Knock on the Right Door . How we are Treating the Patient with Acute Myocardial Infarction

Mailing Address: Clovis Hoepfner Orestes Guimaraes, 422, Apto 901. Postal Code: 89204-060, Centro, Joinville, SC Brazil E-mail: hoepfner@cardiol.br, clinica@espacovitagt.com.br Knock on the Right Door. How we are Treating the Patient with Acute Myocardial Infarction Clóvis Hoepfner,1,3 Edilson Roma,2 Jessé Vinicius Lana,3 Ana Luysa Santin,3 Ana Lavratti Borga,1 Ana Cláudia Yamamoto,1 Juliana Vicente Techentin1 Hospital Municipal São José,1 Joinville, SC Brazil Hospital Regional Hans Dieter Schmidt,2 Joinville, SC Brazil Universidade da Região de Joinville,3 Joinville, SC Brazil


Introduction
Acute myocardial infarction (AMI) is one of the major causes of death in Brazil. 1,2Heart failure and sudden death, the most severe complications of AMI, are the most serious manifestations of atherosclerotic disease.2][3] Similar to the in-hospital mortality, 30-day mortality decreased from 8.6% to 3.6% in some North American states between 1988 and 2000. 3In Brazil, 30-day mortality is 15.4% 2 according to the Brazilian Unified Health System (SUS) Computing Department (DATASUS).

Original Article
For this reason, patients' diagnosis, transportation and treatment should be fast.
In 2011, the Ministry of Health implemented an integrated system for AMI management (the Linha de Cuidado do Infarto Agudo do Miocárdio) through healthcare units of the SUS, and a clinical protocol on acute coronary syndrome (ACS) (the Protocolo Clínico sobre Síndrome Coronariana Aguda). 2 These were created to propose an integrated action for ACS treatment, grounded on its high prevalence and important role in morbidity and mortality.
In the city of Joinville, SUS provides emergency care units, general hospitals and a referral hospital.Coronary angiography and angioplasty are available in the referral hospital only, and none offers cardiac care services available 24 hours a day.Joinville Secretary of Health promoted the publication of a booklet entitled "Bata na porta certa" ("Knock on the right door") to guide healthcare providers and users in directing themselves to the correct units for health assistance. 20For example, the booklet suggests the best emergency care units for chest pain in the city.Our study aimed to identify where AMI patients sought medical care at first place (the "front door") and the time elapsed from initial care received by the patients (first medical contact) and myocardial reperfusion.

Methods
This was a retrospective analysis of medical records, including 112 patients with ST-segment elevation myocardial infarction (STEMI) who had undergone coronary angiography in the period between 09/28/2013 and 05/28/2014.Data were collected at the Catheterization Laboratory, at Santa Catarina State referral hospital, at Joinville Hospital and at three emergency care units of the city.
We registered: the place where patients received initial care, the time (min) between pain onset and the moment the patient was seen at the unit; the time (min) between admission to the first unit and admission to the referral hospital; the time (min) between admission to the referral hospital and coronary angiography test; and whether coronary thrombolysis was performed.Due to missing data, the door-to-balloon time was not recorded.When the "front door" to medical care was not found in patients' records, we attempted to contact patients by telephone.In addition, we also collected data on the occurrence of heart failure, myocardial revascularization and death.
The study was approved by the ethics committee of Joinville Regional University (UNIVILLE), by Joinville Secretary of Health, and by hospitals and catheterization laboratory involved in the study.

Statistical analysis
Statistical analysis was performed using the Statistical Package for the Social Sciences for Windows version 17 (SPSS Inc.Chicago, Illinois).Continuous variables with normal distribution were expressed as mean ± standard deviation, and frequency analysis was used for categorical variables.Data normality was verified by the Kolmogorov-Smirnov test.Between-group comparisons were performed by the Student's t test for independent, continuous variables and by the chi-square test for nominal variables.The level of significance was set at 5% (95% confidence interval, 95%CI).

Results
We studied 87 men and 24 women, mean age of 58.3 (23-82) years.The "front door" to the emergency care was the emergency care unit for 44 patients, the referral hospital for 16 patients, the city hospital for 4, the emergency medical service transport system for 5, and primary health centers for 2 patients; in 29 patients this information was not available.The other patients were transfered from other cities.Event duration (time elapsed between pain onset and coronary angiography) was probably shorter than 12 hours in 71 patients (65.7%) and longer than 12 hours in 39.This was in fact an estimate, calculated as the sum of minutes during the period between the first medical assistance and coronary angiography test, since duration of pain was not recorded in the medical records.In addition, in emergency care units, most of the medical records could not be accessed, since they were usually registered behalf of patients and filled in other institution.The medical records of patients referred from other cities were also not available, and we rarely obtained useful information by phone contact in these cases.Percutaneous transluminal angioplasty (PTA) was performed in 92 (82.1%) patients and the door-toangiography time (DAT) was shorter than 90 minutes in 50 (44.2%)patients (Table 1).No statistically significant difference was seen in DAT, sex or age between patients admitted to the referral hospital and the others.DAT was not available in 14 patients.No patients received thrombolytic drugs.

Discussion
In 2001, Gibson posed a question he was often asked: "what do we need to do to improve mortality by another 1% in the setting of acute myocardial infarction?" and then answered that this could not be achieved exclusively with new drugs and devices but also by reducing the time to treatment. 4Our results suggest that we are far from achieving these objectives.When mentioning the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT 2) report, 5 Gibson emphasized the importance of performing electrocardiography for the diagnosis and a time to treatment < 2 hours.
In the ASSENT-2 trial, the investigators assessed electrocardiographic changes and 1-year mortality in 13,100 patients undergoing primary thrombolysis.Inhospital mortality and late mortality were proportional to pain duration and inversely proportional to ST-T resolution (lower and upper limits of 3.8 and 13%) in one year. 5 our study, analysis of the medical records revealed that results of cardiac enzyme tests for diagnosis and treatment decisions are still lacking in many of them.
Acute coronary syndrome, notably AMI, is the major cause of cardiac deaths in Brazil. 1,22][3] Until 1980, there were insufficient medical resources to achieve significant reductions in in-hospital and late mortality.In 1979, Rentrop published the first results of intracoronary injection of streptokinase.Coronary angiography performed during and after STEMI showed spontaneous recanalization in nearly 40% of patients, increased to 70% with thrombolytic therapy.These findings were confirmed by Ganz in 1982.8][19] A mean reperfusion time < 180min has been reported in attempt to provide adequate assistance to patients before (by administration of thrombolytic drugs) and during hospitalization (primary angioplasty).Systematic reviews by Keeley et al., 13 updated by Asseburg et al., 14 including short term and six-month outcomes, showed that compared with thrombolytic agents, reduction in mortality and in non-fatal outcomes with primary angioplasty was only significant when time delay was shorter than 45 minutes and 90 minutes, respectively. 15,16The use of thrombolytic therapy was even more efficient in reducing mortality according to six randomized studies by Morrison et al. 15 In-hospital thrombolysis and prehospital thrombolysis decreased the mean duration of pain until reperfusion by 162 and 104 minutes, respectively.Thrombolytic therapy followed by short-term angioplasty is efficient in reducing short-term and long-term events, regardless of the presence of multi-vessel or one-vessel injury. 16ny factors can influence the rescue of patients with STEMI -the patient, who should seek medical assistance as soon (and if) he perceives the symptoms; healthcare professionals who should diagnose the condition and provide the patient with adequate treatment as early as possible, and performance of reperfusion therapy.In Joinville, the SUS offers three emergency care units and three public hospitals (including one referral center for coronary angiography and angioplasty).The efficacy of this system was unknown, although there were reports of difficult accessibility of paramedics to the referral hospital and delayed arrival of patients to the catheterization laboratory.With the permission of the catheterization laboratory, we identified the patients with ACS seen at the unit, their "front door" to medical care, and the time from the first assistance to reperfusion with angioplasty.][22][23] It is estimated that approximately 20% of patients arrive at the clinics within two hours of pain onset. 2 In fact, public health systems can provide guidance for their users through several actions. 3,10,204][21][22][23] Electrocardiography (ECG) is an old, cheap test, essential in diagnosing and guiding therapeutic approaches.In 2002, a European task force emphasized the importance for both patients and healthcare providers to identify high-risk chest pain. 24hen symptoms occurred at home, patients wait a mean of 60 minutes before seeking help, and up to 25% of them wait for four hours or more. 7,24In emergency services, the unawareness of the low sensitivity (approximately 50%) of the ECG test in confirming AMI may affect the diagnosis.The authors reinforced the need for serial ECG at short intervals (minutes) to diagnose the disease, in accordance with Brazilian guidelines recommendations, 1 rather than performing ECG tests every three hours, as usually occurs.
Unfortunately, some paramedics do not receive adequate training in ECG and rely on cardiac enzyme tests.3]21 Delay in the results leads to a delayed and inefficient reperfusion therapy.Boersma et al., 12 in a review of 22 studies published between 1983 and 1993 including 50,246 patients undergoing coronary thrombolysis showed that the greatest benefit on 30-day mortality is achieved by the therapy performed within the first two hours.][14][15][16][17] The ACCEPT/SBC (Clinical Outcomes at 30 days in the Brazilian Registry of Acute Coronary Syndromes), 22 a multicenter study of 47 Brazilian hospitals carried out in 2010 and 2011 showed a use of thrombolytic drugs lower than 15%.In addition, reperfusion therapy was not performed in 22.3% of patients with STEMI; mortality in this group was higher than that in the group that received reperfusion therapy (8.1% vs. 2.0%).In the reperfusion group, mean door-to-angiography was 125 (± 90) minutes.
The Global Registry of Acute Coronary Events (GRACE), in a six-month follow-up, also showed greater mortality in patients that did not receive reperfusion therapy. 26In our sample, no patient used thrombolytic drugs (which are not available in the emergency care units but are available in the hospitals).Transluminal angioplasty was performed in 86.1% of patients.Our results indicated that almost all STEMI patients were negatively affected by delayed or absent reperfusion.1][12][13] Several reports 3,6,13,15,[21][22][23] have demonstrated that extensive myocardial infarction depends on the best quality medical care to prevent complications and in-hospital and late mortality.
Due to incomplete or missing data in the medical records, we could not identify the complications of STEMI.In the study group, two in-hospital deaths were registered, suggesting the presence of less severe conditions in this group.One limitation of the study is the lack of documentation of pain duration before medical assistance in all medical reports.If we assume a 2-hour period for that, 1,4,5,24 few patients would have been undergone angioplasty within a four-hour period.Some patients had a very short DAT (10-20 minutes) because the front door, in these cases, was the catheterization laboratory.Only three patients went directly to the referral hospital and hence may have had a pain-doorangiography time shorter than 4 hours.
Wang et al., 27 analyzed the data from 101 hospitals in the "Get With the Guidelines" program of the American Heart Association, started in 2000 and reinforced by the D2B Alliance campaign focused on reducing door-toballoon time.Data of 43,678 AMI patients were compared between 2005 and 2007.After exclusion of patients with non-STEMI, patients transferred in from other hospitals, patients without angioplasty or with late angioplasty, 5,881 patients undergoing primary angioplasty were assessed.Although door-to-balloon time decreased from 101 to 87 minutes, there was no significant reductions (from 5.1% to 4.7%) in in-hospital mortality.Since 2005 data had already revealed satisfactory in-hospital mortality parameters, the authors highlighted the importance of prehospital measures.
Between 2002 and 2008 in Denmark, Terkelsen et al., 10 included 13,439 consecutive patients with STEMI referred for reperfusion therapy.The Danish National Health Service provides ambulances equipped with electrocardiographic system and defibrillator.Users of the health service can call the emergency medical service, and those deemed in need of an ambulance are transported to the catheterization laboratory.The study was designed to evaluate the effect of several variables on late mortality.Patients were allocated into two groups, one transported directly to the percutaneous coronary intervention center and the other group transported to local hospitals first and then transferred to the treatment center.The time from pain onset to initiation of reperfusion therapy was calculated and categorized in patient delay, transportation delay, doorto-balloon time, system delay and total delay in both groups, in addition to hospital delay and prehospital system delay (time between transportation and arrival at the percutaneous coronary intervention center in one of the groups.After exclusion of patients that did not receive reperfusion, patients with a treatment delay longer than 12 hours, and patients with missing data, a total of 6,209 patients were followed-up.Door to balloon time was 39 (24-70) minutes in the group directly transported to treatment center and 29 (21-72) minutes in the other group.The study showed that in the group transferred from other hospitals, treatment delay was significantly longer (240 minutes vs. 170 minutes) than in the group directly transported for treatment.Mean follow-up period was 3.4 (1.8-5.2) years, with mortality of 15.4% in patients with system delays < 60 minutes, 23.3% in those with delays of 61-120 minutes, 28.1% in those with delays of 121-180 minutes, and 30.8% in those with delays of 180-360 minutes.Multivariate analysis showed that both prehospital delay and doorto-balloon time were associated with mortality, and efforts should be made to reduce them.Barreto et al., 28 also demonstrated that transportation delay from other centers to the catheterization laboratory was a predictor of adverse events.Bagai et al., 22,23 compared patients evaluated in the emergency department and those transported directly to the catheterization laboratory.The authors reported that a median time of 30 minutes was spent in the emergency department, with potential decrease.The authors confirmed the beneficial effects of ambulance services and direct transportation of patients to the catheterization laboratory on the door-to-balloon time.However, the authors highlighted that the service is used infrequently and no differences in in-hospital mortality was observed between the groups.Jollis et al., 21 published the first results of the STEMI Systems Accelerator project, a large national effort to adequate regional STEMI care to national guidelines in the USA.The program was developed in 2012 and included emergency medical services and hospitals, regional and central coordinators, training of leaders, physicians and paramedics, ambulance and emergency staff, development of protocols, establishment of common criteria for STEMI diagnosis and treatment, and data storage in a national registry and timely feedback.Analysis of the program during the first two years revealed that the call for medical emergency by the citizens causes a decrease in the pain-to-first medical contact time and in door-to-balloon time, incrementing the percentage of patients who receives primary percutaneous coronary intervention within 90 minutes of paramedic arrival.Shorter delays in emergency services resulted in a reduction in in-hospital mortality.
In our study, prehospital delay was estimated using partial data, and seemed to be greater than 240 minutes in almost all patients.Also, the DAT was elevated, suggesting many possibilities for improvement.
In view of the studies cited in this study, we can say that difficulties in the treatment of STEMI are present (and similar) in many countries, and the strongest difference is in the efforts for their improvement.
0][31][32] Escosteguy et al., 29 published the results of a multidisciplinary program for implementation of clinical guidelines on AMI in a public emergency unit in Rio de Janeiro.Caluza et al., 30 described the implementation steps and the first results of an AMI treatment system in Sao Paulo.The program standardized the processes of clinical diagnosis of STEMI, immediate ECG using tele-ECG, therapy decision (PTA or thrombolysis) and availability of care in the referral hospital.Andrade et al., 31 described an integrated system for cardiovascular emergency services in Marilia, Brazil, with direct transportation of patients to the catheterization laboratory.The authors reported high symptom-to-balloon time in patients transferred from other units (5.0 ± 2.2 hours) and in those directly admitted to the hospital (3.3 ± 2.2 hours).Marcolino et al., 32 reported the results of an integrated system for AMI approach (Linha de Cuidado do Infarto Agudo do Miocárdio) implemented in the city of Belo Horizonte, Brazil, between 2010 and 2011, which included training and motivation programs of the emergency service staff, interaction between the units and accessibility to the catheterization laboratory.

Study limitations
Limitations of the study include its retrospective nature, the limited number of patients, the inclusion of patients undergoing catheterization only, the impossibility of determining the time interval from pain onset, patient admission and procedure, and the lack of data at the time of angioplasty.

Conclusions
We identified a flawed healthcare system for STEMI management, in which the first medical contact rarely occurs in the referral hospital, physicians have difficulties in diagnosing the disease and do not use validated therapeutic approaches, and much data are missing from the medical records (which are filed in inadequate locations).Difficulties are encountered in the transfer of patients to the referral hospital and the emergency medical services are infrequently called, causing a delay in mechanical reperfusion.The importance of the catheterization laboratory is highlighted, with more than half of patients treated within a DAT consistent with current guidelines, reinforcing the need for a direct transportation of patients to this facility.We recommend the implementation of an integrated system for AMI management compatible with local conditions and patients' needs, characterized by centralized coordination, continuing education of the medical staff, presence of paramedics trained in ECG and use of thrombolysis therapy.We believe that the situation here described is not exclusive of the city of Joinville, justifying and encouraging the development of further studies and improvements in the system.We suggest a prospective, continuing study to evaluate the development and adherence of the system to current guidelines.