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DOI: 10.1016/j.rec.2020.08.002
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Available online 9 September 2020
Impact of COVID-19 on ST-segment elevation myocardial infarction care. The Spanish experience
Impacto de la COVID-19 en el tratamiento del infarto agudo de miocardio con elevación del segmento ST. La experiencia española
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Oriol Rodriguez-Leora,b,c,
Corresponding author
oriolrodriguez@gmail.com

Corresponding author: Unidad de Cardiología Intervencionista, Hospital Germans Trias i Pujol. Carretera de Canyet SN, 08916 Badalona, Barcelona, Spain.
, Belén Cid-Álvarezd, Armando Pérez de Pradoe, Xavier Rossellof,g,b, Soledad Ojedah, Ana Serradori,b, Ramón López-Palopj, Javier Martín-MoreiraSk,b, José Ramón Rumorosol, Ángel Cequierm, Borja Ibáñezf,n,b, Ignacio Cruz-Gonzálezk,b, Rafael Romagueram, Raúl Morenoo,b, for the Working Group on the Infarct Code of the Interventional Cardiology Association of the Spanish Society of Cardiology Investigators
a Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
b Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
c Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, Spain
d Servicio de Cardiología, Hospital Clínico de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
e Servicio de Cardiología, Hospital de León, León, España
f Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain
g Servicio de Cardiología, Institut d’Investigació Sanitària de les Illes Balears (IdISBa), Hospital Universitari Son Espases, Palma de Mallorca, Islas Baleares, Spain
h Servicio de Cardiología, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Córdoba, Spain
i Servicio de Cardiología, Hospital Clínico de Valladolid, Valladolid, Spain
j Servicio de Cardiología, Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
k Servicio de Cardiología, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain
l Servicio de Cardiología, Hospital de Galdakao-Usansolo, Galdakao, Vizcaya, Spain
m Servicio de Cardiología, Hospital de Bellvitge-Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
n Servicio de Cardiología, Hospital Universitario IIS-Fundación Jiménez Díaz, Madrid, Spain
o Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain
Manuel Villaaa, Rafael Ruíz-Salmerónbb, Francisco Molanocc, Carlos Sánchezdd, Erika Muñoz-Garcíaee, Luís Íñigoff, Juan Herradorgg, Antonio Gómez-Mencherohh, Antonio Gómez-Mencheroii, Juan Caballerojj, Soledad Ojedakk, Mérida Cárdenasll, Livia Gheorghemm, Jesús Onetonn, Francisco Moralesoo, Félix Valenciapp, José Ramón Ruízqq, José Antonio Diarterr, Pablo Avanzasss, Juan Rondántt, Vicente Peraluu, Lucía Vera Pernasettivv, Julio Hernándezww, Francisco Bosaxx, Pedro Luís Martín Lorenzoyy, Francisco Jiménezab, José M de la Torre Hernándezac, Jesús Jiménez-Mazuecosad, Fernando Lozanoae, José Moreuaf, Enrique Novoag, Javier Roblesah, Javier Martín Moreirasai, Felipe Fernández-Vázquezaj, Ignacio J. Amat-Santosak, Joan Antoni Gómez-Hospitalal, Joan García-Picartam, Bruno García del Blancoan, Ander Regueiroao, Xavier Carrillo-Suárezap, Helena Tizónaq, Mohsen Mohandesar, Juan Casanovaas, Víctor Agudelo-Montañezat, Juan Francisco Muñozau, Juan Francoav, Roberto del Castilloaw, Pablo Salinasax, Jaime Elizagaay, Fernando Sarnagoaz, Santiago Jiménez-Valeroba, Fernando Riverobc, Juan Francisco Oteobd, Eduardo Alegría-Barrerobe, Ángel Sánchez-Recaldebf, Valeriano Ruízbg, Eduardo Pinarbh, Eduardo Pinarbi, Ana Planasbj, Bernabé López Ledesmabk, Alberto Berenguerbl, Agustín Fernández-Cisnalbm, Pablo Aguarbn, Francisco Pomarbo, Miguel Jerezbp, Francisco Torresbq, Ricardo Garcíabr, Araceli Frutosbs, Juan Miguel Ruíz Nodarbt, Koldobika Garcíabu, Roberto Sáezbv, Alfonso Torresbw, Miren Telleríabx, Mario Sadababy, José Ramón López Mínguezbz, Juan Carlos Rama Merchánca, Javier Portalescb, Ramiro Trillocd, Guillermo Aldamace, Saleta Fernándezcf, Melisa Santáscg, María Pilar Portero Pérezch
aa Hospital Universitario Virgen del Rocío
bb Hospital Universitario Virgen Macarena
cc Hospital Universitario Virgen de Valme
dd Hospital Universitario General de Málaga
ee Hospital Universitario Virgen de la Victoria
ff Hospital Costa del Sol
gg Hospital Universitario de Jaén
hh Hospital Universitario Juan Ramón Jiménez
ii Eduardo Molina, Hospital Universitario Virgen de las Nieves
jj Hospital Universitario San Cecilio
kk Hospital Universitario Reina Sofía
ll Hospital Punta de Europa
mm Hospital Universitario Puerta del Mar
nn Hospital Universitario de Jerez de la Frontera
oo Hospital Universitario de Puerto Real
pp Hospital Universitario Torrecárdenas
qq Hospital Clínico Universitario Lozano Blesa
rr Hospital Universitario Miguel Servet
ss Hospital Universitario Central de Asturias
tt Hospital Universitario de Cabueñes
uu Hospital Universitari Son Espases
vv Policlínica Nuestra Señora del Rosario
ww Hospital Universitario Nuestra Señora de Candelaria
xx Hospital Universitario de Canarias
yy Hospital Universitario de Gran Canaria Doctor Negrín
ab Hospital Insular de Gran Canaria
ac Hospital Universitario Marqués de Valdecilla de Santander
ad Hospital General Universitario de Albacete
ae Hospital General Universitario de Ciudad Real
af Complejo Hospitalario de Toledo
ag Hospital Universitario de Guadalajara
ah Hospital Universitario de Burgos
ai Hospital de Universitario de Salamanca
aj Hospital de León
ak Hospital Clínico Universitario de Valladolid, CIBERCV
al Hospital Universitari de Bellvitge
am Hospital de la Santa Creu i Sant Pau
an Hospital Universitari Vall d’Hebron
ao Hospital Clínic de Barcelona
ap Hospital Universitari Germans Trias i Pujol
aq Hospital del Mar
ar Hospital Universitari Joan XXIII
as Hospital Universitari Arnau de Vilanova
at Hospital Universitari de Girona Josep Trueta
au Hospital Universitari Mútua de Tarrassa
av Hospital Universitario Fundación Jiménez Díaz
aw Hospital Universitario Fundació Alcorcón
ax Hospital Clínico San Carlos y Hospital Príncipe de Asturias
ay Hospital General Universitario Gregorio Marañón
az Hospital Universitario 12 de Octubre
ba Hospital Universitario La Paz
bc Hospital Universitario de La Princesa
bd Hospital Universitario Puerta de Hierro Majadahonda
be Hospital Univesitario de Torrejó-Universidad Francisco de Vitoria
bf Hospital Ramón y Cajal
bg Complejo Hospitalario de Navarra
bh Hospital Virgen de la Arrixaca
bi Luciano Consuegra-Sánchez, Hospital Universitario Santa Lucía de Cartagena
bj Hospital General Universitario de Castellón
bk Hospital Universitario y Politécnico La Fe
bl Hospital General Universitario de Valencia
bm Hospital Clínico Universitario de Valencia
bn Hospital Universitario Dr. Peset
bo Hospital Universitario de la Ribera
bp Hospital de Manises
bq Hospitales de Torrevieja-Elche-Vinalopó
br Hospital General Universitario de Elche
bs Hospital General Universitario de San Juan de Alicante
bt Hospital General Universitario de Alicante
bu Hospital Universitario de Cruces
bv Hospital de Basurto
bw Hospital Universitario Araba
bx Hospital Universitario Donostia
by Hospital de Galdakao-Usansolo
bz Complejo Hospitalario Universitario de Badajoz
ca Hospital de Mérida
cb Complejo Hospitalario Universitario de Cáceres
cd Hospital Clínico Universitario Santiago de Compostela
ce Complejo Hospitalario Universitario de A Coruña
cf Complejo Hospitalario Universitario de Vigo
cg Hospital Universitario Lucus Augusti
ch Hospital San Pedro de Logroño
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Received 29 May 2020. Accepted 28 July 2020
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Tables (4)
Table 1. Baseline clinical characteristics of patients with confirmed diagnosis of STEMI
Table 2. Angiographic and procedural characteristics of patients with confirmed diagnosis of STEMI
Table 3. Time intervals between symptom onset and reperfusion
Table 4. In-hospital outcomes of patients with confirmed diagnosis of STEMI
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Abstract
Introduction and objectives

The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak.

Methods

Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19.

Results

Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P<.001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P <.001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P=.017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization.

Conclusions

The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.

Keywords:
STEMI
COVID-19
Primary angioplasty
STEMI network
Abbreviations:
COVID-19
PCI
PCR
pPCI
STEMI
Resumen
Introducción y objetivos

El impacto del brote de COVID-19 en el tratamiento del infarto agudo de miocardio con elevación del segmento ST (IAMCEST) no está claro. El objetivo de este estudio es evaluar los cambios en el tratamiento del IAMCEST durante el brote de COVID-19.

Métodos

Se utilizó un registro multicéntrico, nacional, retrospectivo y observacional de pacientes consecutivos atendidos en 75 centros, se compararon las características de los pacientes y de los procedimientos y los resultados hospitalarios en 2 cohortes según se los hubiera tratado antes o durante la COVID-19.

Resultados

Los casos con sospecha de IAMCEST disminuyeron el 27,6% y los pacientes con IAMCEST confirmado se redujeron de 1.305 a 1.009 (22,7%). No hubo diferencias en la estrategia de reperfusión (más del 94% tratados con angioplastia primaria). El tiempo de isquemia fue más largo durante la COVID-19 (233 [150-375] frente a 200 [140-332] min; p <0,001), sin diferencias en el tiempo primer contacto médico-reperfusión. La mortalidad hospitalaria fue mayor durante la COVID-19 (el 7,5 frente al 5,1%; OR bruta=1,50; IC95%, 1,07-2,11; p <0,001); esta asociación se mantuvo tras ajustar por factores de confusión (OR ajustada=1,88; IC95%, 1,12-3,14; p=0,017). La incidencia de infección confirmada por SARS-CoV-2 fue del 6,3%.

Conclusiones

El brote de COVID-19ha implicado una disminución en el número de pacientes con IAMCEST, un aumento del tiempo entre el inicio de los síntomas y la reperfusión y un aumento en la mortalidad hospitalaria. No se han detectado cambios en la estrategia de reperfusión. La combinación de infección por SARS-CoV-2 e IAMCEST fue relativamente infrecuente.

Palabras clave:
IAMCEST
COVID-19
Angioplastia primaria
Red de atención al infarto
Full Text
INTRODUCTION

On December 31, 2019, a cluster of pneumonia cases of unknown etiology was reported in Wuhan, Hubei Province, China. On January 9, 2020, a new coronavirus, SARS-CoV-2, was identified as the causative agent of this outbreak, and its associated disease was named coronavirus disease 2019 (COVID-19). The infection spread rapidly, and the World Health Organization characterized COVID-19 as a pandemic on March 11.1 By May 1, 2020, more than 1.6 million cases had been diagnosed in 179 countries on 5 continents, with nearly 100 000 confirmed deaths.1 The Spanish Government activated a State of Emergency on March 14, which restricted the movement of all citizens, except those going to work, to hospitals or health centers, and to financial institutions and those shopping for groceries, pharmaceutics, and basic necessities.2

The impact of this new disease on societal behavior and on health care system performance is unprecedented in recent history. During the current COVID-19 outbreak, some preliminary reports have highlighted a decrease in the number of ST-segment elevation myocardial infarction (STEMI) patients attending hospitals in Europe and North America,3–5 but we have limited information on how the outbreak has affected STEMI networks in terms of delays to reperfusion, revascularization strategies, and clinical outcomes.6,7

The objective of this study was to compare clinical characteristics, management, and hospital outcomes in a nationwide cohort between STEMI patients who attended in the first 30 days after the Spanish lockdown during the current COVID-19 outbreak and those who attended in a period prior to COVID-19.

METHODSSpanish STEMI registry

There are 17 regional public service STEMI care networks in Spain, which comprise 83 hospitals capable of performing primary percutaneous coronary interventions (pPCIs) in year-round 24-hour, 7-day a week programs. In 2018, 21 261 interventions were performed for STEMI (91.6% pPCIs, 3.2% rescue percutaneous coronary interventions, and 5.1% routine early percutaneous coronary interventions strategies after fibrinolysis), representing 417 pPCIs per million population.8

In 2019, the Interventional Cardiology Association of the Spanish Society of Cardiology sponsored a prospective registry of consecutive STEMI patients who were treated within these specific STEMI care networks. The aim of this Spanish Infarct Code Registry was to detect interregional differences in the management of STEMI. Information was collected on number of cases, clinical characteristics, clinical management, and outcomes of STEMI patients. This registry enrolled 5240 consecutive patients treated between April and June 2019.

During the current COVID-19 outbreak, the Spanish Interventional Cardiology Association established a twin registry involving the retrospective collection of information on all consecutive STEMI patients by the same centers that participated in the 2019 registry. Information was retrospectively recorded on number of cases, clinical characteristics, clinical management, and outcomes from March 16, which was immediately after the activation of the Spanish State of Emergency and the countrywide lockdown.

The research protocol was approved by the Working Group on STEMI Code of the Spanish Interventional Cardiology Association and by a central ethics committee from León and Bierzo Health Areas.

Study design

This multicenter, retrospective, observational cohort study evaluated procedures recorded in the Spanish Infarct Code Registry database to assess whether the current COVID-19 outbreak has had a relevant impact on STEMI treatment in terms of number of cases, clinical characteristics, reperfusion delays, in-hospital management, and in-hospital clinical outcomes. Two different cohorts of patients were established according to whether they had been treated between April 1 and April 30, 2019 (prior to COVID-19 cohort) or between March 16 and April 14, 2020 (during COVID-19 cohort). The analysis included data from 75 hospitals that enrolled patients in both periods. Delay times were defined according to the relevant European guidelines.9 Patients with a final diagnosis other than STEMI were not included in the final analysis. Data were collected through medical record review. The main outcome measure was in-hospital mortality.

Statistical analysis

Continuous variables are summarized as mean±standard deviation, whereas categorical variables are presented as frequency and percentage. Baseline comparisons between cohorts were performed using t tests or chi-square tests, as appropriate. Variables with highly skewed distributions (ie, times for first medical contact, symptom onset, catheterization laboratory arrival, and reperfusion) are presented as median and interquartile range and were compared using the nonparametric Mann-Whitney U test. Univariate logistic regression models were created to evaluate the association between the cohort group and in-hospital mortality. Multivariate logistic regression modeling was performed to eliminate potential confounders and to assess the consistency of our findings. The covariates included in the multivariate models (symptom onset to reperfusion time, age, sex, Killip class, and a positive polymerase chain reaction [PCR] test for COVID-19) were selected based on medical knowledge and the results of the univariate analysis. Adjusted odds ratios (ORs) and their 95% confidence intervals (95%CIs) were therefore used to estimate the association between cohort and outcomes.

The robustness of our findings was tested through 2 sensitivity analyses by a) removing COVID-19 individuals from the main analyses to account for their potential contribution to the increase in outcomes; and b) using a mixed regression model including hospital as a random variable, which allowed some heterogeneity in order to take into account the expected variation between hospitals (between-hospital variation), weighting each hospital accordingly to obtain an overall estimate. Two-tailed P values <.05 were considered statistically significant. All analyses were performed using STATA software version 15.1 (Stata Corp, College Station, United States).

RESULTSPatients

STEMI networks from 75 hospitals attended a total of 1113 patients during the COVID-19 outbreak, whereas 1538 individuals were treated in the same period the previous year, representing a drop of 27.6%. A flowchart of patients treated in the STEMI networks in the 2 time periods is shown in figure 1. Patients with confirmed STEMI diagnosis comprised 1009 and 1305, respectively (a fall of 22.7%). The trend was consistent among centers (65 of the 75 centers [87%] reported fewer STEMI events). There were also significant differences in the number of patients who required STEMI network assistance but were ultimately diagnosed with a non-ST-segment elevation acute myocardial infarction: 232 individuals (15.1%) in 2019 but 104 individuals (9.3%) in 2020 (P <.001).

Figure 1.

Patient flowchart. NSTEMI, non-ST-segment elevation acute myocardial infarction, PCI, percutaneous coronary intervention; STEMI, non-ST-segment elevation acute myocardial infarction.

(0.16MB).

Figure 2 shows the absolute number of pPCIs per day during both time periods and the official number of confirmed cases according to Spanish government data.7

Figure 2.

Absolute number of primary percutaneous coronary interventions per day during both time periods and the official number of confirmed COVID-19 cases. Numbers of confirmed COVID-19 cases are according to official Spanish government data.7 PCI, percutaneous coronary intervention.

(0.24MB).

During the COVID-19 outbreak, only 33 patients (3.3%) had confirmed COVID-19 diagnosis at admission; during admission, COVID-19 was diagnosed in 30 additional patients (3.0%), giving a total of 63 patients (6.3%) diagnosed with COVID-19. The COVID-19 diagnostic path in the 2020 cohort is shown in figure 3.

Figure 3.

COVID-19 diagnostic path. Patients were categorized on admission according to their COVID-19 status into 4 groups: unknown; no symptoms compatible with COVID-19 and no previous polymerase chain reaction (PCR) test; symptoms compatible with COVID-19 but no previous PCR test; and previous positive PCR test. Although a PCR assay needs to be performed at admission in all patients, it should be noted that PCR was not available in many facilities at the beginning of the pandemic, when this study was carried out.

(0.37MB).

Patients’ baseline clinical characteristics are shown in table 1. With the exception of previous coronary artery disease (more frequent in the COVID-19 cohort), the clinical characteristics were not different between the groups. The mode of presentation significantly differed between groups: during COVID-19, patients more frequently arrived at the hospital via the out-of-hospital emergency medical service and, once at the pPCI hospital, were more frequently admitted directly to the catheterization laboratory.

Table 1.

Baseline clinical characteristics of patients with confirmed diagnosis of STEMI

  Prior to COVID-19N=1305  During COVID-19N=1009  P 
Age, y  63.7±13.2  63.1±12.5  .24 
Male sex  1023 (78.4)  786 (78.4)  .99 
Clinical history
Hypertension  647 (50.0)  520 (51.9)  .36 
Diabetes  324 (25.2)  226 (22.6)  .15 
Hyperlipidemia  592 (45.8)  466 (46.7)  .67 
Current smoker  581 (45.7)  442 (44.6)  .60 
Previous coronary artery disease  131 (10.2)  139 (13.9)  .006 
First medical contact
Out-of-hospital emergency medical service  463 (35.8)  424 (42.3)  .017 
Primary care centers  319 (24.6)  219 (21.8)  .017 
Non-PCI hospitals  266 (20.6)  192 (19.1)  .017 
PCI hospitals  246 (19.1)  168 (16.7)  .017 
Reperfusion strategy at first medical contact
pPCI  1113 (87.7)  881 (87.8)  .86 
Fibrinolysis  51 (4.0)  34 (3.3)  .86 
Diagnostic doubt: transfer to pPCI hospital for decision  85 (6.7)  71 (7.1)  .86 
Diagnostic doubt: transfer to non-pPCI hospital for decision  20 (1.6)  17 (1.7)  .86 
Complications before PCI
Ventricular fibrillation  84 (6.4)  63 (6.2)  .85 
Asystole  15 (1.1)  5 (0.5)  .092 
Cardiogenic shock  53 (4.1)  42 (4.1)  .90 
Mechanical ventilation  42 (3.2)  37 (3.7)  .56 

PCI, percutaneous coronary intervention; PCR, polymerase chain reaction; pPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Values are reported as No. (%) or mean±standard deviation.

Angiographic and procedural characteristics

Angiographic characteristics and the treatment performed are shown in table 2. Radial access was more frequent during COVID-19 and, although there were no differences in the initial and final TIMI flows, there was an increase in mechanical thrombectomy and IIb/IIIa inhibitor administration. There was no difference in the reperfusion strategy after coronary angiography, with up to 94% of patients treated with pPCI in both cohorts and with less than 2% of patients not undergoing any percutaneous coronary intervention.

Table 2.

Angiographic and procedural characteristics of patients with confirmed diagnosis of STEMI

  Prior to COVID-19N=1305  During COVID-19N=1009  P 
Site of patient reception at pPCI hospital
Direct to catheterization laboratory  679 (57.3)  658 (66.0)  <.001 
Emergency department  398 (33.6)  258 (25.9)  <.001 
Critical care unit  49 (4.1)  40 (4.0)  <.001 
Coronary critical care unit  45 (3.8)  25 (2.5)  <.001 
Previously admitted to hospital  14 (1.2)  14 (1.4)  <.001 
Other  1 (0.1)  2 (0.2)  <.001 
Killip class at catheterization laboratory arrival
1024 (81.0)  821 (82.4)  .86 
II  115 (9.1)  83 (8.3)  .86 
III  34 (2.7)  25 (2.5)  .86 
IV  91 (7.2)  67 (6.7)  .86 
Coronary artery disease extent
1-vessel disease  789 (63.1)  597 (60.1)  .003 
2-vessel disease  301 (24.1)  296 (29.8)  .003 
3-vessel disease  161 (12.9)  100 (10.1)  .003 
Radial access  1087 (88.7)  910 (91.4)  .036 
Location of culprit vessel
Left main coronary artery  16 (1.2)  15 (1.5)  .59 
Left anterior descending  542 (41.5)  454 (45.0)  .095 
Left circumflex  198 (15.1)  150 (14.9)  .84 
Right coronary artery  476 (36.5)  388 (38.5)  .33 
Bypass graft  9 (0.7)  5 (0.5)  .55 
Initial TIMI flow
847 (68.9)  724 (72.2)  .18 
114 (9.3)  75 (7.5)  .18 
116 (9.4)  99 (9.9)  .18 
153 (12.4)  105 (10.5)  .18 
Final TIMI flow
22 (1.8)  17 (1.7)  .95 
15 (1.2)  11 (1.1)  .95 
48 (3.9)  43 (4.3)  .95 
1152 (93.1)  925 (92.9)  .95 
PCI characteristics
IIb/IIIa inhibitor administration  112 (8.6)  150 (14.9)  <.001 
Mechanical thrombectomy  337 (25.8)  356 (35.3)  <.001 
Balloon angioplasty  428 (32.8)  361 (35.8)  .13 
Bare-metal stent implantation  97 (7.4)  24 (2.4)  <.001 
Drug-eluting stent implantation  1066 (81.7)  887 (87.9)  <.001 
Decision after coronary angiography
pPCI  1209 (93.9)  943 (94.7)  .74 
Rescue PCI  29 (2.3)  23 (2.3)  .74 
Routine early PCI after fibrinolysis  24 (1.9)  14 (1.4)  .74 
Coronary angiography without PCI  26 (2.0)  16 (1.6)  .74 

PCI, percutaneous coronary intervention; pPCI, primary percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; TIMI, Thrombolysis in Myocardial Infarction.

Values are reported as No. (%).

Time intervals between symptom onset and reperfusion

During the COVID-19 outbreak, there was an increase in both time from symptom onset to first medical contact (105 [45-222] vs 71 [30-180] minutes, P <.001) and time from symptom onset to reperfusion (233 [150-375] vs 200 [140-332] minutes, P <.001). In contrast, no differences were observed in the time from first medical contact to reperfusion (110 [80-155] minutes vs 110 [81-151] minutes, P=.54). Five different time intervals between symptom onset and reperfusion are shown in table 3 and figure 4.

Table 3.

Time intervals between symptom onset and reperfusion

  Median [interquartile range]  P 
Symptom onset to first medical contact, min
Prior to COVID-19 (n=1160)  71 [30-180]  <.001 
During COVID-19 (n=901)  105 [45-222]  <.001 
Symptom onset to reperfusion, min
Prior to COVID-19 (n=895)  200 [140-332]  <.001 
During COVID-19 (n=895)  233 [150-375]  <.001 
First medical contact to reperfusion, min
Prior to COVID-19 (n=892)  110 [81-151]  .54 
During COVID-19 (n=892)  110 [80-155]  .54 
First medical contact to catheterization laboratory arrival, min
Prior to COVID-19 (n=1174)  86 [59-125]  .089 
During COVID-19 (n=904)  83 [55-125]  .089 
Catheterization laboratory arrival to reperfusion, min
Prior to COVID-19 (n=898)  20 [15-30]  <.001 
During COVID-19 (n=906)  24 [17-31]  <.001 
Figure 4.

Time intervals between symptom onset and reperfusion.

(0.22MB).
In-hospital outcomes

Differences in in-hospital outcomes between the 2 cohorts are shown in table 4. All-cause mortality during COVID-19 was 7.5% vs 5.1% in the prior to COVID-19 group (unadjusted OR, 1.50; 95%CI, 1.07-2.11; P <.001). This association remained consistent after adjustment for age, sex, Killip class, and time from symptom onset to reperfusion (OR, 1.88; 95%CI, 1.12-3.14; P=.017), but it was attenuated after additional adjustment for confirmed COVID-19 diagnosis (OR, 1.56; 95%CI, 0.91-2.67; P=.108).

Table 4.

In-hospital outcomes of patients with confirmed diagnosis of STEMI

  Prior to COVID-19N=1305  During COVID-19N=1009  P 
Mortality  67 (5.1)  75 (7.5)  .019 
Acute stent thrombosis  11 (0.8)  11 (1.1)  .54 
Major bleeding  8 (0.6)  11 (1.1)  .21 
Cardiogenic shock after PCI  75 (5.7)  48 (4.8)  .29 
Pulmonary edema after PCI  30 (2.3)  17 (1.7)  .30 
Mechanical ventilation after PCI  31 (2.4)  19 (1.9)  .42 
Mechanical complication  5 (0.4)  9 (0.9)  .12 

PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction.

Values are reported as No. (%).

Sensitivity analyses

The robustness of our findings was tested through 2 sensitivity analyses. By excluding COVID-19 patients from the main analyses, we removed their potential contribution to the increase in outcomes and confirmed that the excess mortality was partly explained by COVID-19 itself: the unadjusted OR (95%CI) for patients in 2020 was 1.28 (0.77-1.83) (P=.173), which remained nonsignificant after adjustment for confounding: 1.56 (0.90-2.68) (P=.11). By using random effects models, we allowed for some random heterogeneity across hospitals and obtained similar statistical significance (P=.044) for the association between in-hospital mortality and patients recruited during the COVID-19 outbreak vs those recruited 1 year before: patients with STEMI during the COVID-19 outbreak were at higher risk of in-hospital mortality after adjustment for confounding (P=.033), but this significant association disappeared when COVID-19 status was introduced into the model (P=.203), suggesting that COVID-19 was the driver of the increase in in-hospital mortality between cohorts.

DISCUSSION

In our study, we evaluated the influence of the COVID-19 outbreak on the management of STEMI patients attended in specific care networks nationwide in Spain, one of the countries most affected by the current pandemic. We compared data from a national registry establishing 2 different 30-day cohorts of patients: prior to the COVID-19 outbreak (from April 1 to April 30, 2019) and during the outbreak (from March 16 to April 14, 2020).

Fewer STEMI patients and longer delays to reperfusion

A previous report from our group revealed a 40% decrease in patients treated for STEMI during the first week of the current outbreak.3 Similarly, an American study revealed an estimated 38% reduction in STEMI-related catheterization laboratory activations in 9 high-volume centers during the early phase of the COVID-19 pandemic.4 Our results confirm a consistent decrease in the number of STEMI patients treated (in up to 87% of centers), albeit of a lower magnitude (22.7%) than initially believed.3 In addition, there was a significant decrease in the number of patients managed in STEMI networks who ultimately received a diagnosis other than STEMI, reinforcing the belief that patients avoided hospitals. Furthermore, patients had longer delays to reperfusion, largely due to later consultation of the health system because we found no differences in the time from first medical contact to reperfusion. Ischemic time duration is a major determinant of infarct size in patients with STEMI, and prompt recognition and early management of acute STEMI is critical in reducing morbidity and mortality.10–12 Interestingly, the COVID-19 cohort showed a higher prevalence of previous coronary artery disease and more multivessel disease, suggesting that patients with a history of ischemic heart disease may have been less reluctant to go to the hospital. Despite the logistical difficulties caused by the COVID-19 outbreak, we did not detect an increase in the time from first medical contact to reperfusion, which indicates a good adaptation of STEMI networks to the current crisis. On the contrary, there was a longer time from catheterization laboratory arrival to reperfusion, probably due to time spent on the protective measures required for the procedures.13

Potential behavioral explanations for these results would be a combination of avoidance of medical care due to social distancing and concerns about contracting COVID-19 in hospitals. The ongoing outbreak has received massive news coverage, with particular emphasis on the most common forms of infection and places where SARS-CoV-2 spreads more easily. Fear is a well-known determinant of medical care avoidance14 and hospital avoidance behaviors have been linked to pandemics.15

Reperfusion strategies and angiographic findings in STEMI during the COVID-19 outbreak

Various scientific societies have developed recommendations on the reperfusion strategy during the COVID-19 outbreak, with advice that may be conflicting, depending on the conditions in each country. In China, the Peking Union Medical College Hospital recommend thrombolysis as first-line treatment and only recommend coronary intervention after COVID-19 is ruled out, even in patients with a thrombolytic contraindication.16 The American College of Cardiology Interventional Council and the Society for Cardiovascular Angiography & Interventions state that fibrinolysis can be considered for relatively stable STEMI patients with active COVID-19 to prevent staff exposure.17 In Spain, there have been no changes to the reperfusion strategy, with more than 98% of STEMIs treated with pPCI and no increase in the use of thrombolysis, in accordance with Spanish Interventional Cardiology Association recommendations on STEMI management during the COVID-19 outbreak.18

Two recently published short series of patients with COVID-19 who had ST-segment elevation showed a high prevalence of nonobstructive disease.19,20 Overall, we did not find an increase in the number of patients without obstructive lesions. This could be a) because we analyzed only patients with confirmed STEMI diagnosis and thus excluded other causes of myocardial infarction with nonobstructive coronary arteries, such as myocarditis, takotsubo syndrome, non-STEMI, and pulmonary embolism, which represented about 10% of patients in our series; or b) because previously published data probably concerned nonconsecutive and highly selected patients.

Impact of the COVID-19 outbreak on STEMI-related mortality

A particularly relevant finding of our study is a disturbing elevation in in-hospital mortality during the COVID-19 outbreak. This increase remained consistent after adjustment for age, sex, Killip class, and time from symptom onset to reperfusion.

Recent epidemiologic data suggest a significant increase in mortality during this period that cannot be fully explained by COVID-19 patients alone.21 In the current situation, patients avoid going to the emergency services, or defer going, which could explain the increase in out-of-hospital cardiac arrest, as recently described in Italy.22 Although it is difficult to determine the real prevalence of out-of-hospital cardiac arrest in the setting of STEMI, we did not observe an increase in cases of ventricular fibrillation or asystole or in a need for mechanical ventilation prior to the catheterization laboratory in patients with confirmed STEMI. Up to 75% of deaths are estimated to occur before contact with the health system23 and the main way to prevent out-of-hospital cardiac arrest is for patients to seek hospital treatment as soon as symptoms of STEMI appear.24 Therefore, it is possible that an increase in out-of-hospital cardiac arrest may not be reflected in our study.

Lack of access to reperfusion treatment would also increase subacute STEMI complications, such as heart failure and/or cardiogenic shock, intraventricular thrombus formation and peripheral embolism, and mechanical complications.25 These patients were not included in the present registry because they were not candidates for pPCI but they undoubtedly contribute to STEMI-related excess mortality.

Finally, in the long term, suboptimal revascularization and a larger infarct size will increase complications related to worse ventricular remodeling, such as chronic heart failure and ventricular arrhythmias.26

Limitations

This study has limitations inherent to the analysis of multicentric observational data. Baseline and follow-up data were assessed at the center-level by each clinician-investigator, without central confirmation, potentially resulting in inaccuracies and misclassifications. Nevertheless, data on interventional cardiology are quite standardized worldwide and the electronic case report form was designed to be intuitively and universally completed by all clinicians. Moreover, we applied a mixed regression model including hospital as a random variable, which considered within- and between-hospital variations over time. In any case, the potential variability among clinicians approximates our findings to those of clinical practice and improves their generalizability. Any potential selection bias was addressed by adjustment of logistic regressions for potential confounders with prognostic implications, although some residual confounding (either measured or unmeasured) might remain after multivariate modeling.

CONCLUSIONS

In conclusion, this nationwide, observational study has revealed a decrease in the number of patients with STEMI managed during the current COVID-19 outbreak, with an increase in time from symptom onset to reperfusion and a significant 2-fold increase in in-hospital mortality. No changes in reperfusion strategy were detected. Concomitant SARS-CoV-2 infection in STEMI patients was infrequent but had an impact on in-hospital mortality.

CONFLICTS OF INTEREST

A. Pérez de Prado has received personal fees from iVascular, Boston Scientific, Terumo, B. Braun, and Abbott Laboratories. Á. Cequier has received personal fees from Ferrer International, Terumo, AstraZeneca, and Biotronik. All other authors have reported that they have no relationship relevant to the contents of this paper to disclose.

WHAT IS KNOWN ABOUT THE TOPIC?

  • -

    Some preliminary reports have highlighted a decrease in the number of STEMI patients attending hospitals during the current COVID-19 outbreak.

  • -

    There is little information on the influence of the COVID-19 outbreak on STEMI care and outcomes.

WHAT DOES THIS STUDY ADD?

  • -

    We found a significant decrease in the number of patients with STEMI managed in specific care networks in Spain during COVID-19.

  • -

    When compared with a cohort from the previous year, patients managed during the COVID-19 outbreak had a longer ischemia time and increased mortality, although there were no differences in the reperfusion strategy.

Appendix A
Material adicional

Key personnel and participating study sites:

Manuel Villa, Hospital Universitario Virgen del Rocío; Rafael Ruíz-Salmerón, Hospital Universitario Virgen Macarena; Francisco Molano, Hospital Universitario Virgen de Valme; Carlos Sánchez, Hospital Universitario General de Málaga; Erika Muñoz-García, Hospital Universitario Virgen de la Victoria; Luis Íñigo, Hospital Costa del Sol; Juan Herrador, Hospital Universitario de Jaén; Antonio Gómez-Menchero, Hospital Universitario Juan Ramón Jiménez; Eduardo Molina, Hospital Universitario Virgen de las Nieves; Juan Caballero, Hospital Universitario San Cecilio; Soledad Ojeda, Hospital Universitario Reina Sofía; Mérida Cárdenas, Hospital Punta de Europa; Livia Gheorghe, Hospital Universitario Puerta del Mar; Jesús Oneto, Hospital Universitario de Jerez de la Frontera; Francisco Morales, Hospital Universitario de Puerto Real; Félix Valencia, Hospital Universitario Torrecárdenas; José Ramón Ruiz, Hospital Clínico Universitario Lozano Blesa; José Antonio Diarte, Hospital Universitario Miguel Servet; Pablo Avanzas, Hospital Universitario Central de Asturias; Juan Rondán, Hospital Universitario de Cabueñes; Vicente Peral, Hospital Universitari Son Espases; Lucía Vera Pernasetti, Policlínica Nuestra Señora del Rosario; Julio Hernández, Hospital Universitario Nuestra Señora de Candelaria; Francisco Bosa, Hospital Universitario de Canarias; Pedro Luis Martín Lorenzo, Hospital Universitario de Gran Canaria Doctor Negrín; Francisco Jiménez, Hospital Insular de Gran Canaria; José M. de la Torre Hernández, Hospital Universitario Marqués de Valdecilla de Santander; Jesús Jiménez-Mazuecos, Hospital General Universitario de Albacete; Fernando Lozano, Hospital General Universitario de Ciudad Real; José Moreu, Complejo Hospitalario de Toledo; Enrique Novo, Hospital Universitario de Guadalajara; Javier Robles, Hospital Universitario de Burgos; Javier Martín Moreiras, Hospital Universitario de Salamanca; Felipe Fernández-Vázquez, Hospital de León; Ignacio J. Amat-Santos, Hospital Clínico Universitario de Valladolid, CIBERCV; Joan Antoni Gómez-Hospital, Hospital Universitari de Bellvitge; Joan García-Picart, Hospital de la Santa Creu i Sant Pau; Bruno García del Blanco, Hospital Universitari Vall d’Hebron; Ander Regueiro, Hospital Clínic de Barcelona; Xavier Carrillo-Suárez, Hospital Universitari Germans Trias i Pujol; Helena Tizón, Hospital del Mar; Mohsen Mohandes, Hospital Universitari Joan XXIII; Juan Casanova, Hospital Universitari Arnau de Vilanova; Víctor Agudelo-Montañez, Hospital Universitari de Girona Josep Trueta; Juan Francisco Muñoz, Hospital Universitari Mútua de Tarrassa; Juan Franco, Hospital Universitario Fundación Jiménez Díaz; Roberto del Castillo, Hospital Universitario Fundación Alcorcón; Pablo Salinas, Hospital Clínico San Carlos y Hospital Príncipe de Asturias; Jaime Elízaga, Hospital General Universitario Gregorio Marañón; Fernando Sarnago, Hospital Universitario 12 de Octubre; Santiago Jiménez-Valero, Hospital Universitario La Paz; Fernando Rivero, Hospital Universitario de La Princesa; Juan Francisco Oteo, Hospital Universitario Puerta de Hierro Majadahonda; Eduardo Alegría-Barrero, Hospital Univesitario de Torrejón-Universidad Francisco de Vitoria; Ángel Sánchez-Recalde, Hospital Ramón y Cajal; Valeriano Ruiz, Complejo Hospitalario de Navarra; Eduardo Pinar, Hospital Virgen de la Arrixaca; Luciano Consuegra-Sánchez, Hospital Universitario Santa Lucía de Cartagena; Ana Planas, Hospital General Universitario de Castellón; Bernabé López Ledesma, Hospital Universitario y Politécnico La Fe; Alberto Berenguer, Hospital General Universitario de Valencia; Agustín Fernández-Cisnal, Hospital Clínico Universitario de Valencia; Pablo Aguar, Hospital Universitario Dr. Peset; Francisco Pomar, Hospital Universitario de la Ribera; Miguel Jerez, Hospital de Manises; Francisco Torres, Hospitales de Torrevieja-Elche-Vinalopó; Ricardo García, Hospital General Universitario de Elche; Araceli Frutos, Hospital General Universitario de San Juan de Alicante; Juan Miguel Ruiz Nodar, Hospital General Universitario de Alicante; Koldobika García, Hospital Universitario de Cruces; Roberto Sáez, Hospital de Basurto; Alfonso Torres, Hospital Universitario Araba; Miren Tellería, Hospital Universitario Donostia; Mario Sadaba, Hospital de Galdakao-Usansolo; José Ramón López Mínguez, Complejo Hospitalario Universitario de Badajoz; Juan Carlos Rama Merchán, Hospital de Mérida; Javier Portales, Complejo Hospitalario Universitario de Cáceres; Ramiro Trillo Hospital Clínico Universitario Santiago de Compostela; Guillermo Aldama, Complejo Hospitalario Universitario de A Coruña; Saleta Fernández, Complejo Hospitalario Universitario de Vigo; Melisa Santás, Hospital Universitario Lucus Augusti; and María Pilar Portero Pérez, Hospital San Pedro de Logroño.

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The investigators, institutions, and organizations participating in the Working Group on the Infarct Code of the Interventional Cardiology Association of the Spanish Society of Cardiology are listed in the Appendix.

Copyright © 2020. Sociedad Española de Cardiología
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