criteria for stopping the test were: severe ischaemia (ST-segment depression >3mm, or elevation >1mm in leads without Q-waves), fatigue, 3 or more consecutive ventricular premature beats, hypertensive response (systolic blood pressure >240mmHg, diastolic blood pressure >120mmHg), hypotensive response (>20mmHg decrease in systolic blood pressure), worsening angina. An ST segment depression >1mm was defined as positive exercise ECG. ST segment analysis was performed on site by the local investigators.

1.2.3. Standard clinical evaluation
The clinical evaluation included chest X-ray at hospital admission, clinical evaluation with electrocardiogram every day, and two-dimensional echocardiography on day 3.

The day of hospital admission was defined as day 1. The length of hospital stay was calculated by subtracting the date of discharge from the date of admission, as the first and last hospital day combined comprised on average approximately 24h of hospitalization.

1.2.4. Follow-up
Primary end-point was cost-effectiveness of the different diagnostic strategies, secondary end-point was quality of life evaluation. Patients were seen at one month after discharge, six months and one year after discharge. Cardiac events, use of resources, costing and quality of life were recorded.

1.3. Cardiac events
Cardiac events were the occurrence of death, non fatal re-infarction or admission for chest pain. In case of multiple events only the first occurrence for each type was considered. For the combined end-point only the first occurrence of any of the end-points was counted. Cardiac events were assessed by the local Investigators on the basis of hospital charts, unblinded to group assignment.

1.3.1. Use of resources and cost of care
Use of resources was calculated considering direct medical costs as follows: hospitalizations, investigations and interventions. Hospitalizations were recorded in terms of number of days for acute hospitalizations and rehospitalizations for any reason. Hospitalizations were divided in categories of care distiguishing coronary care unit (CCU), non-intensive cardiological or general ward, other wards. Investigations recorded were: exercise ECG, echocardiogram and coronary angiography. Interventions recorded were percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass grafting (CABG). For the purpose of the present analysis direct medical costs were calculated related to initial hospital stay, at 1, 6 months and 1 year follow-up. Costs are expressed in Euro. Cost of hospitalization was estimated using the mean reimbursement for the diagnosis-related group in the Friuli Venezia Giulia Region, site of the coordinating Centre. A hospital cost of 407 Euro () was assigned per each day of hospitalization, with the exception of the first day, for which was computed a cost of 460 . Similarly, costs of investigations and interventions were calculated taking the same as a reference, at the following values: coronary angiography 1694 , coronary angioplasty 6044 , coronary artery bypass graft 18763 . Total medical costs per patient were measured as the sum of initial hospital costs and follow-up hospital and outpatient costs through the end of protocol at 1 year follow up. Cost of pharmacological treatment was not included in total costs.



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Fig. 1 Trial profile.

 
1.4. Quality of life
Quality of life was assessed by administering ‘MacNew Heart Disease HRQL’,7a 27-item questionnaire which measures a generic score and three specific domains of the patients’ quality of life, using a Likert type response scale (from 1=All of the time to 7=none of the time). The first one, physical dimension, analyses the limitations in exercising or breathing perceived by patients; the second, social dimension, deals with difficulties in having normal social activities while the third one, emotional dimension, identifies the level of self-confidence and self-esteem.

Each patient received a copy of the questionnaire at 2-4 weeks after AMI and at follow-up visits (at 6 and 12 months).

1.5. Statistical analysis
Power calculation for the study showed that 200 patients per group were needed, at a power of 0.9 and an alpha of 0.05, to detect a reduction in costs of 250 Euro with a standard deviation assumed equal in the two groups up to 750 Euro. Because this was a low risk population, it was expected that the risk of death and reinfarction on 1 year follow-up would be quite low, so that an unrealistically large sample size would be needed to detect any difference in terms of clinical events.

Data are reported as median values, 25th and 75th percentile, means, for continuous variables and as percentages (with absolute number indicated) for categorical variables. Formal tests aimed at evaluating the difference between strategies have been performed modeling separately each outcome (costs and event rates), always adjusting for individual baseline known confounders, i.e.: gender, previous AMI, diabetes, anterior or lateral MI as at the admission ECG, ejection fraction less than 50%, age >70 years and for centre effect.8Variables were all inserted in the model and no formal model selection regarding covariates has been conducted More in detail, the following models have been constructed.

  1. Costs and quality of life scores have been modelled using a linear mixed model, including centre as a random effect, allowing the variance function being a power function of selected covariates (age for costs and age and sex for quality of life). This was needed to eliminate heteroschedasticity detected at residual analysis.9
  2. Times to event have been modelled and adjusted by centre using a marginal estimating equation model in the Cox proportional hazard class.10
  3. Re-hospitalizations and revascularizations have been modelled using a generalized estimating equation (GEE) approach, adjusting for centre effect via an exchangeable correlation structure.11

All P-values less than 0.25 have been reported, otherwise they have been indicated as not significant (ns).

Descriptive and exploratory analysis has been performed in SPSS 7.0, whereas statistical models have been estimated using S plus 2000.12


    2. Results
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 
2.1. Study population
Fig. 1shows the Trial profile. 233 of 458 (51%) patients were randomized to early discharge and 225 (49%) to usual care. Overall, 83% of the patients were men, and the median age was 58 years. Ninety-three (21%) patients had an anterior MI. Median echocardiographic left ventricular ejection fraction on day 3 was 52%. Acoustic window was considered sufficient for eligibility in all patients. No intergroup difference (P=ns) was evidenced for the clinical and MI characteristics of the index infarctions, as well as for medications at hospital discharge (Table 1).


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Table 1 Clinical and electrocardiographic characteristics of the two patient groups

 
2.2. Test results
Stress echocardiography was performed at a median of 4 days from admission (1st quartile 4, 3rd quartile 5) in 216 (93%) of 233 patients randomized to early discharge. Of those, 191 underwent dipyridamole and 25 patients dobutamine stress. In 17 patients (7%) the test was not performed, because of pre-test clinical events (n=8) or inadequate acoustic window (n=9). No complication occurred. The test was positive for ischaemia in 51 patients (24%) and negative in the remaining 165 (76%) (Table 2).


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Table 2 Test results

 
Exercise ECG was performed at a median of 25 days (1st quartile 20, 3rd quartile 31) after admission in 167 (74%) of 225 patients randomized to usual care. In 58 patients (26%) the test was not performed because of pre-test clinical events (n=21), new medical decision after randomization (n=17), inability to exercise (n=6), patient’s refusal (n=4). The test was positive for ischaemia in 37 patients (23%) and negative in 130 patients (78%) (Table 2).

2.3. Clinical outcome
No significant differences at Cox regression analysis were observed between the 2 strategies. Pre-test complications were 2 deaths, 1 reinfarction and 5 unstable angina in the early discharge strategy. In the usual care, the 21 clinical complications were as follows: 2 deaths, 1 reinfarction and 18 unstable angina. All surviving patients with pre-test events underwent early coronary angiography. Up to 1 month there were 4 deaths and 5 re-infarctions in the stress-echo guided early discharge, whilst there were 2 deaths and 5 re-infarctions in the usual care. One-year clinical outcome according to intention to treat analysis is shown in Table 3. Clinical outcome according to test result is shown in Table 4. Chest pain requiring hospitalization recurred in 33 patients with a negative test in the early discharge strategy and in 12 patients with a negative test in the usual care. Out of these patients, 18 had coronary angioplasty and five underwent bypass surgery in the early discharge group, whilst four underwent coronary angioplasty and two bypass surgery in the usual care group.


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Table 3 One year outcome according to intention to treat (HR estimated using Cox regression model)

 

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Table 4 Subgroup analysis: clinical outcome before the test and at 1 year follow up

 
2.4. Use of resources and cost analysis
Number and timing of revascularization procedures were similar as evaluated via GEE model, for the two strategies (Table 5) after adjusting for patient’s characteristics. Patients assigned to the stress-echo guided early discharge had shorter initial hospital stay, with lower costs of initial hospitalization (Table 6). During 1 year follow up, total duration of hospitalization, including index MI and subsequent events, was a median of 8 days (1st quartile 6, 3rd quartile 12) in patients randomized to early discharge as compared to 9 days (1st quartile 7, 3rd quartile 13) in those randomized to usual care. Costs remained lower in patients assigned to early risk stratification and discharge as compared to standard care during follow-up. Patients with a negative early stress echo were at lowest costs during follow-up (Table 6). Results of the statistical analysis performed on the data are given on Table 7.


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Table 5 Use of resources during follow up

 

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Table 6 Total Costs for Early Discharge and Usual Care Strategy; costs are expressed in Euro; differences in costs between the 2 strategies are significant at a 0.05 level at each time in point of follow up, both for the overall costs and those for negative patients only.

 

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Table 7 Estimated differences in costs (effects) between usual care and early discharge strategies; all differences have been adjusted by baseline characteristics of the patients.

 
2.5. Quality of life assessment
No significant differences were found in any measures between the two strategies (Table 8).


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Table 8 Quality of life assessment in the Study Groups

 

    3. Discussion
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 
The main result of this multicentre randomized study is that in patients with uncomplicated acute MI and normal residual LV function, a systematic early search of ischaemia with stress echocardiography gives similar clinical outcome as compared to clinical evaluation and post-discharge exercise ECG. Moreover, this strategy is associated with a reduction in costs.

In the GUSTO trial,2on the basis of simple clinical variables, a retrospective analysis identified a low risk group that could be discharged safely on day 4 with a subsequently very low complication rate. Nevertheless, in this study, as well as in others,13–15after indicating the suitability of early hospital discharge, the actual discharge was performed later. In a recent preliminary trial,16120 patients admitted with an acute MI fulfilling low-risk criteria were randomized 2:1 to a short hospital stay or standard stay. The trial confirmed on a prospective basis that a reduced hospital stay for low risk patients with acute MI is feasible and worthwhile and results in substantial and sustained reduction in days of hospitalization. Nevertheless, to the best of our knowledge our study is the single sizeable randomized trial that compared a stress-echo guided early discharge to standard strategy after MI. Current guidelines suggest that a patient with an uncomplicated course should be submitted to exercise ECG either sub-maximal before or maximal early after their hospital discharge.3However, there is a paucity of studies documenting the safety of an early exercise test, 4 to 6 days after an acute MI, and authoritative opinions have been expressed against this approach.17On the other hand, an ischaemia-guided approach seems warranted in these patients. The DANAMI study18showed that coronary revascularization in post-MI patients with an ischaemic test results in a reduced rate of reinfarction, in fewer admissions for unstable angina and in a lower prevalence of stable angina. In our study, clinical decisions after risk assessment was left to the treating physician and not defined per protocol. Nevertheless, after 1 year follow up 40% of the patients underwent invasive examination on the basis of a previous non-invasive test. The negative predictive value of standard post-discharge exercise ECG is good, even when patients undergo thrombolytic treatment, as shown in the GISSI 2 study in which six months mortality of patients with a negative exercise ECG was only 1.1%.19Consistent with the aforementioned Trial, in our study, patients with negative test result had low 1 year mortality. Nevertheless, in our study soft events were not unusual in the follow-up of patients with a negative exercise ECG. A possible explanation for this finding is that our patients exercised under full therapy, and 2/3 of the patients were on beta blockers at the moment of exercise. Therefore, they attained low maximal rate-pressure product and this might have reduced test sensitivity in revealing residual ischaemia. Recent data from the Veterans Affairs Non-Q-wave Infarction Strategies in Hospital (VANQWISH) trial confirm that a conservative, ischaemia-guided strategy of selective coronary angiography and revascularization for patients who develop objective evidence of recurrent ischaemia during exercise thallium perfusion scintigraphy, is more cost-effective than a strategy of routine coronary angiography after uncomplicated non-Q wave MI.20,21Previous studies have shown that pharmacological stress echocardiography risk stratifies patients recovering from an acute uncomplicated MI and gives incremental information on top of clinical and exercise ECG data.4,5,22–24We gained a large amount of information in patients with high thereshold positive exercise ECG,23whilst in the same study, stress echocardiography did not add prognostic value in patients with negative stress ECG or low-threshold positive exercise ECG. Nevertheless, the main advantage of echocardiography over exercise is represented by its safety in the early days after the acute event, when exercise-induced elevation of double product should be avoided. Safety of pharmacological stress with dipyridamole was demonstrated in previous studies in different patient populations.25,26Important data on feasibility and efficacy of early post-infarct stratification by dipyridamole stress echo have been previously reported.27The present study confirms the safety of pharmacological stress echo even when used early in patients recovering from an uncomplicated acute MI, thereby providing evidence of possible early discharge with consequent cost reduction during follow up. In particular, patients with a negative early stress echo had no death during follow up and costs of management in this patient population was the lowest. In the present era of economical restraint, the impact of these observations is substantial. Moreover, quality of life assessment at discharge and during follow-up did not show any adverse consequences of an early discharge strategy, confirming previous observations.16Dipyridamole perfusion scintigraphy represents an effective alternative to stress echo in terms of early risk stratification.28Nevertheless stress echo has comparable prognostic accuracy29but lower costs and environmental impact.30

3.1. Study limitations
Some limitations of the study should be acknowledged. Only 74% of the patients in the usual care group performed post discharge exercise ECG. Nevertheless, this represents an example of what is the actual practice in the ‘real world’. Patients not submitted to early stress for identification of residual ischaemia are more likely to abandon the process of risk stratification as compared to a strategy based to pre-discharge stress. Second, the trial is a multicentre, international experience and therefore costs in medical care may differ substantially among institutions in different countries. Third, a shorter duration of hospital stay by protocol may have reduced costs in the standard discharge group. Similarly, a shorter stay may have been considered for the early discharge strategy, were an early stress echo showed effective risk stratification capacity. Fourth, exercise ECG was performed on medication, which might have reduced the accuracy of the exercise test in prediction of subsequent angina. Nevertheless, this approach is current clinical practice and represents a reference standard. Fifth, dipyridamole-stress echo sensitivity is lowered by anti-ischaemic therapy.31This may also contribute to explain the relatively high number of non-fatal infarctions and unstable angina in the follow-up of patients with negative stress echo and the finding that, in our population, patients with negative stress echo had more frequently recurrent chest pain during follow up than patients with a negative post discharge exercise ECG.

Sixth, no off-site reading of stress echo was performed, to ensure that performance of the test could be evaluated according to real-world standards. Nevertheless, the enrolling centres passed a quality control to guarantee a homogeneous interpretation in stress echo reading.

Seventh, the rate of early angiography in our population seems low. In particular, the stress imaging protocol that was performed early did not result in a substantially greater number of these patients being referred for angiography rather than usual care. This might have reflected difficulties in these hospitals getting on the angiography schedule. Nevertheless, the patients that had angiography after discharge wereconsidered at low clinical risk and did not experience any major event waiting for the diagnostic procedure.

Eighth, our data are reassuring that there are no major safety issues with the early discharge strategy, that provided an overall 5.5% major events’ rate as compared to an overall 8.4% major events rate in the usual care, albeit the study was not designed to target this issue alone.

In conclusion, this study shows that an early stress echocardiographic examination for risk assessment allows a safe hospital discharge and lowers costs for management of patients recovering from an uncomplicated MI.


    Appendix A — COSTAMI
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 
Steering Committee:

Chairperson: Alessandro Desideri, Cardiovascular Research Foundation, Castelfranco Veneto, Italy. Paolo Fioretti, IRCAB Foundation, Udine, Italy. Salvatore Pirelli, General Hospital, Cremona, Italy. Leopoldo Celegon, Cardiovascular Research Foundation, Castelfranco Veneto, Italy. Clara Carpeggiani, CNR Institute of Clinical Physiology, Pisa, Italy. Eugenio Picano, CNR Institute of Clinical Physiology Pisa, Italy. JeanLouis Vanoverschelde, University of Luvain, Bruxelles, Belgium. Miodrag Ostojic, University Institute for Cardiovascular diseases, Belgrade,Yugoslavia.

Data base and statistical analysis: Dario Gregori, IRCAB Foundation, Udine, Italy. Riccardo Bigi, Cardiovascular Research Foundation, Castelfranco Veneto, Italy. Jeroen Bax, University Medical Center, Leiden, The Netherlands. Marco Ghidina, IRCAB Foundation Udine, Italy. Elena Gremese, IRCAB Foundation Udine, Italy. Massimo Trentin, IRCAB Foundation Udine, Italy.

Psychological assessment and quality of life: Patricia Rozbowsky, IRCAB Foundation Udine, Italy.

Quality Control in Echocardiography: Eugenio Picano, CNR Institute of Clinical Physiology Pisa, Italy.

Enrolling centres and local Investigators:

Italy: Santo Spirito Hospital, Roma (Claudio Coletta, Maurizio Burattini). S. Giacomo Hospital, Castelfranco Veneto (Alessandro Desideri, Gianleone Suzzi, Raffaele Terlizzi). IRCCS General Hospital, San Giovanni Rotondo (Carlo Vigna, Giovanni Pio Siena). Institute of Cardiology, Udine ( Paolo Fioretti, Antonio di Chiara). General Hospital, Bari (Francesco Tota). General Hospital, Bentivoglio (Biagio Sassone, Riccardo Rambaldi). General Hospital, Vasto (Giacomo Levantesi, Giuseppe di Marco). General Hospital, Torino (Enrico Cecchi). Turkey: Cardiology Department, Instanbul University, Instanbul (Baris Ilerigelen). Cardiology Department, General Hospital, Instanbul (Serdar Kucukoglu).


    Acknowledgments
 
This study is a finalized Project of the Veneto Region, Research project no.825/06/98, endorsed by the Working Groups of Cardiac Rehabilitation and Exercise Physiology and Echocardiography of the European Society of Cardiology, by the Italian Society of Cardiology. We acknowledge support by the Cardiovascular Research Foundation, S. Giacomo Hospital and ‘Club Amici del Cuore-ONLUS’, Castelfranco Veneto, Italy and by the IRCAB Foundation, Udine, Italy (Core Lab).


    References
 Top
 Abstract
 1. Methods
 2. Results
 3. Discussion
 Appendix A — COSTAMI
 References
 

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