Emergency percutaneous coronary intervention in patients with ST-elevation myocardial infarction complicated by out-of-hospital cardiac arrest: Early and medium-term outcome

Article Outline

• Abstract
• Materials and methods
  • Study population
  • Prehospital management
  • In-hospital management
  • Follow-up
  • Definitions
  • Statistical analysis
• Results
  • Baseline patient characteristics and procedural aspects
  • In-hospital outcome
  • Midterm outcome
• Discussion
  • Study limitations
• Conclusions
• Appendix A. Centers and physicians participating in the LombardIMA Registry
• References
• Copyright

Background

The role of emergency reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) resuscitated after an out-of-hospital cardiac arrest (OHCA) has not been clearly established yet. The aim of this study was to evaluate the in-hospital and postdischarge outcomes of STEMI patients surviving OHCA and undergoing emergency angioplasty (percutaneous coronary intervention [PCI]) within an established regional network.

Methods

We prospectively collected data on 2,617 consecutive patients with STEMI treated with emergency PCI in 2005; in-hospital and 6-month outcomes of 99 patients who had experienced OHCA were compared with those of 2,518 patients without OHCA. The OHCA patients also underwent a cerebral performance evaluation after 12 months.

Results

OHCA patients were at higher clinical risk at presentation (cardiogenic shock 26% vs 5%, P < .0001). Percutaneous coronary intervention was successful in 80% of the OHCA and 89% of the non-OHCA patients (P = NS). In-hospital mortality rates were 22% and 3%, respectively (P < .0001). Independent predictors of in-hospital mortality among OHCA patients were longer delay between the call to the emergency medical system and the start of cardiopulmonary resuscitation (odds ratio [OR] 3.5, P = .03), nonshockable initial rhythms (OR 10.5, P = .002), cardiogenic shock (OR 3.05, P = .035), and a Glasgow Coma Scale score of 3 on admission (OR 2.9, P = .032). The 6-month composite rate of death, myocardial infarction, and revascularization among OHCA patients surviving the acute phase was comparable to that of non-OHCA patients (16% vs 13.9%, P = NS), and 87% of them showed a favorable neurologic recovery after 1 year.

Conclusions

Resuscitated OHCA patients undergoing emergency PCI for STEMI have worse clinical presentation and higher in-hospital mortality compared to those without OHCA. However, subsequent cardiac events are similar, and neurologic recovery is more favorable than reported in most previous series.

There is considerable variability in the reported outcomes of patients with out-of-hospital cardiac arrest (OHCA) because of differences in the definition and ascertainment of the event, as well as in its etiology and treatment. In particular, the role of coronary reperfusion strategies in patients experiencing a myocardial infarction complicated by OHCA has not been established yet.

Thrombolytic therapy has not been shown to improve outcome in OHCA patients with ST-elevation myocardial infarction (STEMI), with in-hospital and 30-day mortality rates of more than 80%.¹, ² Various studies of emergency percutaneous coronary intervention (PCI) in patients with OHCA have reported in-hospital mortality rates of between 24% and 62%³, ⁴, ⁵; however, in addition to their generally limited sample size, these studies are further limited by the fact that most were retrospective and did not compare management and outcomes of STEMI patients with or without OHCA. Furthermore, few data exist addressing the medium- or long-term outcome of OHCA survivors; in particular, neurologic outcome is poorly described or not available in most of the reports.⁴, ⁵, ⁶, ⁷, ⁸ The aim of this study was to evaluate the in-hospital and postdischarge outcomes with regard to vital and neurologic status of STEMI patients surviving OHCA and undergoing emergency PCI within an established regional network and to identify factors predicting in-hospital mortality.

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Materials and methods 

Study population 

The data come from the LombardIMA (Lombardia acute myocardial infarction) registry, which collects data relating to PCI in STEMI in Lombardy, a region in Northern Italy with a population of nearly 9.5 million inhabitants. The network includes 67% of the PCI centers in the region. A Web-based prospective electronic Case Report Form was used to collect data on 2,617 STEMI patients who underwent PCI between January and December 2005, 99 of whom (3.8%) had experienced OHCA. Demographic, clinical, and angiographic characteristics, as well as in-hospital and 6-month outcomes of OHCA patients were compared with those of the 2,518 patients treated with emergency PCI during the same period of time but did not have an OHCA. In the case of OHCA patients, additional information concerning the times and type of arrest, the presence of witnesses at the time of the event, the initial resuscitation maneuvers of bystanders and subsequent patients' neurologic condition, as well as pharmacologic therapies administered in the ambulance, were obtained post hoc from the records of the emergency medical system (EMS). Resuscitation time was defined as the interval of time elapsed between the call for an advanced life support (ALS) ambulance and the start of resuscitation maneuvers by the ambulance crew: these 2 time points are systematically collected in the EMS report forms.

Prehospital management 

All OHCA patients received prehospital care by ALS ambulances with full resuscitation equipment manned by physicians and nurses trained in emergency medicine. All patients required external defibrillation or external cardiac massage, and 82% of them required endotracheal intubation. Vasopressor drugs (epinephrine or dopamine) were administered in the case of cardiogenic shock or hemodynamic instability, and antiarrhythmic drugs (amiodarone, lidocaine, or atropine) in the case of ventricular fibrillation/tachycardia and asystole, respectively. After the resuscitation maneuvers, all patients included in the present analysis experienced the return of spontaneous circulation. Ninety-seven percent of the OHCA patients were taken directly to a PCI center, whereas 3% were taken first to a non-PCI center and then transferred to a PCI center.

In-hospital management 

As soon as possible, after undergoing 12-lead electrocardiogram (ECG) and a hemodynamic assessment, all patients underwent coronary angiography and subsequent PCI. According to hospital routine, a bolus of unfractionated heparin was administered before angioplasty at a dose of 100 U/kg in the case of no glycoprotein (GP) IIb/IIIa receptor blockers use, 70 U/kg in the case of the concomitant use of GP IIb/IIIa inhibitors, or a lower dose after fibrinolytic therapy; subsequent intraprocedural boluses were administered based on activated clotting time values. Aspirin (250-500 mg) was given intravenously before the procedure. Patients undergoing stent implantation received dual antiplatelet therapy (aspirin 100 mg/d plus clopidogrel at a loading dose of 300 mg followed by 75 mg/d or ticlopidine 500 mg/d) for at least 1 month after bare metal stents, or at least 6 months after of drug-eluting stents. Intraaortic balloon pumping was used for cardiogenic shock or severe hemodynamic instability. After the interventional procedure, patients requiring intubation for ventilatory assistance were initially admitted to a general intensive care unit, whereas the others were admitted to a coronary care unit. The use of controlled hypothermia (32°C-34°C) for 24 hours⁹ was according to hospital routine in individual centers. During the period of hospitalization, major adverse events were prospectively recorded in the electronic Case Report Form, including death due to any cause, reinfarction, need for urgent percutaneous or surgical coronary revascularization, occurrence of stroke, and major hemorrhagic complications according to thrombolysis in myocardial infarction (TIMI) criteria.¹⁰

Follow-up 

The 6-month clinical outcome was obtained in 98% of the survivors and was evaluated by means of a direct visit or telephone contact. None of the OHCA patients but 2% of the controls was lost to follow-up. All of the OHCA patients (but no patient in the non-OHCA group) also underwent a cerebral performance evaluation after 12 months.

Definitions 

ST-elevation myocardial infarction was defined as a 12-lead ECG finding of >2 mm ST-segment elevation in >2 contiguous leads or the new appearance of left bundle-branch block in the presence of at least one angiographically detected culprit lesion. Cardiogenic shock was defined as systolic blood pressure <90 mm Hg lasting >60 minutes; nonresponsive to fluid challenge or requiring the administration of inotropic drugs to obtain a systolic blood pressure of >90 mm Hg; associated with tachycardia (heart rate >100/min); and clinical signs of peripheral hypoperfusion such as low urine output (<30 mL/h), cold sweat, or cyanosis. Percutaneous coronary intervention success was defined as final TIMI 3 flow with residual stenosis <20%. Stroke was defined as any new neurologic deficit lasting >24 hours. Computed tomographic or magnetic resonance imaging was required to confirm the stroke and to distinguish between ischemic and hemorrhagic stroke. Strokes were also to be classified as fatal or nonfatal: nonfatal stroke was also to be classified as disabling and nondisabling.

Neurologic status after the resuscitation maneuvers was evaluated by using the Glasgow Coma Scale (GCS),¹¹ whereas neurologic recovery at follow-up was assessed using the Cerebral Performance Category (CPC) scale,¹², ¹³ which has 4 grades. Briefly, grade 1 corresponds to a good cerebral performance, with the patient being conscious, alert, and able to work and lead a normal life, although he may have minor psychologic or neurologic deficits; grade 2 corresponds to moderate cerebral disability, with the patient being conscious and having sufficient cerebral function to be able to work part-time in a sheltered environment or to perform activities of daily living independently; grade 3 corresponds to severe cerebral disability, with the patient being conscious but dependent on others for daily support, and having at least limited cognitive ability; and grade 4 corresponds to a permanent vegetative state, with the patient being unconscious, unaware of his surroundings, without any cognitive ability, and with no verbal or psychologic interaction with the environment.

Statistical analysis 

Continuous variables are expressed as mean ± SD or median and 25th to 75th percentile, and discrete variables as proportions. Between-group differences were evaluated using the χ² test for the categorical variables (with Yates correction when appropriate) and the t test for continuous variables. In the OHCA patients, the candidate predictors of in-hospital outcome were initially assessed by means of the univariate analysis of demographic, clinical, angiographic, and procedural variables; the variables with a P value of <.10 were included in a multivariate logistic regression model to identify the independent predictors of mortality. The risk estimates for each variable are reported as odds ratio (OR) and 95% CI. Owing to missing information for some variables, the multivariate analysis involved 78 patients (79%). A P value of <.05 was considered statistically significant. All of the analyses were performed using the SPSS 11.0 software package (SPSS Inc, Chicago, IL).

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Results 

Baseline patient characteristics and procedural aspects 

During the study period, 99 (3.8%) of 2,617 consecutive patients undergoing emergency PCI for STEMI had survived OHCA. Table I shows the prehospital data of the OHCA survivors. The median resuscitation time was 7 minutes, although cardiac arrest occurred after the ambulance was called in 19 patients and in the presence of emergency medical team in 3 patients. At the time of first medical aid, 90 patients presented with ventricular fibrillation or pulseless ventricular tachycardia, whereas 9 were in asystole. In the 69 patients with witnessed cardiac arrest, the median resuscitation time was 8 minutes (25th-75th percentile, 5-9 minutes) for the patients with a shockable rhythm but 15 minutes (25th-75th percentile, 8-22 minutes) for those found with asystole.

Table I. Preadmission characteristics and variables of 99 patients with OHCA

Characteristic	Value
Witnessed cardiac arrest
Yes	69
No	9
Unknown	21
Bystander CPR
Yes	36
No	43
Unknown	20
Time between EMS call to CPR start (min)
Median (25th-75th percentile)	7 (5-10)
Initial recorded rhythm
Ventricular fibrillation	88
Pulseless ventricular tachycardia	2
Asystole	9
Vasopressors in ALS ambulance
Yes	61
No	27
Unknown	11
GCS at admission
3	37
>3	51
Unknown	11

The demographic and clinical characteristics of the patients are shown in Table II. The patients with OHCA were younger, whereas the prevalence of risk factors and comorbidities were similar in the 2 groups. Cardiogenic shock was present on admission in 26% of the OHCA patients and 5% of the controls (P < .001). Myocardial infarction was diagnosed in a prehospital setting using a 12-lead ECG more frequently among the patients with OHCA (36% vs 8%, P < .0001). However, only 3% of the OHCA patients, compared with 11% of the non-OHCA (P = .017), received pharmacologic reperfusion therapy, including lytics or a combination of GPIIb/IIIa inhibitors and lytics before PCI.

Table II. Demographic and clinical features

CAD, Coronary artery disease; MI, myocardial infarction; CABG, coronary artery bypass grafting; SBP, systolic blood pressure; HR, heart rate.

Table III shows the angiographic characteristics of the patients and the procedural details. Total ischemic and first aid-to-balloon times were similar in the 2 groups. There were no significant differences between groups in the extent of coronary disease, whereas involvement of the left coronary artery was more frequent among OHCA patients. Among the patients with cardiogenic shock, intraaortic balloon pumping was used in 85% (22/26) of the OHCA patients and 99% (117/118) of the non-OHCA patients. There were no significant differences with regard to the results of the PCI, although there was a trend toward a greater final TIMI 3 flow and more complete ST resolution (>50%) rates in the non-OHCA group.

Table III. Angiographic and procedural features

	With OHCA (n = 99)	Without OHCA (n = 2518)	P
Symptoms to balloon⁎ (min)	168 (131-226)	180 (135-258)	.3
First aid to balloon⁎ (min)	77 (52-96)	74 (50-100)	.5
1-Vessel disease	51 (52%)	1208 (48%)	.7
2-, 3-Vessel disease	48 (48%)	1185 (47%)	.9
Infarct-related vessel
LAD	53 (53%)	1183 (47%)	.5
LCX	21 (21%)	329 (13%)	.07
RCA	22 (22%)	964 (38%)	.03
Graft	2 (2%)	31 (1%)	.8
Left main	1 (1%)	1 (0.0004%)	.1
Stent	90 (90%)	2338 (93%)	.9
IABP	22 (22%)	117 (5%)	<.0001
GPIIb/IIIa inhibitors	68 (68%)	1655 (66%)	.8
Thrombectomy/distal protection	13 (13%)	257 (10%)	.5
Pre-PCI TIMI 0-1 flow	84 (84%)	2038 (82%)	.8
Final TIMI 3 flow	80 (80%)	2239 (89%)	.5
ST-segment resolution >50%	57 (57%)	1767 (70%)	.2

LAD, Left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery; IABP, intraaortic balloon pump.

After PCI, 75% of the OHCA patients were still requiring mechanical support for ventilation and were initially admitted to a general intensive care unit, whereas all other patients were admitted to a coronary care unit. Among the OHCA patients, 30% (12/37) of those admitted with GCS 3 underwent controlled hypothermia for 24 hours.

In-hospital outcome 

As shown in Table IV, in-hospital mortality was significantly higher among the OHCA patients and was mostly due to cardiac causes or irreversible cerebral ischemia. Besides the 5 patients who died because of neurologic causes, further 9 OHCA patients were discharged with diagnosis of cerebrovascular accident (stroke or hypoxic brain injury), whereas in the non-OHCA group, the overall incidence of cerebral ischemic complications during the index admission was 0.7% (all nondisabling ischemic strokes) (P < .0001). The need for further urgent revascularization was similarly low in the 2 groups. Major bleeding was significantly more frequent in OHCA patients, exclusively due to bleeding from instrumented arterial sites. Of the 77 OHCA patients discharged alive, 36 were discharged home 11 ± 3 days after admission, whereas 41 were transferred to rehabilitation hospitals.

Table IV. Major cardiovascular outcomes (in-hospital and at 6 months)

	With OHCA (n = 99)	Without OHCA (n = 2518)	P
In-hospital
Overall mortality	22 (22%)	75 (3%)	<.0001
Cardiac	16 (16%)
Neurologic sequelae	5 (5%)
Sepsis	1 (1%)
Nonfatal cerebrovascular events	9 (10%)	18 (0.7%)	<.0001
Urgent revascularization	1 (1%)	33 (1.3%)	.9
Major bleeding	4 (4%)	23 (0.9%)	.01
From discharge to 6 m
Overall mortality	3 (4%)	49 (2%)	.47
Reinfarction	2 (3%)	29 (1.2%)	.58
Revascularization	7 (9%)	261 (10.7%)	.80

The univariate predictors of in-hospital mortality among OHCA patients are shown in Table V. Longer intervals between the call of the EMS and the start of cardiopulmonary resuscitation maneuvers, a nonshockable rhythm, cardiogenic shock on admission, and a grade 3 GCS were the independent predictors of in-hospital mortality among OHCA patients (Figure 1).

Table V. Predictors of in-hospital death among OHCA patients (univariable analysis)

Values are expressed as mean number with percentages of the total in parentheses, except where indicated otherwise.

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• Figure 1. 

  Independent predictors of death among OHCA patients (multivariate logistic regression analysis).

Midterm outcome 

As shown in Table IV, among the patients discharged alive, the rates of death, myocardial infarction, and revascularization at 6 months were similar among those with or without OHCA (16% vs 13.9%, P = NS). None of the OHCA survivors experienced recurrent cardiac arrest or sudden death at follow-up. At 12 months, 67 (87%) of the 77 OHCA survivors showed almost complete neurologic recovery (CPC 1) and 2 (3%) moderate neurologic disability (CPC 2), whereas 3 patients (4%) were affected by severe neurologic sequelae (CPC 3) and 5 (6%) were in a permanent vegetative status (CPC 4). Of the 20 patients with GCS 3 on admission and discharged alive, 1 died after 5 months, whereas 6 (30%) had poor neurologic outcome (CPC 3 or 4) at 12-month follow-up.

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Discussion 

The present study reports the largest prospective population, described so far, of consecutive STEMI patients with OHCA treated by emergency angioplasty and allows the formulation of more firm conclusions compared with previously available evidence. A first piece of information is the incidence of OHCA among STEMI patients treated with emergency PCI, which in our registry was 3.8%, a figure lower than previously reported.¹⁴ Second, the present study shows that OHCA patients admitted with a clinical evidence of STEMI and treated by emergency PCI have a much higher in-hospital mortality compared with non-OHCA patients but a much lower mortality compared with previous series of OHCA. As in previous studies,³, ⁴, ⁵ the high absolute mortality is likely due to the high-risk presentation in the OHCA group, with a much higher prevalence of cardiogenic shock on admission compared with controls. On the other end, the lower than reported mortality may represent the result of early cardiopulmonary resuscitation (CPR), implemented in parallel with the regional network for emergency PCI in STEMI, also of the more efficient myocardial reperfusion and circulatory support allowed by early PCI. Prior studies¹⁵, ¹⁶ have shown that prompt CPR can favorably affect the outcome of OHCA patients and, more specifically, that a time interval of less than 6 minutes between onset of cardiac arrest and first intervention is predictive of survival.⁵ In the present study, the median resuscitation time was 7 minutes, and this relatively short time to intervention may have been the main reason for the high prevalence of shockable initial rhythms (91%) that, as in other series,¹⁷, ¹⁸, ¹⁹ was found to be an independent predictor of survival in the present study. Because ventricular fibrillation tends to convert in nonshockable rhythms over time, asystole is considered to reflect a longer duration of the hypoxic insult or a more extensive cardiac damage.¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹ Also, in the present study, the median resuscitation time of patients found with asystole was almost twice as long as that of patients with a shockable rhythm.

A measure of the impact of emergency PCI on outcome of OHCA cannot be derived from randomized trials comparing primary PCI with lytic therapy because those trials excluded OHCA patients. However, because primary PCI has been shown to be particularly effective in higher-risk patients, such as those with cardiogenic shock,¹⁹ which in the present series represent 26% of the OHCA population, it is reasonable to conclude that emergency PCI may be lifesaving in OHCA survivors with a clinical diagnosis of STEMI.

Outcome of OHCA patients was dependent not only on the extent of cardiac damage but also on the severity of the neurologic deficit on admission, which was also an independent predictor of in-hospital death among these patients. Contrary to previous findings, showing no relation between the neurologic status very early after resuscitatory maneuvers and subsequent clinical outcome,²² we found that a GCS score of 3 was an independent predictor of in-hospital mortality. As suggested by cerebral computed tomographic or magnetic resonance scans performed during hospital stay, the neurologic impairment observed in OHCA patients who died during index hospital stay was almost exclusively attributable to prolonged cerebral hypoxia. A further 9 OHCA patients were discharged with a diagnosis of cerebrovascular accident; however, in these patients, it cannot be determined if the cerebrovascular events should be attributed only to hypoxic sequelae or also to further ischemic complications occurring during hospital stay.

Another important finding of the present study is the positive vital outcome of the OHCA patients surviving hospitalization which, at 6 months, did not differ significantly compared with that of non-OHCA patients. Bunch et al²³ found that, after 5 years, the clinical outcome in survivors after cardiac arrest was similar to that observed among age-, sex-, and disease-matched controls. However, in that study, the cause of arrest could be attributed to an acute coronary syndrome only in about half of the patients. Moreover, whereas most of the follow-up studies in OHCA patients have shown that about a half of all survivors have cognitive or motor deficits that require a major lifestyle change,⁶, ⁷, ⁸ the 1-year neurologic outcome was much more favorable in our patients because 87% of them were found to run an active life without functional limitations and only 13% were affected by severe neurologic disability or were in a vegetative status. This rather benign outcome may be attributed to the fact that STEMI is a curable pathophysiologic substrate for cardiac arrest, and immediate CPR followed by systematic early mechanical revascularization and circulatory support may actually have represented a significant step forward for the fate of this dramatic condition. The fact that no patient in our series experienced recurrent cardiac arrest at 1-year follow-up represents further proof of this concept.

The 12-month mortality of patients with CGS 3 on admission but surviving the acute phase is superimposable to that of patients on GCS >3, whereas the neurologic outcome is much worse. However, it is hard to conclude that the neurologic status on admission should be used as a tool for decision making because, in the present study, two thirds of the patients on CGS 3 on admission showed an almost complete neurologic recovery, and it has been shown that only a GCS <5 persisting after 72 hours, but not on admission, has a negative predictive value for awakening of nearly 100%.²⁴

Study limitations 

The LombardIMA registry is a prospective and systematic database on emergency angioplasty in STEMI, but the prehospital data on OHCA patients shown in the present study were collected retrospectively from the EMS records. Therefore, whereas the in-hospital and follow-up data are almost complete, some of the prehospital data were incomplete for 20% of the patients, a value not dissimilar from other reports of OHCA.²⁵ Because of this missing data, the logistic regression analysis of the predictors of in-hospital mortality refers only to the 78 patients with complete prehospital data, which may have limited the power of the analysis. However, as shown in Table V, of the 4 prehospital variables with missing data (witnessed cardiac arrest, bystander CPR, vasopressors and GCS on admission), the first 3 had largely insignificant (between .4 and .8) P levels for the difference between dead and alive at univariate analysis, whereas the latter was clearly significant (P = .014) despite some missing values. Therefore, it seems unlikely that the missing data have significantly affected the results of logistic regression analysis. Moreover, it should be kept in mind that the present study reflects the point of view of the cardiologist or ER physician rather than that of the emergency physician, that is, what should be done when a patient arrives to hospital after an OHCA and the ECG demonstrates a STEMI. At this point, immediate decision making is more dependent on the actual patient condition (ECG, cardiac rhythm, and hemodynamics) rather than on accurate information about prehospital issues.

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Conclusions 

Patients with STEMI complicated by OHCA who were resuscitated by the EMS and surviving up to emergency PCI have a worse clinical presentation and experience a higher in-hospital mortality compared with those who did not have OHCA. Unfavorable prognostic factors are a longer resuscitation time, the presence of nonshockable rhythms, cardiogenic shock, and severe neurologic impairment on admission. However, an aggressive approach including rapid out-of-hospital rescue and emergency PCI, with mechanical hemodynamic support as indicated, seems to provide much better outcome compared with historical controls. Following this approach, 60% of OHCA patients survive at 6 months without experiencing further cardiovascular events or with neurologic sequelae. The 6-month outcome of OHCA patients discharged alive is comparable to that of those who have not experienced cardiac arrest. One-year neurologic recovery is favorable in most of the cases; even among the patients admitted with GCS 3 and surviving index admission, two thirds of them had favorable neurologic outcome at 1 year.

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Appendix A. Centers and physicians participating in the LombardIMA Registry 

Cliniche Gavazzeni, Bergamo: Dr Paolo Sganzerla, Dr Carlo Savasta.

Ospedali Riuniti di Bergamo: Dr Giulio Guagliumi, Dr Giuseppe Musumeci, Dr Luigi Fiocca.

Ospedali Civili di Brescia: Dr Luigi Niccoli, Dr Federica Ettori.

Ospedale di Circolo, Busto Arsizio: Dr Marco Onofri.

Ospedale di Chiari: Dr Franco Bortolini, Dr Claudio Gentilini.

Azienda Ospedaliera S. Anna, Como: Dr Giovanni Ferrari, Dr Laura Cattaneo.

Ospedale di Crema: Dr Paolo Valentini.

Istituti Ospitalieri di Cremona: Dr Salvatore Pirelli, Dr Enrico Passamonti.

Ospedale di Desio: Dr Pietro Vandoni.

Ospedale di Erba: Dr Camillo Falcone.

Ospedale S. Antonio Abbate, Gallarate: Dr Francesco Galdangelo.

Ospedale Moriggia-Pelascini, Gravedona: Dr Alessandro Politi.

Ospedale Civile “Manzoni,” Lecco: Dr Luigi Piatti, Dr Gianluca Tiberti.

Ospedale Civile di Legnano: Dr Stefano De Servi, Dr Maurizio D'Urbano.

Azienda Aspedaliera “Carlo Poma,” Mantova: Dr Roberto Zanini, Dr Corrado Lettieri,

Dr Luca Tomasi.

Azienda Ospedaliera “Niguarda Cà Granda,” Milano: Dr Silvio Klugmann, Dr Roberto Pirola, Dr Paola Colombo, Dr Giovanni Sesana.

Centro Cardiologico “Monzino,” Milano: Dr Antonio Bartorelli, Dr Franco Fabbiocchi, Dr Cesare Fiorentini.

Istituto Clinico S. Ambrogio, Milano: Dr Francesco Bedogni, Dr Paolo Salvadè.

Ospedale Sacco, Milano: Dr Maurizio Viecca, Dr Emanuela Piccaluga.

Ospedale S. Carlo, Milano: Dr Maurizio Marzegalli, Dr Marco Caprari.

Ospedale San Paolo, Milano: Dr Carlo Sponzilli.

Ospedale S. Raffaele, Milano: Dr Antonio Colombo, Dr Giuseppe Sangiorgi, Dr Tiziana Aranzulla.

Ospedale San Gerardo, Monza: Dr Virgilio Colombo.

Policlinico San Matteo, Pavia: Dr Ezio Bramucci, Dr Alessandra Repetto.

Ospedale Civile di Rho: Dr Gianni Rovelli.

Istituto Clinico Humanitas, Rozzano: Dr Patrizia Presbitero, Dr Elena Corrada, Dr Guido Belli.

Policlinico Multimedica, Sesto San Giovanni: Dr Luigi Maiello.

Azienda Ospedaliera di Treviglio: Dr Antonio Pitì.

Ospedale di Circolo, Varese: Dr Battistina Castiglioni.

Azienda Ospedaliera di Vimercate: Dr Stefano Garducci, Dr Tiziana Zaro.

Policlinico San Marco, Zingonia: Dr Nicoletta De Cesare.

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