Coronary artery disease (CAD) accounts for about two-thirds of cases of heart failure with reduced ejection fraction (HFrEF) [1]. Angina symptoms and cardiovascular risk factors (CVRF) are not sufficient to establish an ischemic etiology and according to recommendations coronary angiography (CA) is the gold standard [1–3]. There is a paucity of information on the performance of CA for detecting CAD in HFrEF without known CAD [4]. We aimed to determine the frequency of CAD in HFrEF patients of unknown etiology and without known CAD, and to identify variables associated with the presence and severity of CAD

Azevedo, A

Bettencourt, P

Borges, T

Magalhães, D

Mesquita, R

Ribeiro, A

Rocha, OL

Silva, F

Silva, JC

International Journal of Cardiology

Repositório Aberto da Universidade do Porto

International Journal of Cardiology 190 (2015) 131–132Contents lists available at ScienceDirectInternational Journal of Cardiologyj ourna l homepage: www.e lsev ie r .com/ locate / i j ca rdLetter to the EditorHeart failure with reduced ejection fraction: Should we submit patientswithout angina to coronary angiography?Filipa Silva a,⁎,1, Tiago Borges a,1, Ana Ribeiro a, Raquel Mesquita a, Olga Laszczynska b, Domingos Magalhães a,João Carlos Silva a, Ana Azevedo b,c, Paulo Bettencourt aa Serviço de Medicina Interna, Centro Hospitalar de São João, Porto, Portugal, Serviço de Cardiologia, Centro Hospitalar de São João, Porto, Portugal,UniC — Unidade de investigação e Desenvolvimento Cardiovascular, Porto, Portugalb EPIUnit — Institute of Public Health of the University of Porto (ISPUP), Porto, Portugalc Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal⁎ Corresponding author at: Serviço de Medicina InternaE.P.E.. Alameda Prof. Hernâni Monteiro, 4200-319 Porto, PE-mail address: ﬁlipadcs@gmail.com (F. Silva).1 The ﬁrst two authors contributed equally to this workhttp://dx.doi.org/10.1016/j.ijcard.2015.04.1150167-5273/© 2015 Elsevier Ireland Ltd. All rights reserveda r t i c l e i n f oArticle history:Received 11 April 2015Accepted 14 April 2015Available online 15 April 2015Keywords:Coronary artery diseaseHeart failureSystolic dysfunctionAngiographyDiagnosisknown previous diagnosis or current prescription for these diseases.The angiographic data included the number of arteries with signiﬁcantdisease and the degree of stenosis. Signiﬁcant CAD was deﬁned as≥70% luminal diameter narrowing in at least one coronary artery(N50% for the proximal left anterior descending artery). Severe CADwas deﬁned as the presence of signiﬁcant CAD of proximal left anteriordescending artery, three-vessel CAD or two-vessel CAD involving theleft anterior descending artery [5].Stata version 11.1 for Windows (StataCorp LP, College Station, TX)was used for statistical analysis. Continuous variables are expressed asmean ± standard deviation, except those without normal distribution,Coronary artery disease (CAD) accounts for about two-thirds ofcases of heart failure with reduced ejection fraction (HFrEF) [1]. Anginasymptoms and cardiovascular risk factors (CVRF) are not sufﬁcient toestablish an ischemic etiology and according to recommendations coro-nary angiography (CA) is the gold standard [1–3]. There is a paucity ofinformation on the performance of CA for detecting CAD in HFrEF with-out known CAD [4]. We aimed to determine the frequency of CAD inHFrEF patients of unknown etiology and without known CAD, and toidentify variables associated with the presence and severity of CAD.We retrospectively identiﬁed patients from a HF clinic, submitted toCA until the end of 2013. Exclusion criteria were HFwith left ventricularejection fraction N50%, other etiologies for HF, angina, known CAD(previous myocardial infarction (MI), coronary revascularization) andindication for CA for other purposes. The study protocol conforms tothe ethical guidelines of the declaration of Helsinki and was approvedby the local ethics committee. Data were abstracted from the clinicalrecords, including demographic variables, HF characteristics, routinelaboratory values, CVRF: history of smoking, body mass index, hyper-tension, dyslipidemia, diabetesmellitus (DM) and family history of pre-mature MI; and comorbidities: atrial ﬁbrillation and chronic kidney, Centro Hospitalar de São João,ortugal...disease. Dyslipidemia, hypertension and DM were deﬁned as either aexpressed as median (interquartile range). The qualitative variablesare expressed as absolute frequencies and percentages. Comparison ofabove-mentioned variables in both groups (with or without CAD) wasperformed by using t-test and the Mann–Whitney test for continuousvariables with skewed distribution, and the chi-square test for categor-ical variables. For all analyses, p b 0.05 was considered statisticallysigniﬁcant.We included 168 patients with HFrEFwho fulﬁlled the inclusion andexclusion criteria. Baseline characteristics are summarized in Table 1. Ofthese, 70% had no CAD, 31% had signiﬁcant CAD, among whom 23.1%had severe CAD. Patients with CAD were older, more frequently maleand had a higher prevalence (despite non-signiﬁcantly) of several CVRF.The diagnostic yield of CA, in women and men, according to thehistory of risk factors is summarized in Table 2. Signiﬁcant CAD wasmore than twice as prevalent in the presence than in the absence ofrisk factors. The presence of signiﬁcant CAD in the latter group was14.3% in men and 12.5% in women.Our results show that CAD is the etiology of HFrEF in a third ofpatientswithout angina and noprevious coronary event. Even in the ab-sence of CVRF, more than 10% of both men and women had signiﬁcantCAD. These results, although involving a young population, supportthe routine performance of CA in HFrEF independently of CAD risk fac-tors. CAD is the most frequent HFrEF etiology, although the prevalencevaries markedly according to populations [1,6]. The determination ofischemic etiology in HF patients is of major signiﬁcance since it can dic-tate treatment options and ischemic HF is independently associatedwith a worse long-term outcome [7,8]. In patients with angina or MI,Table 1Patient characteristics.Signiﬁcant CAD Severe CADAll No Yes p-Value No Yes p-ValueNo. of patients 168 112 56 129 39Age (years), mean (SD) 59.7 (11.8) 57.7 (11.6) 63.7 (11.3) 0.002 58.3 (11.5) 64.5 (11.8) 0.004Male sex, n (%) 119 (70.8) 75 (67.0) 44 (78.6) 0.119 89 (69.0) 30 (76.9) 0.340LVEF (%), mean (SD) 27.0 (9.8) 26.1 (10.3) 28.5 (8.8) 0.232 26.6 (10.0) 28.2 (9.4) 0.483Severe LVSD, n (%) 126 (77.3) 84 (78.5) 42 (75.0) 0.612 98 (79.0) 28 (71.8) 0.347Diabetes mellitus, n (%) 61 (36.3) 35 (31.3) 26 (46.4) 0.054 44 (34.1) 17 (43.6) 0.281Hypertension, n (%) 98 (58.3) 63 (56.3) 35 (62.5) 0.439 75 (58.1) 23 (59.0) 0.926Dyslipidemia, n (%) 90 (53.6) 53 (47.3) 37 (66.1) 0.022 66 (51.2) 24 (61.5) 0.255Smoking, n (%) 84 (53.8) 53 (51.5) 31 (58.5) 0.404 63 (52.5) 21 (58.3) 0.538Creatinine (mg/dL), median (IQR) 1.03 (0.64–2.70) 1.00 (0.68–1.79) 1.08 (0.67–2.39) 0.352 1.01 (0.66–2.05) 1.05 (0.73–1.48) 0.570CAD, coronary artery disease; IQR, interquartile range; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; SD, standard deviation.Table 2Diagnostic yield, according to cardiovascular risk factors.Signiﬁcant CAD Severe CADNo Yes No YesWomen No risk factors, n (%)a 14 (87.5) 2 (12.5) 14 (87.5) 2 (12.5)Any risk factor, n (%)a 23 (69.7) 10 (30.3) 26 (78.8) 7 (21.2)Men No risk factors, n (%)a 12 (85.7) 2 (14.3) 12 (85.7) 2 (14.3)Any risk factor, n (%)a 63 (60.0) 42 (40.0) 77 (73.3) 28 (26.7)CAD, coronary artery disease.a Risk factors: diabetes mellitus, dyslipidemia, and smoking.132 F. Silva et al. / International Journal of Cardiology 190 (2015) 131–132the extent of CAD, deﬁned by angiography, is a predictor of mortality.Also, the extent of CAD is a signiﬁcant risk factor for cardiovascular out-comes after MI is complicated by HF [9]. Additionally, patients with is-chemic HF may beneﬁt from secondary preventive measures andcoronary revascularization [1,3,4].According to the 2014 guidelines on myocardial revascularization,CA continues to be the gold standard for the assessment of CAD severity[2,3,9]. Some authors propose routine angiography in all patients withHFrEF, because the presence of CAD is not uncommon among patientswith HF of unknown etiology [10]. In our population of 168 patientswithHFrEF andno angina, the prevalence of angiographically signiﬁcantCAD was high (31%).A clinical tool has been recently validated to help clinicians predictthe absence of severe CAD in patients with HFrEF and therefore elimi-nate unnecessary CA. Independent predictors of severe CAD includedDM, electrocardiographic Q waves or left bundle branch block and atleast two nondiabetic risk factors. The presence of at least one of thesefactors identiﬁed more than 95% of CAD cases and all of the patientswith severe disease [10]. This study, as ours, was limited, by havingincluded only those patients who had undergone angiography.Our results corroborate previous observations, showing similar ratesof CAD in HFrEF patients without angina [4,10]. In our study, althoughpatients with signiﬁcant CAD had a higher prevalence of CVRF theywere not statistically signiﬁcantly different from patients withoutCAD. We observed that both male groups (with or without CVRF) hadsigniﬁcant CAD, which support the use of CA. Even 12.1% of womenwithout CVRF had signiﬁcant CAD.Our study is a retrospective analysis with limitations and biases thatare inherent. Besides being a single center study, the patients weresubmitted to CA at the physicians' discretion. Also, known CAD wasbased on the reported symptoms of typical angina and a history ofprevious MI or coronary revascularization, which may have beenunderreported. The relatively small sample size limits the generaliza-tion of results and can underestimate the interactions between CVRFand CAD. Additionally our population was relatively young, precludinggeneralization of the observations, but one can speculate that withincreasing age the yield would be even higher, as CAD prevalenceincreases with age.In conclusion, our study shows that among HFrEF patients withoutangina the prevalence of angiographically signiﬁcant CAD was high,suggesting that the performance of routine CA should be considered inHFrEF patients.Conﬂict of interestThe authors report no relationships that could be construed as aconﬂict of interest.References[1] J. McMurray, S. Adamopoulos, S. Anker, et al., ESC guidelines for the diagnosis andtreatment of acute and chronic heart failure 2012, Eur. Heart J. 33 (14) (2012)1787–1847.[2] S. Windecker, P. Kolh, F. Alfonso, et al., 2014 ESC/EACTS guidelines on myocardialrevascularization, Eur. J. Cardiothorac. Surg. 46 (2014) 517–592.[3] L.D. Hillis, P.K. Smith, J.L. Anderson, et al., 2011 ACCF/AHA guideline for coronary ar-tery bypass graft surgery: executive summary: a report of the American College ofCardiology Foundation/American Heart Association Task Force on practice guide-lines, Circulation 124 (2011) 2610–2642.[4] W. Pitts, R. Lange, D. Hillis, J. Cigarroa, Coronary arterial anatomy in patients withleft ventricular systolic dysfunction without chest pain or previous myocardialinfarction, Am. J. Cardiol. 82 (1998) 1530–1531.[5] G. Levine, E. Bates, J. Blankenship, et al., 2011 ACCF/AHA/SCAI guideline for percuta-neous coronary intervention, J. Am. Coll. Cardiol. 58 (2011) e44–e122.[6] M. Gheorghiade, G. Sopko, L. De Luca, et al., Navigating the crossroads of coronaryartery disease and heart failure, Circulation 114 (2006) 1202–1213.[7] J. McMurray, Systolic heart failure, N. Engl. J. Med. 362 (2010) 228–238.[8] K.F. Adams Jr., S.H. Dunlap, C.A. Sueta, et al., Relation between gender, etiology andsurvival in patients with symptomatic heart failure, J. Am. Coll. Cardiol. 28 (1996)1781–1788.[9] R. Janardhanan, S. Kenchaiah, E. Velasquez, et al., Extent of coronary artery diseaseas a predictor of outcomes in acute myocardial infarction complicated by heartfailure, left ventricular dysfunction, or both, Am. Heart 152 (2006) 183–189.[10] R. Doukky, M.J. Shih, M. Rahaby, et al., A simple validated clinical tool to predict theabsence of coronary artery disease in patients with systolic heart failure of unclearetiology, Am. J. Cardiol. 112 (2013) 1165–1170.

Heart failure with reduced ejection fraction: Should we submit patients without angina to coronary angiography?

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Heart failure with reduced ejection fraction: Should we submit patients without angina to coronary angiography?

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