Publish in this journal
Journal Information
Vol. 72. Issue 5.
Pages 383-391 (May 2019)
Share
Share
Download PDF
More article options
Visits
Not available
Vol. 72. Issue 5.
Pages 383-391 (May 2019)
Original article
DOI: 10.1016/j.rec.2018.03.002
Full text access
New-onset or Pre-existing Atrial Fibrillation in Acute Coronary Syndromes: Two Distinct Phenomena With a Similar Prognosis
La fibrilación auricular de nueva aparición o preexistente en los síndromes coronarios agudos: dos fenómenos distintos con un pronóstico comparable
Visits
...
Luigi Biascoa, Dragana Radovanovicb, Marco Moccettia, Hans Ricklic, Marco Roffid, Franz Eberlie, Raban Jegerf, Tiziano Moccettia, Paul Erneg, Giovanni Pedrazzinia,
Corresponding author
giovanni.pedrazzini@cardiocentro.org

Corresponding author: Division of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, 6900 Lugano, Switzerland.
a Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland
b AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
c Division of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
d Division of Cardiology, University Hospital of Geneva, Geneva, Switzerland
e Division of Cardiology, Stadtspital Triemli, Zurich, Switzerland
f Division of Cardiology, University Hospital Basel, Basel, Switzerland
g AMIS Plus, Zurich and Department of Biomedicine, University of Basel, Basel, Switzerland
Related content
Rev Esp Cardiol. 2019;72:367-810.1016/j.rec.2018.11.003
Victoria Johnson, Joern Schmitt
This item has received
...
Visits
(Daily data update)
Article information
Abstract
Full Text
Bibliography
Download PDF
Statistics
Figures (3)
Show moreShow less
Tables (4)
Table 1. Baseline Clinical Characteristics
Table 2. In-hospital Acute Treatments and Discharge Therapies
Table 3. In-hospital and 1-year Outcome
Table 4. Independent Predictors of In-hospital Mortality in Acute Coronary Syndrome Patients
Show moreShow less
Abstract
Introduction and objectives

The management and risk stratification of patients with atrial fibrillation (AF) and acute coronary syndromes constitute a challenge. We aimed to evaluate the prognostic impact of AF whether present at admission or occurring during hospitalization for acute coronary syndromes, as well as trends in treatments and outcome.

Methods

Data derived from 35 958 patients enrolled between 2004 and 2015 in the AMIS Plus registry were retrospectively analyzed.

Results

Pre-existing AF (pre-AF) was present in 1644 (4.7%) while new-onset AF (new-AF) was evident in 309 (0.8%). Presentation with ST-segment elevation myocardial infarction and need for hemodynamic support was frequent in patients with AF, especially in those with new onset of the arrhythmia. A change of the medical and interventional approaches was observed with a progressive increase in oral anticoagulation prescription and referral for angiography and percutaneous coronary interventions in pre-AF patients. Despite different baseline risk profile and clinical presentations, both AF groups showed high in-hospital and 1-year mortality (in-hospital new-AF vs pre-AF [OR, 0.79; 95%CI, 0.53-1.17; P = .246]; 1-year mortality new-AF vs pre-AF [OR, 0.72; 95%CI, 0.31-1.67; P = .448]) Pre-AF but not new-AF independently predicted in-hospital mortality. While mortality declined over the study period for patients with pre-AF, it remained stable among new-AF patients.

Conclusions

While pre-AF is independently associated with in-hospital mortality, new-AF may reflect a worse hemodynamic impact of the acute coronary syndromes, with the latter ultimately driving the prognosis.

Keywords:
Atrial fibrillation
Acute coronary syndrome
ST-segment elevation myocardial infarction
Mortality
Abbreviations:
ACS
AF
New-AF
PCI
Pre-AF
Resumen
Introducción y objetivos

El tratamiento y la estratificación del riesgo de los pacientes con fibrilación auricular (FA) y síndromes coronarios agudos son todo un reto. El objetivo es evaluar el impacto pronóstico de la FA, ya sea al ingreso como la aparecida durante la hospitalización por síndrome coronario agudo, así como las tendencias en los tratamientos y el resultado.

Métodos

Se analizaron retrospectivamente los datos procedentes de 35.958 pacientes incluidos entre 2004 y 2015 en el registro AMIS Plus.

Resultados

Había FA preexistente (FApre) en 1.644 pacientes (4,7%), mientras que se evidenció FA de nueva aparición (FAnueva) en 309 (0,8%). La presentación con infarto agudo de miocardio con elevación del segmento ST y la necesidad de asistencia hemodinámica fueron frecuentes en los pacientes con FA, especialmente aquellos con FA nueva. Se observó un cambio en los enfoques médicos e intervencionistas, con un progresivo aumento de la prescripción de anticoagulación oral y las derivaciones para angiografías e intervenciones coronarias percutáneas de pacientes con FApre. A pesar de los diferentes perfiles de riesgo iniciales y presentaciones clínicas, ambos grupos de FA mostraron grandes y comparables mortalidades hospitalaria y a 1 año (FAnueva frente a FApre: mortalidad hospitalaria, OR = 0,79; IC95%, 0,53-1,17; p = 0,246; mortalidad a 1 año, OR = 0,72; IC95%, 0,31-1,67; p = 0,448). La FApre, pero no la FAnueva, predijo de manera independiente la mortalidad hospitalaria. Si bien la mortalidad de aquellos con FApre disminuyó durante el periodo de estudio, se mantuvo estable entre los pacientes con FAnueva.

Conclusiones

Mientras que la FApre se asocia de manera independiente con la mortalidad hospitalaria, la FA nueva puede reflejar un peor impacto hemodinámico del síndrome coronario agudo, lo que en última instancia determina el pronóstico.

Palabras clave:
Fibrilación auricular
Síndrome coronario agudo
Infarto agudo de miocardio con elevación del segmento ST
Mortalidad
Full Text
INTRODUCTION

The management of patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) constitutes a challenge due to the paucity of data on the patient's specific bleeding and embolic risks and on appropriate antithrombotic treatment.1 In the absence of dedicated randomized controlled trials, the available evidence is mainly derived from subgroup analyses of stent or AF trials as well as registries. Overall, in the setting of ACS, AF patients appear to have worse prognosis and less access to invasive treatments compared with non-AF patients.2–11 However, it is still a matter of debate whether AF adversely affects prognosis in ACS per se or whether it is a marker of comorbidities, the latter effectively driving the outcome.2,5,6,8,9,11

While in most cases, AF is chronic and unrelated to ACS, on occasion patients develop AF in the acute setting. The pathophysiological mechanisms, the relative clinical impact on short and long-term outcomes and the management of AF in these 2 circumstances differ substantially.5,6,8–11 Moreover, whether the occurrence of AF during an ACS represents a predictor of in-hospital mortality or a marker of hemodynamic instability, the latter ultimately driving the prognosis, is still unknown.

The aim of this study was to evaluate the differential prognostic impact of AF, whether present at admission or occurring during hospitalization for ACS, as well as trends in treatments and outcomes according to the time of onset of AF.

METHODSPatient Population

Acute Myocardial Infarction in Switzerland (AMIS) Plus is a nationwide prospective registry enrolling patients admitted with ACS with or without ST-segment elevation in more than 80 hospitals recruiting since 1997.12,13 Patients are enrolled on a voluntary basis by signing a written informed consent form. Participating centers provide data for each patient through a standardized questionnaire including 200 items.

Data collection is centralized at the Institute of Social and Preventive Medicine of the University of Zürich. All data are checked for completeness, plausibility, and consistency by the AMIS Plus Data Center, querying treating physicians if the data are incomplete. Since 2010, external monitoring is regularly performed in randomly selected hospitals. The registry was approved by the Swiss Federal Ethics Committee for Clinical Studies, the Swiss Board for Data Security, and the appropriate Cantonal Ethics Commissions. The study protocol adheres to the ethics guidelines of the Declaration of Helsinki.

In this analysis, patients enrolled between January 1st, 2004 to July 1st, 2015 were considered. For all patients, detailed clinical history, in-hospital medical/interventional treatments and complications, therapy and vital status at discharge were available. Data from patients evaluated with coronary angiography are also reported. The Charlson comorbidity index, a quantitative estimate of associated comorbidities, was calculated.14,15

Among all in-hospital complications collected in the registry, those considered in the present analysis were defined as follows: a) cardiogenic shock: persistent hypotension (systolic blood pressure < 90mmHg) with clinical signs of severe reduction in cardiac index; b) stroke or transient ischemic attack: as any event due to ischemic, thrombotic or hemorrhagic disturbances confirmed by a neurologist or imaging modality; c) reinfarction: clinical signs or symptoms of ischemia with electrocardiogram changes indicative of new ischemia (new ST-changes or new left bundle branch block) and a new rise of biomarkers following the initial infarction; d) bleedings: recorded if deemed clinically relevant by the individual physician caring for the patient, without the use of a classification system.

At the time of the initial hospitalization, patients included in the registry may consent on an individual basis to a 1-year follow-up by telephone interview. Therefore the 1-year follow-up reported here reflects events occurring between the time of hospital discharge and 1 year only in the subgroup of patients accepting a telephone follow-up visit.

To better evaluate the clinical and prognostic impact of different timing of onset of AF in ACS, we classified patients on the basis of the time when the arrhythmia became clinically evident. Patients with AF documented at admission were classified as patients with pre-existing AF (pre-AF). This group therefore included patients with permanent or persistent AF and those who developed AF before hospital admission. Patients showing sinus rhythm at admission and developing AF at any time during hospitalization persisting until discharge, were considered as those with episodes of new-onset AF (new-AF).

Statistical Analysis

Data are presented as the proportion of valid cases for discrete variables and as mean ± standard deviation and/or medians with interquartile ranges for continuous variables. Differences in baseline characteristics were compared using the unpaired t test or Mann-Whitney U test, if appropriate, and the Pearson chi-square test. Bonferroni correction for multiple comparisons was adopted. Statistics for each table are based on all cases with valid data in the specified ranges for all variables in each table.

Univariate and multivariate analyses were performed using logistic regression analysis with a stepwise approach to identify predictors of in-hospital mortality in the whole population. The results of logistic regression are reported as odds ratios (OR) with a 95% confidence interval (95%CI). For the trend analysis, the Mantel Haenszel linear by linear association chi-square test with 1 degree of freedom was used. A probability value of P < .05 was considered significant. The IBM SPSS Statistics Version 22 (Armonk, New York: IBM Corp) was used for other statistical analyses.

RESULTSPatient Characteristics

The AMIS Plus registry included 35 958 patients admitted for ACS in the predefined study period, and data on heart rhythm at admission were available for 34 377. Of them, 1644 (4.7%) had AF at admission. In 309 (0.8%) patients, initially admitted with stable sinus rhythm, episodes of AF occurred during the hospital stay. Figure 1 reports patient flow according to group allocation with in-hospital and 1-year mortality, while Table 1 reports baseline characteristics.

Figure 1.

Patient flow according to group allocation with in-hospital and 1-year mortality. AF, atrial fibrillation; No-AF: patients without atrial fibrillation; New-AF: patients with new-onset atrial fibrillation; Pre-AF: patients with pre-existing atrial fibrillation. *Subgroups of patients followed up to 1-year. A total of 8534 had no AF, 357 had AF at admission and 68 had AF during hospitalization.

(0.15MB).
Table 1.

Baseline Clinical Characteristics

  Non-AF patients
(A) 
Patients with history of AF
(B) 
P
A vs B 
Patients with new-onset AF
(C) 
P
A vs C 
P
B vs C 
Number of patients  32 424  1644    309     
Female sex, %  26.3  34.0  < .001  31.4  .02  .180 
Age, y  65.6 ± 13.2  76.8 ± 10.7  < .001  74.6 ± 10.9  < .001  .001 
Risk factors
Family history, %  34.0  26.6  < .001  24.4  .001  .481 
Smoking, %  39.4  22.6  < .001  23.5  < .001  .739 
Dyslipidemia, %  58.2  53.5  .006  52.0  .041  .659 
Hypertension, %  61.6  79.3  < .001  68.4  .010  < .001 
Diabetes, %  20.0  29.0  < .001  26.1  .009  .324 
BMI > 30, %  21.3  21.4  .964  24.1  .284  .336 
Comorbidities
CAD, %  33.9  42.8  < .001  24.6  .799  < .001 
Heart failure, %  2.6  10.4  < .001  5.4  .003  .007 
CVD, %  5.4  11.4  < .001  8.8  .010  .181 
PVD, %  5.1  10.0  < .001  8.8  .002  .623 
Renal impairment (KDOQI class > 3), %  6.6  17.2  < .001  9.1  < .001  .041 
CHADS2 score, median  1 [0-2]  2 [1-3]    2 [1-3]     
CHA2DS2-VASC score, median  2 [1-3]  3 [2-4]    3 [2-4]     
Presentation
STEMI, %  55.3  47.5  < .001  61.5  .028  < .001 
Out of hospital CA, %  4.8  7.8  < .001  9.1  < .001  .447 
Killip class 3 or 4, %  6.5  15.7  < .001  13.4  < .001  .319 
Chest pain, %  87.6  75.4  < .001  85.2  .209  < .001 
Dyspnea, %  29.6  49.6  < .001  44.0  < .001  .092 

AF, atrial fibrillation; BMI, body mass index; CA, cardiac arrest; CAD, coronary artery disease; CVD, cerebrovascular disease; KDOQI, Kidney Disease Outcomes Quality Initiative; PVD, peripheral vascular disease; STEMI, ST-segment elevation myocardial infarction.

Data are expressed as No. (%), mean ± standard deviation or median [interquartile range].

Patients with pre-AF were older and showed a greater burden of associated comorbidities such as hypertension, diabetes, known coronary/peripheral artery disease, heart failure and cerebrovascular disease than those without the arrhythmia. Of note, acute admissions for ST-segment elevation myocardial infarction (STEMI) or typical chest pain were less frequent, while more severe presentations such as cardiogenic shock with pulmonary overload and out of hospital cardiac arrest were more frequent in pre-AF than in non-AF patients.

Patients with new-AF showed some distinguishing peculiarities compared with patients without AF as well as those with pre-AF. In fact, while being older than non-AF patients, they were significantly younger than patients with known AF and had fewer comorbidities. New-AF patients had the highest rates among the 3 groups of STEMI presentation (61.5%), as well as out of hospital cardiac arrest (9.1%).

Acute Management

Table 2 reports the in-hospital acute treatments and discharge therapy of patients according to their allocation group. Pre-AF patients less frequently received invasive diagnostics and percutaneous coronary interventions (PCI) than patients without known AF (angiograms pre-AF 56.5% vs non-AF 83.8%, P < .001; PCI pre-AF 53.2% vs non-AF 80.7%, P < .001; Table 2). In pre-AF patients, a trend toward increased referrals for coronary angiography and PCI was evident between 2004 and 2015 with an approximate 2 fold rise in the number of PCI (Figure 2A and B). When angiograms were performed, transfemoral access was chosen in 3 out of 4 patients.

Table 2.

In-hospital Acute Treatments and Discharge Therapies

  Non-AF patients
(A) 
Patients with history of AF
(B) 
P
A vs B 
Patients with new-onset AF
(C) 
P
A vs C 
P
B vs C 
Invasive evaluation
Coronary angiography  83.8  56.5  < .001  81.2  .226  < .001 
PCI performed  80.7  53.2  < .001  77.3  .143  < .001 
Femoral access  68.0  75.8  .025  69.2  .818  .260 
Radial access  32.0  24.2    30.8     
IABP treated  3.9  4.8  .075  12.4  < .001  < .001 
Coronary disease
One vessel  40.1  31.5  < .001  42.5  .064  .001 
Multivessel disease  59.9  68.5    57.5     
LVEF < 35%  5.9  11.2  < .001  13.3  < .001  .172 
CABG  2.8  2.4  .673  4.6  .358  .316 
Acute medical treatment
Aspirin  96.0  86.5  < .001  86.1  < .001  .919 
P2Y12inhibitors  83.9  61.3  < .001  85.1  .580  < .001 
Clopidogrel  64.2  52.9    59.6     
Prasugrel  25.3  9.7    19.8     
Ticagrelor  36.4  20.1    35.1     
GPIIb/IIIa inhibitors  24.3  11.3  < .001  20.5  .013  < .001 
Bivalirudin  1.7  1.7  .842  1.3  .657  .632 
Beta-blockers  61.9  61.2  .934  54.2  .026  .038 
Nitrates  51.5  48.4  .014  54.1  .367  .066 
ACE inhibitor/ARB  54.6  49.3  < .001  55.7  .692  < .001 
Ca2+channel blockers  8.7  12.4  < .001  9.5  .996  .147 
Diuretics  20.4  47.2  < .001  37.8  < .001  .002 
Statins  76.8  60.2  < .001  67.8  < .001  .013 
Vasopressors  7.4  11.3  < .001  17.7  < .001  .002 
Discharge therapy
Aspirin  96.9  81.1  < .001  88.6  < .001  .004 
P2Y12inhibitors  86.5  62.2  < .001  77.3  < .001  < .001 
Clopidogrel  63.8  54.3  < .001  66.4  .365  < .001 
Prasugrel  28.6  9.2  < .001  8.4  < .001  .741 
Ticagrelor  31.6  12.5  < .001  12.7  < .001  .961 
OAC  6.2  43.4  < .001  43.5  < .001  .934 
Triple therapy  3.6  18.7  < .001  27.9  < .001  < .001 
OAC + any P2Y12  4.0  21.4  < .001  32.3  < .001  < .001 
Dual antiplatelet  84.8  56.6  < .001  71.4  < .001  < .001 
Beta-blockers  79.1  78.6  .099  74.4  .012  .121 
Nitrates  0.8  13.9  < .001  10.8  < .001  .161 
ACE inhibitor/ARB  76.4  76.4  .110  77.6  .588  .415 
Ca2+channel blockers  10.0  14.6  < .001  14.4  .017  .928 
Diuretics  24.8  56.3  < .001  53.5  < .001  .393 
Statins  90.6  76.3  < .001  83.9  < .001  .005 

ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft; GPIIb/IIIa, glycoprotein IIb/IIIa; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; OAC, oral anticoagulant; PCI, percutaneous coronary intervention.

Data are expressed as No. (%).

Figure 2.

A, B: trends of referrals for CA and PCI according to time of onset of atrial fibrillation. C, D: trends in prescription of triple therapy (OAC + DAPT) or OAC + any antiplatelet (OAC + SAP, either aspirin or any P2Y12 inhibitor) at discharge according to the time of onset of AF. AF, atrial fibrillation; CA, coronary angiography; DAPT, dual antiplatelet therapy; PCI, percutaneous coronary intervention; pre-AF, pre-existing atrial fibrillation; new-AF, new-onset atrial fibrillation; OAC, oral anticoagulant; SAP, single antiplatelet.

(0.24MB).

In pre-AF patients, acute management with aspirin, P2Y12 inhibitors, glycoprotein IIb/IIIa inhibitors, angiotensin-converting enzyme inhibitors/receptor blockers and beta-blockers were less frequently adopted than in non-AF patients. In contrast, vasopressors and symptomatic treatments with Ca2+ channel blockers and diuretics were frequently prescribed.

No differences in terms of referral for invasive diagnostics and PCIs were observed between new-AF and non-AF patients. As for patients with pre-AF, a trend toward an increased referral to coronary angiography and PCIs was evident during the study period. Also, in this case, femoral access was chosen in most patients. Hemodynamic support with vasopressors or balloon counterpulsation was relatively common in new-AF patients, needed in almost 1 out of 5. Evidence of severe left ventricular dysfunction was more frequent in patients with pre-AF (11.2%) and new-AF (13.3%) than in those without the arrhythmia (5.9%, P < .001 for both AF groups vs non-AF).

Acute management with P2Y12 inhibitors was comparable among new-AF patients and those without AF.

Aspirin was prescribed to most patients, while a dual antiplatelet regimen was less frequently prescribed both in pre-AF (56.6%) and in new-AF patients (71.4%) compared with non-AF patients (P < .001 for both). Nonetheless, a progressive increase in triple therapy counterbalanced by a decline in the use of any single antiplatelet + oral anticoagulation was evident for pre-AF but not new-AF (P for trends .002 and .36 respectively; Figure 2C and D).

In both AF subgroups, an oral anticoagulant was prescribed in only about 40% of patients (and almost a quarter were discharged to secondary care facilities while on iv/subcutaneous heparin). Both triple therapy (ie, the association between aspirin + any P2Y12 inhibitor + oral anticoagulant) and a dual antiplatelet regimen were prescribed more often in patients with new-AF than in patients with known AF (27.9% vs 18.7%, P < .001 and 71.4% vs 56.6%, P < .001, respectively). Beta-blockers were less frequently used in patients with AF, while prescriptions of symptomatic medications such as nitrates and diuretics were significantly higher when compared with non-AF patients.

In-hospital Outcome

Table 3 reports details on in-hospital and 1-year outcome.

Table 3.

In-hospital and 1-year Outcome

  Non-AF patients
(Group A = 32 424) 
Patients with pre-AF
(Group B = 1644) 
Patients with new-AF
(Group C = 309) 
OR B vs A
OR (95%CI) 
OR C vs A
OR (95%CI) 
OR C vs B
OR (95%CI) 
In-hospital outcome
Length of stay, d (95%CI)  5 (2-8)  7 (3-13)  9 (6-15)       
Cardiogenic shock, No. (%)  1095/32 281 (3.4)  111/1638 (6.8)  30/309 (9.7)  2.07 (1.69-2.53), P < .001  3.06 (2.09-4.48), P < .001  1.47 (0.96-2.25), P = .069 
Reinfarction, No. (%)  277/32 284 (0.9)  23/1639 (1.4)  6/309 (1.9)  1.64 (1.07-2.52), P = .022  2.28 (1.01-5.17), P = .047  1.39 (0.56-3.44), P = .475 
Clinically relevant bleedings, No. (%)  777/30 139 (2.6)  49/1547 (3.2)  30/309 (6.5)  1.23 (0.92-1.65), P = .156  4.06 (2.76-5.96), P < .001  3.28 (2.05-5.27), P < .001 
Cerebrovascular events, No. (%)  209/32 284 (0.6)  22/1639 (1.3)  13/309 (4.2)  2.08 (1.34-3.24), P = .001  6.74 (3.80-11.94), P < .001  3.22 (1.60-6.47), P = .001 
Mortality, No. (%)  1642/32 424 (5.1)  215/1644 (13.1)  33/309 (10.7)  2.82 (2.42-3.28), P < .001  2.24 (1.55-3.22), P < .001  0.79 (0.53-1.17), P = .246 
1-year outcome  (8061)  (343)  (68)       
Rehospitalization, No. (%)  1796/7769 (23.1)  86/296 (29.1)  20/52 (38.5)  1.36 (1.05-1.76), P = .018  2.07 (1.18-3.65), P = .010  1.52 (0.82-2.81), P = .176 
Any re-intervention, No. (%)  980/6839 (14.3)  39/262 (14.9)  13/49 (26.5)  1.04 (0.73-1.47), P = .801  2.39 (1.28-4.62), P = .006  2.12 (1.03-4.37), P = .040 
Reinfarction, No. (%)  250/7721 (3.2)  21/298 (7.3)  1/50 (2.0)  2.26 (1.42-3.59), P = .005  0.60 (0.08-4.43), P = .625  0.26 (0.03-2.04), P = .204 
Cerebrovascular events, No. (%)  45/1734 (2.6)  5/79 (6.3)  0/48 (0)  2.92 (1.02-6.57), P = .045  0.38 (0.02-6.33), P = .501  0.17 (0.01-3.24), P = .239 
Mortality, No. (%)  255/8061 (3.1)  47/343 (13.7)  8/68 (11.8)  4.86 (3.47-6.77), P < .001  3.51 (1.59-7.75), P = .001  0.72 (0.31-1.67), P = .448 

95%CI, 95% confidence interval; AF, atrial fibrillation; new-AF, new-onset AF; OR, odds ratio; pre-AF, pre-existing atrial fibrillation.

Pre-AF patients had a longer hospital stay (7 interquartile range [3-13] vs 5 interquartile range [2-8] days; P < .001) and showed higher rates of in-hospital complications such as cardiogenic shock (OR, 2.07; 95%CI, 1.69-2.53; P < .001), reinfarction (OR, 1.64; 95%CI, 1.07-2.52; P = .022), and cerebrovascular events (OR, 2.08; 95%CI, 1.34-3.24; P = .001), while no differences in clinically relevant bleedings (OR, 1.23; 95%CI, 0.92-1.65; P = .156) were evident when compared with non-AF patients. Crude in-hospital mortality was also higher (non-AF 5.1% vs pre-AF 13.1%; OR, 2.82; 95%CI, 2.24-3.28; P < .001).

Between the first and last third of the study period analyzed (ie, 2004-2007 and 2015) in-hospital mortality declined from 15.0% to 10.7% in pre-AF patients (P for trend = .035).

New-AF patients showed the highest rate of in-hospital bleedings and cerebrovascular events among the 3 groups. In-hospital mortality among both AF groups was comparable (new-AF vs pre-AF [OR, 0.79; 95%CI, 0.57–1.17; P = .246]).

In-hospital mortality remained substantially stable in new-AF patients throughout the whole study period (P for trend = .42). Figure 3 describes trends of in-hospital mortality according to the presence and type of AF during the first, second and last third of the study period.

Figure 3.

Trends in in-hospital mortality according to the presence and type of AF during the first, second and last third of the study period. AF, atrial fibrillation; new-AF, new-onset atrial fibrillation; pre-AF, pre-existing atrial fibrillation.

(0.08MB).
Outcome at Follow-up

In the subpopulation of patients scheduled for 1-year follow-up (n = 8959; 24.9% of the entire population), those with AF at admission had more rehospitalizations for any cardiovascular reason (OR, 1.36; 95%CI, 1.07-1.76; P = .01), reinfarction (OR, 2.26; 95%CI, 1.42-3.59; P = .001) and cerebrovascular events (OR, 2.92; 95%CI, 1.02-6.57; P = .045), while no significant differences were evident in terms of recurrent invasive procedures such as angiographies, PCI, bypass surgery, or pacemaker/implantable cardioverter-defibrillator implantation (OR, 1.04; 95%CI, 0.73-1.47; P = .801) compared with non-AF patients. One year mortality in pre-AF was 4 times higher than that of non-AF patients (13.7% vs 3.1%; OR, 4.86; 95%CI, 3.47-6.77; P < .001).

At 1-year follow-up, more than 1 out of 3 patients with episodes of AF during the index admission had a new hospitalization for any cardiovascular reason (OR, 2.07; 95%CI, 1.18-3.65; P = .01 vs non-AF patients) and referrals for invasive procedures (OR, 2.39; 95%CI, 1.28-4.62; P = .006) but rates of recurrent cardiac ischemic events (OR, 0.60; 95%CI, 0.08-4.43; P = .625) and cerebrovascular events (OR, 0.38; 95%CI, 0.02-6.33; P = .501) were similar to those observed in non-AF patients.

No strokes were evident in new-AF patients during follow-up. One year mortality was 11.8%, higher than that observed in non-AF patients (OR, 3.51; 95%CI, 1.59-7.75; P = .001), but comparable to that in pre-AF patients (OR, 0.72; 95%CI, 0.31-1.67; P = .625).

Outcome Predictors

Table 4 shows the results of the univariable and multivariable analyses.

Table 4.

Independent Predictors of In-hospital Mortality in Acute Coronary Syndrome Patients

  Univariate  Multivariate 
  OR (95%CI)  OR (95%CI) 
History of AF  2.77 (2.36-3.22)  1.29 (1.08-1.53) 
New onset of AF  2.09 (1.46-3.01)  1.11 (0.74-1.69) 
Age (per additional year)  1.06 (1.06-1.07)  1.06 (1.05-1.07) 
Female sex  1.58 (1.43-1.74)  1.02 (0.92-1.14) 
STEMI  1.59 (1.44-1.76)  1.74 (1.56-1.93) 
Killip class > 2  13.2 (11.8-14.7)  11.0 (9.88-12.3) 
Charlson comorbidity index > 1  2.74 (2.49-3.02)  1.61 (1.44-1.80) 

95%CI, 95% confidence interval; AF, atrial fibrillation; OR, odds ratio; STEMI, ST-segment elevation myocardial infarction.

All the above variables were used in the adjusted model.

A multivariable analysis was performed that included history of AF, intercurrent episodes of AF, age, female sex, STEMI presentation, Killip class > 2 at admission and Charlson comorbidity index > 1. History of AF (OR, 1.29; 95%CI, 1.08-1.53; P = .005), age (OR per additional year, 1.06; 95%CI, 1.05-1.07; P < .001), STEMI presentation (OR, 1.74; 95%CI, 1.56-1.93; P < .001), Killip class > 2 (OR, 11.0; 95%CI, 9.88-12.3; P < .001) and Charlson Comorbidity index > 1 (OR, 1.61; 95%CI, 1.45-1.80; P < .001) were independent predictors of in-hospital mortality, while new-onset AF during hospitalization was not independently associated with in-hospital mortality (OR, 1.02; 95%CI, 0.74-1.69; P = .614).

DISCUSSION

To the best of our knowledge, this is the largest European contemporary registry evaluating the relative impact on morbidity and mortality of pre-existing vs new-onset AF in the setting of an ACS.

The following key messages can be drawn from our data:

  • Despite different baseline clinical profiles, patients with pre-existing AF and those with new-onset AF both experienced high and comparable in-hospital and 1-year mortality.

  • Pre-existing AF but not new-onset AF was an independent predictor of in-hospital mortality.

  • New-onset AF, being frequently associated with STEMI presentation, out of hospital cardiac arrest and risk of hemodynamic deterioration, was a marker of worse hemodynamic impact of ACS.

  • During the 10 years evaluated, a progressive increase in referrals to PCI with a concomitant reduction of mortality was observed in patients with pre-existing AF. In contrast, mortality remained substantially stable and high in patients with new-onset AF.

Previous works have analyzed the clinical characteristics and prognostic impact of known and de novo AF associated with an ACS. Data derived from the GRACE/CANRACE and Medicare registries showed that the incidence of known AF ranged from 7.6% to 22.1% in ACS patients. AF patients were older, with an increased burden of cardiovascular risk factors as well as known coronary disease, heart failure, and renal impairment, with lesser access to evidence-based therapies and a noteworthy in-hospital mortality.2,5,10 Moreover, the paradigm that pre-existing compared with newly discovered AF had a different mode of onset, pathophysiology, and in-hospital and long-term outcomes was emphasized and a prognostic role for newly developed AF was also hypothesized.5

Our data propose a comprehensive interpretation for both types of AF. Despite different clinical characteristics and pathophysiological mechanisms, the comparable and high in-hospital and 1-year mortality observed in both AF groups unifies those 2 entities from a prognostic perspective. Independently from different modes and timing of onset, both AF groups showed a high and comparable in-hospital mortality, this representing a marker of clinical interest.

There is conflicting evidence on the relative role of the 2 different AF forms. While some authors do not recognize a clear role as a predictor of in-hospital mortality for pre-existing AF2,5,16,17 the worse in-hospital outcome not being attributed to a direct role of AF but rather to the associated prognosticators such as age or poorer overall clinical status at presentation, others postulate a causative effect.8,9

Our analysis shows that pre-existing AF, but not new-onset AF, was an independent predictor of in-hospital mortality. This finding highlights the role of the arrhythmia as a prognosticator in ACS, to be potentially considered in association with currently recommended–or in the development of future–risk estimation scores.18,19 On the other hand, the occurrence of new episodes of AF was frequently associated with STEMI presentation, out of hospital cardiac arrest, hemodynamic deterioration requiring mechanical or pharmacological support, underscoring the role of the hemodynamic impact of the ACS as a trigger for AF.20 Those associations were considered as the factors leading to the lack of significance for new-AF as a predictor of in-hospital mortality in our population. Nonetheless, regardless of statistical nonsignificance, the clinical importance of the new episodes of AF in the setting of AF remains. In fact, despite a younger age and a lower burden of associated comorbidities observed in patients with new onset of the arrhythmia, the hemodynamic impact of ACS overrides their better baseline overall status driving morbidity/mortality.

Trend analysis clearly underlined a progressive decline of in-hospital mortality for pre-existing AF patients. This confirms a tendency evident in the literature reporting in-hospital and 1-year deaths exceeding 20% and 40% in the mid 1990s,5 15% and 30% in early 2000,9 and 10% in more contemporary series.7,10 While this trend was clear in patients with pre-existing AF, mortality remained stable and high in patients with new-onset AF, strengthening once more the clinical importance of this entity.

Furthermore, while no causative relation can be drawn from our data, between the first and last year analyzed (ie, 2004 and 2014) the decline of in-hospital mortality observed in patients with pre-existing AF was mirrored by an increased referral for PCI. This represents an interesting hypothesis-generating finding, potentially related to the recent improvements in interventional tools and techniques (such as the adoption of radial access or third generation stents allowing shortened antiplatelet therapies) that might further enhance the benefits of percutaneous revascularization even in frail patients.

Beside prognostic implications, physicians are called to face difficult therapeutic decisions when managing AF during the acute phase of a coronary ischemic event, and have to balance the embolic and hemorrhagic risks; these decisions are often based on expert consensus, due to the lack of evidence-based confirmations.1,21,22

Our data clearly show that multiple therapeutic regimens are adopted, potentially leading to misleading impacts on morbidity and mortality. Both underuse of anticoagulant/antiplatelet therapies and revascularizations in patients with known AF may explain the observed increased incidence of reinfarction and cerebrovascular events at 1-year.In addition, in the setting of new-AF, increased rates of in-hospital bleedings and cerebrovascular events were observed, probably due to an overestimation of their embolic risk.

The adoption of proven measures known to be effective in reducing hemorrhagic complications and mortality such as the radial should be further encouraged.23

Strengths and Limitations

Several strengths and limitations of our work should be mentioned.

This analysis, evaluating the relationships between AF and ACS, derived from the data of the Swiss national registry, provides a western updated overview allowing us to depict a national real-life scenario and to provide clues for optimization of current standards of care. Nonetheless, as an observational nonrandomized investigation, our data are subject to certain limitations such as missing data and patient selection or other unforeseen confounders. First, the large number of our population with AF both and admission as well as those with intercurrent episodes is a limitation to the external validity of our observations. While vital status at discharge was available for the whole set of enrolled patients, follow-up was available for a large portion but not for the whole population, thus allowing us to report only an estimate of postdischarge morbidity/mortality. Moreover, the progresses of medical/interventional treatments are mirrored by the transformations of the registry. Even in this relatively short observation period, some major innovations have been introduced such as standardized definitions for in-hospital complications or data regarding treatments that are available only in a proportion of our patients. Finally, the registry design did not allow us to classify patients according to the type of AF (whether paroxysmal, persistent or chronic), or to exclude the possibility that a certain percentage of patients classified as new-AF might have had an arrhythmia onset close to the hospital admission, thus being potentially ACS-related. Equally, we did not provide any data about the outcome of rhythm disturbance at follow-up.

CONCLUSIONS

Our data confirm that AF in the setting of ACS is a major clinical problem. Both patients with history of AF and those with new-onset AF showed in-hospital complications and significantly increased and comparable in-hospital and 1-year mortality. While a history of AF is independently associated with in-hospital mortality, new-onset AF episodes may mirror a worse hemodynamic impact of the ACS, this ultimately driving the prognosis. Despite different clinical characteristic, burden of associated comorbidities and pathophysiological mechanism and in-hospital morbidity, pre-existing and new-onset AF share high and comparable acute and long-term mortality.

FUNDING

The AMIS Plus registry is funded by unrestricted grants from the Swiss Heart Foundation and from Abbot AG, Amgen AG, AstraZeneca AG, Bayer (Schweiz) AG, Biotronik AG, Boston Scientific AG, B. Braun Medical AG, Daiichi-Sankyo /Lilly AG, GE Healthcare AG, Johnson & Johnson AG – Cordis Division, Medtronic AG, A. Menarini AG, Merck Sharp & Dohme AG, Mepha Pharma AG, Novartis Pharma Schweiz AG, Sanofi-Aventis (Schweiz) AG, Servier (Suisse) AG, St. Jude Medical (Schweiz) AG, Vascular Medical GmbH; all in Switzerland. The sponsors did not play any role in the design, data collection, analysis, or interpretation of the registry.

CONFLICTS OF INTERESt

None declared.

WHAT IS KNOWN ABOUT THE TOPIC?

  • -

    In the setting of ACS, patients with AF are known to have a worse prognosis and lesser access to invasive treatments. Nonetheless, it is still a matter of debate whether AF adversely affects prognosis in ACS per se or is a marker of comorbidities, which effectively drive the outcome. Moreover, the relative impact of pre-existing compared with new-onset AF is debated.

WHAT DOES THIS STUDY ADD?

  • -

    Despite being intrinsically different from a pathophysiological perspective, pre-existing and new-onset AF showed a high and comparable in-hospital and 1-year mortality. While pre-existing AF was an independent predictor of in-hospital mortality, new-onset AF, being frequently associated with STEMI presentation, out of hospital cardiac arrest and risk of hemodynamic deterioration, was interpreted as a marker of worse hemodynamic impact of the ACS.

.

References
[1]
G.Y. Lip, S. Windecker, K. Huber, Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS), et al.
Eur Heart J., 35 (2014), pp. 3155-3179
[2]
D. Al Khdair, L. Alshengeiti, B. Elbarouni, et al.
Global Registry of Acute Coronary Events (GRACE/GRACE2) and the Canadian Registry of Coronary Events (CANRACE) Investigators. Management and outcome of acute coronary syndrome patients in relation to prior history of atrial fibrillation.
Can J Cardiol, 28 (2012), pp. 443-449
[3]
A.M. Chamberlain, B.J. Gersh, R.M. Mills, et al.
Antithrombotic strategies and outcomes in acute coronary syndrome with atrial fibrillation.
Am J Cardiol., 115 (2015), pp. 1042-1048
[4]
M. Lehto, S. Snapinn, K. Dickstein, et al.
OPTIMAAL investigators. Prognostic risk of atrial fibrillation in acute myocardial infarction complicated by left ventricular dysfunction: the OPTIMAAL experience.
Eur Heart J., 26 (2005), pp. 350-356
[5]
S.S. Rathore, A.K. Berger, K.P. Weinfurt, et al.
Acute myocardial infarction complicated by atrial fibrillation in the elderly: prevalence and outcomes.
Circulation., 101 (2000), pp. 969-974
[6]
J. Schmitt, G. Duray, B.J. Gersh, S.H. Hohnloser.
Atrial fibrillation in acute myocardial infarction: a systematic review of the incidence, clinical features and prognostic implications.
Eur Heart J., 30 (2009), pp. 1038-1045
[7]
R.D. Lopes, K.S. Pieper, J.R. Horton, et al.
Short- and long-term outcomes following atrial fibrillation in patients with acute coronary syndromes with or without ST-segment elevation.
Heart., 94 (2008), pp. 867-873
[8]
D.H. Lau, L.T. Huynh, D.P. Chew, C.M. Astley, A. Soman, P. Sanders.
Prognostic impact of types of atrial fibrillation in acute coronary syndromes.
Am J Cardiol., 104 (2009), pp. 1317-1323
[9]
T. Podolecki, R. Lenarczyk, J. Kowalczyk, et al.
Effect of type of atrial fibrillation on prognosis in acute myocardial infarction treated invasively.
Am J Cardiol., 109 (2012), pp. 1689-1693
[10]
D.D. McManus, W. Huang, K.V. Domakonda, et al.
Trends in atrial fibrillation in patients hospitalized with an acute coronary syndrome.
Am J Med., 125 (2012), pp. 1076-1084
[11]
H. González-Pacheco, G. Eid-Lidt, A. Altamirano-Castillo, et al.
Prevalence and prognostic implications of different types of atrial fibrillation in patients admitted to a coronary care unit.
Int J Cardiol., 172 (2014), pp. e379-e381
[12]
D. Radovanovic, P. Erne, P. Urban, et al.
AMIS Plus Investigators. Gender differences in management and outcomes in patients with acute coronary syndromes: results on 20,290 patients from the AMIS Plus registry.
Heart., 93 (2007), pp. 1369-1375
[13]
G.B. Pedrazzini, D. Radovanovic, G. Vassalli, et al.
AMIS Plus Investigators. Primary percutaneous coronary intervention for unprotected left main disease in patients with acute ST-segment elevation myocardial infarction the AMIS (Acute Myocardial Infarction in Switzerland) plus registry experience.
JACC Cardiovasc Interv., 4 (2011), pp. 627-633
[14]
M.E. Charlson, P. Pompei, K.L. Ales, C.R. MacKenzie.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
J Chronic Dis., 40 (1987), pp. 373-383
[15]
J.R. Ouellette, D.G. Small, P.M. Termuhlen.
Evaluation of Charlson-age comorbidity index as predictor of morbidity and mortality in patients with colorectal carcinoma.
J Gastrointest Surg., 8 (2004), pp. 1061-1067
[16]
B.S. Crenshaw, S.R. Ward, C.B. Granger, A.L. Stebbins, E.J. Topol, R.M. Califf.
Atrial fibrillation in the setting of acute myocardial infarction: the GUSTO-I experience. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.
J Am Coll Cardiol., 30 (1997), pp. 406-413
[17]
K. Kinjo, H. Sato, H. Sato, Osaka Acute Coronary Insufficiency Study (OACIS) Group, et al.
Prognostic significance of atrial fibrillation/atrial flutter in patients with acute myocardial infarction treated with percutaneous coronary intervention.
Am J Cardiol., 92 (2003), pp. 1150-1154
[18]
K.A. Eagle, M.J. Lim, O.H. Dabbous, et al.
GRACE investigators. A validated prediction model for all forms of acute coronary syndrome. Estimating the risk of 6-month postdischarge death in an international registry.
JAMA., 291 (2004), pp. 2727-2733
[19]
P. De Araújo Gonçalves, J. Ferreira, C. Aguiar, R. Seabra-Gomes.
TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS.
Eur Heart J., 26 (2005), pp. 865-872
[20]
J. Wang, Y.M. Yang, J. Zhu.
Mechanisms of new-onset atrial fibrillation complicating acute coronary syndrome.
Herz., 40 Suppl 1 (2015), pp. 18-26
[21]
D. Capodanno, D.J. Angiolillo.
Management of antiplatelet and anticoagulant therapy in patients with atrial fibrillation in the setting of acute coronary syndromes or percutaneous coronary interventions.
Circ Cardiovasc Interv., 7 (2014), pp. 113-124
[22]
D.S. Ice, T.A. Shapiro, E.M. Gnall, P.R. Kowey.
Unanswered questions in patients with concurrent atrial fibrillation and acute coronary syndrome.
Am J Cardiol., 113 (2014), pp. 888-896
[23]
S.R. Mehta, S.S. Jolly, J. Cairns, et al.
RIVAL Investigators. Effects of radial versus femoral artery access in patients with acute coronary syndromes with or without ST-segment elevation.
J Am Coll Cardiol, 60 (2012), pp. 2490-2499
Copyright © 2018. Sociedad Española de Cardiología
Idiomas
Revista Española de Cardiología (English Edition)

Subscribe to our newsletter

Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.