European Heart Journal Advance Access originally published online on May 27, 2008
European Heart Journal 2008 29(14):1739-1752; doi:10.1093/eurheartj/ehn196
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Awareness and perception of heart failure among European cardiologists, internists, geriatricians, and primary care physicians
1 Sticares Cardiovascular Research Foundation, PO Box 882, 3160 AB Rhoon, The Netherlands
2 University of Glasgow, Glasgow, UK
3 Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK
4 Hôpital Lariboisière, Paris, France
5 Hospital Universitario Gregorio Maranon, Madrid, Spain
6 Ospedale S. Giovanni-Addolorata, Rome, Italy
7 CHU Nancy Hôpital de Brabois, Nancy, France
8 Institut für Herzinfarktforschung, Ludwigshafen am Rhein, Germany
9 Institulul de Boli Cardiovasculare, C.C.Iliescu, Bucharest, Romania
10 National Institute of Cardiology, Warsaw, Poland
11 Karolinska University Hospital, Stockholm, Sweden
Received 20 December 2007; revised 9 April 2008; accepted 17 April 2008; online publish-ahead-of-print 27 May 2008.
* Corresponding author. Tel: +31 10 485 51 77, Fax: +31 10 485 48 33, Email: w.j.remme{at}sticares.org
See page 1706 for the editorial comment on this article (doi:10.1093/eurheartj/ehn256)
| Abstract |
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Aims: To assess awareness of heart failure (HF) management recommendations in Europe among cardiologists (C), internists and geriatricians (I/G), and primary care physicians (PCPs).
Methods and results: The Study group on HF Awareness and Perception in Europe (SHAPE) surveyed randomly selected C (2041), I/G (1881), and PCP (2965) in France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden, and the UK. Each physician completed a 32-item questionnaire about the diagnosis and treatment of HF (left ventricular ejection fraction <40%). This report provides an analysis of HF awareness among C, I/G, and PCP. Seventy-one per cent I/G and 92% C use echocardiography, and 43% I/G and 82% C use echo-Doppler as a routine diagnostic test (both P < 0.0001). In contrast, 75% PCP use signs and symptoms to diagnose HF. Fewer I/G would use an angiotensin-converting enzyme (ACE)-inhibitor in >90% of their patients (64 vs. 82% C, P < 0.0001), whereas only 47% PCP would routinely prescribe an ACE-inhibitor. Worsening HF was considered a risk of ACE-inhibitor therapy by 35% PCP. I/G and PCP consistently do not prescribe target ACE-inhibitor doses (P < 0.0001 vs. C). Only 39% I/G would use a β-blocker in >50% of their patients (vs. 73% C, P < 0.0001). Also, only 5% PCP would always, and 35% often, prescribe a β-blocker and reach target doses in only 7–29%. Moreover, 34% PCP and 26% I/G vs. 11% C (P < 0.0001) do not start a β-blocker in patients with mild HF, who are already on an ACE-inhibitor and are on diuretic. In mild, stable HF, 39% PCP and 18% I/G would only prescribe diuretics, vs. 7% C (P < 0.0001). In patients with worsening HF in sinus rhythm and on an optimal ACE-inhibitor, β-blockade and diuretics, significantly more C would add spironolactone, but I/G would more often add digoxin.
Conclusion: Although each physician group lacks complete adherence to guideline-recommended management strategies, these are used significantly less well by I, G, and PCPs, indicating the need for education of these essential healthcare providers.
Key Words: Heart failure Awareness Perception Europe Guidelines Diagnosis Treatment Advice Cardiologists Internists Geriatricians Primary care physicians ACE inhibition β-Blockade Aldosterone antagonists Diuretics Echocardiography Heart failure nurses
| Introduction |
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Two decades of controlled clinical trials have led to significant developments in drug and device treatment of heart failure (HF). When and how to apply these evidence-based treatments is detailed in several international guidelines.1,2 These guidelines also provide recommendations on diagnostic investigations and non-pharmacological treatments, including lifestyle advice, exercise, and surgery. Despite the availability of guidelines for more than a decade in Europe,1,3–5 HF management still appears to be suboptimal, possibly because physicians do not implement guideline recommendations. Whereas surveys have been carried out among cardiologists (C) in Europe,6 the picture among internists (I) and geriatricians (G) is not clear, and a detailed comparison between different specialists involved in HF care across Europe is lacking.7 In contrast, previous surveys have clearly indicated that adherence to guideline-recommended practice is low among primary care physicians (PCPs).8,9 However, the most recent and largest of these studies, IMPROVEMENT-HF,9 started in 1999, around the time evidence was emerging of the benefit of β-blockers and spironolactone in addition to ACE-inhibitors to treat HF.10–13 Subsequently, other non-pharmacological treatments have been shown to reduce morbidity and mortality.14,15 Since these surveys, new national and international evidence-based guidelines have been published and widely disseminated. It is appropriate therefore to re-examine contemporary understanding of and attitudes to HF treatment in Europe.
The Study of HF Awareness and Perception in Europe (SHAPE) was designed to evaluate HF awareness among the general public and physicians involved in HF care. Here, the findings among C, I, G, and PCP are compared across nine European countries.
| Methods |
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The rationale and design of the SHAPE study have been previously published in detail.16 The study was carried out in France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden, and the UK, and aimed at including at least 300 PCP, 150 C, and 150 I/G combined per country. For the PCP survey, a questionnaire containing 33 questions was developed to gather PCPs knowledge of HF (including prevalence, aetiology, new diagnostic and therapeutic developments, and healthcare costs); the diagnostic procedures and treatments carried out by the PCPs in their own practices, their referral patterns for diagnostic procedures and specialist care; and the type of practice and number of patients in each primary care practice. The questionnaires sent to C, I, and G (in combination referred to as specialists) contained 32 questions covering epidemiology, aetiology, and diagnostic and therapeutic strategies in congestive heart failure (CHF), as well as some demographic and practice-related questions. In both questionnaires, treatment questions were specifically about CHF with a reduced left ventricular ejection fraction (<40%). Where applicable, respondents were requested to indicate their order of preference for a diagnostic or therapeutic intervention and the questions were based on the available European guidelines on diagnosis and treatment of HF. The questions were ordered so as not to influence answers. The questionnaires were piloted for reliability and validity, and final versions translated into each country's native language and checked for content and accuracy of translation by native-speaking physicians of the relevant countries and members of the SHAPE study group.
Questionnaires were coded by country and individual physician to preserve anonymity.
Primary care physician survey
A total of 18 000 PCPs were randomly selected from the nine countries. The minimum number of completed questionnaires required per country was set at 300. Assuming a 15% response rate, questionnaires were mailed to 2000 PCPs per country, randomly selected using a pre-specified algorithm from lists of all PCPs received from the respective PCP organizations in each country. In countries where the response was <15% in the first round, a second mailing was done following a second random selection from the remaining PCPs, the number based on the response rate from the first mailing.
In Italy, Romania, Sweden, and the UK, one mailing was sufficient. In the other countries, between 2139 (Spain) and 3881 (Germany) questionnaires were sent out in total.
Specialist survey
To achieve a minimum of 300 completed questionnaires per country (at least 150 C and 150 I/G), the questionnaire was sent to all specialists, in countries with
1500 specialists (using computer lists containing the names, specialization and addresses of each specialist), whereas in other countries a random selection of 1500 physicians (50% C and 50% I/G) was made using computer algorithms. If the response rate following the first mailing was insufficient, a second mailing, excluding responders to the first, followed. The number of questionnaires sent out during the second mailing was based on the percentage response (per specialist group) to the first mailing in a particular country, if sufficient additional addresses were available. If not, the complete mailing was repeated. Due to meagre responses to the first mailing, a second one was carried out in all countries.
The first questionnaires of the PCP and specialist surveys were sent out between October 2002 and January 2003. The databases were closed in June 2003.
Data analysis
The database was created in Microsoft Access. All questionnaires were single-entered into this database and checked for inconsistencies. In addition, one out of 15 records was double-entered and was checked for data entry mistakes. After closing the database, variables were recoded where appropriate. Results were tabulated in a descriptive way. For each possible answer, the counts and proportions were given for the separate countries and the overall total. To test the differences between C and I/G, within each physician group, and between countries, the Chi-square test was used. Countries with non-overlapping confidence intervals were considered different from each other. For all analyses, a value of P< 0.01 was considered significant. All analyses were performed with STATA version 6.0.
| Results |
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Response rate
Completed questionnaires were returned by 2041 C and 1881 I/G (29% of these were geriatricians). Response rates for C varied from 11% (160) in Spain to 35% (182) in the Netherlands (overall 25%) and for I/G between 11% (the Netherlands, 156 I/G) and 40% (Romania, 73 I/G) (overall 18%). Completed questionnaires were available from 2965 PCP. The average response rate overall was 13% and varied between countries, with the highest response from Romania (23% to the first mailing, 462 PCP) and the lowest from France and Germany (9% response rate each over two mailings, 292 and 331 PCPs, respectively).
Diagnosis of congestive heart failure
Specialists
Only 71% I/G indicated that they would routinely perform an echo and 43% an echo-Doppler, compared with 92 and 82% C, respectively (both P < 0.0001) (Table 1).
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Nearly all C and I/G performed a 12-lead ECG and chest X-ray routinely, but other investigations only on clinical indication. However, there were significant between-country differences (Table 1).The use of natriuretic peptides was low overall. More than one-third of C and I/G would not use natriuretic peptides for the diagnosis of HF.
Primary care physician
Seventy five per cent PCP reported that they often or always diagnosed HF by signs and symptoms alone (and 21% often or always by symptoms alone) (Table 2). Only 35% would often arrange for further investigations, whereas 22% thought that a response to diuretics was necessary to confirm the diagnosis. Only 9% PCP reported that they would reach a diagnosis of HF after referral to a specialist. Approximately 60% of respondents considered an ECG, chest X-ray, and echocardiogram necessary for diagnosis (Table 2). Again, the proportion varied by country. Echocardiography was considered necessary by 85% of Italian compared with 49% of Dutch PCPs.
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Only 50% could obtain an echocardiogram directly (16%) or via specialists (34%) within 1 month compared with 94% and 91% for an ECG or a chest X-ray, respectively (Table 3). There were large differences between countries. Direct access to echocardiography was poor in nearly all countries.
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Pharmacotherapy
Angiotensin-converting enzyme-inhibitors
Significantly fewer I/G than C indicated that they use an ACE-inhibitor in
90% of their patients (64 vs. 83% C, P < 0.0001, Table 4) and only 43% PCP would always (51% often) prescribe an ACE-inhibitor (Table 5); 13% I/G and 24% PCP would not prescribe an ACE-inhibitor in asymptomatic patients with LV dysfunction already on a diuretic (vs. 4% C, P < 0.0001). Also, more C than I/G and PCP would reach target doses of ACE-inhibitors (Figure 1).
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Approximately half of all C and I/G considered renal impairment, hypotension and hyperkalaemia a high risk of ACE-inhibitor use and approximately 25% C and 30% I/G would stop or adapt therapy in these instances. PCPs were less concerned, except for cough (55%) (Figure 2). Thirty-eight per cent C and 35% I/G would change or stop (and 47% PCP stop) treatment because of cough. Of interest, quite a few physicians in each group believed that ACE-inhibitors carried some risk of bronchospasm, cold extremities, impotence, and even worsening HF.
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β-Blockers
Only 5% PCP stated that they would always and 35% often prescribe a β-blocker (although there were considerable between-country differences, Table 5) and 11% would never prescribe it. Moreover, target doses of β-blockade would only be reached in seven (metoprolol) to 29% (carvedilol) of cases. Also, considerably fewer I/G (39%) than C (73%) would prescribe a β-blocker in
50% of their patients (P < 0.0001) (Table 4). More I/G (26%) than C (11%, P < 0.0001) and 35% PCP indicated that they would not treat patients with mild HF already on an ACE-inhibitor and a diuretic with a β-blocker. Conversely, only 45% PCP would not prescribe this treatment to a patient with unstable HF. Significantly less I/G than C would prescribe a β-blocker in case of old age, NYHA class IV, a systolic blood pressure <100 mmHg, heart rate <60 beats/min and chronic obstructive pulmonary disease (COPD) (Table 4), whereas >80% of PCP would not prescribe in case of bradycardia and COPD (Table 6).
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Other pharmacotherapy
The majority of C and I/G stated that they would prescribe an angiotensin receptor blocker (ARB) only in case of intolerance to ACE inhibition. Less than 10% reported adding an ARB to an ACE-inhibitor with persisting symptoms (PCP 7%). Significantly more Dutch C (37%) and I/G (46%) would use an ARB as a routine alternative to ACE inhibition (compared with C and I/G in other countries).
Most C and I/G indicated that they would prescribe digoxin in mild (NYHA I–II) HF only in selected cases (e.g. those with atrial fibrillation). Conversely, approximately half of C and I/G would prescribe digoxin regularly (i.e. in >30%) in patients with NYHA III and IV HF. Slow-release dihydropyridine calcium antagonists were prescribed by significantly more I/G (30%) than C (15%) in >10% of their patients. Also, significantly more I/G than C would use verapamil or diltiazem in >10% of their patients (31 vs. 5%, respectively).
Prescription rates for digoxin, aldosterone antagonists and nitrates by PCP mimicked those for β-blockers, although there were considerable between-country differences (Table 5).
Order of treatment
Primary care physician
Diuretics were the preferred single agent for initiation of treatment (Table 7). ACE-inhibitors (either alone or in combination with a diuretic) would be used to initiate treatment by only just over 50% of respondents. An average 34% of respondents would add a β-blocker in a patient who continued to have symptoms or worsened despite optimal treatment with a diuretic and an ACE-inhibitor. More would prescribe spironolactone (44%) or digoxin (38%), and approximately 50% would refer the patient for specialist care.
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Specialists
In mild–moderate, stable HF without signs of fluid retention, 58% C and 64% I/G reported they would start treatment with an ACE-inhibitor, whereas 25% C would start with an ACE-inhibitor and a β-blocker, up-titrated one after the other (vs. 13% I/G, P < 0.001). Few would start with only β-blockade.
If signs of fluid retention were present, most C and I/G (48 and 50%, respectively) would start with a diuretic only, and 40% C and 37% I/G with a diuretic and an ACE-inhibitor at the same time.
When asked whether, in mild HF (NYHA class I–II), diuretics alone are sufficient, 18% I/G agreed (31% in Germany) vs. 7% C (P < 0.001).
Worsening HF symptoms in a patient in sinus rhythm and already receiving optimal doses of ACE inhibition, β-blockade and diuretics would prompt more C than I/G to add spironolactone, whereas more I/G would add digoxin (Figure 3).
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Referral to a specialist
Only 55% PCP would send patients with mild-to-moderate HF, aged 65–80 years, to a specialist and only 32% would refer patients over 80 years (10% in the Netherlands).
How medical specialists obtain information on heart failure
Although guidelines scored the highest among C, they were only chosen by 32%, followed by expert opinion (30%), and review articles (18%). Expert opinion scored the highest among I/G (31%), whereas only 27 and 21% selected guidelines and review articles, respectively. Guidelines scored the highest in the Netherlands, but very low in Romania where expert opinion was particularly highly regarded.
| Discussion |
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This survey into the awareness and perception of different aspects of HF among C, I/G and PCP in nine European countries, selected to represent Europe geographically, indicates that, despite widespread availability of evidence-based HF guidelines, differences between physicians and countries exist in HF management. These differences were particularly apparent in the necessity to determine cardiac function (in particular the use of echocardiography as a routine diagnostic tool), prescription of ACE inhibition and β-blockade, use of low doses of these agents, reliance on diuretics as single treatment in HF, use of inappropriate drugs, and timing of medication.
The SHAPE survey is the only prospective multi-country European study to provide a comparison between awareness and perception of HF among C and I, and a contemporary analysis of those of PCPs in the same countries.
There are several prior between-specialist comparisons of HF management from single countries in Europe, which have reported differences in practice. A French study, conducted in 1997, showed no difference in the use of echocardiography and ACE-inhibitors by I compared with C but both were used less by geriatricians.17 In contrast, an Italian study, conducted in 1998, showed higher rates of the use of echocardiography, ACE-inhibitors, and β-blockers (and adherence to guidelines) by C compared with I.18 The only prior multinational data come from the Euro HF I study that provided information on ACE-inhibitor and β-blocker use at discharge from cardiology and general internal medicine wards in 24 European countries in 2000–1. These drugs were prescribed significantly less often in patients discharged from internal medicine wards.7 Because, however, the patients discharged from these two types of wards differed (those from internal medicine wards were older, had more co-morbidity, etc.), it was difficult to know whether the prescribing differences reflected physician knowledge and practice or patient characteristics.19 Our data suggest that the different treatment of patients discharged from internal medicine and cardiology wards, at least in part, reflects differences between specialists in their perception of the diagnosis and treatment of patients with HF.
PCPs perception of recommended diagnostic approaches and treatment options in HF are of concern. Most think that diagnosis can be made on the basis of symptoms and signs alone. Although 64% of PCPs consider an echocardiogram necessary and 32% supportive to establish the diagnosis of heart failure (a figure not too different from the 92% of specialists who perform echocardiography routinely in this case), only one-third would often arrange for it to diagnose HF. This might be at least partly explained by the availability of echocardiography; in most countries, echocardiography was not available to more than half of the PCPs within 1 month, or not available at all (e.g. Romania), and this would obviously impact on their usage by the PCP. It is very disappointing that lack of access may still be a problem, as this had been highlighted in earlier surveys such as the Euro-HF study8 (which, like SHAPE, was a questionnaire-based survey) and in the IMPROVEMENT-HF study9 (interview-based and an actual practice survey) which were conducted almost a decade ago. Of interest, in the IMPROVEMENT study, 48% PCPs reported to routinely use an echo for the diagnosis of HF20 as compared with our later survey, in which only 35% indicated to often arrange for investigations, including echo. Whether this failure to improve over time is the fault of healthcare providers (to recognize this as a public health problem and provide funding and resources), secondary care physicians (to be interested in the problem of HF in the community and provide service to their primary care colleagues) or PCPs (to recognize the need for echocardiography and demand its availability), or some combination of these, is unknown. Clearly, this needs to be identified and resolved before the most valuable diagnostic investigation is made universally available to European HF patients.
Our results also show that HF treatment in primary care has changed little due to the previous surveys.8,9 PCPs still do not follow the European and other guidelines, which consistently recommend ACE-inhibitors as first-line therapy for all patients with reduced left ventricular systolic function.3–5 Indeed, we found that many respondents stated that they would start their treatment with only a diuretic and less than half of them perceived the need to use ACE-inhibitors in all HF.
That β-blockers further reduce morbidity and mortality when added to an ACE-inhibitor became evident in 199911,12 and was clearly stated in guidelines available before our survey.3,4 Despite this, only 5% PCPs in SHAPE state that they would always (and 35% often) prescribe a β-blocker. Indeed, 11% would never prescribe a β-blocker and 35% would not prescribe it to a patient with mild symptoms on treatment with an ACE-inhibitor and diuretic. Moreover, a large majority of physicians reported that they would not reach the recommended target dosages of ACE-inhibitors or β-blockers.4 One contributing reason may be that there is a general concern and over-estimation of the risk of side-effects with these drugs,8 increasing the likelihood of not starting them or inappropriate dosing. These concerns were expressed by PCPs and I/G (more than by C). Changes in blood pressure and serum creatinine are usually small with ACE inhibition in normotensive patients without severe HF, and symptomatic hypotension is uncommon. Also, whereas β-blockade may lead to worsening HF, bradycardia, and hypotension in a few patients, these effects are usually not dangerous, and are rapidly reversible, provided that patients are stable and up-titration is slow, starting from a low dose. In MERIT-HF21 study, blood pressure in patients receiving β-blockade fell less than in the placebo group. Furthermore, there is a misconception that bronchospasm often occurs with β-blockade in HF. Combined non-selective β- and
-adrenergic blockade is well tolerated in HF patients with COPD.22
Only
50% PCPs said that they would refer a patient in the typical age range of HF (65–80 years) to a specialist, and few would do this in the elderly. In this context, the fact that many PCPs believe that they can, or are obliged to, detect HF based on symptoms and signs alone, is of concern. A correct diagnosis of HF requires objective evaluation of cardiac function. This is particularly important in the elderly, in whom the preponderance of women and high prevalence of co-morbidities make a correct diagnosis based on symptoms and signs alone even more hazardous.
Our finding that I/G report practices that frequently deviate from those recommended in guidelines is also of concern, as many patients admitted to hospital with HF are cared for by these specialists.
One obvious reason for why I/G report poor adherence to guideline-recommended practice is that they have not read the relevant guidelines. And that is exactly what we found when we asked physicians in our survey to report what influenced their practice. That I/G do not read the guidelines has also been reported in a single country survey.23 Moreover, the same authors reported from a similar PCP survey that while most PCPs were aware of the existence of a national guideline (SIGN), many had not read it.24 This is a worrying finding that points to a failure of international and national societies to reach an important target audience. Guidelines on the management of HF have been written mainly by C and published by cardiac societies and in cardiology journals. Consequently, non-cardiologists may not have access to the guidelines or may not feel that they are relevant to them. Ideally, guidelines should be put together by an optimal mix of C, I/G, PCP, and HF nurses, to assure their proper representation, and should be disseminated by appropriate medical and nursing organizations, and not just cardiac societies.
Although C may do better than I/G, they are not perfect in their adherence to guideline-recommended practice (not surprising, as only 32% C stated that guidelines had most influence on their decisions in HF management). For example, only 58% C would add spironolactone in a patient in sinus rhythm with worsening symptoms of HF despite optimal treatment with an ACE-inhibitor, β-blocker, and diuretic. In Romania, Italy, and Spain, this proportion was even lower. As SHAPE was carried out before August 2003, the results of the CHARM25,26 trial did not affect the SHAPE survey—in fact angiotensin receptor blockers only scored 1% in this question. Approximately 20% of C in Romania, Poland, and Italy stated that they would use digoxin instead, whereas similar percentages in Spain and France would reduce the dose of β-blocker. These findings highlight the need for continuing reinforcement of evidence-based practice through any possible means, e.g. registries aiming at improving outpatient HF care, such as IMPROVE HF,27 targeted at C.
Limitations
In both surveys, there was a relatively low response rate, which was expected based on experiences in earlier similar type of surveys. Nevertheless, the target numbers were reached. Whether those who responded were representative of the overall physician's group receiving a questionnaire would require a sensitivity analysis, which was not possible in this survey. Although a small response rate may introduce a bias, it is likely that those physicians who responded were the ones more interested in and more aware of HF. Accordingly, the knowledge of guideline-recommended approaches to the diagnosis and treatment of HF may be even less in the majority of physicians who did not respond to the survey.
An interview-based survey in contrast to an actual-practice study may not reflect what really happens with the patients in physicians' practices, but rather their perception of what they do or should do in managing them. It is likely that collecting data directly from patients could have further reduced the rate of adherence to guidelines.
A further limitation is that there are no data on the typical age of patients in different specialist practices nor in those of PCPs. Patients are likely to be older in geriatric and possibly internist and PCP practices than those seen by C. Age and greater co-morbidity in the elderly may influence perception and practice of different healthcare providers and their adherence to guidelines. Indeed, in a previous survey PCPs did indicate that they felt comfortable treating older patients with significant co-morbidity on the basis of a clinical diagnosis of HF.24 This may explain in part the different diagnostic and therapeutic approaches of these physicians.
| Conclusion |
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In conclusion, despite evidence-based guidelines, between-physician differences in the management of HF persist. In particular, the perceptions of the European PCP and I/G in aspects of HF, including the use of diagnostic techniques and pivotal therapies such as ACE-inhibitors and β-blockade, are not optimal. Consequently, there is significantly less uptake of recommended management strategies in their practices. As these non-cardiology physicians care for many HF patients educational programmes to increase their awareness and perception of HF are clearly needed. In addition, research on methods to improve implementation of evidence-based medicine and the European guidelines for management of HF in primary and non-cardiologist secondary care should be encouraged. Education apart, integration in multidisciplinary groups, including specialized nurses and C, may further increase the pivotal role of both the PCP and I/G in the management of HF.
| Study of Heart Failure Awareness and Perception in Europe steering committee |
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W.J. Remme (Chairman), A. Boccanelli, C. Cline, A. Cohen-Solal, R. Dietz, F.D.R. Hobbs, J. Lopez Sendon, C. Macarie, J. McMurray, B. Rauch, W. Ruzyllo, F. Zannad.
| Study of Heart Failure Awareness and Perception in Europe study group |
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The following members of the SHAPE study group critically reviewed the questionnaires:
France: J.M. Boivin, S. Briancon, A. Cohen-Solal, F. Zannad; Germany: W. Assen, Ch. Zugck, R. Dietz, B. Rauch; Italy: A. Boccanelli, G.F. Gensini, P. di Giulio, B. Guillaro, C. Opasisch, M. Scherillo; The Netherlands: D. Grobbee, A. Hoes, T. Jaarsma, W.J. Remme, D.J. van Veldhuisen; Poland: J. Grzybowski, M. Jedras, W. Ruzyllo; Romania: I. Bruckner, R. Cristodorescu, D.E. Falnita, C. Macarie, E. Petromaneantu; Spain: P. Conthe Gutierrez, J.M. Lobos Bejarano, J. Lopez Sendon; Sweden: N. Göran Ahlin, C. Cline, A. Iwarsson, G. Johansson; UK: F.D.R. Hobbs, M. Lye, J. McMurray.
Conflict of interest: none declared.
| Funding |
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The study was funded by an unrestricted grant from The Sticares Cardiovascular Research Foundation; Pfizer Inc.; F. Hoffmann-La Roche; Servier International; Medtronic Foundation; Guidant Europe Nv/Sa; GlaxoSmithKline; Abbott International; Chiesi Farmaceutici S.p.A.; Merck KGaA.
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