Diabetologia (2012) 55:2154–2162 DOI 10.1007/s00125-012-2579-0
ARTICLE
High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes L. J. M. Boonman-de Winter & F. H. Rutten & M. J. M. Cramer & M. J. Landman & A. H. Liem & G. E. H. M. Rutten & A. W. Hoes
Received: 24 January 2012 / Accepted: 11 April 2012 / Published online: 18 May 2012 # The Author(s) 2012. This article is published with open access at Springerlink.com
Abstract Aims/hypothesis The aim of this study was to assess the prevalence of (unknown) heart failure and left ventricular dysfunction in older patients with type 2 diabetes. Methods In total, 605 patients aged 60 years or over with type 2 diabetes in the south west of the Netherlands participated in this cross-sectional study (response rate 48.7%), including 24 with a cardiologist-confirmed diagnosis of heart failure. Between February 2009 and March 2010, the patients without known heart failure underwent a standardised diagnostic work-up, including medical history, physical examination, ECG and echocardiography. An expert panel used the criteria of the European Society of Cardiology to diagnose heart failure. Results Of the 581 patients studied, 161 (27.7%; 95% CI 24.1%, 31.4%) were found to have previously unknown heart failure: 28 (4.8%; 95% CI 3.1%, 6.6%) with reduced ejection fraction, and 133 (22.9%; 95% CI 19.5%, 26.3%) with preserved ejection fraction. The prevalence of heart failure increased steeply with age. Heart failure with preserved L. J. M. Boonman-de Winter : F. H. Rutten : G. E. H. M. Rutten : A. W. Hoes Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands L. J. M. Boonman-de Winter (*) Department of Scientific Research, Center for Diagnostic Support in Primary Care (SHL-Groep), Bredaseweg 165, 4872 LA Etten-Leur, the Netherlands e-mail:
[email protected] M. J. M. Cramer Department of Cardiology, Heart-Lung Center, University Medical Center Utrecht, Utrecht, the Netherlands
ejection fraction was more common in women. Left ventricular dysfunction was diagnosed in 150 patients (25.8%; 95% CI 22.3%, 29.4%); 146 (25.1%; 95% CI 21.6%, 28.7%) had diastolic dysfunction. Conclusions/interpretation This is the first epidemiological study that provides exact prevalence estimates of (previously unknown) heart failure and left ventricular dysfunction in a representative sample of patients with type 2 diabetes. Previously unknown heart failure and left ventricular dysfunction are highly prevalent. Physicians should pay special attention to ‘unmasking’ these patients. Keywords Diagnosis . Echocardiography . Epidemiology . Heart failure . Left ventricular dysfunction . Prevalence . Type 2 diabetes Abbreviations A Atrial contraction E Early diastolic mitral flow velocity E′ Early diastolic mitral annular velocity M. J. Landman Meander Hospital, Amersfoort, the Netherlands A. H. Liem Department of Cardiology, Admiraal de Ruyter Hospital, Goes, the Netherlands Present address: M. J. Landman Van Hardenbroeklaan 21, 3832CK Leusden, the Netherlands Present address: A. H. Liem Department of Cardiology, Sint Franciscus Hospital, Rotterdam, the Netherlands
Diabetologia (2012) 55:2154–2162
E/A E/e' ESC HFPEF HFREF LA LVEF MDRD NT-proBNP NYHA S/D
Early-to-atrial left ventricular filling ratio Early filling to early diastolic mitral annular velocity ratio European Society of Cardiology Heart failure with preserved ejection fraction Heart failure with reduced ejection fraction Left atrial Left ventricular ejection fraction Modification of diet in renal disease N-terminal pro B-type natriuretic peptide New York Heart Association Systolic-to-diastolic pulmonary venous flow ratio
Introduction Cardiovascular diseases are of major importance in patients with type 2 diabetes, accounting for up to 80% of the excess mortality in these patients [1]. Processes underlying the excess cardiovascular mortality risk include coronary atherosclerosis, generalised microvascular disease and autonomic neuropathy [1]. In addition, myocardial abnormalities (‘diabetic cardiomyopathy’) and heart failure seem to play a role [2, 3]. In general, underdiagnosis of heart failure is common [4]; a prevalence of unrecognised heart failure of up to 20.5% has been reported in specific patient groups, such as patients with chronic obstructive pulmonary disease [4, 5]. Previously reported heart failure prevalence estimates in patients with type 2 diabetes were based on medical records or heart failure scores, lacking echocardiography in all patients. Reported prevalence ranged from 9.5% to 22.3% [6–9], and the incidence of heart failure in patients with type 2 diabetes was about 2.5 times that in people without diabetes [10]. In one study, echocardiography was used to diagnose heart failure with reduced ejection fraction (HFREF), resulting in a prevalence of 7.7%, but diastolic dysfunction and heart failure with preserved ejection fraction (HFPEF) was not assessed [11]. To our knowledge, exact prevalence estimates of (unrecognised) heart failure, with and without reduced ejection fraction, and systolic and diastolic dysfunction in a representative sample of all older patients with type 2 diabetes are lacking. We therefore assessed this prevalence in patients aged 60 years and older with type 2 diabetes, all undergoing echocardiography.
Methods Participants The study was conducted between February 2009 and March 2010, in the province of Zeeland, in the
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south west of the Netherlands. We were able to invite a representative group of patients with type 2 diabetes, at least for Western Europe, because all patients with type 2 diabetes in this region are enrolled in the Diabetes Care programme of the Center for Diagnostic Support in Primary Care (SHL), including those (co-)treated by hospital specialists (~50,000 patients during the period of this study). Of all the patients with type 2 diabetes from the participating physicians in this study, 1,243 were 60 years or older, and were invited. All participants gave written informed consent, and the institutional review board of the University Medical Center Utrecht and the Admiraal de Ruyter Hospital in Goes, the Netherlands approved the study protocol. The protocol of the study has been published previously [12] and the study is registered at www.ccmo.nl, NL2271704108. Measurements The patients without a cardiologist-confirmed diagnosis of heart failure (i.e. including echocardiographic evidence of left ventricular dysfunction) underwent a standardised diagnostic assessment, which was executed in the cardiology outpatient department of the Admiraal de Ruyter Hospital in Goes. Information on duration of diabetes, smoking habits and comorbidities was obtained from the patients and the registry. Patients were asked to bring their medication packages so that current drug treatment could be checked. The presence of angina pectoris and shortness of breath was assessed with the WHO questionnaires [13]. Symptoms and signs were assessed by a trained physician in a standardised manner. A standard 12-lead ECG was recorded and classified according to the Minnesota coding criteria by a single experienced cardiologist, blinded to all other test results. Systolic and diastolic blood pressure was measured once electronically, after 5 min of rest in a supine position. Blood was taken within 2 weeks of the diagnostic assessment, with measurement of serum B-type natriuretic peptide (NT-proBNP), blood glucose, creatinine and HbA1c. NT-proBNP was measured with a non-competitive immunoradiometric assay (Roche Diagnostics, Mannheim, Germany). Echocardiography was performed with a General Electric, Vivid 7 imaging system device (GE Vingmed Ultrasound AS, Horten, Norway) by well-trained and experienced cardiac sonographers. Variables from Doppler analysis, M-mode echocardiography and two-dimensional transthoracic echocardiography were used. Where image quality was adequate, left-ventricular ejection fraction (LVEF) was calculated from the endocardial surface tracings in the apical four-chamber view and two-chamber view, using Simpson’s rule (disc summation method) [14, 15]. LVEF could be assessed in 97.5% of the patients by a quantitative method or the two-dimensional visual estimate method (‘eyeballing’) [16]. The accuracy of eyeballing has been validated previously [17]. Wall motion abnormalities were visually analysed and summarised in a wall motion
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score [18]. Left ventricular mass was calculated using M-mode measurements and the formula of Devereux and Reichek [19]. Valve regurgitation was graded semi-quantitatively, and, in the case of aortic stenosis, the pressure gradient was measured. Left atrial (LA) volume was assessed by the biplane area– length method from apical four- and two-chamber views [20]. Indexed values were corrected for body surface area. The cut-off values 28 and 34 ml/m2 were used for normal and definitely increased LA volume index, respectively [21]. Mitral inflow and pulmonary venous inflow were assessed by means of pulsed-wave Doppler echocardiography. From the mitral inflow profile, the early diastolic mitral flow velocity (E) and atrial contraction (A)-wave velocity and the Edeceleration time were measured, and the early-to-atrial left ventricular filling ratio (E/A) was calculated. The flow velocities of the left or right upper pulmonary vein were recorded, and the ratio of systolic to diastolic forward flow (S/D) was calculated. We measured the peak velocity of the tricuspid regurgitated signal with continuous-wave Doppler and calculated the systolic pulmonary artery pressure with the modified Bernoulli’s equation [22]. Diastolic function was assessed by an approach that integrates Doppler measurements of the mitral inflow and Doppler tissue imaging of the mitral annulus using the early diastolic septal annular velocity (e’) [23]. E’(early diastolic mitral annular velocity) is a measure of the relaxation of the ventricle. We calculated the early filling to early diastolic mitral annular velocity ratio (E/e') as a measure of filling pressures [24]. Criteria to establish diastolic and systolic dysfunction and heart failure An E/e' value below 8 was considered normal, and 8–15 indeterminate. An E/e'≥15 was considered abnormal [25], and these patients were classified as having diastolic dysfunction. When E/e' was between 8 and 15 and a septal e'
