Accepted on 05 Oct 2022            Submitted on 16 Dec 2021

Background

Acute coronary syndromes (ACS) include ST-segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina (UA) [1]. Globally, ischaemic heart disease was the leading cause of death and the second leading cause of disability-adjusted life years in 2019. World Health Organization indicators determined the leading cause of mortality in Guatemala to be ischaemic heart disease [2]. Currently, there is no established standard of care for ACS in Guatemala [3].

ACCESS (Acute Coronary Event Strategies Survey), an international observational registry, determined STEMI to be the most prevalent type of ACS in Guatemala. The ACCESS registry was the first to provide relevant information about acute myocardial infarction (AMI) management in Guatemala. However, it only included two public and a few private health centres located in Guatemala City. It provided evidence that no patients received primary Percutaneous Coronary Intervention (pPCI), and only 12% received elective PCI [3].

STEMI mortality is directly dependent on early reperfusion therapy, which in turn, relies on the structure and process of the healthcare system. Early administration of fibrinolytic therapy has proven to reduce the size of the infarct, preserve ventricular function and reduce mortality [4]. This is true 10 years after the event, particularly in patients that received fibrinolysis three hours after symptom onset [5].

In Guatemala, pharmacological reperfusion is the main method available given the lack of access to PCI centres [6]. When fibrinolysis is administered less than two hours after symptom onset, mortality reduction can be greater than with PCI [4]. Therefore, timely administration of fibrinolytic therapy is crucial. A meta-analysis demonstrated that the benefit of thrombolytic therapy initiated within 60–90 minutes after onset of symptoms can be estimated at 60–80 additional patients alive at 1 month per 1000 treated with conventional therapy [7]. Despite substantial evidence of the effectiveness of fibrinolytic therapy, its use remains low. In the PRIAMHO study, fibrinolytic use was 41% and in the GESIR-5 study 35% [8, 9].

There are various prognostic time intervals measured from symptom onset to reperfusion, which are useful in evaluating the efficacy of the health care system: first medical contact, door-in to door-out, door-balloon, door-needle, and total ischaemic time. By measuring and analysing these delays, it is possible to identify the step in which the treatment system is deficient.

Direct comparison between fibrinolysis and PCI is controversial. European Society of Cardiology (ESC) guidelines for STEMI management recommend pPCI as the preferred reperfusion strategy within indicated timeframes [4]. Performing pPCI requires a coordinated interdisciplinary effort including adequate transport and availability of experienced health professionals and resources. If deficiencies of the structure and system of care are known, it will be possible to establish adequate protocols and decentralize treatment for timely reperfusion and improvement of patient prognosis.

This registry was created in order to collect ACS data representative of the national health system. It pretends to describe the process, structure, and outcome of ACS care in Guatemala based on the Donabedian health model [10].

Objectives

Describe the main factors that influence patients’ ACS health outcome in Guatemala. Determine demographic and clinical characteristics among study subjects and outline the process and structure of the national healthcare care system.

Methods Study design and population

The methodology has been previously described [11]. Briefly, the ACS-Gt study is an observational, multicentre, prospective registry that included adult patients with ACS admitted at five regional second level hospitals and one tertiary hospital part of Guatemala’s National Healthcare System. These represent six out of the country’s eight geographic regions. The National Ministry of Public Health is a healthcare provider for nearly 75% of the population [6].

Patients with signs, symptoms, electrocardiogram findings, and cardiac biomarkers compatible with ACS were eligible for enrolment from February 2020 to January 2021. Out of 112 collected patients, 109 met inclusion criteria. This study was approved by the Bioethics Committee in Health Investigation of Universidad de San Carlos de Guatemala (a public higher-education institution).

Data collection

Data was collected by trained physicians working at six designated hospitals. All investigators underwent training in bioethics, data collection, and received a standardized manual with operational definitions. The survey was filled out using the electronic database system REDCap (Research Electronic Data Capture) composed of sociodemographic questions and those that described the process, structure, and outcome of the healthcare system of ACS (Figure 1).

Figure 1 

ACS-Gt Registry Methodology.

The survey was completed in three stages. The first was conducted at hospital admission and composed of baseline characteristics, traditional risk factors, clinical presentation, electrocardiogram (ECG) findings, laboratory data, risk stratification, and reperfusion therapy. The second was conducted during hospital stay, composed of follow-ups related to non-cardiovascular and cardiovascular outcomes. At hospital discharge, treatment, left ventricular ejection fraction (LVEF), and future appointments were taken into account. Finally, a follow-up 30 days after the event was assessed to evaluate vital status. All patients were given an informed consent form for participation and follow-up approval.

Collected data underwent a weekly review by at least three physicians from the research team. Data integrity was verified according to inclusion criteria and correction of discrepancies to ensure the collection of high-quality data. All cases with a debatable diagnosis were analysed by members of the scientific committee composed of cardiologists and internal medicine physicians.

Variable definition

The research team combined international ACS guidelines and Guatemala’s healthcare context to provide standardized variable definitions (supplement Table 1).

STEMI was considered when a patient with ACS symptoms had persistent ST-segment elevation in at least two contiguous leads (≥2.5 mm in men <40 years, ≥2 mm in men ≥40 years, ≥1.5 mm in women in leads V2–V3 and/or ≥1 mm in the other leads, or ≥0.5 mm in leads V7–V9) [4]. Diagnosis was confirmed with abnormality of cardiac enzymes. The presence of a right bundle branch block with ST-segment elevation or left bundle branch block that met Sgarbossa criteria was also considered STEMI [4, 12, 13]. NSTEMI/UA criteria are detailed in supplement Table 1. Failed thrombolysis was defined as ST-segment descent failure of at least 50% in the most prominent lead, persistence of angina, and/or worsening of hemodynamic parameters 90 minutes after thrombolysis [14, 15].

Optimal medical therapy (OMT) at admission was defined by the combined prescription of aspirin, P2Y12 inhibitors, heparin or enoxaparin, and fibrinolytic therapy according to 2017 STEMI and 2015 NSTEMI European guidelines [4, 16]. OMT at discharge (DOMT) was considered with prescription of aspirin, P2Y12 inhibitors, and statins. Prescription of angiotensin-converting enzyme (ACE) or inhibitors/angiotensin-receptor blockers (ARB), β-blockers, or angiotensin receptor-neprilysin inhibitor (ARNI) in patients with reduced left ventricular ejection fraction (rLVEF) (≤40%), was also regarded as DOMT.

Data analysis

SPSS.24 system was used for data analysis. Continuous variables were expressed as mean and standard deviations (± SD) or medians and interquartile ranges. Categorical variables were described as frequency and percentages. Statistical tests, Chi-square, Student’s t-test, or Mann-Whitney U test were performed, whichever applied. A p-value < 0.05 was considered statistically significant.

Results

The registry collected 109 patients with ACS; mean age was 61.6 years and the majority were male (68%). Almost 45% lived in rural areas, most of them had elementary school education level and worked in informal commerce. No difference was found between demographic variables in STEMI and NSTEMI/UA patients, although NSTEMI/UA patients were older. Most STEMI and NSTEMI/UA patients had a past medical history of systemic hypertension and diabetes mellitus. However, more STEMI patients smoked and more NSTEMI/UA had history of an ACS event. While previously used medications were similar between STEMI and NSTEMI/UA, the latter had higher use of ACEI/ARB, aspirin, statins, and insulin (Table 1).

Table 1

Demographic and clinical characteristics.

STEMI NSTEMI/UA TOTAL P N = 88 N = 21 N = 109 x̄ ± SD x̄ ± SD x̄ ± SD Age ∼ years 60.9 ± 11.2 64.9 ± 12.6 61.6 ± 11.6 0.15 Weight ∼ kg 72.7 ± 10.4 70.6 ± 12.3 70.8 ± 14 0.43 N (%) N (%) N (%) Gender 0.25     Male 69 (78) 14 (66.7) 83 (68) Housing 0.98     Rural 38 (43.2) 9 (42.9) 47 (43.1) Educational level 0.43     Illiterate 11 (12.6) 4 (19) 15 (13.9)     Elementary school 37 (42.5) 12 (57.1) 49 (45.4)     High school 25 (28.7) 2 (9.5) 27 (25)     Technical degree 10 (11.5) 2 (9.5) 12 (11.1)     Bachelor’s degree or higher 4 (4.6) 1 (4.8) 5 (4.6) Occupation 0.41     Informal commerce 19 (21.8) 8 (38.1) 27 (25)     Housewife 16 (18.4) 5 (23.8) 21 (19.4)     Unemployed 18 (20.7) 1 (4.8) 19 (17.6)     Technical 14 (16.1) 3 (14.3) 17 (15.7)     Professional 8 (9.2) 2 (9.5) 10 (9.3)     Agriculture 6 (6.9) 2 (9.5) 8 (7.4)     Formal commerce 6 (6.9) 0.0 6 (5.6) Established hospital protocol for acute coronary syndrome 11 (12.5) 1 (4.8) 12 (11) 0.31 Medical history     Systemic hypertension 43 (48.9) 11 (52.4) 54 (49.5) 0.77     Diabetes mellitus 40 (45.5) 10 (47.6) 50 (45.9) 0.85     Smoking 24 (27.3) 3 (14.3) 27 (24.8) 0.22     Dyslipidaemia 19 (21.8) 2 (9.5) 21 (19.4) 0.2     Acute coronary syndrome 11 (12.6) 4 (19) 15 (13.9) 0.44     Other 20 (22) 6 (21) 26 (23) 0.62 Medication history     ACEI/ARB 34 (39.1) 9 (42.9) 43 (39.8) 0.75     Acetylsalicylic acid 7 (8) 5 (23.8) 12 (11.1) 0.03     Insulin 9 (10.3) 3 (14.3) 12 (11.1) 0.6     CCB 5 (5.7) 4 (19) 9 (8.3) 0.04     P2Y12 inhibitor 5 (5.7) 1 (4.8) 6 (5.6) 0.86     β-blocker 5 (5.7) 1 (4.8) 6 (5.6) 0.86     Statins 3 (3.4) 2 (9.5) 5 (4.6) 0.24     Nitrites 1 (1.1) 1 (4.8) 2 (1.9) 0.27

STEMI: ST-elevation myocardial infarction, NSTEMI: non-ST elevation myocardial infarction, ACEI: Angiotensin-converting enzyme inhibitors, ARB: Angiotensin II receptor blocker, CCB: Calcium channel blocker.

Most STEMI patients had an anterior myocardial infarction, only 59% received fibrinolysis (no pPCI was performed due to lack of public-PCI centres). Alteplase was the most commonly used fibrinolytic, mostly at a third level hospital. Regional hospitals used Streptokinase. Fibrinolysis was not performed in 50% of patients due to late presentation (>12 hours from symptom onset) and in 36% of patients due to lack of consideration by physician (error in clinical scenario or unskilled ECG interpretation). Fibrinolysis was mostly performed at a public hospital, however, 13.5% was performed at a private hospital by patient’s out-of-pocket expense. Fibrinolysis was considered successful in 65% of patients but none were taken to PCI after the procedure (pharmacoinvasive strategy) during the recommended time period. One rescue PCI was performed at a private hospital. Nearly 20% of non-reperfused patients underwent angiography or PCI, nevertheless, only 57% had an ischaemia or viability test completed. Patients with NSTEMI/UA rarely had angiography or PCI performed, and most were diagnosed with multivessel disease (Table 2).

Table 2

STEMI and NSTEMI individual characteristics.

STEMI CHARACTERISTICS STEMI N = 88N (%)Electrocardiographic location     Anterior 45 (51.1)     Inferior 38 (43.2)     Lateral 5 (5.7) Reperfusion 52 (59.1) Type of reperfusion     Fibrinolysis 52 (100) Fibrinolytic     Alteplase 34 (65.4)     Streptokinase 17 (32.7)     Tenecteplase 1 (1.9) * Reason PCI was not performed     No cardiac catherization laboratory 65 (73.9)     Time from symptom onset > 12 hours 13 (14.8)     Not considered by physician 7 (8)     Patient refused treatment 2 (2.3)     Hospital transfer not accepted 1 (1.1) Reason fibrinolysis was not performed     Time from symptom onset > 12 hours 18 (50)     Not considered by physician 13 (36.1)     Lack of medical supplies 3 (8.3)     Contraindicated 1 (2.8)     Patient refused treatment 1 (2.8) Angiography/PCI use in non-reperfused myocardial infarction 7 (19.4) Ischaemia or viability evaluated prior to angiography/PCI in non-reperfused myocardial infarction 4 (57) Treatment centre where fibrinolysis was performed     Public hospital (MSPAS) 44 (84.6)     Private hospital 7 (13.5)     Guatemalan social security institute (IGSS) 1 (1.9) Successful fibrinolysis 34 (65.4) Angiography/PCI after successful fibrinolysis 17 (50) Within first 24 hours 0.0 After 24 hours 17 (100) Cause of failed fibrinolysis     Both 6 (50)     Persistent ischaemia 5 (41.7)     Failure of ST segment descent 1 (8.3) Rescue angioplasty 1 (14.3) * NSTEMI/UA CHARACTERISTICS NSTEMI/UA N = 21N (%)Angiography/PCI performed 5 (23.8)     Diagnostic 4 (80)     PCI 1 (20) X̄± SD     Days until angiography/PCI was performed 6.4 ± 2.8 Electrocardiographic findings at admission     T-wave inversion 5 (29.4)     ST-segment depression 5 (29.4)     No alterations 4 (23.5)     ST-depression in more than 6 leads and ST-elevation in aVR 2 (11.8)     Left Bundle Branch Block 1 (5.9) Crusade 35.8 ± 20.8

* Performed at a private hospital (after the procedure patient was transferred back for treatment at public hospital).

STEMI: ST-elevation myocardial infarction, NSTEMI: non-ST elevation myocardial infarction, PCI: percutaneous coronary intervention, MSPAS: “Ministerio de Salud Pública y Asistencia Social” (ministry of public health and social assistance), IGSS: “Instituto Guatemalteco de Seguridad social” (Guatemalan social security institute), UA: unstable angina.

Clinical presentation between study groups was similar. However, GRACE score was significantly higher in the NSTEMI/UA group, whereas TIMI score was higher in STEMI. Electrocardiographic findings demonstrated that most third-degree AV block patients had STEMI and all patients with pacemaker rhythm had a NSTEMI/UA (Table 3). Biochemical characteristics at hospital admission can be found in supplement Table 2.

Table 3

Clinical Presentation.

STEMI NSTEMI/UA TOTAL P N = 88 N = 21 N = 109 x̄ ± SD x̄ ± SD x̄ ± SD Heart rate ∼ Bpm 80.3 ± 24.9 91.4 ± 31.7 82.4 ± 26.5 0.08 GRACE 129 ± 32 109 ± 32 125 ± 32.7 0.01 MEDIAN (25–75) MEDIAN (25–75) MEDIAN (25–75) Systolic blood pressure ∼ mmHg 115 (91.2–134.7) 130 (110–140) 120 (100–139) 0.06 Oxygen saturation ∼ % 95 (91.7–97) 92 (86–96) 94 (90.2–97) 0.07 Diastolic blood pressure ∼ mmHg 70 (60–84.5) 80 (70–86) 70 (60–84) 0.22 Temperature ∼ °C 37 (36.5–37) 37 (36.7–37) 37 (36.5–37) 0.36 Respiratory rate ∼ Rpm 18 (16–22) 20 (17–24) 19 (16–22) 0.23 N (%) N (%) N (%) Typical angina 76 (86.4) 16 (76.2) 92 (84.4) 0.24 Dyspnoea 18 (20.5) 9 (42.9) 27 (24.8) 0.03 Atypical angina 8 (9.1) 1 (4.8) 9 (8.3) 0.51 Syncope 8 (9.1) 1 (4.8) 9 (8.3) 0.51 Cardiac arrest 1 (1.1) 0.0 1 (0.9) 0.62 Electrocardiographic findings at admission    Sinus rhythm 66 (75) 19 (90.5) 85 (78) 0.12     Third-degree AV block 14 (15.9) 0.0 14 (12.8) 0.05     Ventricular extrasystoles 4 (4.5) 1 (4.8) 5 (4.6) 0.96     Second-degree AV block 4 (4.5) 0.0 4 (3.7) 0.32     Other 2 (2.3) 1 (4.8) 3 (2.8) 0.53     Pacemaker rhythm 0.0 2 (9.5) 2 (1.8) <0.01     Atrial fibrillation 1 (1.1) 0.0 1 (0.9) 0.62     First-degree AV block 1 (1.1) 0.0 1 (0.9) 0.62 Killip-Kimball 0.04     I 43 (48.9) 13 (61.9) 56 (51.4)     II 27 (30.7) 4 (19) 31 (28.4)     III 5 (5.7) 4 (19) 9 (8.3)     IV 13 (14.8) 0.0 13 (11.9) TIMI <0.01     0 0.0 2 (9.5) 2 (1.8)     1 3 (3.4) 2 (9.5) 5 (4.6)     2 8 (9.1) 6 (28.6) 14 (12.8)     3 11 (12.5) 8 (38) 19 (17.4)     4 9 (10) 2 (9.5) 11 (10)     5 12 (13.6) 0.0 12 (11)     6 8 (9.1) 1 (4.8) 9 (8.3)     ≥7 37 (42) 0.0 37 (34)

STEMI: ST-elevation myocardial infarction, NSTEMI: non-ST elevation myocardial infarction, UA: unstable angina, Bpm: beats per minute, GRACE: Grace Risk Score, Rpm: respirations per minute, mmHg: millimetres of mercury, °C: degrees Celsius, AV: atrioventricular, Killip-Kimball: prognostic score in acute coronary syndrome evaluating the risk of death during the first 30 days, TIMI: score that assesses mortality, reinfarction or recurrent ischaemia during the first 14 days.

As mentioned previously, there were various points in the ACS system of care measured. These were divided into two main categories: prehospital and intrahospital care. Within prehospital delay, first medical contact (FMC) was longer in STEMI. One-third of ambulances were provided by the Public National Health System, and the rest by patient’s expense or the Social Security Institute. For the most part, transfer destination was a public hospital, but 13% of STEMI patients were transferred to a private hospital. The most common reason for a second transfer in STEMI was for fibrinolysis and in NSTEMI/UA elective PCI. Transfer conditions were suboptimal (Table 4).

Table 4

Process and delay.

STEMI NSTEMI/UA TOTAL P N = 88 N = 21 N = 109 x̄ ± SD x̄ ± SD x̄ ± SD Prehospital delayTime between ambulance call and arrival ∼ minutes* 18.4 ± 14.6 30 ± 23.7 20.7 ± 16.8 0.17 MEDIAN (25–75) MEDIAN (25–75) MEDIAN (25–75) Transfer time to FMC ∼ minutes 22.5 (20–38.7) 30 (12.5–60) 25 (17.5–42.5) 0.56 FMC ∼ minutes 300 (126.2–842.2) 185 (75–1035) 180 (74–465) 0.37 Transfer time from FMC to final treatment centre ∼minutes 30 (20–60) 120 (10–180) 80 (30–141) 0.46 N (%) N (%) N (%) P Ambulance provided by 0.96 Public hospital (MSPAS) 11 (37.9) 1 (33.3) 12 (37.5) Patient expense 8 (27.6) 1 (33.3) 9 (28.1) Social security institute (IGSS) 8 (27.6) 1 (33.3) 9 (28.1) Patient transport 2 (6.9) 0.0 2 (6.3) Transfer destinationPublic hospital (MSPAS) 24 (82.8) 3 (100) 27 (84.4) Private hospital** 4 (13.8) 0.0 4 (12.5) Social security institute (IGSS) 1 (3.4) 0.0 1 (3.1) Reason for second transfer <0.01 Elective PCI 8 (27.6) 1 (33.3) 9 (28.1) Family request 3 (10.3) 0.0 3 (9.4) Intensive care 2 (6.9) 0.0 2 (6.3) Lack of physical space 0.0 1 (33.3) 1 (3.1) Diagnostic approach 0.0 1 (33.3) 1 (3.1) Fibrinolysis 11 (37.9) – – Pharmaco-invasive strategy (after successful fibrinolysis) 3 (10.3) – – Rescue PCI 2 (6.9) – – Transfer characteristics Performed by paramedic 14 (56) 2 (66.7) 16 (57.1) 0.9 Ambulance oxygen tank 15 (65.2) 1 (33.3) 16 (61.5) 0.34 Ambulance heart monitor 8 (34.8) 0.0 8 (30.8) 0.34 Ambulance defibrillator 5 (21.7) 0.0 5 (19.2) 0.53

* Only applies if the patient was transferred by ambulance.

** Only applies to patients who were evaluated or treated at a private hospital and later referred to a public hospital. Patients who only received treatment at a private hospital were not included.

STEMI: ST-elevation myocardial infarction, NSTEMI: non-ST elevation myocardial infarction, UA: unstable angina, FMC: first medical contact, PCI: percutaneous coronary intervention, MSPAS: “Ministerio de Salud Pública y Asistencia Social” (ministry of public health and social assistance), IGSS: “Instituto Guatemalteco de Seguridad social” (Guatemalan social security institute).

Prognostic delays in STEMI were measured in order to understand the process and structure of the current health system. We compared time intervals recommended by ESC guidelines with ACS-Gt results (Table 5). Within intrahospital delay, all intervals were significantly prolonged in comparison with ESC guidelines, except the time from ECG to STEMI diagnosis.

Table 5

STEMI–delay in definitive treatment: ACS-Gt registry vs. ESC guidelines.

ACS-GT ESC-STEMI DIFFERENCE P MEDIAN (25–75) Time between ECG and STEMI diagnosis ∼ minutes 10 (5-20) <10 0.0 0.44 Door to needle ∼ minutes 52.5 (27.7-71) <10 + 42 <0.01 Door-in to door-out ∼ minutes 120 (35-285) <30 + 90 <0.01 Total ischaemic time ∼ minutes 500 (388-720) <120 + 380 <0.01 X̄ ± SD Total ischaemic time (patients presenting <12 h) ∼ minutes 439.5 ± 139.6 <120 + 319 <0.01 Time in which Angiography/PCI was performed after successful fibrinolysis ∼ hours* 205.1 ± 102.9 2-24 + 181 <0.01

* Pharmaco-invasive strategy refers to angiography or PCI in a period of 2-24 hours; in the present study, no patient met this criterion. STEMI: ST-elevation myocardial infarction, ACS-Gt: Acute coronary syndrome-Guatemala, ESC: European society of cardiology, ECG: electrocardiogram, PCI: percutaneous coronary intervention.

Results regarding healthcare system structure (Table 6) demonstrated that only 6.4% of ACS management was dictated by a cardiologist and the majority by an internal medicine resident. Quantitative and qualitative troponin was available in 81% and 9.2% of cases respectively. The National Cardiovascular Surgery Unit of Guatemala (UNICAR), a semi-public institution, was the only centre that performed elective coronary angiography on those referred by National Health System centres. Patients discharged with an appointment to UNICAR (whenever the patient wasn’t transferred during hospital stay, needed a second catheterization or coronary artery bypass graft) was around 10% in both groups. At discharge, the median time for a follow-up appointment was 20 days in STEMI and 7.5 days in NSTEMI/UA.

Table 6

Structure in the attention of the acute coronary syndrome.

STEMI NSTEMI/UA TOTAL P N = 88 N = 21 N = 109 N (%) N (%) N (%) Physician responsible 0.42     Internal medicine/emergency medicine resident 61 (69.3) 14 (66.7) 75 (68.8)     Internist 13 (14.8) 6 (28.6) 19 (17.4)     Cardiolo